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## Complete Summary

#### GUIDELINE TITLE

VA/DoD clinical practice guideline for the management of dyslipidemia.

#### BIBLIOGRAPHIC SOURCE(S)

Management of Dyslipidemia Working Group. VA/DoD clinical practice
guideline for the management of dyslipidemia. Washington (DC):
Department of Veterans Affairs, Department of Defense; 2006. 140 p.

#### GUIDELINE STATUS

This is the current release of the guideline.

This guideline updates a previous version: Veterans Health
Administration, Department of Defense. VHA/DoD clinical practice
guideline for the management of dyslipidemia in primary care. Washington
(DC): Veterans Health Administration, Department of Defense; 2001 Dec.
Various p.

### \*\* REGULATORY ALERT \*\*

#### FDA WARNING/REGULATORY ALERT

**Note from the National Guideline Clearinghouse**: This guideline
references drugs for which important revised regulatory information has
been released.

-   [March 2, 2005, Crestor (rosuvastatin
    calcium)](http://www.fda.gov/medwatch/SAFETY/2005/safety05.htm#crestor):
    Revisions to the WARNINGS, DOSAGE AND ADMINISTRATION, CLINICAL
    PHARMACOLOGY, and PRECAUTIONS sections of the labeling.

### COMPLETE SUMMARY CONTENT

 \*\* REGULATORY ALERT \*\*\
 SCOPE\
 METHODOLOGY - including Rating Scheme and Cost Analysis\
 RECOMMENDATIONS\
 EVIDENCE SUPPORTING THE RECOMMENDATIONS\
 BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS\
 CONTRAINDICATIONS\
 QUALIFYING STATEMENTS\
 IMPLEMENTATION OF THE GUIDELINE\
 INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT
CATEGORIES\
 IDENTIFYING INFORMATION AND AVAILABILITY\
 DISCLAIMER

### SCOPE

#### DISEASE/CONDITION(S)

Dyslipidemia

#### GUIDELINE CATEGORY

Diagnosis\
Management\
Prevention\
Screening\
Treatment

#### CLINICAL SPECIALTY

Cardiology\
Family Practice\
Internal Medicine\
Nutrition

#### INTENDED USERS

Advanced Practice Nurses\
Allied Health Personnel\
Dietitians\
Nurses\
Physician Assistants\
Physicians

#### GUIDELINE OBJECTIVE(S)

-   To promote reduction of cardiovascular risk via evidence-based
    management of dyslipidemia, thereby improving clinical outcomes

-   To assist primary care providers or specialists in the detection of
    high blood cholesterol, assessment of the global risk for
    cardiovascular disease (CVD), determination of treatment goals and
    appropriate therapies, and delivery of individualized interventions

-   To incorporate information from several existing, national
    recommendations into a format that would maximally facilitate
    clinical decision-making

#### TARGET POPULATION

Adults (age 17 years or older) eligible for care in the Veterans Health
Administration/Department of Defense (VHA/DoD) health care system

#### INTERVENTIONS AND PRACTICES CONSIDERED

**Assessment/Diagnosis/Screening**

1.  Patient history and assessment of risk factors for cardiovascular
    disease

2.  Measurement of total cholesterol and high-density lipoprotein (HDL)
    or total cholesterol (TC), high-density lipoprotein, triglycerides
    (TG), and low-density lipoprotein (LDL)

3.  Fasting lipid profile, including low-density lipoprotein

4.  Assessment of body mass index and waist circumference

5.  Diagnosis of possible secondary causes of elevated low-density
    lipoprotein cholesterol using measurement of serum
    thyroid-stimulating hormone (TSH), blood urea nitrogen
    (BUN)/creatinine, liver function tests, and dipstick urinalysis

6.  Assessment of baseline serum transaminases

**Management/Treatment/Primary and Secondary Prevention**

1.  Age-appropriate lifestyle education on smoking, diet, and exercise

2.  Non-pharmacological management, including therapeutic lifestyle
    changes (TLC), medical nutrition therapy (MNT), and exercise

3.  Pharmacological therapy (monotherapy or combination therapy),
    including statins, niacin, resins, ezetimibe, fish oil/omega-3 fatty
    acids, n-3 polyunsaturated fatty acid (PUFA) supplements, fibrates

4.  Addressing adherence to therapy and safety concerns

5.  Repetition of dyslipidemia evaluation

#### MAJOR OUTCOMES CONSIDERED

-   Total cholesterol, low-density lipoprotein cholesterol, high-density
    lipoprotein cholesterol and triglyceride levels

-   Risk of developing coronary heart disease

-   Risk of developing atherosclerotic cardiovascular disease

-   Response to lifestyle changes and therapy, such as dietary changes,
    exercise, weight reduction, smoking cessation, reduction of
    excessive alcohol, and drug therapy

-   Adherence to diet, exercise and drug therapy

-   Cardiovascular disease outcomes (myocardial infarction, mortality,
    strokes)

### METHODOLOGY

#### METHODS USED TO COLLECT/SELECT EVIDENCE

Hand-searches of Published Literature (Primary Sources)\
Hand-searches of Published Literature (Secondary Sources)\
Searches of Electronic Databases

#### DESCRIPTION OF METHODS USED TO COLLECT/SELECT THE EVIDENCE

**Formulating of Questions**

The Working Group developed researchable questions and associated key
terms after orientation to the seed guideline and to goals that had been
identified by the Working Group. The questions specified: (adapted from
the Evidence-Based Medicine \[EBM\] toolbox, Centre for Evidence-Based
Medicine, \[[http://www.cebm.net](http://www.cebm.net/)\]):

-   **P**opulation - Characteristics of the target patient population

-   **I**ntervention - Exposure, diagnostic, or prognosis

-   **C**omparison - Intervention, exposure, or control used for
    comparison

-   **O**utcome - Outcomes of interest

These specifications served as the preliminary criteria for selecting
studies. Research questions focused on the following areas of inquiry:
screening, risk assessment, strategies, metabolic syndrome, non-drug
therapy, drug monotherapy, drug combination therapy, and adverse
effects.

**Selection of Evidence**

Published, peer-reviewed, randomized controlled trials (RCTs) were
considered to constitute the strongest level of evidence in support of
guideline recommendations. This decision was based on the judgment that
RCTs provide the clearest, scientifically sound basis for judging
comparative efficacy. The Working Group made this decision recognizing
the limitations of RCTs, particularly considerations of generalizability
with respect to patient selection and treatment quality. Evidence-based
systematic reviews were considered to be the strongest level of evidence
as well as meta-analyses that included randomized controlled studies.
The evidence selection was designed to identify the best available
evidence to address each key question and ensured maximum coverage of
studies at the top of the hierarchy of study types: evidence-based
guidelines, meta-analyses, and systematic reviews. When available, the
search sought out critical appraisals already performed by others that
described explicit criteria for deciding what evidence was selected and
how it was determined to be valid. The sources that have already
undergone rigorous critical appraisal include Cochrane Reviews, Best
Evidence, Technology Assessment, and evidence-based practice center
(EPC) reports.

The search was performed using the National Library of Medicine\'s (NLM)
MEDLINE database. The term \"hyperlipidemia\" was used together with the
following Boolean expressions and terms:

-   Epidemiology

-   Screening

-   Diagnosis

-   Primary Care

-   Protocols

-   Therapy

-   Patient Education

-   Economics

In addition to Medline/PubMed, the following databases were searched:
Database of Abstracts of Reviews of Effectiveness (DARE) and Cochrane
Central Register of Controlled Trials (CCTR). For Medline/PubMed
searches, limits were set for language (English), date of publication
(1999 through August 2004) and type of research (RCT and meta-analysis).

Once definitive reviews or clinical studies that provided valid relevant
answers to the question were identified, the search ended. The search
was extended to studies/reports of lower quality (observational studies)
only if there were no high quality studies.

Exclusion criteria included reviews that omitted clinical course or
treatment. Some retrieved studies were rejected on the basis of
published abstracts, and a few were rejected after the researchers
scanned the retrieved citation for inclusion criteria. Typical
exclusions included studies with physiological endpoints or studies of
populations that were not comparable to the population of interest
(e.g., studies of dyslipidemia in children). The bibliographies of the
retrieved articles were hand-searched for articles that may have been
missed by the computer search. Working Group members also contributed
articles as part of the evidence gathering process.

The results of the search were organized and evidence reports as well as
copies of the original studies were provided to the Working Group for
further analysis.

**Literature Review and Inclusion Criteria**

As a result of the original and updated literature reviews, articles
were identified for possible inclusion. These articles formed the basis
for formulating the guideline recommendations. The following inclusion
criteria were used for selecting randomized controlled trial studies:

-   Articles published between 1999 and 2004, with some exceptions

-   English language only

-   Full articles only

-   Age limited to adults \>18 years

-   Minimum study size of 100 patients per arm

-   Randomized controlled trials only; no cross-over trials

-   Minimum 1 year for cardiovascular (CVD) outcomes (myocardial
    infarctions, mortality, strokes, etc.)

-   Minimum 12 weeks for intermediate outcomes (total cholesterol,
    low-density lipoproteins \[LDL\], high-density lipoproteins,
    triglycerides)

-   Baseline LDL levels reported

-   Sufficient information to identify patient risk level

-   Key outcomes cited

For some questions, special inclusion criteria (mostly related to
minimum clinical trial size) were developed based upon research question
content and available literature.

The literature search for the guideline update was validated by: (1)
comparing the results to a search conducted by the independent research
and appraisal team; (2) a review of the database by the expert panel;
and (3) requesting articles pertaining to special topics from the
experts in the Working Group. It is important to note that due to
application of article screening criteria in the updated guideline, some
of the studies that were included in the original guideline were not
included in the updated analyses.

The guideline also drew heavily from the following sources for
recommendations:

-   Executive summary of the third report of the National Cholesterol
    Education Program (NCEP) expert panel on the detection, evaluation,
    and treatment of high blood cholesterol in adults (Adult Treatment
    Panel III).  *Journal of the American Medical Association 2001*, 285
    (19), 2486-2497.

-   NCEP ATP-III, 2002: Third Report of the National Cholesterol
    Education Program (NCEP) Expert Panel on Detection, Evaluation, and
    Treatment of High Blood Cholesterol in Adults (Adult Treatment
    Panel III) final report. Circulation 2002, 106, (25), 3143-421.

-   The U.S. Preventive Services Task Force Guide to Clinical Preventive
    Services. Second Edition 2001.

-   Pharmacy Benefits Management---Medical Advisory Panel. The
    pharmacologic management of hyperlipidemia. VHA PBM-SHG Publication.
    Hines, IL: Pharmacy Benefits Management Strategic Health Group,
    Veterans Health Administration, Department of Veterans Affairs.

#### NUMBER OF SOURCE DOCUMENTS

Not stated

#### METHODS USED TO ASSESS THE QUALITY AND STRENGTH OF THE EVIDENCE

Weighting According to a Rating Scheme (Scheme Given)

#### RATING SCHEME FOR THE STRENGTH OF THE EVIDENCE

**Quality of Evidence**

**I**: At least one properly done randomized controlled trial

**II-1**: Well designed controlled trails without randomization

**II-2**: Well designed cohort or case-control analytic study,
preferably from more than one source

**II-3**: Multiple time series evidence with/without intervention;
dramatic results of uncontrolled experiment

**III**: Opinion of respected authorities, descriptive studies, case
reports, and expert committees

**Overall Quality**

**Good**: High grade evidence (I or II-1) directly linked to health
outcome

**Fair**: High grade evidence (I or II-1) linked to intermediate
outcome; or moderate grade evidence (II-2 or II-3) directly linked to
health outcome

**Poor**: Level III evidence or no linkage of evidence to health
outcome.

**Net Effect of Intervention**

**Substantial**:

-   More than a small relative impact on a frequent condition with a
    substantial burden of suffering, *or*

-   A large impact on an infrequent condition with a significant impact
    on the individual patient level

**Moderate**:

-   A small relative impact on a frequent condition with a substantial
    burden of suffering, *or*

-   A moderate impact on an infrequent condition with a significant
    impact on the individual patient level

**Small**:

-   A negligible relative impact on a frequent condition with a
    substantial burden of suffering, *or*

-   A small impact on an infrequent condition with a significant impact
    on the individual patient level

**Zero or Negative**:

-   Negative impact on patients, *or*

-   No relative impact on either a frequent condition with a substantial
    burden of suffering*, or*

-   An infrequent condition with a significant impact on the individual
    patient level

#### METHODS USED TO ANALYZE THE EVIDENCE

Review of Published Meta-Analyses\
Systematic Review with Evidence Tables

#### DESCRIPTION OF THE METHODS USED TO ANALYZE THE EVIDENCE

**Preparation of Evidence Tables (Reports) and Evidence Rating**

A group of research analysts, with experience in evidence-based
appraisal, independently read and coded each article that met inclusion
criteria.  The research team prepared a brief summary of the critical
appraisal of each article that included the following components:

-   Description of patient population

-   Interventions

-   Comparisons

-   Outcomes

-   Summary of results

-   Analysis of findings

-   Evidence Appraisal

-   Clinical significance

Quality of evidence ratings were assigned for each source of evidence
using the grading scale presented in \"Rating Scheme for the Strength of
the Evidence\" in this summary. The quality rating procedure used in
this update was different from the rating scale used in the development
of the original guideline in 1999. Where adjustments to the update
process were made, articles from the original process were re-graded to
reflect the changed rating scale (e.g., the Strength of Recommendation
\[SR\] was assigned for each evidence, based on study design and
significance of the quality of the evidence).

#### METHODS USED TO FORMULATE THE RECOMMENDATIONS

Expert Consensus

#### DESCRIPTION OF METHODS USED TO FORMULATE THE RECOMMENDATIONS

The development of the 2005 Dyslipidemia Guideline Update (version 2.0)
was initiated in September 2004 and continued through November 2005. The
development process followed the steps described in \"Guideline for
Guideline,\" an internal working document of Veterans Health
Administration\'s (VHA\'s) National Clinical Practice Guideline Council,
which requires an ongoing review of the work in progress. The 1999
Veterans Administration/Department of Defense (VA/DoD) Dyslipidemia
Guideline represented a \"seed document\" that was updated and adapted
by the joint VA/DoD Dyslipidemia Working Group. As with the original
Working Group, the charge of the VA/DoD group was to provide
evidence-based action recommendations whenever possible; hence, major
clinical randomized controlled trials (RCTs) and observational studies
published from August 1999 through August 2004 in the areas of diagnosis
and treatment of dyslipidemia.

