Guideline Development Conference:

*The Treatment of Dyslipidemias*

*in Native Americans*

**[Guidelines Steering Committee]{.underline}\
***Chairman:* James M. Galloway, M.D., F.A.C.P., F.A.C.C.

*Members:*

Barbara Howard, Ph.D.

Wm. James Howard, M.D.

Jacques Rossouw, M.D.

Jonathan Krakoff, M.D.

Kermit Smith, M.D.

Justin L. Sewell, M.P.H.

Robert McNamara, M.D., M.H.S., F.A.C.C.

Andrew Narva, M.D.

Thomas Richtsmeier, M.D.

Charles Reidhead, M.D.

Kelly Acton, M.D.,F.A.C.P.

Matt Schnellbaecher, M.D.

Peter Reaven, M.D.

Eliot A. Brinton, M.D.

Eric A. Brody, M.D., F.A.C.C.

Randy Burden, Pharm.D., C.D.E.

Gwen Hosey, M.S., A.R.N.P., C.D.E.

Tony Fisher, R.Ph.

Ann Bullock, M.D.

Stephen Rith-Najarian, M.D.

James Bresette, Pharm.D.

Lani Desaulniers, M.D.

Diane Phillips, R.D., L.D.

**[Guidelines Development Committee]{.underline}**

Linda Aranaydo, M.D.

Gerard Bazile, M.D.

AnnMarie Bosma

Rosinna Briones

Nathaniel Cobb, M.D.

Martha Cotten, M.D.

Scott Doughty, M.D.

Mary Lynn Eaglestaff

Gretchen Esplund, M.D.

Bruce Finke, M.D.

Michelle Garland, Pharm.D.

Patricia Nez Henderson, M.D.

Betty Jarvis

Cathy Johnson, R.D.

Gerard Kisto

John Kittredge, M.D.

Theresa Kuracina, R.D., C.D.E.

Chris Lamer, Pharm.D.

Bert Lewis

Amy Light, M.D.

Laura Longstaff

Beth Malasky, M.D., F.A.C.C.

Perry Mitchell, M.D.

Julien Naylor, M.P.H.

Jeff Newman, PharmD

Richard Olson, M.D.

Edith A. Pacheco, R.N.

Douglas Peter, M.D.

Diane Pratt, M.D.

Terry Raymer, M.D., C.D.E.

Charles Rhodes, M.D.

Andy Schatzki, M.D.

## Pam Schweitzer, Pharm.D.

Pearish Smith, M.D.

Edward Stein, Pharm.D.

Bernadine Tolbert, M.D.

Leeanna Travis, R.D., C.D.E.

Lorraine Valdez, M.P.A., C.D.E.

F. Eileen Wall, M.S., F.N.P., C.D.E.

Paul Weintraub, M.D.

Brian Wickwire, M.D.

Charlton Wilson, M.D.

Terri Wilson, R.N., C.D.E.

Edward Zastawny, Pharm.D., B.C.P.S.

Al Zavatsky, M.D.

Ellie Zephier, M.P.H., R.D.

Mary Jo Zunic, Pharm.D.

Made possible through a generous unrestricted educational grant from the
Bayer Corporation.

**[Introduction]{.underline}**

While the mortality rate for cardiovascular disease (CVD) in the general
United States population has declined by more than 50% since the
mid-1960's, incidence rates in Native American populations have,
unfortunately, increased remarkably during this period. Recent studies
of the incidence of coronary artery disease have demonstrated a marked
and concerning upward trend with rates now almost double that of the
general United States population.

The prevalence of many of the classic risk factors for CVD have likewise
been noted to be increasing and appear responsible for this worrisome
trend in CVD. Clearly, a number of recent reports have noted a
significant increase in the prevalence of hypertension. Tobacco use
among Native Americans, especially in the teen years, appears to be
increasing. As obesity becomes more prevalent, the presence of the
"insulin resistance syndrome," currently referred to as the "metabolic
syndrome" is increasing and fuels the current epidemic of diabetes among
Native Americans. This epidemic of diabetes, in turn, adds another
powerful CVD risk factor. Diabetes appears to be the major risk factor
contributing to the rapidly rising rates of CVD in Native Americans.

Many of us working in the field serving Native Americans have noted
these events with alarm. We have also noted the simultaneous and
significant development of dyslipidemia in this population, as a
component of the "metabolic syndrome." Current evidence suggests that
dyslipidemias play a major role in the development of CVD and may be
more easily amenable to intervention than some of the other risk
factors. As a sense of urgency was noted related to these trends in CVD,
many of the clinical leaders in Indian Health throughout the nation came
together on December 11, 12 and 13, 2000 in Scottsdale, Arizona to
address the special issues of lipid management in adult Native American
populations and developing a consensus on the optimal approach.

Over 50 of the national leaders in Indian Health were present, primarily
physicians, including cardiologists, endocrinologists, internists,
nephrologist, and family physicians, as well as nurses, physician
assistants, nurse practitioners, nutritionists, dietitians, health
educators, and pharmacists. A number of Native American providers and
clinicians were present as well as a traditional healer, Mr. Gerard
Kisto, were present to assist us in the development of these guidelines.
Our efforts were joined by nationally renowned outside faculty,
including Dr. Barbara Howard, one of the authors of the American Heart
Association Scientific Guidelines of Diabetes and Heart Disease (as well
as a Principal Investigator of the Strong Heart Study) as well as Wm.
James Howard, MD and Jacque Rossouw, MD, two committee members working
on the National Cholesterol Education Program (NCEP) ATP III guidelines.
We were also honored to have Drs. Eliot Brinton, Peter Reaven and
Johnathan Krakoff work with us in this effort. Over the next eight
months, this document has undergone a number of subsequent rounds of
clarification and refinement for the development of an optimal set of
guidelines through contributions from the participants.

While dyslipidemia intervention is considered vitally important, the
group acknowledged there are many additional aspects of CVD and diabetes
prevention also requiring additional attention and would be addressed
both as part of this conference as well as in future guideline
conferences and major preventative efforts.