**Guideline Development Process**

The Offices of Quality and Performance and Patient Care Service, in
collaboration with the network Clinical Managers, the Deputy Assistant
Under Secretary for Health, and the Medical Center Command of the DoD
identified clinical leaders to champion the guideline development
process. During a preplanning conference call, the clinical leaders
defined the scope of the guideline and identified a group of clinical
experts from the VA and DoD that formed the Guideline Development
Working Group. Working Group members included representatives of the
following specialties: internal medicine, cardiology, endocrinology,
medical nutrition therapy, social work, family practice, nursing,
pharmacy, and rehabilitation medicine.

At the start of the update process, the clinical leaders, guideline
Working Group members, outside experts, and experts in the field of
guideline and algorithm development were consulted to determine which
aspects of the 1999 guideline required updating. These consultations
resulted in the following recommendations that guided the update
efforts: (1) update any recommendations from the original guideline
likely to be affected by new research findings; (2) provide information
and recommendations on health systems changes relevant to dyslipidemia
screening and treatment; (3) address content areas and models of
treatment for which little data existed during the development of the
original guideline; and (4) review the performance and lessons learned
since the implementation of the original guideline.

The Working Group participated in an initial face-to-face meeting to
reach consensus about the guideline algorithm and recommendations and to
prepare a draft document. The draft continued to be revised by the
Working Group at-large through numerous conference calls and individual
contributions to the document. Following the initial effort, an
editorial panel of the Working Group convened to further edit the draft
document. Recommendations for the performance or exclusion of specific
procedures or services derived through a rigorous methodological
approach that includes the following:

-   Determination of appropriate criteria, such as effectiveness,
    efficacy, population benefit, or patient satisfaction

-   Literature review to determine the strength of the evidence in
    relation to these criteria

-   Formulation of the recommendations and grading of the level of
    evidence supporting the recommendation

**Selection of Evidence**

Each reference was appraised for scientific merit, clinical relevance,
and applicability to the populations served by the Federal healthcare
system. Recommendations were based on consensus of expert opinions and
clinical experience only when scientific evidence was unavailable.
Although the Strength of Recommendation (SR) rating was influenced
primarily by the science, other factors were taken into consideration
when assigning a SR rating such as: the burden of suffering imposed on
the patient.

**Recommendation and Overall Quality Rating**

Evidence-based practice involves integrating clinical expertise with the
bets available clinical evidence derived from systematic research. The
Working Group received an orientation and tutorial on the evidence U.S.
Preventive Services Task Force (USPSTF) 2001 rating process, reviewed
the evidence, and independently formulated Quality of Evidence Ratings,
a rating of Overall Quality, and a Net Effect of the Intervention (see
\"Rating Scheme for the Strength of the Evidence\" in this summary) and
a Final Grade of Recommendation (see \"Rating Scheme for the Strength of
the Recommendations\" in this summary).

**Lack of Evidence -- Consensus of Experts**

The majority of the literature supporting the science for these
guidelines is referenced throughout the document and is based upon key
RCTs and longitudinal studies published from 1999 through 2004.
Following the independent review of the evidence, a consensus meeting
was held to discuss discrepancies in ratings and formulate
recommendations. Where existing literature was ambiguous or conflicting,
or where scientific data was lacking on an issue, recommendations were
based on the clinical experience of the Working Group. These
recommendations are indicated in the evidence tables as based on
\"Working Group Consensus.

#### RATING SCHEME FOR THE STRENGTH OF THE RECOMMENDATIONS

  -------------------------------------------------------------------------------------
  ** **                 **Net Benefit of                             
                        the                                          
                        Intervention**                               
  --------------------- ----------------- -------------- ----------- ------------------
  ***Quality of         **Substantial**   **Moderate**   **Small**   **Zero or
  Evidence***                                                        Negative**

  **Good**              A                 B              C           D

  **Fair**              B                 B              C           D

  **Poor**              I                 I              I           I
  -------------------------------------------------------------------------------------

**A**: A strong recommendation that the clinicians provide the
intervention to eligible patients.\
*Good evidence was found that the intervention improves important health
outcomes and concludes that benefits substantially outweigh harm.*

**B**: A recommendation that clinicians provide (the service) to
eligible patients.\
*At least fair evidence was found that the intervention improves health
outcomes and concludes that benefits outweigh harm.*

**C**: No recommendation for or against the routine provision of the
intervention is made.\
*At least fair evidence was found that the intervention can improve
health outcomes but concludes that the balance of benefits and harms is
too close to justify a general recommendation.*

**D**: Recommendation is made against routinely providing the
intervention to asymptomatic patients.\
*At least fair evidence was found that the intervention is ineffective
or that harms outweigh benefits.*

**I**: The conclusion is that the evidence is insufficient to recommend
for or against routinely providing the intervention.\
*Evidence that the intervention is effective is lacking, or poor
quality, or conflicting and the balance of benefits and harms cannot be
determined.*

#### COST ANALYSIS

Published cost analyses were reviewed in the preparation of the
guideline.

#### METHOD OF GUIDELINE VALIDATION

Internal Peer Review

#### DESCRIPTION OF METHOD OF GUIDELINE VALIDATION

Experts from the Veterans Administration (VA) and Department of Defense
(DoD) internal medicine, cardiology and primary care reviewed the final
draft. Their feedback was integrated into the final draft.

### RECOMMENDATIONS

#### MAJOR RECOMMENDATIONS

The recommendations for the management of dyslipidemia in the primary
care setting are organized into 3 major algorithms. Each algorithm, the
objectives and recommendations that accompany it, and the evidence
supporting the recommendations are presented below. The quality of
evidence **(QE)** grading (I-III); overall quality (**Good, Fair,
Poor**); and final grade of recommendations **(R)** (A-D, I) are
provided for specific statements. These grades, along with \"net effect
of the interventions\" are defined at the end of the \"Major
Recommendations\" field.

[Screening
Algorithm](http://www.oqp.med.va.gov/cpg/DL/dl_cpg/algo1frameset.htm)

*Note: A list of all abbreviations is provided at the end of the \"Major
Recommendations\" field*.

A.  **Adult Patient Enrolled in the Health Care System**

> *Definition*
>
> This guideline addresses adults (age 17 years or older) eligible for
> care in the Veterans Health Administration/ Department of Defense
> (VHA/DoD) healthcare systems.

B.  **Does Patient Have a History of Cardiovascular Disease (CVD)?**

> *Objective*
>
> Identify patients who may benefit from lipid lowering therapy.
>
> *Recommendations*

1.  All patients with known CVD are considered high-risk and should be
    treated with aggressive lipid-lowering therapy to prevent acute
    vascular events. These include, but are not limited to, acute
    myocardial infarction (AMI) or cerebrovascular accident (CVA).

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C.  **Does Patient Have Diabetes Mellitus?**

> *Objective*
>
> Identify patients known to be at high-risk due to diabetes mellitus
> (DM).
>
> *Recommendation*

1.  Patients with Type 2 DM are at significantly increased risk of CVD
    compared with non-diabetic patients of similar age and should,
    therefore, be treated more aggressively according to secondary
    prevention protocols. **\[A\]**

  ------------------------------------------------------------------------------------------
  ** **   **Recommendation**        **Sources of Evidence**     **QE**   **Overall   **R**
                                                                         Quality**   
  ------- ------------------------- --------------------------- -------- ----------- -------
  1       Persons with Type-2 DM,   Haffner et al., 1998\       I        Good        A
          even in the absence of    Yusuf et al., 2000\                              
          CVD, should be treated as Heart Protection Study                           
          CVD equivalent            Collaborative Group (HPS),                       
                                    2002\                                            
                                    Malmberg et al., 2000                            

  ------------------------------------------------------------------------------------------

QE = Quality of Evidence; R = Strength of Recommendation (see Appendix A
in the original guideline document)

D.  **Assess Risk Factors for Cardiovascular Disease**

> *Objective*
>
> Identify clinical markers that predict an increased risk for
> developing CVD, thereby changing the interpretation of low-density
> lipoprotein (LDL) levels.
>
> *Recommendations*

1.  Patients screened for dyslipidemia should be assessed for risk
    factors for CVD. Assessment should include, but not be limited to,
    the following:

    a.  Age (males [\>]{.underline}age 45 and females
        [\>]{.underline}age 55)

    b.  Family history of premature coronary artery disease; definite
        myocardial infarction (MI) or sudden death before age 55 in
        father or other male first-degree relative, or before age 65 in
        mother or other female first-degree relative

    c.  Current tobacco use/cigarette smoking (or within the last month)

    d.  Hypertension (systolic blood pressure [\>]{.underline}140 mmHg
        or diastolic blood pressure [\>]{.underline}90 mmHg confirmed on
        more than one occasion, or current therapy with
        anti-hypertensive medications)

    e.  Diabetes mellitus (DM) (elevated fasting blood sugar
        \[[\>]{.underline}126 mg/dL\], or a random blood sugar
        \[[\>]{.underline}200 mg/dL\] confirmed on more than one
        occasion, an abnormal glucose tolerance test or current therapy
        with anti-diabetic medications)

    f.  Level of high-density lipoprotein cholesterol (HDL-C) (less than
        40 mg/dL confirmed on more than one occasion).

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2.  In obese patients (body mass index \[BMI\] [\>]{.underline}30),
    waist circumference measurement should be obtained to assist in the
    diagnosis of metabolic syndrome.

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E.  **Lipid Screening Criteria**

> *Objective*
>
> Appropriately target individuals for lipid profile screening.

+-----------------------------------------------------------------------+
| **Lipid Screening Criteria**                                          |
+=======================================================================+
| 1.  Male age 35 or older OR female age 45 or older OR                 |
|                                                                       |
| 2.  Young adults with more than one of the following:                 |
|                                                                       |
|     a.  Family history of premature CVD                               |
|                                                                       |
|     b.  Patient is smoking                                            |
|                                                                       |
|     c.  Patient has or is being treated for hypertension              |
|                                                                       |
| ```{=html}                                                            |
| <!-- -->                                                              |
| ```                                                                   |
| 3.  Consider obtaining lipid profile for young adults with abdominal  |
|     obesity                                                           |
+-----------------------------------------------------------------------+

> *Recommendations*

1.  Fasting lipid profile testing should be obtained in all men age 35
    and older and women age 45 years or older every 5 years. **\[A\]**

2.  Fasting lipid profile testing should be obtained in individuals with
    a family history or clinical evidence of familial hyperlipidemia.
    **\[A\]**

3.  Fasting lipid profile testing in young adults may be considered
    depending upon the association with other risk factors. Younger
    adults (men younger than age 35 and women age 45 or younger) should
    be screened for lipid disorders if they have one or more of the
    following risk factors: family history of premature CVD,
    hypertension (or under treatment for hypertension \[HTN\]), or
    smoking. **\[B\]**

4.  A lipid profile should be obtained for individuals with abdominal
    obesity (waist circumference \>40 inches in men and \>35 inches in
    women) to aid in assessment of metabolic syndrome. **\[B\]**

5.  All persons with average or below average risk for atherosclerotic
    events should be screened for dyslipidemia every five years.
    **\[I\]**

6.  Elderly patients age 75 or older should be screened if they have
    multiple CVD risk factors, or a history of CVD and good quality of
    life with no other major life-limiting diseases. **\[I\]**

+-----------------------------------------------------------------------+
| **The Recommended Screening Schedules for Dyslipidemia**              |
+=======================================================================+
| *For young adults (men \<age 35; women \<age 45)*                     |
|                                                                       |
| -   Every 5 years when no CVD risk factors are present                |
|                                                                       |
| -   More often, if family history of premature CVD exists (definite   |
|     MI or sudden death before 55 years of age in father or other male |
|     first-degree relative or before age 65 in mother or other female  |
|     first-degree relative)                                            |
|                                                                       |
| *For middle-aged adults (men [\>]{.underline}age 35; women            |
| [\>]{.underline}age 45)*                                              |
|                                                                       |
| -   Every 5 years, when no CVD risk factors are present               |
|                                                                       |
| -   Annually, if CVD risk factors exist (HTN, smoking, family history |
|     of premature CVD)                                                 |
|                                                                       |
| *For elderly patients up to age 75 years*                             |
|                                                                       |
| -   Every 5 years when no CVD risk factors are present                |
|                                                                       |
| -   More often if CVD risk factors exist                              |
|                                                                       |
| *For elderly patients \>age 75*                                       |
|                                                                       |
| -   Evaluate if patient has multiple CVD risk factors, established    |
|     CVD, *or* a history of revascularization procedures *and* good    |
|     quality of life with no other major life-limiting diseases.       |
+-----------------------------------------------------------------------+

  ------------------------------------------------------------------------------------------
  ** **   **Recommendation**        **Sources of Evidence**     **QE**   **Overall   **R**
                                                                         Quality**   
  ------- ------------------------- --------------------------- -------- ----------- -------
  1       Fasting lipid profile     Third Report of the         I        Good        A
          should be obtained in men National Cholesterol                             
          [\>]{.underline}age 35    Education Program Expert                         
          and women                 Panel (NCEP) on Detection,                       
          [\>]{.underline}age 45    Evaluation, and Treatment                        
                                    of High Blood Cholesterol                        
                                    in Adults (Adult Treatment                       
                                    Panel III) final report                          
                                    (NCEP ATP-III), 2002\                            
                                    U.S. Preventive Services                         
                                    Task Force (USPSTF), 2001                        

  2       Fasting lipid profile     NCEP ATP-III, 2002          I        Good        A
          should be obtained in                                                      
          patients with family                                                       
          history or clinical                                                        
          evidence of familial                                                       
          hyperlipidemia                                                             

  3       Consider screening        NCEP ATP-III, 2002\         I        Fair        B
          fasting lipid profile in  Pignone et al., 2001\                            
          young adults with other   USPSTF, 2001\                                    
          risk factors (family      \"A multicenter comparative                      
          history of premature CVD, trial,\" 1993                                    
          HTN, or smoking)                                                           

  4       Fasting lipid profile     NCEP ATP-III, 2002          I        Good        B
          should be obtained for                                                     
          patients with increased                                                    
          waist circumference (men                                                   
          \>40 inches , women \>35                                                   
          inches) to aid in                                                          
          assessment of metabolic                                                    
          syndrome                                                                   

  5       Persons with average or   Working Group Consensus     III      Poor        I
          below average CV risk                                                      
          should be screened every                                                   
          five years                                                                 

  6       Elderly patients age \>75 Working Group Consensus     III      Poor        I
          should be screened if                                                      
          they have multiple CVD                                                     
          risk factors, a history                                                    
          of CVD *and* good quality                                                  
          of life with no other                                                      
          major life-limiting                                                        
          diseases                                                                   
  ------------------------------------------------------------------------------------------

QE = Quality of Evidence; R = Strength of Recommendation (see Appendix A
in the original guideline document)

F.  **Obtain a Fasting Lipid Profile**

> *Objective*
>
> Screen appropriate patients for the presence of dyslipidemia.

+-----------------------------------------------------------------------+
| **Lipid Screening Test**                                              |
+=======================================================================+
| -   Ensure test obtained in fasting state (9 to 14 hour fast)         |
|                                                                       |
| -   Total cholesterol (TC), triglycerides (TG), and HDL-C are         |
|     measured directly                                                 |
|                                                                       |
| -   LDL-C is calculated, therefore, TG level should be considered     |
|                                                                       |
| (If TG \>400 mg/dL, try to reduce with diet and exercise, or consider |
| direct measurement of LDL-C)                                          |
+-----------------------------------------------------------------------+

> *Recommendations*

1.  A complete fasting lipid profile should be obtained in an individual
    with other risk factors for coronary disease. **\[A\]**

2.  Clinical decisions should be based upon lipid profiles done 1 to 8
    weeks apart (fasting) with an LDL-C or TC difference of \<30 mg/dL.
    **\[I\]**

3.  Lipid profiles should not be obtained within 8 weeks of acute
    hospitalization, surgery, trauma, or infection unless they are
    obtained within 12 to 24 hours of the event to ensure accuracy.
    **\[I\]**

4.  Lipid profiles should not be measured in pregnant women until three
    to four months post partum. **\[I\]**

  ------------------------------------------------------------------------------------------
  ** **   **Recommendation**        **Sources of Evidence**     **QE**   **Overall   **R**
                                                                         Quality**   
  ------- ------------------------- --------------------------- -------- ----------- -------
  1       A complete fasting lipid  USPSTF, 2001                I        Good        A
          profile should be                                                          
          obtained in individuals                                                    
          with other risk factors                                                    
          for coronary artery                                                        
          disease (CAD)                                                              

  2       Clinical decisions should Working Group Consensus     III      Poor        I
          be based upon lipid                                                        
          profiles done 1 to 8                                                       
          weeks apart (fasting or                                                    
          no fasting) with an LDL-C                                                  
          or TC difference of less                                                   
          than 30 mg/dL                                                              

  3       Lipid profiles should not Working Group Consensus     III      Poor        I
          be obtained within 8                                                       
          weeks post-acute                                                           
          hospitalization, surgery,                                                  
          trauma, or infection                                                       
          unless they are obtained                                                   
          within 12 to 24 hours of                                                   
          the event to ensure                                                        
          accuracy                                                                   

  4       Lipid profiles should not Working Group Consensus     III      Poor        I
          be measured in pregnant                                                    
          women until three to four                                                  
          months post partum                                                         
  ------------------------------------------------------------------------------------------

QE = Quality of Evidence; R = Strength of Recommendation (see Appendix A
in the original guideline document)

G.  **TG \>400 mg/dL, Apply Diet and Exercise to Reduce TG; Consider
    Direct Measurement of LDL-C**

> *Objective*
>
> Identify patients whose LDL-C is confounded by secondary/modifiable
> causes of hypertriglyceridemia.
>
> *Recommendations*

1.  If TG levels can be brought to \<400 mg/dL by dietary or other
    interventions, then Friedewald\'s formula can be used to calculate a
    more exact LDL-C level. **\[C\]**

2.  If TGs cannot be brought to levels less than 400 mg/dL, then
    consider measuring LDL-C directly, or estimate the LDL-C using the
    following equation: **\[I\]**

> Estimated LDL-C = (TC -- HDL) -- 30

3.  Screen and treat common causes of elevated TGs: fatty diet, high
    carbohydrate diets, alcohol use, hypothyroidism, and hyperglycemia.
    **\[B\]**

4.  In the absence of secondary causes, the first-line therapy for
    elevated TGs should be therapeutic life-style changes. **\[C\]**

  ------------------------------------------------------------------------------------------
  ** **   **Recommendation**        **Sources of Evidence**     **QE**   **Overall   **R**
                                                                         Quality**   
  ------- ------------------------- --------------------------- -------- ----------- -------
  1       Use Friedewald\'s formula Friedewald et al., 1972\    III      Fair        C
          to calculate LDL-C --     NCEP ATP-III, 2002                               
          when TG levels can be                                                      
          brought to \<400 mg/dL by                                                  
          dietary or other                                                           
          interventions                                                              

  2       If TGs are \>400 consider Friedewald et al., 1972\    III      Poor        I
          directly measuring LDL-C  NCEP ATP-III, 2002\                              
                                    Stone & Blum, 2002                               

  3       Screen and treat common   Cleeman, 1998\              II-3     Fair        B
          causes of elevated TGs    Friedewald et al., 1972\                         
                                    NCEP ATP-III, 2002\                              
                                    Stone & Blum, 2002                               

  4       In the absence of         Cleeman, 1998\              II-3     Poor        C
          secondary causes, the     Friedewald et al., 1972\                         
          first-line therapy for    NCEP ATP-III, 2002\                              
          elevated TGs should be    Stone & Blum, 2002                               
          therapeutic life-style                                                     
          changes                                                                    
  ------------------------------------------------------------------------------------------

QE = Quality of Evidence R = Strength of Recommendation (see Appendix A
in the original guideline document)

H.  **Is Lipid Profile Abnormal?**

> *Objective*
>
> Identify patients who require further evaluation and/or therapy for
> dyslipidemia.

  -----------------------------------------------------------------------
  **Classification of Serum Lipids**               
  ------------------------------------------------ ----------------------
  **Total Cholesterol (TC) mg/dL (mmol/L)**        **Category**

  \<200 (\<5.2)\                                   Normal\
  200 to 239 (5.2 to 6.1)\                         Borderline high\
  [\>]{.underline}240 ([\>]{.underline} 6.2)       High

  **LDL-Cholesterol mg/dL (mmol/L)**               

  \<100 (\<2.6)\                                   Normal\
  100 to 129 (2.6 to 3.3)\                         Above, near optimal\
  130 to 159 (3.4 to 4.0)\                         Borderline high\
  160 to 189 (4.1 to 4.8)\                         High\
  [\>]{.underline}190 ([\>]{.underline}4.9)        Very high

  **HDL- Cholesterol mg/dL (mmol/L)**              

  \<40 (\<1.0)\                                    Low\
  [\>]{.underline}60 ([\>]{.underline}1.6)         High

  **Triglycerides (TG) mg/dL (mmol/L)**            

  \<150 mg/dL (\<1.7)\                             Normal\
  150 to 199 mg/dL (1.7 to 2.2)\                   Borderline High\
  200 to 499 mg/dL (2.3 to 5.6)\                   High\
  [\>]{.underline}500 mg/dL ([\>]{.underline}5.6)  Very High
  -----------------------------------------------------------------------

> *Recommendation*

1.  Patients with LDL [\>]{.underline}130 mg/dL, HDL \<40 mg/dL, or TG
    \>200 mg/dL should be assessed for further management of
    dyslipidemia. **\[C\]**

  ------------------------------------------------------------------------------------------
  ** **   **Recommendation**        **Sources of Evidence**     **QE**   **Overall   **R**
                                                                         Quality**   
  ------- ------------------------- --------------------------- -------- ----------- -------
  1       Classify Serum Lipid      NCEP ATP-III, 2002          II-2     Good        C
          levels based on degree of                                                  
          elevation of LDL, TG, or                                                   
          low HDL                                                                    

  ------------------------------------------------------------------------------------------

QE = Quality of Evidence; R = Strength of Recommendation (see Appendix A
in the original guideline document)

I.  **Encourage Healthy Lifestyle**

> *Objective*
>
> Promote lifestyle changes that will decrease the risk of CVD.
>
> *Recommendations*

1.  All adults should be encouraged to adopt healthy lifestyles that may
    reduce the risk of cardiovascular disease, to include:

    a.  Tobacco cessation interventions offered to all smokers **\[A\]**

    b.  Eat a healthy diet **\[B\]**

    c.  Engage in 30 minutes or more of moderate intensity physical
        activity on most days of the week. **\[B\]**

  ------------------------------------------------------------------------------------------
  ** **   **Recommendation**        **Sources of Evidence**     **QE**   **Overall   **R**
                                                                         Quality**   
  ------- ------------------------- --------------------------- -------- ----------- -------
  1       Advise patients to stop   Fiore et al., 2000\         I        Good        C
          smoking                   Silagy & Stead, 2001                             

  2       Provide tobacco cessation Fiore et al., 2000          I        Good        A
          interventions to smokers                                                   

  3       Provide interventions to  Beresford et al., 1997\     I        Fair        B
          encourage a healthy diet  McCarron et al., 1997                            

  4       Encourage 30 minutes or   Pate et al., 1995\          I\       Fair        B
          more of moderate          American College of Sports  IIa                  
          intensity aerobic         Medicine (ACSM), 1995\                           
          physical activity on most Pollock & Wilmore, 1990\                         
          days of the week          Spate-Douglas & Keyser.,                         
                                    1999                                             
  ------------------------------------------------------------------------------------------

QE = Quality of Evidence; R = Strength of Recommendation (see Appendix A
in the original guideline document)

J.  **Repeat Dyslipidemia Evaluation in 1 to 5 Years**

> *Objective*
>
> Provide appropriate clinical follow-up for patients initially at
> low-risk for CVD.
>
> *Recommendations*

1.  Patients with average or below average risk for atherosclerotic
    events should be screened for dyslipidemia every five years.
    **\[B\]**

  ------------------------------------------------------------------------------------------
  ** **   **Recommendation**        **Sources of Evidence**     **QE**   **Overall   **R**
                                                                         Quality**   
  ------- ------------------------- --------------------------- -------- ----------- -------
  1       Patients with average or  NCEP ATP-III, 2002\         III      Fair        B
          below average risk for    \"A multicenter comparative                      
          atherosclerotic events    trial,\" 1993                                    
          should be screened for                                                     
          dyslipidemia every                                                         
          five-year period                                                           

  ------------------------------------------------------------------------------------------

QE = Quality of Evidence; R = Strength of Recommendation (see Appendix A
in the original guideline document)

[Initiation of Therapy
Algorithm](http://www.oqp.med.va.gov/cpg/DL/dl_cpg/algo2frameset.htm)

K.  **Patient with Abnormal Lipid Profile or History of CVD or
    Diabetes**

> Patients managed by this guideline algorithm have abnormal lipid
> profiles (dyslipidemia) or evidence of cardiovascular disease (CVD) or
> diabetes.

L1. **Obtain History, Physical Examination, and Laboratory Tests. Assess
for Secondary Causes, Familial Disorders, and Comorbidities**

*Objective*

Detect and if needed treat health disorders that present with an
elevated LDL-C or TG, low HDL-C, or metabolic syndrome.

*Recommendations*

1.  Adults with abnormal lipid profiles (dyslipidemia) should be
    assessed for secondary causes, familial disorders, and other
    underlying conditions that may influence lipid levels. **\[I\]**

2.  Assessment for secondary causes should be based on medical history,
    physical examination and laboratory tests:

    a.  Measurement of serum thyroid-stimulating hormone (TSH), blood
        urea nitrogen (BUN)/creatinine, liver function tests (LFTs), and
        a dipstick urinalysis should be obtained to exclude
        hypothyroidism, chronic renal failure, obstructive liver
        disease, and nephrotic syndrome conditions. **\[I\]**

    b.  If dipstick urine protein is \>1+ (detected in two urine tests),
        nephrotic syndrome as a secondary cause of elevated LDL-C should
        be ruled out. **\[I\]**

    c.  Serum lipids should be assayed six to eight weeks post-TSH
        normalization to determine the need for additional treatment.
        **\[I\]**

    d.  Patients with hypertriglyceridemia should be evaluated for
        alcohol use, diabetes, and hypothyroidism. Addressing these
        underlying conditions can improve or normalize triglyceride
        levels, and failure to address these can render therapy
        ineffective. **\[I\]**

    e.  Lipid levels in patients treated for secondary hyperlipidemia
        should be repeated six to eight weeks post correction of the
        underlying disorder.

    f.  Family members of patients presenting with very severe
        hypercholesterolemia should be screened to detect other
        candidates for therapy.

    g.  Consider consulting with a specialist to assist the primary care
        clinician in co-managing patients with familial disorders who do
        not respond to therapy. **\[I\]**

  ------------------------------------------------------------------------
  **Secondary Causes of Lipid                  
  Abnormalities**                              
  ------------------------------- ------------ ---------------------------
  **Disorder/Patient              **Effect on  **Laboratory Test for
  Characteristic**                Lipids**     Diagnosis**

  Chronic renal failure/postrenal Increase TG\ S~Cr~
  transplantation                 Increase TC\ 
                                  Decrease     
                                  HDL-C        

  DM                              Increase TG\ Glucose, HbA1c
                                  Increase TC\ 
                                  Decrease     
                                  HDL-C        

  Ethanol use                     Increase TG\ \--
                                  Increase     
                                  HDL-C        

  HIV/AIDS Wasting                Increase TG\ \--
                                  Decrease TC\ 
                                  Decrease     
                                  HDL-C\       
                                  Decrease     
                                  LDL-C        

  HIV/AIDS (HAART)                Increase TG\ \--
                                  Increase TC\ 
                                  Increase     
                                  HDL-C        

  Hypothyroidism                  Increase TG\ TSH
                                  Increase TC\ 
                                  Increase     
                                  LDL-C        

  Inactivity                      Decrease     \--
                                  HDL-C        

  Nephrotic syndrome              Increase TC\ Urinalysis, serum albumin
                                  Increase     
                                  LDL-C        

  Obesity                         Increase TG\ \--
                                  Decrease     
                                  HDL-C        

  Obstructive liver disease       Increase TC  LFTs (Alkaline phosphatase,
                                               total bilirubin)

  Estrogen therapy                Increase TG\ \--
                                  Decrease     
                                  LDL\         
                                  Increase HDL 

  Medications                     Variable     \--
  ------------------------------------------------------------------------

AIDS = acquired immune deficiency syndrome; DM = diabetes mellitus;
HAART = highly active antiretroviral therapy; HbA1c = glycosylated
hemoglobin; HDL-C = high-density lipoprotein cholesterol; HIV = human
immunodeficiency virus; LDL-C = low-density lipoprotein cholesterol;
LFTs = liver function tests; SCr = serum creatinine; TC = total
cholesterol; TG = triglycerides; TSH = thyroid-stimulating hormone

  ------------------------------------------------------------------------------------------
  ** **   **Recommendation**        **Sources of Evidence**     **QE**   **Overall   **R**
                                                                         Quality**   
  ------- ------------------------- --------------------------- -------- ----------- -------
  1       Detect and treat          NCEP ATP-III, 2002\         III      Poor        I
          secondary cause of        Stone et al., 1997\                              
          dyslipidemia              Stone & Blum, 2002                               

  2       Refer familial            Working Group Consensus     III      Poor        I
          hypercholesteremia to                                                      
          specialist                                                                 
  ------------------------------------------------------------------------------------------

QE = Quality of Evidence; R = Strength of Recommendation (see Appendix A
in the original guideline document)

L2. **Obtain Baseline Serum Transaminase (ALT/AST) Prior to Starting
Lipid Lowering Therapy**

*Objective*

Establish baseline transaminase monitoring parameters prior to
initiating lipid lowering therapy.