Several major issues became evident as the conference developed,
including the economic impact of the therapeutic interventions
considered. Although concerns related to the health care costs have had
significant impact nationally related the general US population, the
funding limitations within the Indian Health Service are even more
stringent. In fact, congressionally allocated funding available for the
delivery of health care within the Indian Health Service is only at 71%
of the average cost of a mainstream health plan and is \$1.3 billion
short of parity with a benchmark mainstream health plan in 1999.

However, regardless of funding limitations, the care provided to Native
Americans clearly **[must]{.underline}** be held to the same standard as
the general US population. Unfortunately, due to the high incidence of
diabetes in Native Americans, a higher percentage of the population
require intervention and preventative therapy than the general US
population - with its attendant costs. Nevertheless, due to the high
risk of this population, intervention is more cost effective as well.

***General overview recommendations from the conference***

The participants expressed strong support for the following:

1.  Additional and separate line item congressional budgetary funding
    within the IHS budget to eliminate the disparities between Native
    American and non-Native American communities in the availability of
    standard of care medications (in addition to increased general
    funding support).

2.  A **team approach** to CVD risk reduction, incorporating Tribal
    health directors, nutritionists, dietitians, nurses, pharmacists,
    educators, physicians and other appropriate staff through well
    organized and funded interventional programs.

3.  The development of a culturally sensitive **public
    education/health** campaign related to CV (and other chronic
    disease) risk factor reduction.

Acknowledgements:

The following document is the result of a significant effort by multiple
individuals. This consensus statement has been developed through many
hours of hard work in an attempt to stem the rising tide of CVD in
Native Americans. This manuscript is a tribute to the participants and
all those who have spent many hours dedicated to the completion of this
project. These efforts are greatly appreciated. This document is
dedicated to the Native American people we serve.

**Preface**

Several differences will be noted between these guidelines and the
recently released Third Report of the National Cholesterol Education
Program Adult Treatment Panel III (ATP III), despite having membership
crossover in both guideline development panels. A major difference
between these two is that our guidelines focus substantially more on the
metabolic syndrome than ATP III due to its high prevalence and its major
contribution to the increasing incidence and prevalence of CVD among
Native Americans. In that light, the lipid goals for those with impaired
fasting glucose and the triglyceride goal for those with both diabetes
and cardiovascular disease are more stringent than those in ATP III.

Another substantial difference is that we chose to continue to use the
risk factor counting approach in determining lipid goals and treatment
choices as opposed to the ATP III Framingham risk factor assessment.
This preference was made for simplicity of use and because there is no
directly applicable risk assessment tool yet available for Native
Americans. Additionally, the Framingham risk factor assessment
underestimates the calculated CVD risks in Native Americans.

In addition, our committee's setting of an LDL goal of \<130 after
lifestyle modification for all adults with 2 or more risk factors
constitutes a somewhat more aggressive approach than ATP III, as ATP III
recommends drug treatment if LDL \> 160 after lifestyle modification
(with the same goal of \< 130) for patients with 10-year risk of less
than 10%, although the guidelines have identical recommendations if the
individual with 2 risk factors has a 10-year risk of between 10 and 20%.
Similarly, our setting a goal of LDL \<160 after lifestyle modification
for all with 0-1 RF without having a requirement threshold of an LDL
\>190 constitutes a more aggressive approach than was used in ATP III.

Our committee clearly recognizes that the guidelines we have produced
present a somewhat more aggressive approach to the treatment of
hyperlipidemia. As the rates of cardiovascular risk factors continue to
grow and the incidence of CVD in Native Americans now approaching twice
that of the general US population, we feel that this approach is not
only justified, but essential to improve the health and prevent the
mortality and disability of CVD among Native Americans.

# **[Executive Summary]{.underline}**

## ***Introduction***

The *Lipids Guidelines Conference* addressed the global issues of
dyslipidemia in the adult Native American population through several
central sessions. More specific, detailed topics were covered in
multiple breakout sessions. Each of the breakout groups developed a
rough set of guidelines for presentation to the conference group as a
whole. These guidelines were then integrated into a set of consensus
recommendations. The results of each breakout group, after modification
and approval by the entire group, are presented in detail later in this
text. Following are the abbreviated summaries of the materials covered
and recommendations developed for each breakout subject area and
includes the revisions, modifications and endorsements of the entire
conference.

### ***Initial Evaluation***

Initial evaluation of hyperlipidemia should investigate secondary causes
and should include a thyroid stimulating hormone (TSH) measurement,
urinalysis, liver function tests, review of current medications, fasting
plasma or serum glucose and a history of alcohol use.

***[Elevated LDL-C]{.underline}***

The most effective clinically proven drugs to lower LDL-Cholesterol
(LDL-C) are the HMG-CoA reductase inhibitors (statins). Other agents
useful in lowering LDL cholesterol include bile-acid binding resins,
fibric acid derivatives, and nicotinic acid (niacin).

### *Recommendations*

-   The use of the direct LDL-C measurement should be considered for
    those with diabetes, triglycerides \> 250 mg/dL (due to inaccuracy
    of LDL-C calculations with triglycerides above this level), or when
    fasting lipids are difficult to obtain. The direct LDL-C measurement
    is now widely available, relatively inexpensive, and does not
    require patients to fast. For effective evaluation, fasting lipid
    levels are also necessary to assess other parameters, including
    HDL-C and triglycerides, however.

-   The following LDL-C goals and actions to meet those goals are
    recommended:

  ----------------------- ---------------- ------------------------------
  Risk Level              LDL-C Goal       Action

  IFG/IGT/DM/CVD\*        \<100 mg/dL      Diet/lifestyle/pharmacologic
                                           agents

  2+ risk factors\*\*     \< 130 mg/dL     Diet/lifestyle/pharmacologic
                                           agents

  0-1 risk factors\*\*    \< 160 mg/dL     Diet/lifestyle
  ----------------------- ---------------- ------------------------------

*\*CVD includes patients with a global risk assessment of \>20% 10-year
risk of CHD. See Risk Assessment module.*

*IFG = impaired fasting glucose; IGT= impaired glucose tolerance; DM=
diabetes mellitus; CVD= cardiovascular disease*

*\*\*Risk factors other than LDL-C include: cigarette smoking, high
blood pressure (\>140/90 mm Hg or on treatment), low HDL (\< 40 mg/dL),
family history of premature CVD (in first degree males age \<55 years
and first degree females age \< 65 years), age (men \> 45 years and
women \> 55 years or premature menopause without estrogen replacement).*

-   The following drug choices (in order of priority) are recommended
    for primary LDL-C lowering.

  -----------------------------------------------------------------------
  1\. Statin

  2\. Resin (if non-diabetic and absence of triglyceride elevation)

  3\. Niacin formulation (depending on glucose control)
  -----------------------------------------------------------------------

#### 

#### ***[Low HDL & High Triglycerides: The Metabolic Syndrome]{.underline}*** 

The triad of low HDL cholesterol, high triglycerides, and abnormal
levels of small, dense LDL cholesterol forms are the dyslipidemias that
form part of the metabolic syndrome. A crucial understanding to any
discussion of lipid treatment for primary and secondary prevention for
CHD is the fact that **diabetes alone (without CHD) represents a CHD
risk equal to or greater than known prior CHD. Due to this fact,
diabetes is generally considered a "CHD risk equivalent".** Because of
the tremendous increases in diabetes and cardiovascular disease noted in
Native Americans, early recognition and a low intervention threshold are
essential to prevent cardiovascular disease. Because of the increased
risk for the entire population of Native Americans, interventions should
be considered against a backdrop of the larger intervention of community
and individual lifestyle changes.

### 

### *Recommendations:*

Lipoprotein evaluation in patients with known atherosclerosis, diabetes,
IGT, IFG, and multiple risk factors should consist of a full lipid
profile, including total cholesterol, triglycerides, LDL-C, and HDL. If
the patient is diabetic, has significant triglyceride elevation (above
250), or difficulty in obtaining fasting lipids, a direct LDL-C should
be considered, rather than a calculated LDL-C from the lipid profile.
For effective evaluation, fasting lipid levels are also necessary to
assess other parameters, including HDL-C and triglycerides, however.

-   The following medications are potential agents for addressing the
    metabolic syndrome in Native American populations.

-   Statins are primarily beneficial when triglycerides are \< 400
    mg/dL.

-   Resins are generally not recommended as primary therapy if
    triglyceride levels are borderline or high (although they may be
    used adjunctively when triglycerides are controlled). However, new
    agents are being released that may prove to be useful in patients
    with mild hypertriglyceridemia.

-   Fibric acid derivatives may be the first choice for patients with
    triglyceride elevations of greater than 400 mg/dL and some may be
    considered in combination with statins.

-   The use of niacin have been controversial due to concerns over
    precipitation of diabetes or worsening of glycemic control, although
    two recent studies have suggested that these issues may be minor.

The group recommends the following treatment goals for Native American
patients

with the metabolic syndrome:

  ---------------------------- -------- --------- --------- --------------
  **HDL‑C/TG/LDL-C goals**     HDL-C              TG        LDL-C

                               Male     Female              

  Normal Glucose Tolerance     \> 40    \> 45     \< 200    \< 130

  IGT, IFG, DM without CVD\*,  \> 40    \> 45     \< 150    \< 100
  CHD without DM                                            

  DM and CVD\*                 \> 40    \> 45     \<        \< 100
                                                  100\*\*   
  ---------------------------- -------- --------- --------- --------------

*\*CVD includes: CHD, PVD, and/or other known atherosclerotic events*

*All patients with dyslipidemia should be assessed for reversible
etiologies, including thyroid abnormalities (assess with a thyroid
stimulating hormone, TSH), liver function abnormalities (assess liver
function tests), nephrotic syndrome (assess with urine analysis) and, if
not already assessed, diabetes as well as levels of alcohol intake and
medication use (check for potential dyslipidemic effects).*

*\*\*Some authors felt that a TG of 150 or less would be a more
reasonable goal in this category.*

***Diet, weight loss, and physical activity must be integral parts of
treatment.***

#### ***[Risk Assessment Methodologies Session]{.underline}***

It is often helpful to patients and their providers to have a reasonable
assessment of CHD risk for individual risk level identification as well
as a motivational tool for patient compliance. In addition, the level of
intervention aggressiveness is most appropriate if they are matched to
the risk of the individual. It has been suggested that the optimal
approach is to divide the 10-year risk of cardiac events into three
categories as determined by level of risk: high risk (greater than 20%),
intermediate risk (10%-20%), and lower risk (less than 10%). Efforts are
underway to develop a more accurate global risk score for Native
Americans. Until this information is available, a global risk score
evaluation based on the Framingham data will give us a useful estimate
(although likely an underestimate) of the risk of individual Native
American patients and may help providers more appropriately treat
cardiac risk factors and help public health workers tailor
interventions.

*Recommendations*

1.  Risk assessment evaluations should optimally be based on 10-year
    global risk of cardiovascular disease, categorizing patients into
    high (\>20%), intermediate (10%-20%), and lower risk (\<10%).
    However, in the absence of a global risk score for Native Americans,
    a risk factor counting methodology is indicated and reasonable to
    initially assess CVD risk.

2.  Development of a global risk score specific for the Native American
    population based on the data from the Strong Heart Study, with
    assessment of the value of a separate global risk score for diabetic
    patients.

3.  Lipid levels and risk evaluation in general adult population should
    be performed at least once every 5 years. For diabetics, lipid
    levels and risk evaluation should be performed at least annually.
    More frequent evaluations may be necessary based on clinical
    considerations such as use of lipid lowering therapy and intervening
    change in clinical status.

4.  All non-diabetic patients greater than 45 years of age with
    cardiovascular risk factors and without contraindications should be
    on aspirin 81 -- 325 mg/day. Diabetic patients over 30 years of age
    should be on 162 -- 325 mg daily, unless contraindicated, due to the
    increased thrombotic tendencies associated with diabetes.