*Recommendations*

1.  Baseline serum transaminase (alanine aminotransferase
    \[ALT\]/aspartate aminotransferase \[AST\]) should be obtained prior
    to starting lipid-lowering therapy. **\[I\]**

2.  Levels of serum transaminase (ALT/AST) should be obtained in
    patients on statin, 6 to 12 weeks after starting statin therapy,
    and/or change in dose or combination therapy, then annually or more
    frequently, if indicated. **\[I\]**

3.  Levels of serum transaminase (ALT/AST) should be obtained in
    patients on niacin, 6 to 12 weeks after reaching a daily dose of
    1,500 mg and 6 to 12 weeks after reaching the maximum daily dose,
    then annually or more frequently, if indicated. **\[I\]**

  ------------------------------------------------------------------------------------------
  ** **   **Recommendation**        **Sources of Evidence**     **QE**   **Overall   **R**
                                                                         Quality**   
  ------- ------------------------- --------------------------- -------- ----------- -------
  1       Statins---\               NCEP ATP-III, 2002          III      Poor        I
          Evaluate ALT/AST                                                           
          initially, approximately                                                   
          6 to 12 weeks after                                                        
          starting, then annually                                                    
          or more frequently, if                                                     
          indicated                                                                  

  2       Nicotinic Acid---\        NCEP ATP-III, 2002          III      Poor        I
          Evaluate ALT/AST                                                           
          initially, 6 to 12 weeks                                                   
          after reaching a daily                                                     
          dose of 1,500 mg, 6 to 12                                                  
          weeks after reaching the                                                   
          maximum daily dose, then                                                   
          annually or more                                                           
          frequently, if indicated                                                   
  ------------------------------------------------------------------------------------------

QE = Quality of Evidence; R = Strength of Recommendation (see Appendix A
in the original guideline document)

M1. **History of Acute Coronary Syndrome in Past 6 Months?**

*Objective*

Identify patients with recent acute coronary syndrome (ACS) for whom
there is a compelling need for statin therapy regardless of current
lipid levels.

*Recommendations*

1.  A lipid panel should be drawn at the time of admission for all
    patients with suspected acute coronary syndrome (ACS). **\[C\]**

2.  Initiating a moderate- to high-dose statin therapy prior to hospital
    discharge may be considered in patients admitted with ACS
    irrespective of their lipid profile. **\[B\]**

3.  Patients with recent ACS (within the past 6 months) should be on a
    moderate dose of statin therapy to reduce LDL-C level below 100
    mg/dL. **\[A\]**

4.  A lower target (70 mg/dL) may be considered for very high-risk
    patients. **\[B\]**

  ------------------------------------------------------------------------------------------
  ** **   **Recommendation**        **Sources of Evidence**     **QE**   **Overall   **R**
                                                                         Quality**   
  ------- ------------------------- --------------------------- -------- ----------- -------
  1       For patients admitted     Working Group Consensus     III      Poor        I
          with ACS, a lipid panel                                                    
          should be drawn at the                                                     
          time of admission                                                          

  2       Patients should be        Bybee et al., 2002\         I        Good        B
          started on moderate- to   Lorenz et al., 2005\                             
          high-dose statins prior   Stenestrand & Wallentin,                         
          to hospital discharge and 2001                                             
          irrespective of their                                                      
          lipid profile                                                              

  3       If not started on a       de Lemos et al., 2004\      I        Good        A
          statin prior to hospital  Cannon et al., 2004                              
          discharge, then one                                                        
          should be started within                                                   
          6 months post-ACS                                                          

  4       An optional lower target  Cannon et al., 2004         I        Good        B
          for LDL-C may be                                                           
          considered for post-ACS                                                    
          patients                                                                   
  ------------------------------------------------------------------------------------------

QE = Quality of Evidence; R = Strength of Recommendation (see Appendix A
in the original guideline document)

M2. **History of CVD or DM and LDL-C Above Goal?**

(See Screening Algorithm,  Annotations B and C)

M3. **Calculate 10-Year Risk Score for CVD**

*Objective*

Determine short-term risk (i.e., over ten years) as the basis for
determining the type and intensity of interventions.

*Recommendations*

1.  A global 10-year risk for CVD should be calculated to assess the
    short-term (10-year) absolute risk of a CVD event. **\[A\]**

2.  The Framingham Risk Calculator should be used, as it is the most
    commonly used and readily available calculator validated in numerous
    populations. **\[I\]**\
    <http://hin.nhlbi.nih.gov/atpiii/calculator.asp?usertype=prof>

3.  Other risk markers or measure of atherosclerotic burden may be
    useful to adjust the risk category, if they have been validated to
    have independent prognostic value. **\[C\]**

  ------------------------------------------------------------------------------------------
  ** **   **Recommendation**        **Sources of Evidence**     **QE**   **Overall   **R**
                                                                         Quality**   
  ------- ------------------------- --------------------------- -------- ----------- -------
  1       A global 10-year risk for Grover, Coupal, & Hu, 1995\ I        Good        A
          CVD should be calculated  Grover et al., 2000\                             
          to assess the short-term  Grundy et al., 2004                              
          (10 years) absolute risk                                                   
          of a CVD event                                                             

  2       The Framingham Risk       Grundy et al., 1999\        III      Poor        I
          Calculator is the most    Sheridan, Pignone, &                             
          commonly used and readily Mulrow, 2003\                                    
          available calculator      Wilson et al., 1998                              
          validated in numerous                                                      
          populations                                                                

  3       Other risk markers or     Ford et al., 1998\          III      Fair        C
          measures of               Greenland et al., 2000;                          
          atherosclerotic burden    2004\                                            
          may be useful to adjust   O\'Donnel, 2004\                                 
          the risk category         Pearson et al., 2003\                            
                                    Pletcher et al., 2004\                           
                                    Ridker, 2001                                     
  ------------------------------------------------------------------------------------------

QE = Quality of Evidence; R = Strength of Recommendation (see Appendix A
in the original guideline document)

N.  **Determine Risk for CVD and Establish the Goal for Interventions**

> *Recommendations*

1.  Goals of lipid lowering therapy should be tailored to risk level and
    based upon the balance between benefits, risks, and patient
    preferences. **\[C\]**

> ***Goals of Therapy for Secondary Prevention***

2.  LDL-C should be lowered to \<100 mg/dL for patients with a recent
    ACS. **\[A\]**

3.  An optional lower target for LDL-C (\<70 mg/dL) may be considered
    for very high-risk post-ACS patients. **\[B\]**

4.  LDL-C should be lowered to \<100 mg/dL for patients with previous
    documented CHD or CVD equivalent (DM with other major risk factors)
    for secondary prevention. **\[A\]**

5.  LDL-C should be lowered to \<130 mg/dL for patients with DM without
    other major risk factors for secondary prevention. **\[C\]**

> ***Goals of Therapy for Primary Prevention***

6.  LDL-C should be lowered to \<100 mg/dL for patients with high
    10-year risk \>20 percent. **\[B\]**

7.  LDL-C should be lowered to \<130 mg/dL for patients with
    intermediate 10-year risk (15 to 20 percent). **\[B\]**

8.  LDL-C should be lowered to \<130 mg/dL for patients with
    intermediate 10-year risk (10 to 14 percent). **\[C\]**

9.  LDL-C should be lowered to \<160 mg/dL for patients with low 10-year
    risk. **\[I\]**

10. LDL-C reduction of 30 to 40 percent from baseline may be considered
    an alternative therapeutic strategy for patients who cannot meet the
    above goal.

> **Table. Goals of Lipid Lowering Therapy**

  ----------------------------------------------------------------------------------------------
  ** **   **Risk Category**    **Number of    **10-Year Risk**      **LDL-C   **Remarks**
                               Risk Factors                         Goal\     
                               (RF)**                               mg/dL     
                                                                    \***      
  ------- -------------------- -------------- --------------------- --------- ------------------
  1       Recent ACS           N/A            N/A                   \<100     Option \<70 mg/dL

  2       CHD or equivalent    N/A            N/A                   \<100     Optional \<130 for
          (DM with other risk                                                 DM with no other
          factors)                                                            risk factors

  3       High                 2 + RF         [\>]{.underline}20%   \<100     \--

  4       Intermediate         2 +RF          15 to 20%             \<130     \--

  5                                           10 to 14% \*\*        \<130     \--

  6       Low                  0-1 RF         N/A                   \<160     \--
  ----------------------------------------------------------------------------------------------

> N/A = Not applicable\
> \* Recommendations are based on quality of evidence for improving CVD
> outcomes.\
> \*\* There is insufficient evidence at this time to recommend routine
> screening for other risk markers not included in the risk index (e.g.,
> FH, high sensitive C-reactive protein \[hsCRP\], metabolic syndrome,
> depression), or evidence of significant atherosclerotic burden (e.g.,
> high coronary artery calcification scores, intima medial thickness,
> abnormal brachial reactivity, or abnormal ankle-brachial index). These
> risk markers have independent prognostic value whereby abnormal values
> can shift risk percent upward across treatment thresholds with more
> robust evidence for efficacy. Therefore, they may be useful in the
> intermediate risk patient for whom it is less convincing that drug
> therapy would have a meaningful impact on outcomes. Example: Patient
> with a 10-year risk of 13 percent in whom an abnormal test with a
> proven adjusted relative risk of \>2 would shift the patient to a
> high-risk category (across a 20 percent, 10-year risk threshold).

  ------------------------------------------------------------------------------------------
  ** **   **Recommendation**        **Sources of Evidence**     **QE**   **Overall   **R**
                                                                         Quality**   
  ------- ------------------------- --------------------------- -------- ----------- -------
  1       Target lipid lowering     \"27th Bethesda             I        Good        C
          therapy to risk           Conference,\" 1996\                              
                                    Grundy et al., 2004                              

          **Secondary Prevention**                                                   

  2       Goal \<100 mg/dL for      Schwartz et al., 2001\      I        Good        A
          recent ACS patients       Cannon et al., 2004\                             
                                    Nissen et al., 2004                              

  3       An optional lower target  Cannon et al., 2004         I        Good        B
          for LDL-C may be                                                           
          considered for severe                                                      
          post-ACS patients                                                          

  4       Goal \<100 mg/dL for      Sacks et al., 1996\         I        Good        A
          patients with previous    Heart Protection Study                           
          documented CHD or CVD or  Collaborative Group, 2002\                       
          CVD equivalent = DM       LaRosa, He, & Vupputuri,                         
                                    2005                                             

  5       Goal \<130 mg/dL for      Haffner et al., 1998\       III      Poor        C
          patients with DM without  NCEP Consensus                                   
          other major risk factors                                                   

          **Primary Prevention**                                                     

  6       Goal \<100 mg/dL for      Sever et al., 2003\         I        Fair        B
          high-risk group           Heart Protection Study                           
                                    Collaborative Group, 2002\                       
                                    \"Screening experience and                       
                                    baseline characteristic in                       
                                    the West of Scotland                             
                                    Coronary Prevention                              
                                    Study,\" 1995                                    

  7       Goal \<130 mg/dL for      Downs et al., 1998          I        Fair        B
          patients with                                                              
          intermediate 10-year risk                                                  
          (15 to 20%)                                                                

  8       Goal \<130 mg/dL for      NCEP ATP-III, 2002          III      Poor        C
          intermediate-risk group                                                    
          10 to 14%                                                                  

  9       Goal \<160 mg/dL for      Consensus Group             III      Poor        I
          low-risk group                                                             
  ------------------------------------------------------------------------------------------

QE = Quality of Evidence; R = Strength of Recommendation (see Appendix A
in the original guideline document)

O.  **Initiate Lipid Lowering Therapy to Achieve Goal**

> *Objective*
>
> Select an appropriate therapy based on LDL-C baseline level and other
> risk factors for CVD.
>
> *Recommendations*
>
> ***Non-Pharmacologic Therapy***

1.  Therapeutic lifestyle changes (TLC) should be recommended for ALL
    patients with dyslipidemia, regardless of risk or baseline LDL-C
    level. **\[C\]**

> ***Drug Therapy for Secondary Prevention***

2.  All patients with a recent ACS should be on at least a moderate dose
    of statin therapy. **\[A\]**

3.  Statin drug therapy should be initiated for patients with previous
    documented CHD or CVD equivalent (diabetes with other major risk
    factors) if baseline LDL-C is [\>]{.underline}100 mg/dL. **\[A\]**

4.  Statin drug therapy should be initiated for patients with documented
    DM with no major risk factors if baseline LDL-C is
    [\>]{.underline}130 mg/dL. **\[C\]**

5.  Statin drug therapy may be considered optional for all patients with
    CHD or CVD equivalent (diabetes with other major risk factors)
    regardless of LDL-C baseline. **\[B\]**

> ***Drug Therapy for Primary Prevention***

6.  Drug therapy should be initiated for high-risk patients (\>20%) if
    baseline LDL is [\>]{.underline}130 mg/dL. **\[B\]**

7.  Drug therapy is optional to consider in high-risk patients (\>20%)
    if baseline LDL is 100 to 129 mg/dL. **\[B\]**

8.  Drug therapy may be offered to patients with high-intermediate risk
    (15 to 20 percent) if baseline LDL is [\>]{.underline}130 mg/dL.
    **\[B\]**

9.  Drug therapy may be offered to patients with low-intermediate risk
    (10 to 14 percent) if baseline LDL is [\>]{.underline}160 mg/dL.
    **\[C\]**

10. Drug therapy may be offered to low-risk patients (\<10 percent) if
    baseline LDL is [\>]{.underline}190 mg/dL. **\[I\]**

> The following table summarizes the lipid lowering strategy for
> patients in primary prevention. Individual management of
> cardiovascular risk should be informed mainly by the probable absolute
> magnitude of treatment benefits. Lowering absolute risk involves
> modification of multiple risk factors/co-morbidities, not only LDL-C
> levels. Therefore, these goals should serve as a general guide and
> clinical judgment should be used to modify the goals as appropriate
> for each patient.
>
> **Table. Dyslipidemia Therapy Thresholds and Goals**

  -----------------------------------------------------------------------------------------------------------
  ** **          **Risk         **Disease   **Calculated 10-Year  **TLC**   **LDL-C Level for     **LDL Goal
                 Category**     Status or   Risk**                          Considering Statin    of
                                Risk                                        Drug Therapy**        Therapy**
                                Factors**                                                         
  -------------- -------------- ----------- --------------------- --------- --------------------- -----------
  **Secondary\   Very high      Recent ACS  N/A                   All       All                   \<100
  Prevention**                                                                                    mg/dL\
                                                                                                  \<70
                                                                                                  optional

                                CHD or DM   N/A                   All       [\>]{.underline}100   \<100 mg/dL
                                with other                                  mg/dL                 
                                risk                                                              
                                factors                                                           

                                DM with no  N/A                   All       [\>]{.underline}130   \<130 mg/dL
                                other risk                                  mg/dL\                
                                factors                                     100 to 129 optional   

  **Primary\     High           More than 2 [\>]{.underline}20%   All       [\>]{.underline}130   \<100 mg/dL
  Prevention**                  RF                                          (or HDL \<40)\        
                                                                            100 to 129 optional   

                 Intermediate   More than 2 15 to 20%             All       [\>]{.underline}130   \<130 mg/dL
                                RF                                          mg/dL                 

                                            10 to 14% \*          All       [\>]{.underline}160   \<130 mg/dL
                                                                            mg/dL                 

                 Low            0 or 1 RF   N/A                   All       [\>]{.underline}190   \<160 mg/dL
                                                                            mg/dL                 
  -----------------------------------------------------------------------------------------------------------

> LDL-C reduction of 30-40 percent from baseline may be considered an
> alternative therapeutic strategy for patients who cannot meet the
> above goals.
>
> N/A = Not applicable; TLC = Therapeutic Lifestyle Changes; RF = Risk
> Factor\
> \* There is insufficient evidence at this time to recommend routine
> screening for other risk markers not included in the risk index (e.g.,
> FH, hsCRP, metabolic syndrome, depression), or evidence of significant
> atherosclerotic burden (e.g., high coronary artery calcification
> scores, intima medial thickness, abnormal brachial reactivity, or
> abnormal ankle-brachial index). These risk markers may be useful in
> the intermediate risk patient for whom it is less convincing that drug
> therapy would have a meaningful impact on outcomes.

  ------------------------------------------------------------------------------------------
  ** **   **Recommendation**        **Sources of Evidence**     **QE**   **Overall   **R**
                                                                         Quality**   
  ------- ------------------------- --------------------------- -------- ----------- -------
  1       Therapeutic lifestyle     NCEP ATP-III, 2002          III      Fair        C
          changes should be                                                          
          recommended for ALL                                                        
          patients                                                                   

  2       For recent ACS patients,  de Lemos et al., 2004\      I        Good        A
          moderate to high-dose     Schwartz et al., 2001\                           
          statins should be given   Cannon et al., 2004                              
          prior to hospital                                                          
          discharge; If not started                                                  
          prior to discharge, then                                                   
          statin therapy should be                                                   
          started within 6 months                                                    
          post ACS                                                                   

  3       Initiate drug therapy in  Sacks et al., 1996\         I        Good        A
          all patients with         \"Randomised trial,\" 1994\                      
          previous documented CHD   Heart Protection Study                           
          or CVD equivalent (DM     Collaborative Group 2002\                        
          with other major risk     \"Prevention of                                  
          factors) if baseline      cardiovascular events,\"                         
          LDL-C is                  1998\                                            
          [\>]{.underline}100 mg/dL Shepherd et al., 2002\                           
                                    LaRosa, He, & Vupputuri,                         
                                    2005                                             

  4       Drug therapy should be    NCEP Consensus of Experts   III      Poor        C
          initiated for patients                                                     
          with DM and NO major risk                                                  
          factors) if baseline                                                       
          LDL-C is                                                                   
          [\>]{.underline}130 mg/dL                                                  

  5       Drug therapy may be       Colhoun et al., 2004\       I        Fair        B
          considered for all        LaRosa, He, & Vupputuri,                         
          patients with DM and      2005                                             
          other risk factors                                                         
          regardless of LDL                                                          
          baseline                                                                   

  6       Drug therapy should be    Downs et al., 1998\         I        Good        A
          initiated for high-risk   Sever et al., 2003\                              
          patients (10-year risk    \"Screening experience and                       
          \>20%) if baseline LDL is baseline characteristics in                      
          [\>]{.underline}130 mg/dL the West of Scotland                             
                                    Coronary Prevention                              
                                    Study\", 1995                                    

  7       Consider drug therapy in  Heart Protection Study      I        Fair        B
          high-risk patients if     Collaborative Group, 2002                        
          baseline LDL is 100 to                                                     
          129 mg/dL                                                                  

  8       Offer drug therapy for    Sever et al., 2003\         I        Fair        B
          high-and                  Downs et al., 1998\                              
          intermediate-risk (15 to  \"Screening experience and                       
          20%) if baseline LDL is   baseline characteristics in                      
          [\>]{.underline}130 mg/dL the West of Scotland                             
                                    Coronary Prevention                              
                                    Study,\" 1995                                    

  9       Offer drug therapy for    NCEP ATP-III, 2002          III      Poor        C
          low-intermediate risk                                                      
          (10-15%) patients if                                                       
          baseline LDL is                                                            
          [\>]{.underline}160                                                        

  10      Offer drug therapy for    NCEP ATP-III, 2002          III      Poor        I
          low-risk patients (\<10%)                                                  
          if baseline LDL is                                                         
          [\>]{.underline}190 mg/dL                                                  
  ------------------------------------------------------------------------------------------

QE = Quality of Evidence; R = Strength of Recommendation (see Appendix A
in the original guideline document)

P.  **Therapeutic Lifestyle Change (TLC)**

> **For secondary prevention** of recurrent CVD events,
> non-pharmacologic therapy is always indicated, but should not delay
> appropriate pharmacotherapy.
>
> **For primary prevention** of CVD, emphasis on TLC is an important
> component and is effective in reducing CVD risk by lowering LDL-C and
> blood pressure. Ample time should be given (3 to 6 months) for
> patients to improve their LDL-C and total lipid profile prior to
> starting lipid-lowering medication. Patients failing primary clinician
> efforts may benefit from medical nutrition therapy (MNT) provided by a
> registered dietician or other qualified nutritionist (see [Appendix
> C](http://www.oqp.med.va.gov/cpg/DL/LIP_CPG/content/appendices/Appn_C.htm),
> *Medical Nutrition Therapy* in the original guideline document).
>
> TLC is provided in a step-wise approach focused on initiating TLC
> components and followed by subsequent evaluation of the effect on
> LDL-C and moving to intensify MNT as indicated. See Figure 2 \"Step
> Wise Care Approach\" in the original guideline document.

P1. **Medical Nutrition Therapy**

*Objective*

Improve dyslipidemia using medical nutrition therapy (MNT).

*Recommendations*

1.  Diet intervention should be the first step in lipid lowering
    therapy. **\[B\]**

2.  Patients whose initial treatment is TLC should be given 3 to 6
    months of dietary therapy prior to beginning medication and longer,
    if lipids are improving and nearing LDL thresholds. **\[B\]**

3.  Initial diet should focus on reduction of saturated fats to \<7
    percent of total calories and dietary cholesterol to \<200 mg/day
    similar in composition to the TLC diet (formerly Step II diet).
    **\[B\]**

    a.  The range of 25 to 35 percent of total calories from fat is to
        be paired with keeping saturated fats and trans-fatty acid
        percents of total calories low.

    b.  Advise 10 percent monounsaturated fat, \<7 percent saturated
        fat, \<200 mg cholesterol diet.

    c.  If TGs are elevated, ensure that blood glucose is under control,
        limit alcohol and simple sugars, and evaluate need for weight
        loss. Emphasis should be placed on weight reduction and physical
        activity.

    d.  Limit foods with trans fatty acids (e.g., stick margarine,
        shortening, and commercially baked products and processed food).

    e.  Select \>5 to 6 servings/day fruits and vegetables and six
        servings/day whole-grain products.

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4.  Patient\'s specific diet should be individualized based on nutrition
    assessment, other CVD risk factors, other disease conditions, and
    patient\'s lifestyle. **\[I\]**

5.  Patients should be evaluated 4 to 6 weeks after their initial
    consultation. A lipid profile and anthropometric data should be
    analyzed. Further dietary intervention may include:

    a.  Increase soluble (viscous) fiber to 10 to 25 g/day to lower
        LDL-C. **\[B\]**

    b.  Increase plant sterols/stanols to 2 g/day to lower LDL-C.
        **\[B\]**

    c.  Include nuts such as walnuts and almonds (1 oz. \~5 times/week)
        and soy protein (25 g/day or 8 oz. of tofu) to lower LDL-C.
        **\[B\]**

    d.  Select fatty fish (average of 7 oz./week) (fish oil) to lower
        TG. **\[B\]**

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6.  Weight management for overweight and obese patients should be
    encouraged to lower LDL-C and TG and to reduce CV risk. **\[B\]**

7.  Patients in whom triglycerides \>500 mg/dL should receive strict
    diet therapy including avoidance of alcohol, restriction of dietary
    fat, and avoidance of concentrated carbohydrates (sweets). For
    triglycerides \>1000 mg/dL a very low fat diet should be instituted
    quickly to reduce chylomicronemia and risk of acute pancreatitis.

8.  Patients with evidence of metabolic syndrome should receive MNT that
    incorporates the additional protocol for weight management with
    increased physical activity. **\[B\]**

  -----------------------------------------------------------------------
  **Table. Essential           
  Components of Therapeutic    
  Lifestyle Changes (TLC)**    
  ---------------------------- ------------------------------------------
  **Component**                **Recommendation**

  LDL-raising nutrients\       Less than 7% of total calories
  Saturated fats\*             

  Dietary cholesterol          Less than 200 mg/day

  Therapeutic options for LDL  
  lowering                     

  Plant stanols/sterols        2 grams per day

  Increased viscous (soluble)  10 to 25 grams per day
  fiber                        

  Total calories (energy)      Adjust total caloric intake to maintain
                               desirable body weight/prevent weight gain

  Physical activity            Include enough moderate exercise to expend
                               at least 200 kcal per day

  *\*Trans fatty acids are     
  another LDL-raising fat that 
  should be kept at a low      
  intake.*                     
  -----------------------------------------------------------------------

 

  -----------------------------------------------------------------------
  **Table. Macronutrient       
  Recommendations for the TLC  
  Diet**                       
  ---------------------------- ------------------------------------------
  **Component**                **Recommendation**

  Polyunsaturated fat          Up to 10% of total calories

  Monounsaturated fat          Up to 20% of total calories

  Total fat                    25 to 35% of total calories\*

  Carbohydrate\*\*             50 to 60% of total calories\*

  Dietary fiber                20 to 30 grams per day

  Protein                      Approximately 15% of total calories

  *\*ATP-III allows an         
  increase of total fat to 35  
  percent of total calories    
  and a reduction in           
  carbohydrates to 50 percent  
  for persons with the         
  metabolic syndrome. Any      
  increase in fat intake       
  should be in the form of     
  either polyunsaturated or    
  monounsaturated fat.*\       
  *\*Carbohydrate should       
  derive predominantly from    
  foods rich in complex        
  carbohydrates including      
  grains---especially whole    
  grains---fruits, and         
  vegetables.*                 
  -----------------------------------------------------------------------

 

  ------------------------------------------------------------------------------------------
  ** **   **Recommendation**        **Sources of Evidence**     **QE**   **Overall   **R**
                                                                         Quality**   
  ------- ------------------------- --------------------------- -------- ----------- -------
  1       Use MNT for lowering      Delahanty et al., 2001;     I        Good        B
          LDL-C.                    2002\                                            
                                    Sikand et al., 2000\                             
                                    Yu-Poth et al., 1999                             

  2       Recommend 3 to 6 months   NCEP ATP-III, 2002          I        Fair        B
          of diet therapy prior to                                                   
          pharmacotherapy, if                                                        
          needed                                                                     

  3       Recommend a low saturated NCEP ATP-III, 2002          II       Good        B
          fat, low cholesterol diet                                                  

  4       Reduce saturated fats to  Hooper et al., 2001\        I        Fair        B
          less than 7% of total     Krauss et al., 2000\                             
          calories                  Lichtenstein et al., 2002\                       
                                    NCEP, 2001                                       

  5       Provide individualized    NCEP ATP-III, 2002\         I        Fair        B
          dietary counseling with   Tang et al., 1998                                
          reinforcement during                                                       
          follow-up                                                                  

  6       Consume viscous fiber (at Brown et al., 1999\         I        Fair        B
          least 10-25 grams/day)    Kris-Etherton et al.,                            
                                    \"High-soluble fiber                             
                                    food,\" 2002                                     

          Eat plant sterols/stanol  Christiansen et al., 2001\  I        Fair        B
          esters (2 to 3 g/day)     Jenkins et al., 2003; 2005\                      
                                    Lichtenstein & Deckelbaum,                       
                                    2001\                                            
                                    Maki et al., 2001                                

          Eat 5 ounces of nuts per  Jenkins et al., 2003\       I        Fair        B
          week                      Krauss et al., 2000\                             
                                    Lovejoy et al., 2002\                            
                                    Sabate, 2003                                     

          Eat 25 grams/day of soy   Anderson, Johnstone, &      I        Fair        B
          protein                   Cook-Newell, 1995 Erdman,                        
                                    2000\                                            
                                    Merritt, 2004\                                   
                                    Meyer et al., 2004                               

          Eat at least two servings Kris-Etherton, \"Fish       I        Fair        B
          of fish per week          consumption,\" 2002\                             
                                    NCEP ATP-III, 2002                               

  7       Reduce caloric intake and Krauss et al., 2000\        I        Fair        B
          increase physical         NCEP ATP-III, 2002                               
          activity to maintain                                                       
          desirable body weight                                                      

  8       Low fat diet for TGs      American Dietetic           I        Fair        B
          \>500 mg/dL;\             Association (ADA), 2001\                         
          Very low fat diet if TGs  NCEP ATP-III, 2002                               
          \>1000 mg/dL                                                               

  9       Recommend MNT for         ADA, 2001\                  I        Fair        B
          management of metabolic   NCEP ATP-III, 2002\                              
          syndrome                  Nieman et al., 2002\                             
                                    Sartorio et al., 2003                            
  ------------------------------------------------------------------------------------------

QE = Quality of Evidence; Strength of Recommendation (see Appendix A in
the original guideline document)

P2. **Physical Activity/Exercise and Weight Control**

*Recommendations*

1.  Moderate intensity levels of physical activity should be performed
    for at least 30 minutes most, preferably all, days of the week.
    **\[B\]**

2.  In patients with CVD, aerobic exercise should not precipitate
    angina.

3.  Increased physical activity through lifestyle change should be
    encouraged, as it is equally as effective as structured exercise in
    reducing body fat, improving cardiorespiratory fitness, and
    improving cardiovascular risk factors. **\[B\]**

4.  Physical activity, through lifestyle change or structured exercise,
    should be encouraged to maintain weight control (or weight loss if
    overweight or obese), to improve insulin resistance, and increase
    HDL-C. **\[B\]**

  ------------------------------------------------------------------------------------------
  ** **   **Recommendation**        **Sources of Evidence**     **QE**   **Overall   **R**
                                                                         Quality**   
  ------- ------------------------- --------------------------- -------- ----------- -------
  1       Increase physical         Fahlman et al., 2002\       I        Fair        B
          activity to improve lipid Halbert et al., 1999\                            
          profile                   Kraus et al., 2002\                              
                                    Stefanick et al., 1998                           

  2       Engage in moderate levels ACSM 2002\                  I        Fair        B
          of exercise/physical      Pate et al., 1995\                               
          activity for at least 30  U.S. DHHS, 1996                                  
          minutes, on most days of                                                   
          the week                                                                   

  3       Increased physical        Lee et al., 2001\           II       Fair        B
          activity is just as       Manson et al., 1999; 2002\                       
          effective as structured   Wannamethee, Shaper, &                           
          exercise in reducing body Walker, 2000                                     
          fat, improving                                                             
          cardiorespiratory fitness                                                  

  4       Exercise should be        National Heart Lung, and    II       Fair        B
          encouraged to maintain    Blood Institute (NHLBI),                         
          weight control (or weight 1998\                                            
          loss if overweight or     Scranton et al., 2004                            
          obese)                                                                     
  ------------------------------------------------------------------------------------------

QE = Quality of Evidence; R = Strength of Recommendation (see Appendix A
in the original guideline document)

Q1. **Pharmacotherapy: Monotherapy**

*Objective*

Reduce the risk of CVD events and achieve lipid goals through the use of
optimal pharmacotherapy.