#### 

#### ***[Cardiovascular Health Promotion Programs Session]{.underline}***

Since cardiovascular morbidity and mortality are related to CHD risk
factors, it has been postulated that by targeting and aggressively
treating secondary and high-risk primary prevention patients to modify
or control risk factors, the result would lead to long-term reduction of
CHD rates in American Indians. It has been shown that physician directed
multidisciplinary programs, where CHD risks were managed by clinical
pharmacists, registered nurses or advance practice nurses, were more
effective than individual physician management efforts.

### *Recommendations*

-   Health promotion programs that effectively "team manage" patient CHD
    risks are excellent methods to address these concerns in American
    Indian communities.

-   These teams should be multidisciplinary and involve, where possible,
    physicians and mid-level providers (clinical pharmacy specialists,
    nurse practitioners, clinical nurse specialists, and/or physician
    assistants) as well as dietitians and appropriate ancillary staff
    (diabetes educator, exercise physiologist, etc.).

-   Mid-level providers must be certified and current in risk reduction
    practice.

-   Certificate programs should be established and implemented
    specifically designed to train and update practitioners, covering
    American Indian cultural, psychological and social values,
    motivational interviewing, exercise physiology, medical nutrition
    therapy, weight loss, tobacco cessation, diabetes, hypertension and
    dyslipidemias using available national consensus clinical practice
    guidelines.

#### ***[Effective Lifestyle Modifications in a Cultural Context Session]{.underline}***

Healthy lifestyles that include regular physical activity and balanced
nutrition are essential and may be paramount to the health of Native
Americans. Lives that incorporate healthy habits on a daily basis will
not only improve dyslipidemia, but decrease morbidity and mortality from
cardiac disease, prevent other significant medical illnesses, and
promote improved mental health and a general sense of well being. The
American Heart Association and the American Diabetes Association have
both developed guidelines emphasizing weight management, regular
physical activity, and individualized dietary recommendations. These
recommendations are relevant to Native Americans; however, they need to
be tailored to the specific traditions and cultures of Native American
communities. In general, a teamwork approach is encouraged. This should
include available health professionals, such as dietitians, pharmacists,
nurses, physicians, physical therapists, certified diabetes educators,
and ancillary heath care staff, as well as local Tribal members. The
development of support for these efforts with the Tribal health board
and, where appropriate, the Tribal council among other local community
is essential.

The Diabetes Prevention Program has recently released their results
revealing a striking 58% reduction in the onset of type 2 diabetes
mellitus with diet and lifestyle interventions, when compared to an
untreated control group. These results were seen in a mixed U.S.
population group, including Native Americans, selected for the presence
of impaired glucose tolerance as a marker of high risk for the
development of type 2 diabetes mellitus.

### *Dietary Recommendations*

-   The 2000 AHA Dietary Guidelines should be followed while
    accommodating the local diets. Specific foci include the following:

-   General reductions in sugar-based beverages.

-   Reductions in total calorie intake.

-   Reductions in total fat, saturated fat, and trans fatty acids.

-   Increases in dietary fiber and complex carbohydrates (whole grains).

-   Increase intake of vegetables and whole fruit.

*[Implementation of Dietary Changes]{.underline}*

-   Referral of dyslipidemic and other high-risk patients to a
    registered dietitian for

medical nutrition therapy

-   Modeling of healthy food options at hospitals and community
    facilities.

-   Easily understandable community education.

### *Physical Activity Recommendations*

-   Guidelines for physical activity from both the Surgeon General and
    the AHA should be followed with an emphasis upon lifestyle
    modifications from a culturally appropriate perspective.

-   If no contraindications exist, the level of physical activity should
    be assessed and goals tailored towards a gradual increase working up
    to 30 to 60 minutes of activity on most, if not all, days per week.
    In addition, emphasis should be placed on increasing routine
    non-strenuous physical activity, such as stair climbing (rather than
    elevator use) and walking, throughout the day.

### *Obesity Management and Other Lifestyle Recommendations*

-   It is important to include tobacco cessation as a routine part of
    health maintenance.

-   All patients with a BMI ≥ 30.0 or BMI ≥ 25.0 with other risk factors
    or co-morbidities should be offered a formal weight management
    program.

-   Behavior modification, including avoidance of inappropriate use of
    food

-   Diagnosis and treatment of psychopathology (depression, anxiety,
    etc.) and emotional needs (loneliness, boredom, etc.) through
    direct, non-caloric means.

-   Combined efforts are strongly encouraged; for instance, a
    combination of moderate physical activity and good nutrition can
    make substantial contributions to the treatment of hyperlipidemia.

-   Two medications appear initially to be safe and effective adjuncts
    to the above measures for obesity management, orlistat and
    sibutramine. They could be considered for use in high-risk patients
    for weight loss and especially long-term maintenance of weight loss.

#### ***[Public Health and Community Education Session]{.underline}***

Community education for dyslipidemia in Native American communities is
an essential aspect of an overall effort to reduce the rising tide of
CVD in Native Americans. Such education must be addressed at several
levels to insure an appropriate and effective campaign.

### *Recommendations*

-   The inclusion and guidance of national Native American leaders and
    organizations is vital.

-   Community level education is greatly enhanced by the inclusion and
    support of local leaders. These may include tribal leaders, tribal
    council members, traditional healers/medicine people, community
    health representatives, local health board members, educators,
    athletes, entertainers, etc.

-   The following measures should be taken at the local level:

-   Emphasize proactive/positive message of wellness through lifestyle,
    diet, etc.

-   Utilize patient role models as examples of treatment successes along
    with patient support groups for those with established CHD/CVD.

-   Identify unique potential settings in which community education can
    occur.

-   Providers must be considered an integral part of the community, both
    as role models for healthy lifestyles and as participants in the
    educational process.

-   In communities with established medical facilities, we recommend the
    consideration of the appointment of one health care professional
    with special interest in cardiovascular risk reduction as a
    dyslipidemia coordinator (DC), analogous to the diabetes coordinator
    position already established at many IHS facilities.

-   Consider privileging other staff within the hospital to order lipid
    profiles. RNs, pharmacists and others are in a unique situation to
    identify patients at high cardiovascular risk and, if allowed to
    order lipid tests, may help assure that adequate lipid screening is
    occurring.

-   Periodic evaluation of educational program efficacy should be
    performed, including at least semi-annual assessment of rates of
    lipid profile and risk factor assessment as well as intervention.

#### ***[Secondary Prevention Session]{.underline}***

Lipid lowering in patients with known coronary artery disease (CAD) is
termed "secondary prevention." A crucial understanding to any discussion
of lipid treatment for secondary prevention of CHD is the fact that
**diabetes alone (without CVD) represents a CHD risk equal to or greater
than known prior CHD, and, due to this fact, diabetes is often
considered a "CHD risk equivalent." Thus, lipid management goals for
diabetics without CAD should be at the levels established for secondary
prevention, even without known CAD.** Furthermore, because the risk
increases even further in diabetes with established CAD, many suggest
that even lower goals could be considered. Previously, coronary
atherosclerosis was considered to be a relentless progressive disease,
where disability and death from CAD were almost inevitable. In the last
decade, numerous multi-center, randomized clinical trials have
conclusively proven that lowering elevated low density lipoprotein (LDL)
cholesterol levels in patients with established CAD sharply reduces the
risk of future MI, revascularization procedures, death from CAD, stroke
and death from all causes. The intensity of lipid therapy and its cost
effectiveness depends on the patient's clinical risk status, and those
patients at higher risk should receive the more aggressive
interventions.

### *Recommendations*

-   For the diagnosis and management of patients needing secondary
    prevention a complete lipid profile is required, including total
    cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides. If
    there is diabetes, significant triglyceride elevation (above 250),
    or difficulty in obtaining fasting lipids, a direct LDL-C should
    also be strongly considered.

-   The goals for lipid lowering therapy in patients needing secondary
    prevention are listed below.

\* Some authors felt that TG of 150 mg/dl was more appropriate in those
with DM and CVD.

-   All secondary prevention patients should be referred to a registered
    dietician for medical nutrition therapy to improve lipid levels and
    lower the risk of MI and CAD death.

-   If no contraindications exist, the level of physical activity should
    be assessed and goals tailored to a gradual increase, working up to
    30 to 60 minutes of activity on most, if not all, days. In addition,
    emphasis should be placed on increasing routine non-strenuous
    physical activity, such as stair climbing (rather than elevator use)
    and walking throughout the day.

-   Most patients receiving secondary prevention will require
    pharmacological intervention in addition to dietary and lifestyle
    intervention to adequately lower their risk of future CAD events. A
    summary of lipid therapy recommendations is shown on the following
    table:

+--------+------+-------+-------+-----+-------+-------+-------------+
| Lipid  |      |       |       |     |       |       |             |
| T      |      |       |       |     |       |       |             |
| herapy |      |       |       |     |       |       |             |
| S      |      |       |       |     |       |       |             |
| ummary |      |       |       |     |       |       |             |
| for    |      |       |       |     |       |       |             |
| Sec    |      |       |       |     |       |       |             |
| ondary |      |       |       |     |       |       |             |
| Preve  |      |       |       |     |       |       |             |
| ntion. |      |       |       |     |       |       |             |
+--------+------+-------+-------+-----+-------+-------+-------------+
| LDL-C  | L    |       |       | LD  |       |       | HDL \< 40   |
| \< 100 | DL-C |       |       | L-C |       |       | mg/dL       |
| mg/dL  | 100  |       |       | \>  |       |       |             |
|        | --   |       |       | 130 |       |       |             |
|        | 130  |       |       | mg  |       |       |             |
|        | m    |       |       | /dL |       |       |             |
|        | g/dL |       |       |     |       |       |             |
|        |      |       |       | Add |       |       |             |
|        | Add  |       |       | d   |       |       |             |
|        | drug |       |       | rug |       |       |             |
|        | the  |       |       | t   |       |       |             |
|        | rapy |       |       | her |       |       |             |
|        | to   |       |       | apy |       |       |             |
|        | diet |       |       | to  |       |       |             |
|        | and  |       |       | d   |       |       |             |
|        | phys |       |       | iet |       |       |             |
|        | ical |       |       | and |       |       |             |
|        | acti |       |       | ph  |       |       |             |
|        | vity |       |       | ysi |       |       |             |
|        | as   |       |       | cal |       |       |             |
|        | foll |       |       | ac  |       |       |             |
|        | ows: |       |       | tiv |       |       |             |
|        |      |       |       | ity |       |       |             |
|        |      |       |       | as  |       |       |             |
|        |      |       |       | fo  |       |       |             |
|        |      |       |       | llo |       |       |             |
|        |      |       |       | ws: |       |       |             |
+--------+------+-------+-------+-----+-------+-------+-------------+
| Diet   | TG\  | TG    | TG    | T   | TG    | TG    | Emphasize   |
| and    | <200 | 200   | \>400 | G\< | 200   | \>400 | weight loss |
| ph     | m    | --    | mg/dL | 200 | --    | mg/dL | and         |
| ysical | g/dL | 400   |       | mg  | 400   |       | physical    |
| act    |      | mg/dL |       | /dL | mg/dL |       | activity.   |
| ivity. |      |       |       |     |       |       |             |
|        |      |       |       |     |       |       | Advise      |
| Co     |      |       |       |     |       |       | smoking     |
| nsider |      |       |       |     |       |       | cessation.  |
| low    |      |       |       |     |       |       |             |
| dose   |      |       |       |     |       |       | Consider    |
| s      |      |       |       |     |       |       | niacin,     |
| tatin. |      |       |       |     |       |       | fibrates or |
|        |      |       |       |     |       |       | statins as  |
|        |      |       |       |     |       |       | necessary   |
|        |      |       |       |     |       |       | based on    |
|        |      |       |       |     |       |       | remainder   |
|        |      |       |       |     |       |       | of profile. |
+--------+------+-------+-------+-----+-------+-------+-------------+
|        | Sta  | S     | Fibr  | St  | Sta   | Fibr  |             |
|        | tin. | tatin | ates. | ati | tins. | ates. |             |
|        |      | or    |       | ns. |       |       |             |
|        | C    | Fib   | May   |     | May   | May   |             |
|        | ould | rates | comb  |     | be    | be    |             |
|        | also | or    | ine\* |     | combi | combi |             |
|        | use  | comb  | with  |     | ned\* | ned\* |             |
|        | Re   | inati | St    |     | with  | with  |             |
|        | sin. | on\*, | atins |     | Fib   | St    |             |
|        |      | if    | if    |     | rates | atins |             |
|        |      | ne    | neces |     | (or   | if    |             |
|        |      | eded. | sary. |     | ni    | neces |             |
|        |      |       |       |     | acin) | sary. |             |
|        |      | Could | Could |     | if    |       |             |
|        |      | also  | also  |     | neces |       |             |
|        |      | con   | con   |     | sary. |       |             |
|        |      | sider | sider |     |       |       |             |
|        |      | Ni    | Ni    |     |       |       |             |
|        |      | acin. | acin. |     |       |       |             |
+--------+------+-------+-------+-----+-------+-------+-------------+