*Recommendations*

1.  Pharmacologic treatment of dyslipidemia should be individualized and
    dictated by lipid levels. **\[B\]**

***Elevated LDL-C***

2.  Statins are first line agents in primary and secondary prevention of
    CVD regardless of HDL-C or TG level. **\[A\]**

3.  Moderate doses of formulary statins (to achieve an LDL-C reduction
    of 25 percent or greater) should be initiated unless a patient is
    considered to be at greater than usual risk for adverse events from
    statins (e.g., myopathy). **\[A\]**

4.  For patients who cannot tolerate statins, niacin or resins should be
    considered for treatment. **\[A\]**

5.  There is insufficient clinical outcome evidence to recommend
    ezetimibe monotherapy for reduction of CV risk. **\[I\]**

6.  Ezetimibe can be considered for lowering LDL-C in patients who are
    unable to tolerate other lipid-lowering drugs. **\[A\]**

7.  The dose of statin should be adjusted at 6 to 12 week intervals
    until individual LDL-C goals are achieved or statin doses have been
    maximized. **\[I\]**

***Isolated Hypertriglyceridemia***

8.  Niacin, fibrates, or fish oil supplements may be used in treatment
    of hypertriglyceridemia. **\[B\]**

***Isolated Low HDL-C***

9.  For secondary prevention, gemfibrozil or niacin may be used in
    patients with isolated low HDL-C and normal LDL-C.
    **\[A-Gemfibrozil; B-Niacin\]**

***Safety and Follow-Up***

10. Patients treated with statins or fibrates should be educated
    regarding the importance of recognizing and reporting any
    unexplained muscle tenderness, pain, or weakness. **\[I\]**

11. Lipid profiles should be repeated 6-12 weeks after initiation of
    therapy and/or change in dose and/or combination therapy. **\[B\]**

12. Liver function tests (LFTs) should be performed prior to and after
    12 weeks following initiation of treatment, any elevation in dose,
    and periodically thereafter in those receiving statins, fibrates, or
    niacin. **\[I\]**

13. Creatine kinase (CK) levels should be obtained in patients who
    develop muscle pain, weakness, or tenderness after institution of
    statin or fibrate therapy. **\[I\]**

  -----------------------------------------------------------------------------------------------------------
  ** **                    **Recommendation**        **Sources of Evidence**     **QE**   **Overall   **R**
                                                                                          Quality**   
  ------------------------ ------------------------- --------------------------- -------- ----------- -------
  1                        Pharmacologic treatment   NCEP ATP-III, 2002          I        Fair        B
                           of dyslipidemia should be                                                  
                           individualized and is                                                      
                           dictated by lipid levels                                                   

  2                        Statins are first line    [Primary                    I        Good        A
                           agents in primary and     Prevention:]{.underline}\                        
                           secondary prevention      Downs et al, 1998\                               
                           regardless of baseline TG Sever et al., 2003\                              
                           or HDL-C level            Colhoun et al., 2004\                            
                                                     \"Screening experience and                       
                                                     baseline characteristics in                      
                                                     the West of Scotland                             
                                                     Coronary Prevention                              
                                                     Study,\" 1995\                                   
                                                     \                                                
                                                     [Secondary                                       
                                                     Prevention:]{.underline}\                        
                                                     Sacks et al., 1996\                              
                                                     4S, 1994\                                        
                                                     Heart Protection Study                           
                                                     Collaborative Group, 2002\                       
                                                     \"Prevention of                                  
                                                     cardiovascular events,\"                         
                                                     1998\                                            
                                                     Shepherd et al., 2002                            

  3                        Moderate doses of         [Primary                    I        Good        A
                           formulary statins (to     Prevention]{.underline}:\                        
                           achieve an LDL-C          Downs et al., 1998\                              
                           reduction of 25% or       \"Screening experience and                       
                           greater) should be        baseline characteristics in                      
                           initiated (unless greater the West of Scotland                             
                           than usual risk for       Coronary Prevention                              
                           adverse events)           Study,\" 1995\                                   
                                                     \                                                
                                                     [Secondary                                       
                                                     Prevention:]{.underline}\                        
                                                     Sacks et al., 1996\                              
                                                     4S, 1994\                                        
                                                     Heart Protection Study                           
                                                     Collaborative Group, 2002\                       
                                                     \"Prevention of                                  
                                                     cardiovascular events,\"                         
                                                     1998\                                            
                                                     Serruys et al., 2002\                            
                                                     Shepherd et al., 2002\                           
                                                     Cannon et al., 2004                              

  4                        Consider treatment with   [Primary                    I        Good        A
                           other lipid lowering      Prevention:]{.underline}\                        
                           agents (niacin or resins) Frick et al., 1993\                              
                           for patients who cannot   Lipid Research Clinics                           
                           tolerate statins          Program--Coronary Primary                        
                                                     Prevention Trial                                 
                                                     (LRC-CPPT), 1984\                                
                                                     \                                                
                                                     [Secondary                                       
                                                     Prevention:]{.underline}\                        
                                                     \"Clofibrate and niacin in                       
                                                     coronary heart disease,\"                        
                                                     1975\                                            
                                                     Jamshidi et al., 2002\                           
                                                     Robins, Collins, & Rubins,                       
                                                     1999                                             

  5                        Use of ezetimibe          Working Group Consensus     III      Poor        I
                           monotherapy for                                                            
                           preventing CVD                                                             

  6                        Ezetimibe can be          Bays et al., 2001\          I        Good        A
                           considered for lowering   Knopp et al., \"Evaluation                       
                           LDL-C in patients who are of the efficacy,\" 2003\                         
                           unable to tolerate other  Knopp et al., \"Effects of                       
                           lipid-lowering drugs      ezetimibe,\" 2003\                               
                                                     Sudhop et al., 2002                              

  7                        Aggressive early          Cannon et al., 2004\        I        Good        A
                           treatment with a moderate Nissen et al., 2004                              
                           dose of statins for all                                                    
                           patients with recent ACS                                                   

  8                        Dose of statin should be  Working Group Consensus     III      Poor        I
                           adjusted at 6 to 12 week                                                   
                           intervals until                                                            
                           individual LDL-C goals                                                     
                           are achieved or statin                                                     
                           doses have been maximized                                                  

  **Isolated                                                                                          
  Hypertriglyceridemia**                                                                              

  9                        Consider niacin,          [Niacin]{.underline}\       I        Fair        B
                           fibrates, or fish oil     NCEP ATP-III, 2002\                              
                           supplements to lower TGs  \                                                
                                                     [Fibrates]{.underline}\                          
                                                     NCEP ATP-III, 2002\                              
                                                     \                                                
                                                     [Fish Oils]{.underline}\                         
                                                     Harris 1997\                                     
                                                     Farmer et al., 2001                              

  **Isolated Low HDL-C**                                                                              

  10                       Gemfibrozil               Robins, Collins, & Rubins,  I        Good        A
                                                     1999                                             

  11                       Niacin to increase HDL-C  King et al., 1994\          I        Fair        B
                                                     Lavie, Mailander, & Milani,                      
                                                     1992\                                            
                                                     Miller et al.,1993; 1995\                        
                                                     Vega & Grundy, 1989                              

  **Safety and Follow-Up**                                                                            

  12                       Provide patients with     NCEP ATP-III, 2002          III      Poor        I
                           education about                                                            
                           unexplained muscle                                                         
                           tenderness, pain, or                                                       
                           weakness                                                                   

  13                       Repeat lipid profile in   Benner et al., 2004\        II       Fair        B
                           6-12 weeks after          NCEP ATP-III, 2002                               
                           initiation of therapy                                                      
                           and/or change in dose                                                      
                           and/or with combination                                                    
                           therapy                                                                    

  14                       LFT should be performed   NCEP ATP-III, 2002          III      Poor        I
                           prior to and after 6-12                                                    
                           weeks following                                                            
                           initiation/change of                                                       
                           dose, and periodically                                                     
                           thereafter in those                                                        
                           receiving statins,                                                         
                           fibrates, or niacin                                                        

  15                       Obtain CK levels in       NCEP ATP-III, 2002          III      Poor        I
                           patients who develop                                                       
                           muscle pain, weakness, or                                                  
                           tenderness after                                                           
                           institution of statin or                                                   
                           fibrate therapy                                                            
  -----------------------------------------------------------------------------------------------------------

QE = Quality of Evidence; R = Strength of Recommendation (see Appendix A
in the original guideline document)

Q2. **Pharmacotherapy: Combination Therapy**

*Objective*

Achieve lipid goals through the use of combination pharmacologic agents.

*Recommendations*

***LDL-C Lowering Combination Therapy \[ONLY FOR SECONDARY
PREVENTION\]***

1.  For patients not at goal, monotherapy should be titrated until goal
    is achieved or maximum tolerable dose has been reached. **\[C\]**

2.  Combination therapy to achieve LDL-C goal may be considered for
    carefully selected patients who do not achieve the LDL-C goal with
    maximally tolerated monotherapy. **\[I\]**

3.  Combination lipid-lowering therapy should include a statin unless
    the patient is unable to tolerate statins. **\[A\]**

4.  Addition of a resin to the statin can be considered for secondary
    prevention in patients not meeting their LDL-C goals on maximally
    tolerated doses of statins. **\[B\]**

5.  Addition of niacin or a resin to the statin can be considered in
    patients not meeting their LDL-C goals to further reduce the LDL-C
    level. **\[B\]**

6.  Addition of ezetimibe to the statin can be considered in patients
    not meeting their LDL-C goals on maximally tolerated doses of
    statins and unable to tolerate niacin or a resin to reduce the LCL-C
    level. **\[I\]**

7.  In patients unable to tolerate statins and not achieving their LDL-C
    goals with niacin or resins, a combination of both resin and niacin
    may be considered. **\[B\]**

8.  In any combination therapy the lowest possible dose of statin should
    be used to achieve lipid goals. When combined with fibrates
    (greatest risk), niacin, or possibly ezetimibe, the risk of adverse
    events with statins (e.g., muscle toxicity) appears to increase with
    increasing statin doses. **\[C\]**

***Elevated LDL-C and Very High Triglycerides (\>500 mg/dL)***

If non-HDL goals cannot be achieved with a statin (or other LDL-lowering
regimen) alone, a TG-lowering drug may be added to the statin. Choices
are niacin, a fibrate, and fish oils.

9.  Combination therapy with statins and niacin, fish oils, or fibrates
    can be considered for the secondary prevention of CVD in patients
    with elevated LDL-C and very high TGs. **\[C\]**

10. Combination therapy with niacin and fibrates can be considered for
    the secondary prevention of CVD in patients with elevated LDL-C and
    very high TGs in patients unable to tolerate statins. **\[C\]**

***Very High Triglycerides and/or Low HDL-C Without Elevated LDL-C***

11. For secondary prevention of CVD in patients with either low HDL-C or
    very high triglycerides and no elevation of LDL-C levels,
    combination therapy with statin plus niacin, fibrate, or fish oil
    may be considered. **\[C\]**

12. Combination therapy with niacin and fibrates and/or fish oils can be
    considered in patients unable to tolerate statins. **\[C\]**

  ------------------------------------------------------------------------------------------
  ** **   **Recommendation**       **Sources of Evidence**    **QE**   **Overall     **R**
                                                                       Quality**     
  ------- ------------------------ -------------------------- -------- ------------- -------
  1       Combination              Colhoun et al., 2004\      I        Substantial   A
          lipid-lowering therapy   Heart Protection Study                            
          should include a statin  Collaborative Group, 2004                         
          unless the patient is                                                      
          unable to tolerate                                                         
          statins                                                                    

  2       In combination therapy   Work Group Consensus       III      Poor          C
          with a statin, the                                                         
          lowest possible dose of                                                    
          statin should be used to                                                   
          achieve lipid goals and                                                    
          minimize complications                                                     

  3       Combination therapy      Work Group Consensus       III      Poor          I
          should be reserved for                                                     
          patients on secondary                                                      
          prevention                                                                 

  4       Addition of niacin to    Zhou et al., 2004          I        Good          B
          the statin can be                                                          
          considered in patients                                                     
          on secondary prevention                                                    
          not meeting their LDL-C                                                    
          goals on maximally                                                         
          tolerated doses of                                                         
          statins                                                                    

  5       Addition of a resin to   Brown et al., 1990         I        Good          B
          the statin can be                                                          
          considered in patients                                                     
          not meeting their LDL-C                                                    
          goals on maximally                                                         
          tolerated doses of                                                         
          statins                                                                    