\* with appropriate monitoring, especially liver function tests

-   Patients considered for secondary prevention should be evaluated for
    ischemia and left ventricular (LV) dysfunction.

-   Patients indicated for secondary prevention should take aspirin
    (unless contraindicated or not tolerated) and often have indications
    for non-lipid lowering drugs such as beta-blockers, and angiotensin
    II antagonists.

-   Aggressive glycemic and blood pressure control is warranted in
    patients with diabetes.

-   Time must be taken for discussion of clinical concepts and should
    include the reasons for treatment and therapy goals, in
    understandable terms. Native-speaking health educators, dietitians,
    pharmacists and other professionals, as well as key family members,
    should always be included when possible.

***[Compliance Development and Recommendations for Counseling
Session]{.underline}***

Successful treatment of dyslipidemia in Native American individuals
requires the development of an interpersonal trust between the provider
and the patient as well as similar beliefs related to the importance and
effect of the goal. Successful outcomes will result if a variety of
methods are used to enhance patient adherence, tailored to the
individual, and efforts should be undertaken by local providers to
tailor these recommendations according to the local culture and belief
systems as well as the availability of resources and the needs of the
community.

### *Recommendations*

-   Treating patients with dyslipidemia should involve a holistic
    approach. Providers should treat the whole patient with attention to
    physical, mental, cultural, and spiritual dimensions.

-   Patient education and treatment strategies should be developed which
    take into account patients learning styles, traditions, values and
    personal goals.

-   Providers should empower patients and encourage self-management.

-   Goals for lifestyle change should be developed with the patient, and
    providers should be attentive to cultural, psychosocial and
    socioeconomic issues that may present barriers to achieving these
    goals.

#### 

#### ***[Hypertensive Therapeutic Interventions Session]{.underline}***

Hypertension is another significant CHD risk factor (which is also a
part of the metabolic syndrome) that requires close attention for the
prevention of CHD. In fact, results from the UKPDS show that "tight"
blood pressure control has a dramatic and beneficial reduction on the
incidence of CHD, even to a significantly greater degree than "tight"
glucose control. In hypertensive patients, angiotensin converting enzyme
inhibitors (ACEI's) provide a significant additional benefit when
compared to other anti-hypertensives with the same level of blood
pressure control and, in addition, have generally become the first line
agent in hypertensive diabetic patients unless contraindicated or
another agent specifically indicated.

A recent NIH-sponsored management conference recommended that ACE
inhibitors be initiated in adult diabetic patients with any one of the
following: hypertension (\>140/90), creatinine\>1.5, or proteinuria \>
300 mg/day. There is also evidence that treatment of normotensive Type
II DM patients with microalbuminuria may benefit from treatment with ACE
inhibitors. Angiotensin converting enzyme inhibitors are also indicated
for patients post-MI with significant LV dysfunction, or clinical
congestive heart failure, as well as diabetic patients with hypertension
and/or nephropathy. The recent HOPE Trial suggests that patients at high
risk for atherosclerosis, including diabetics, should be strongly
considered for ACE inhibitors.

In Type 2 diabetes, if the maximal dosage of the ACE-I (with or without
diuretics) does not control the blood pressure to the desired goal of
130/80, the addition of beta blockers, unless contraindicated, is
generally preferred over long acting non-dihydropyridine calcium channel
blockers by the participants at our conference, unless contraindicated
or not tolerated.

The consensus statement attempts to synthesize evidence in the
literature into a cost-effective algorithm for non-diabetics and to
provide optimal renal and cardiovascular protection to the diabetic
patient. Key elements developed at this conference and based, in part,
on the NIH consensus were: 1) Blood pressure goal of \<130/80 for
diabetics, \<140/90 in non-diabetics 2) Use of ACE inhibitor as first
line agents with appropriate renal monitoring (generally using
concurrent if renal dysfunction), and 3) the utility of beta-blockers as
second line (unless contraindication or specific indication for another
medication), 4) Frequent necessity to use multiple drugs (including
diuretics) in diabetics if initial blood pressure is \>15/10 mm Hg above
goal.

[Figure 12. Blood Pressure Goals and Treatment Regimen]{.underline}

Guideline Development Conference:

***The Treatment of Dyslipidemias***

***in Native Americans***

[FULL GUIDELINES]{.underline}

######## I. Elevated LDL-C {#i.-elevated-ldl-c .unnumbered}

# 

### ***Introduction and rationale***

LDL-C is the main cholesterol-bearing lipoprotein in the plasma; it
transports cholesterol to cells in the vessel wall. Numerous studies
have shown that lowering LDL-C cholesterol reduces atherosclerotic
plaque and risk for cardiovascular morbidity and mortality. In diabetes,
LDL-C concentrations are often not elevated, but LDL-C is altered in
size and composition. In association with elevated triglycerides, LDL-C
particles are often smaller and more dense. These changes promote entry
and retention in the artery wall, as well as oxidation, glycation, and
other pro-atherosclerotic modifications and effects.