  6       Addition of ezetimibe to Gagne et al., 2002         I        Good          I
          the statin can be                                                          
          considered for lowering                                                    
          LDL-C levels in patients                                                   
          not meeting their LDL-C                                                    
          goals on maximally                                                         
          tolerated doses of                                                         
          statins and unable to                                                      
          tolerate niacin or a                                                       
          resin                                                                      

  7       Combination of resin and Blankenhorn et al., 1987\  II       Good          B
          niacin can be considered Brown et al, 1990                                 
          in patients unable to                                                      
          tolerate statins and not                                                   
          achieving their LDL-C                                                      
          goals with niacin or                                                       
          resins alone                                                               

  8       Combination of statins   Working Group Consensus    III      Poor          C
          and niacin, fish oils,   based upon clinical                               
          or fibrates can be       reasoning                                         
          considered in patients                                                     
          with elevated LDL-C and                                                    
          very high TGs                                                              

  9       Combination of niacin    Working Group Consensus    III      Poor          C
          and fibrates can be      based upon clinical                               
          considered in patients   reasoning                                         
          with elevated LDL-C and                                                    
          very high TGs who are                                                      
          unable to tolerate                                                         
          statins                                                                    

  10      Combination of statin    Working Group Consensus    III      Poor          C
          and niacin, fibrate, or  based upon clinical                               
          fish oil may be          reasoning                                         
          considered in patients                                                     
          who have achieved their                                                    
          LDL-C goal or are                                                          
          without elevated LDL-C,                                                    
          and have either low                                                        
          HDL-C or very high TGs                                                     

  11      Combination of niacin    Working Group Consensus    III      Poor          C
          and fibrates and/or fish based upon clinical                               
          oils can be considered   reasoning                                         
          in patients with                                                           
          elevated LDL-C very high                                                   
          TGs who are unable to                                                      
          tolerate statins                                                           
  ------------------------------------------------------------------------------------------

QE = Quality of Evidence; OQ = Overall Quality; SR = Strength of
Recommendation (see Appendix A in the original guideline document)

R.  **Repeat Dyslipidemia Evaluation in 1 to 2 Years (Patients *NOT* on
    Therapy)**

> *Objective*
>
> Provide appropriate clinical follow-up for patients not on therapy.
>
> *Recommendation*

1.  If the initial dyslipidemia screening reveals TC \>200 mg/dL, or
    fasting LDL-C \>130 mg/dL or HDL-C \<40 mg/dL, but LDL-C level is
    under the recommended goal level based upon CV risk, the patient
    will be at low-risk for lipid-related events over a one to two-year
    period and thus, should be reevaluated for dyslipidemia in one to
    two years.

[Follow-up of Therapy
Algorithm](http://www.oqp.med.va.gov/cpg/DL/dl_cpg/algo4frameset.htm)

S.  **Address Adherence to Therapy**

> *Objective*
>
> Identify causes of inadequate response to therapy following dose or
> stepwise titration.
>
> *Recommendations*

1.  Adherence to therapy should be assessed at every visit, through
    history, pill count, and/or administrative records especially if
    therapeutic goals have not been reached **\[I\]**

2.  Adherence to lipid-lowering medication regimens may be improved by a
    multi-pronged approach **\[I\]** including:

    a.  Evaluation of medication side effects

    b.  Simplifying medication regimens to incorporate patient
        preference

    c.  Addressing barriers for obtaining the medications
        (administrative, economic, etc.)

    d.  Coordination with other healthcare team members to improve
        monitoring of adherence with prescriptions of pharmacological
        and lifestyle modification

    e.  Patient and family education about their disease/treatment
        regimens

    f.  Evaluation for depression

  ------------------------------------------------------------------------------------------
  ** **   **Recommendation**        **Sources of Evidence**     **QE**   **Overall   **R**
                                                                         Quality**   
  ------- ------------------------- --------------------------- -------- ----------- -------
  1       Assess medication         Working Group Consensus     III      Poor        I
          adherence at each visit                                                    
          through history, pill                                                      
          count, or medical record                                                   
          review                                                                     

  2       Consider a multi-pronged  Working Group Consensus     III      Poor        I
          approach to improve                                                        
          adherence to medication                                                    
          regimens                                                                   
  ------------------------------------------------------------------------------------------

QE = Quality of Evidence; R = Strength of Recommendation (see Appendix A
in the original guideline document)

T.  **Does The Patient Have Elevated TG Level, or Low HDL-C Level, or
    Metabolic Syndrome?**

> The goal of dyslipidemia management is ultimately to decrease CV risk,
> and the evidence is best at reducing such risk through LDL-C lowering
> therapies. LDL-C remains the treatment priority, and should be
> addressed regardless of the TG level. Once the LDL-C goal has been
> reached, treatment attention may shift to obtain optimal lipoprotein
> profiles.

U.  **Evaluation and Treatment of High Triglycerides**

> *Objective*
>
> Evaluate and treat TG levels above 200 mg/dL.

+-----------------------+-----------------------+-----------------------+
| **Treatment for       |                       |                       |
| H                     |                       |                       |
| ypertriglyceridemia** |                       |                       |
+=======================+=======================+=======================+
| **TG \>200 to 499     | **TG                  | **TG \>1000 mg/dL**   |
| mg/dL**               | [\>]{.underline}500   |                       |
|                       | mg/dL**               |                       |
+-----------------------+-----------------------+-----------------------+
| -   Lifestyle         | -   Very low fat diet | -   Strict MNT        |
|     management        |                       |     (avoidance of     |
|                       | -   Low concentrated  |     alcohol, fat, and |
| -   Weight loss       |     carbohydrate diet |     restrict          |
|                       |                       |     calories)         |
| -   Alcohol cessation | -   Alcohol cessation |                       |
|                       |                       | -   Secondary causes  |
| -   Secondary causes  | -   Secondary causes  |                       |
|                       |                       | -   Drug therapy, if  |
|                       | -   Consider drugs,   |     no response to    |
|                       |     if no response to |     above             |
|                       |     above             |                       |
|                       |                       | -   Consider referral |
|                       | -   Consider referral |                       |
+-----------------------+-----------------------+-----------------------+

> *Recommendations*

1.  Patients with elevated TG ([\>]{.underline}200 mg/dL) should have a
    repeat fasting lipid profile and, if persistent, receive intensive
    MNT, an appropriate exercise program, and be screened for underlying
    causes. **\[B\]**

2.  Drug therapy may be considered in patients with very high TG levels
    ([\>]{.underline} 500 mg/dL) that do not respond to lifestyle
    interventions and the treatment of underlying causes of elevated TG,
    for the purpose of preventing pancreatitis. **\[I\]**

3.  Effective drugs for lowering hypertriglyceridemia include fibrates,
    niacin, and fish oil. **\[B\]**

> **Table. Drug Treatment for Hypertriglyceridemia**

  --------------------------------------------------------------------------
  **TG 500 to                                    
  1000                                           
  mg/dL**                                        
  ----------- ---------------------------------- ---------------------------
  ** **       **Drug**                           **Efficacy (Expected %
                                                 Reduction in TG)**

  Initial     Fibrates                           -20 to -50

  Alternate   Niacin                             **-20 to -35**

              n-3 PUFA Supplements, Omega-3      -20 to -30
              Fatty Acids/Fish Oils              
  --------------------------------------------------------------------------

-   Fibrates are contraindicated in severe renal disease.

-   Niacin is contraindicated in hepatic disease and relatively
    contraindicated in DM, gout, and history of complicated/active
    peptic ulcer disease (PUD).

  ------------------------------------------------------------------------------------------
  ** **   **Recommendation**        **Sources of Evidence**     **QE**   **Overall   **R**
                                                                         Quality**   
  ------- ------------------------- --------------------------- -------- ----------- -------
  1       Elevated TG should        NCEP ATP-III, 2002\         II-3     Fair        B
          receive intensive MNT,    Stone & Blum, 2002                               
          exercise, and screening                                                    
          for underlying causes                                                      

  2       Consider drug therapy to  Cleeman, 1998\              III      Poor        I
          prevent pancreatitis      NCEP ATP-III, 2002\                              
                                    Stone & Blum, 2002                               

  3       Use of fibrates, niacin,  Farmer et al., 2001\        I        Fair        B
          and fish oil to lower     Harris, 1997                                     
          hypertriglyceridemia                                                       
  ------------------------------------------------------------------------------------------

QE = Quality of Evidence; R = Strength of Recommendation (see Appendix A
in the original guideline document)

V.  **Evaluation and Treatment of Low HDL-C**

> *Objective*
>
> Reduce risk of CVD through raising the level of HDL-C.
>
> *Recommendations*

1.  Patients with CVD who have low HDL-C (\<40 mg/dL), TG \>200 mg/dL,
    and normal levels of LDL-C may benefit from gemfibrozil therapy.
    **\[A\]**

2.  Lifestyle modifications, including weight loss, exercise, and
    smoking cessation should be given high priority in the therapeutic
    plan for patients with low HDL-C. **\[B\]**

3.  CVD patients with low HDL-C (\<40 mg/dL) may be considered for
    treatment with niacin. **\[B\]**

> **Table. Drug Treatment for Isolated Low HDL-C**

  -----------------------------------------------------------------------
  **LDL-C \<130                                  
  and Low                                        
  HDL-C**                                        
  -------------- ------------------------------- ------------------------
  **Drug**       **Efficacy (Expected %          
                 Reduction in TG)**              

  Gemfibrozil    **LDL-C\                        **HDL-C\
                 +10 to --35**                   +2 to 34**
  -----------------------------------------------------------------------

 

  ------------------------------------------------------------------------------------------
  ** **   **Recommendation**        **Sources of Evidence**     **QE**   **Overall   **R**
                                                                         Quality**   
  ------- ------------------------- --------------------------- -------- ----------- -------
  1       CVD patients with HDL-C   Robins, Collin, & Rubins,   I        Good        A
          \<40 mg/dL, triglycerides 1999                                             
          \>200 mg/dL, benefit from                                                  
          gemfibrozil therapy                                                        

  2       Lifestyle modifications,  Dattilo & Kris-Etherton,    II       Fair        B
          including weight          1992\                                            
          reduction, smoking        Haskell et al., 1988\                            
          cessation, and exercise   Kokkinos et al., 1995\                           
          improve HDL-C level.\     Superko & Haskell, 1987\                         
          Aerobic exercise\         Wood et al., 1991                                
          Weight loss                                                                

  3       CVD patients with low     King et al., 1994\          I        Fair        B
          HDL-C, may benefit from   Lavie et al., 1992\                              
          niacin                    Miller et al., 1993; 1995\                       
                                    Vega & Grundy, 1989                              
  ------------------------------------------------------------------------------------------

QE = Quality of Evidence; R = Strength of Recommendation (see Appendix A
in the original guideline document)

W.  **Evaluation and Treatment of Metabolic Syndrome**

> *Objective*
>
> Identify therapeutic treatment options for individuals with metabolic
> syndrome.
>
> *Recommendations*

1.  TLC should be initiated for patients diagnosed with metabolic
    syndrome. **\[B\]**

2.  Lifestyle modification for weight reduction through diet and
    increased physical activity is indicated for patients diagnosed with
    metabolic syndrome. **\[B\]**

3.  Drug therapy to alter insulin resistance or low HDL-C or elevated TG
    has not been demonstrated to improve CVD outcomes in patients with
    metabolic syndrome and as such, clinicians will have to
    individualize therapy. **\[I\]**

  ------------------------------------------------------------------------------------------
  ** **   **Recommendation**        **Sources of Evidence**     **QE**   **Overall   **R**
                                                                         Quality**   
  ------- ------------------------- --------------------------- -------- ----------- -------
  1       TLC should be initiated   NCEP ATP-III, 2002          III      Fair        B
          for patient in which                                                       
          metabolic syndrome is                                                      
          indicated                                                                  

  2       Lifestyle modification    NCEP ATP-III, 2002          III      Fair        B
          for weight reduction                                                       
          through diet and                                                           
          increased physical                                                         
          activity is indicated for                                                  
          obese patients (BMI is                                                     
          [\>]{.underline}30)                                                        

  3       Individualize drug        Working Group Consensus     III      Poor        I
          therapy for modification                                                   
          of insulin resistance or                                                   
          dyslipidemia in the                                                        
          presence of metabolic                                                      
          syndrome using clinical                                                    
          judgment                                                                   
  ------------------------------------------------------------------------------------------

QE = Quality of Evidence; R = Strength of Recommendation (see Appendix A
in the original guideline document)

X.  **Reschedule Lipids Evaluation at Appropriate Time and Follow Up to
    Maintain Goals**

> *Objective*
>
> Measure the efficacy of prescribed therapy for hyperlipidemia after
> allowing sufficient time to reach a new steady state.
>
> *Recommendations*

1.  Lipid profiles should be reevaluated after at least 6 to 12 weeks of
    drug therapy or change in dose or after at least three to six months
    of dietary therapy to document efficacy, identify adverse effects,
    and to titrate medication dose. **\[I\]**

2.  Follow-up visits should **\[I\]** include:

    -   Patient history

    -   Physical exam

    -   Laboratory tests

    -   Documentation of adverse events

3.  Once the goal is achieved, therapy for dyslipidemia should be
    continued to maintain the goal. Treatment of dyslipidemia is a
    lifelong process; however, adjustments may be necessary if the
    patient develops medical conditions that affect the severity of
    comorbidity or life expectancy.