American Indians have lower average LDL cholesterol levels than the U.S.
population. However, there are convincing data in both nondiabetic and
diabetic American Indians that LDL cholesterol concentration is a strong
predictor of cardiovascular events, and there is a linear relationship
between LDL-C and increasing risk for cardiovascular disease (CVD) for
LDL-C concentrations \>70 mg/dL.[^1] In diabetic (compared to
nondiabetic) American Indians, LDL-C has been shown to be denser and
thus more atherogenic.[^2] In comparison to Framingham Heart Study data,
the regression line between LDL cholesterol and CVD events is much
steeper, indicating that similar levels of LDL cholesterol in American
Indians confer greater risk for CVD. (Personal communication, B. Howard
and E. Lee, 2001)

*Evidence for the benefits of LDL-C lowering*

Although no studies have been conducted specifically in American Indians
on the safety and efficacy of cholesterol-lowering drugs, there are very
convincing data in other populations. The most effective drugs to lower
LDL-C are statins. Five large, long-term clinical trials  three for
secondary prevention and two for primary prevention  have established
their efficacy in lowering LDL cholesterol and cardiovascular and total
mortality.[^3]^,^[^4]^,^[^5]^,^[^6]^,^[^7] Secondary analyses in
diabetic subgroups confirmed that LDL-C lowering reduced cardiovascular
and total mortality to an extent at least approaching, if not greater
than, that of nondiabetic individuals. Other agents that are known to
lower LDL cholesterol include bile-acid binding resins, fibric acid
derivatives, and nicotinic acid/niacin. Of these three classes of
agents, colestipol (a bile acid resin),[^8] gemfibrozil[^9] and
fenofibrate[^10] (both fibric acid derivatives), and nicotinic
acid/niacin[^11] were shown in long-term studies to reduce
cardiovascular mortality.

######### **Recommendations**

I.  **Recommendation for use of direct LDL-C measure**

> The use of the direct LDL-C measurement should be strongly considered
> for those with diabetes, triglycerides \> 250 mg/dL (due to inaccuracy
> of LDL-C calculations above this level), or when fasting lipids are
> difficult to obtain. The direct LDL-C measurement is now widely
> available, relatively inexpensive, and does not require patients to
> fast. For optimal evaluation, fasting lipid levels remain necessary to
> assess other parameters, including HDL-C and triglycerides.

###### Recommendations for LDL-C goals and actions to meet goals

######   {#section-5 .unnumbered}

-   The following LDL-C goals and actions to meet those goals are
    recommended.\*\*\*

  ----------------------- ----------------- ------------------------------
  [Figure 1. LDL-C                          
  Goals]{.underline}                        

  Risk Level              LDL-C Goal        Action

  IFG/IGT/DM/CVD\*        \<100 mg/dL       Diet/lifestyle/pharmacologic
                                            agents

  2+ risk factors\*\*     \< 130 mg/dL      Diet/lifestyle/pharmacologic
                                            agents

  0-1 risk factors\*\*    \< 160 mg/dL      Diet/lifestyle
  ----------------------- ----------------- ------------------------------

*\*CVD includes patients with a global risk assessment of \>20% 10-year
risk of CHD.*

*IFG = impaired fasting glucose; IGT= impaired glucose tolerance; DM=
diabetes mellitus; CVD= cardiovascular disease*

*\*\*Risk factors other than LDL-C include: cigarette smoking, high
blood pressure (\>140/90 mm Hg or on treatment), low HDL (\< 40 mg/dL),
family history of premature CVD (in first degree males age \<55 years
and first degree females age \< 65 years), age (men \> 45 years and
women \> 55 years or premature menopause without estrogen replacement).*

*\*\*\*Notes:*

## *Appropriate glucose control should be instituted for all diabetics.*

-   *Patient input should assist in the determination of the balance of
    diet vs. pharmacological intervention.*

##### *Pharmacologic therapy should be monitored closely in women who may become pregnant.*

#### *If CVD and/or diabetes is present, start pharmacologic therapy at same time as diet.* 

#### *Pay particular attention to women with history of gestational diabetes. Six-month follow-up is important. Such women should receive aggressive lifestyle intervention.*

######   {#section-6 .unnumbered}

###### The following drug choices (in order of priority) are recommended for primary LDL-C lowering

  -----------------------------------------------------------------------
  [Figure 2. Drug Choices for LDL-C Lowering:]{.underline}

  1\. Statin

  2\. Resin (if nondiabetic and without triglyceride elevation)

  3\. Niacin (depending on of glucose control)
  -----------------------------------------------------------------------

*[Notes:]{.underline}*

*Medications should be based on total lipid profile.*

> *Timing and dose escalation depends of extent of LDL-C increase, CVD,
> and other risk factors.*
>
> *Consider hepatic function, alcohol use, pregnancy and uric acid
> levels during drug selection.*

**[II. Low HDL & High Triglycerides: The Metabolic
Syndrome]{.underline}**

***Introduction***

Forty percent of patients with myocardial infarctions have an LDL
cholesterol (LDL-C) \< 130mg/dL. Many of these patients had a triad of
low HDL cholesterol (HDL-C), high triglycerides (TG), and excess small
dense LDL-C. This triad composes an atherogenic phenotype.[^12] These
lipid abnormalities are often associated with hypertension, central
obesity, and insulin resistance. Together, this combination has been
called the metabolic syndrome.

Low HDL-C is a risk factor for coronary heart disease (CHD) independent
of LDL-C, hypertension, body mass index (BMI) and
smoking.[^13]^,^[^14]^,^[^15]^,^[^16] Framingham data suggest that
individuals with HDL‑C \< 35 mg/dL have an eight-fold increased risk of
CHD compared to those with an HDL-C \> 65 mg/dL. Low HDL-C confers
excess risk across all levels of LDL-C.