  ------------------------------------------------------------------------------------------
  ** **   **Recommendation**        **Sources of Evidence**     **QE**   **Overall   **R**
                                                                         Quality**   
  ------- ------------------------- --------------------------- -------- ----------- -------
  1       Reevaluate serum lipids   Working Group Consensus     III      Poor        I
          after at least 6 to 12                                                     
          weeks of therapy or after                                                  
          at least three to six                                                      
          months of TLC                                                              

  2       Follow-up visits should   Working Group Consensus     III      Poor        I
          include: patient history,                                                  
          physical exam, lab tests,                                                  
          and adverse event                                                          
          documentation                                                              
  ------------------------------------------------------------------------------------------

QE = Quality of Evidence; R = Strength of Recommendation (see Appendix A
in the original guideline document)

Y.  **Follow Up, Repeat Lipid Evaluation At Least Annually**

> *Objective*
>
> Ensure that patients initially treated for dyslipidemia receive
> periodic reassessment of the efficacy of treatment.
>
> *Recommendations*

1.  Lipid evaluations should be repeated at least annually. **\[I\]**

  ------------------------------------------------------------------------------------------
  ** **   **Recommendation**        **Sources of Evidence**     **QE**   **Overall   **R**
                                                                         Quality**   
  ------- ------------------------- --------------------------- -------- ----------- -------
  1       Perform periodic follow   NCEP ATP-III, 2002          III      Poor        I
          up                                                                         

  ------------------------------------------------------------------------------------------

QE = Quality of Evidence; R = Strength of Recommendation (see Appendix A
in the original guideline document)

**Definitions**:

**Strength of the Recommendations**

**A**: A strong recommendation that the clinicians provide the
intervention to eligible patients.\
*Good evidence was found that the intervention improves important health
outcomes and concludes that benefits substantially outweigh harm.*

**B**: A recommendation that clinicians provide (the service) to
eligible patients.\
*At least fair evidence was found that the intervention improves health
outcomes and concludes that benefits outweigh harm.*

**C**: No recommendation for or against the routine provision of the
intervention is made.\
*At least fair evidence was found that the intervention can improve
health outcomes but concludes that the balance of benefits and harms is
too close to justify a general recommendation.*

**D**: Recommendation is made against routinely providing the
intervention to asymptomatic patients.\
*At least fair evidence was found that the intervention is ineffective
or that harms outweigh benefits.*

**I**: The conclusion is that the evidence is insufficient to recommend
for or against routinely providing the intervention.\
*Evidence that the intervention is effective is lacking, or poor
quality, or conflicting and the balance of benefits and harms cannot be
determined.*

  -------------------------------------------------------------------------------------
  ** **                 **Net Benefit of                             
                        the                                          
                        Intervention**                               
  --------------------- ----------------- -------------- ----------- ------------------
  ***Quality of         **Substantial**   **Moderate**   **Small**   **Zero or
  Evidence***                                                        Negative**

  **Good**              A                 B              C           D

  **Fair**              B                 B              C           D

  **Poor**              I                 I              I           I
  -------------------------------------------------------------------------------------

**Quality of Evidence**

**I**: At least one properly done randomized controlled trial

**II-1**: Well designed controlled trails without randomization

**II-2**: Well designed cohort or case-control analytic study,
preferably from more than one source

**II-3**: Multiple time series evidence with/without intervention;
dramatic results of uncontrolled experiment

**III**: Opinion of respected authorities, descriptive studies, case
reports, and expert committees

**Overall Quality**

**Good**: High grade evidence (I or II-1) directly linked to health
outcome

**Fair**: High grade evidence (I or II-1) linked to intermediate
outcome; or moderate grade evidence (II-2 or II-3) directly linked to
health outcome

**Poor**: Level III evidence or no linkage of evidence to health
outcome.

**Net Effect of Intervention**

**Substantial**:

-   More than a small relative impact on a frequent condition with a
    substantial burden of suffering, *or*

-   A large impact on an infrequent condition with a significant impact
    on the individual patient level

**Moderate**:

-   A small relative impact on a frequent condition with a substantial
    burden of suffering, *or*

-   A moderate impact on an infrequent condition with a significant
    impact on the individual patient level

**Small**:

-   A negligible relative impact on a frequent condition with a
    substantial burden of suffering, *or*

-   A small impact on an infrequent condition with a significant impact
    on the individual patient level

**Zero or Negative**:

-   Negative impact on patients, *or*

-   No relative impact on either a frequent condition with a substantial
    burden of suffering*, or*

-   An infrequent condition with a significant impact on the individual
    patient level

**Abbreviations and Acronyms List**

ACS -- acute coronary syndrome

AIDS -- acquired immune deficiency syndrome

ALT -- alanine aminotransferase

AST-- aspartate aminotransferase

AMI-- acute myocardial infarction

BMI -- body mass index

CAD -- coronary artery disease

CHD -- coronary heart disease

CK -- creatine kinase

CV -- cardiovascular

CVA -- cerebrovascular accident

CVD -- cardiovascular disease

DM -- diabetes mellitus

HbAlc -- glycosylated hemoglobin A1C

HDL-C -- high density lipoprotein cholesterol

HIV -- human immunodeficiency virus

HsCRP -- high sensitive C-reactive protein

HTN -- hypertension

LDL-C -- low density lipoprotein cholesterol

LFT -- liver function tests

MI -- myocardial infarction

MNT -- Medical Nutrition Therapy

PUD -- peptic ulcer disease

SCr -- serum creatine

TC -- total cholesterol

TG -- triglycerides

TLC -- therapeutic lifestyle change

TSH -- thyroid-stimulating hormone

#### CLINICAL ALGORITHM(S)

Algorithms are provided for:

-   Screening

-   Initiation of Therapy

-   Follow-up of Therapy

### EVIDENCE SUPPORTING THE RECOMMENDATIONS

#### REFERENCES SUPPORTING THE RECOMMENDATIONS

[References open in a new
window](http://www.guideline.gov/summary/select_ref.aspx?doc_id=9907)

#### TYPE OF EVIDENCE SUPPORTING THE RECOMMENDATIONS

The majority of the literature supporting the science for these
guidelines is referenced throughout the original guideline document and
is based upon key randomized controlled trials and longitudinal studies
published from 1999 through 2004.

Where existing literature was ambiguous or conflicting, or where
scientific data was lacking on an issue, recommendations were based on
the clinical experience of the Working Group. These recommendations are
indicated in the evidence tables as based on \"Working Group
Consensus.\" A complete bibliography is provided at the end of the
document.

The quality of the evidence supporting individual recommendations is
given for selected recommendations (see \"Major Recommendations\"
field).

### BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS

#### POTENTIAL BENEFITS

Dyslipidemia is a major risk factor for coronary heart disease and
atherosclerotic cardiovascular disease and its subsequent morbidity and
mortality. Lipid-related interventions, including lifestyle
modifications, such as diet and exercise, and drug therapy can reduce
the risk of atherosclerotic cardiovascular disease in patients with high
cholesterol.

#### POTENTIAL HARMS

-   Potential adverse effects and precautions for drug therapy used in
    dyslipidemia are provided in Appendix E-1 and E-3 of the original
    guideline document.

-   There are significant drug interactions noted with bile acid resins,
    fibrates, niacin, and statins. See Appendix E-2 in the original
    guideline document for a list of known drug interactions to date.

### CONTRAINDICATIONS

#### CONTRAINDICATIONS

-   Statins are contraindicated in active liver disease, in those
    persons with persistent elevation of liver transaminases, and in
    pregnancy.

-   Niacin is contraindicated in hepatic disease and relatively
    contraindicated in gout or history of complicated/active peptic
    ulcer disease (PUD). Use niacin with caution in patient with
    diabetes, since it may alter glucose control.

-   Fibrates are contraindicated in severe renal or hepatic disease,
    including primary biliary cirrhosis and preexisting gallbladder
    disease.

-   Refer to Appendix E-1 and E-3 of the original guideline for
    additional information on contraindications.

### QUALIFYING STATEMENTS

#### QUALIFYING STATEMENTS

-   Although this guideline was developed for a broad range of clinical
    settings, it should be applied with enough flexibility to
    accommodate local practice and individual situations.

-   Specific recommendations for the management of lipid disorders in
    those with metabolic syndrome have been described in recent national
    guidelines (National Cholesterol Education Program Adult Treatment
    Panel III \[NCEP ATP-III\]). The recommendations emphasize lifestyle
    management (weight loss, physical activity, dietary fat
    restriction). Medications can potentially favorably alter low levels
    of high-density lipoprotein (HDL) and high levels of triglycerides
    (TG) and in theory reduce the risk of cardiovascular disease in
    individuals with metabolic syndrome. However, specific treatment
    targets and recommendations have not been fully clarified,
    particularly with regards to drug therapy, largely on the basis of a
    lack of hard outcomes data from clinical trials. Further clinical
    trial data will be required before more specific recommendations can
    be made regarding the treatment of low level of HDL and high level
    of TG in metabolic syndrome. These issues will be addressed in
    detail in future revisions of the guidelines as more definitive data
    become available.

-   Although this guideline represents the best evidence-based practice
    on the date of its publication, it is certain that medical practice
    is evolving and that this evolution will require continuous updating
    of published information. In addition, the reader is reminded that
    this document is intended as a guideline and can never supersede the
    clinical judgment of the healthcare provider.

### IMPLEMENTATION OF THE GUIDELINE

#### DESCRIPTION OF IMPLEMENTATION STRATEGY

The Veterans Health Administration (VHA) instituted performance measures
for implementation of clinical practice guidelines in fiscal year 1998.
These measures included screening for lipid abnormalities in diabetic
patients with established coronary heart disease. Along with the work in
the current guideline itself, both the Veterans Health Administration
and the Department of Defense (DoD) are developing additional
performance measures.

#### IMPLEMENTATION TOOLS

Clinical Algorithm\
Pocket Guide/Reference Cards\
Quick Reference Guides/Physician Guides\
Resources

For information about
[availability](#identifying-information-and-availability), see the
\"Availability of Companion Documents\" and \"Patient Resources\" fields
below.

### INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT CATEGORIES

#### IOM CARE NEED

Getting Better\
Living with Illness\
Staying Healthy

#### IOM DOMAIN

Effectiveness\
Patient-centeredness

### IDENTIFYING INFORMATION AND AVAILABILITY

#### BIBLIOGRAPHIC SOURCE(S)

Management of Dyslipidemia Working Group. VA/DoD clinical practice
guideline for the management of dyslipidemia. Washington (DC):
Department of Veterans Affairs, Department of Defense; 2006. 140 p.

#### ADAPTATION

This guideline drew heavily from the following sources:

-   Executive summary of the third report of the National Cholesterol
    Education Program (NCEP) expert panel on the detection, evaluation,
    and treatment of high blood cholesterol in adults (Adult Treatment
    Panel III).  *Journal of the American Medical Association* 2001, 285
    (19), 2486-2497.

-   NCEP ATP-III, 2002: Third Report of the National Cholesterol
    Education Program (NCEP) Expert Panel on Detection, Evaluation, and
    Treatment of High Blood Cholesterol in Adults (Adult Treatment
    Panel III) final report. Circulation 2002, 106, (25), 3143-421.

-   The U.S. Preventive Services Task Force Guide to Clinical Preventive
    Services. Second Edition 2001.

-   Pharmacy Benefits Management---Medical Advisory Panel.  The
    pharmacologic management of hyperlipidemia. VHA PBM-SHG Publication.
    Hines, IL: Pharmacy Benefits Management Strategic Health Group,
    Veterans Health Administration, Department of Veterans Affairs

#### DATE RELEASED

2001 Dec (revised 2006)

#### GUIDELINE DEVELOPER(S)

Department of Defense - Federal Government Agency \[U.S.\]\
Department of Veterans Affairs - Federal Government Agency \[U.S.\]\
Veterans Health Administration - Federal Government Agency \[U.S.\]

#### SOURCE(S) OF FUNDING

United States Government

#### GUIDELINE COMMITTEE

The Management of Dyslipidemia Working Group

#### COMPOSITION OF GROUP THAT AUTHORED THE GUIDELINE

**Guideline Update Working Group**

*Veterans Affairs Working Group Members*: John R. Downs, MD
(*Co-chairman*); C. Bernie Good, MD; Leonard Pogach, MD; Robert L.
Jesse, MD; Teresa M. Hoos, MS, RD; Catherine L. Kelley, PharmD, BCPS;
Connie Foster, MSN, APRN; Acquanetta Lancaster, RN, NP

*Department of Defense Working Group Members*: Vincent F. Carr, Col, MC,
CFS (*Co-chairman*); Patrick G. O\'Malley, LTC, MD, MPH; Carl A. Gibson,
LTC, MC; Zoë C. Hawes, Capt, NC; Janetta R. Blackmore, Capt, MS, RD, LD;
Vincent P. Fonseca, LtCol, MD, MPH; Angela V. Klar, MSN, RN, ANP-CS

*Guideline Facilitator*: Oded Susskind, MPH

*Research Team-Evidence Appraisal*: Vivian H. Coates, MPH; Charles
Turkelson, PhD; Eileen G. Erinoff; Wendy Bruening, PhD; Stephen Tregear,
PhD

*Staff*: Rosalie Fishman, RN, MSN; Martha D\'erasmo, RN, MPH; Joanne
Marko, MS, SLP; Pam Zingeser; Kristyn O\'Reilly

#### FINANCIAL DISCLOSURES/CONFLICTS OF INTEREST

Not stated

#### ENDORSER(S)

Veterans Health Administration National Clinical Practice Guideline
Council - Federal Government Agency \[U.S.\]

#### GUIDELINE STATUS

This is the current release of the guideline.

This guideline updates a previous version: Veterans Health
Administration, Department of Defense. VHA/DoD clinical practice
guideline for the management of dyslipidemia in primary care. Washington
(DC): Veterans Health Administration, Department of Defense; 2001 Dec.
Various p.

#### GUIDELINE AVAILABILITY

Electronic copies: Available from the [Department of Veterans Affairs
(VA) Web site](http://www.oqp.med.va.gov/cpg/DL/DL_base.htm).

Print copies: Available from the Department of Veterans Affairs,
Veterans Health Administration (VHA), Office of Quality and Performance
(10Q), 810 Vermont Ave. NW, Washington, DC 20420.

#### AVAILABILITY OF COMPANION DOCUMENTS

The following are available:

-   Diagnosis and management of dyslipidemia guideline summary --
    update 2006. Washington (DC): Department of Veterans Affairs
    (U.S.); 2006. 25 p.

-   Diagnosis and management of dyslipidemia pocket guide --
    update 2006. Washington (DC): Department of Veterans Affairs
    (U.S.); 2006. 2 p. See the related QualityTool summary on the
    [Health Care Innovations Exchange Web
    site](http://innovations.ahrq.gov/content.aspx?id=348).

-   Diagnosis and management of dyslipidemia key points card --
    update 2006. Washington (DC): Department of Veterans Affairs
    (U.S.); 2006. 2 p. See the related QualityTool summary on the
    [Health Care Innovations Exchange Web
    site](http://innovations.ahrq.gov/content.aspx?id=350).

Electronic copies: Available from the [Department of Veterans Affairs
(VA) Web site](http://www.oqp.med.va.gov/cpg/DL/DL_base.htm).

Print copies: Available from the Department of Veterans Affairs,
Veterans Health Administration (VHA), Office of Quality and Performance
(10Q), 810 Vermont Ave. NW, Washington, DC 20420.

The following is also available:

-   Putting clinical practice guidelines to work \[online tutorial\].
    Available from the [Department of Veterans Affairs Web
    site](http://www.oqp.med.va.gov/Training/WWW/010000000010.html).

#### PATIENT RESOURCES

None available

#### NGC STATUS

This NGC summary was completed by ECRI on August 9, 2002. The
information was verified by the guideline developer on September 25,
2002. This NGC summary was updated by ECRI on November 7, 2006.

#### COPYRIGHT STATEMENT

No copyright restrictions apply.

### DISCLAIMER

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© 1998-2008 National Guideline Clearinghouse

Date Modified: 11/3/2008