The case for TG as a risk factor for CHD independent of other risks has
been more difficult to establish. In many populations, elevated TGs are
a strong risk factor in univariate analysis, but not in multivariate
analysis when HDL‑C is included in the models. Nevertheless, a recent
meta-analysis of 17 population-based prospective studies, which included
46,000 men and 11,000 women, demonstrated a 30% and 75% excess risk for
men and women respectively for every 88 mg/dL increase in TG.[^17] The
excess risk diminished but was still significant after adjustment for
HDL‑C. The Copenhagen Male Study found increasing risk of cardiovascular
events along tertiles of TG even after stratifying by HDL‑C.[^18] The
atherogenic potential of elevated triglyceride levels likely is
determined by the particular triglyceride-rich lipoprotein that is in
excess. IDL and other remnant particles appear atherogenic, while large
VLDL and large chylomicrons appear less so.

Small dense LDL enters the arterial wall more readily and is more easily
oxidized than normal-sized LDL.[^19] Distinguishing small dense LDL as
an independent risk for CHD is difficult because LDL size is highly
correlated with TG level.[^20] Nevertheless, several studies have found
small dense LDL to be a risk factor independent of TG.[^21]^,^[^22]

***Rationale***

While there are established guidelines for primary and secondary
prevention for LDL-C lowering, the treatment of low HDL‑C and high TG
have been less well studied. The Helsinki Heart Study (HHS) used
gemfibrozil for primary prevention of CHD (defined as fatal and
non-fatal MI and sudden death).Error: Reference source not found Those
treated had a 35% decrease in TG, 9% increase in HDL‑C and 8% decrease
in LDL‑C. Over the 5 year study period CHD was reduced by 34% with most
of the reduction occurring in the low HDL/high TG group. Later data
analysis suggested that for every 1% increase in HDL, there was 3%
decrease in CHD.

The available evidence on secondary prevention in patients with low
HDL‑C and high TG come from trials using the fibric acid derivatives,
which lower TG and raise HDL‑C but have modest effects on LDL‑C. The
Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT) studied
young, post-infarct patients with a 90% stenosis and total cholesterol
levels of greater than 200mg/dL and TG levels greater than 140mg/dL
randomized to placebo or bezafibrate.[^23] HDL-C rose and TG fell but
LDL‑C did not change in the intervention group. Coronary luminal
diameter was stabilized in those treated while coronary diameter
narrowing was noted in the placebo group.

The Lopid Coronary Angiographic Trial (LOCAT) randomized subjects post
CABG with low HDL-C (\< 42.5 mg/dL) to gemfibrozil or placebo.[^24] In
the gemfibrozil treated group, HDL-C increased 21% and TG decreased by
36%. The number of new lesions in venous grafts was reduced
significantly in the treated group. The Bezafibrate Infarction
Prevention (BIP) Trial randomized subjects with known CHD aged 45-74
years with HDL-C \<40 mg/dl and TG \< 300mg/dl to bezafibrate or
placebo.[^25] There was a nonsignificant trend toward decreased CHD
events in the overall intervention group (9% reduction). However in the
subgroup with elevated TG \> 200 mg/dl, a significant decrease was noted
(p=0.002). The VA-HDL-C Intervention Trial (VA-HIT) is the most
convincing evidence for use of fibric acid derivatives in secondary
prevention.[^26] This study recruited 2531 men under age 74 with a
history of CHD and HDL-C \< 40 mg/dl, LDL-C \< 140 mg/dl, and TG \<300
mg/dl. Subjects were randomized to gemfibrozil or placebo. The
gemfibrozil group had a 22% risk reduction (RR) in fatal and non-fatal
MIs; HDL-C rose 6%, TG declined 31% and LDL-C did not change in the
intervention group. VA-HIT compares favorably to secondary prevention
trials in statins (CARE, LIPID)Error: Reference source not
found^,Error:\ Reference\ source\ not\ found^ on a numbers needed to
treat basis. VA-HIT also had impressive reductions in new stroke (25%
RR) and transient ischemic attacks (59% RR). A non-significant trend
(11%) toward lower overall morality was also found. Subsequent analysis
of VA-HIT has suggested that the RR may be primarily due to the HDL-C
effect (S. Robbins; presentation at American Heart Association, 1999).
Another study which provides additional support of the aggressive
treatment of individuals with diabetes (and in this case CVD as well) is
the DAIS study which found that the use of fenofibrate (vs placebo)
produced a 23% reduction in combined coronary events with few serious
adverse events.[^27]

*Treatment levels for HDL‑C/TG*

Defining treatment thresholds and goals for HDL-C and TG is difficult
because of the relative lack of clinical trial data in this regard.
Therefore, decisions regarding target levels for HDL-C and TG must rely
in part upon knowledge of physiology and epidemiologic data. Data from
Framingham suggest that low HDL‑C is associated with CHD risk across all
levels of LDL‑C. As HDL increased, the CVD risk decreased in all LDL‑C
groups.[^28] At HDL‑C \> 45 mg/dl risk of CHD diminished across LDL‑C
sub-groups and risk for CHD fell even further when HDL was \> 65 mg/dl.
The feasibility of achieving HDL \> 65 mg/dl with current treatment
regimens is limited, but HDL‑C goals of 40 mg/dl for men and 45 mg/dl
for women are more readily achieved and should provide a reduction in
CHD risk across all LDL‑C levels. VA-HIT findings show that for every 1
mg/dl increase in HDL‑C there was an 11% decrease in CHD endpoints.[^29]
Therefore, even modest increases in HDL offer clinical benefit.

Defining treatment targets for TG is even more difficult. TG level is
important in determining LDL‑C size and physiologic evidence suggests
that change in TG over a range as small as 80-250 mg/dl correlates with
a downward shift in LDL‑C size. By the time TG levels reach 250mg/dl,
90% of subjects will have a predominance of small, denser LDL‑C
particles.Error: Reference source not found Furthermore, data from the
Copenhagen Male Study suggest that in men in the middle and highest
tertiles of TG had relative CHD risks of 1.5 and 2.2 even after
adjustment for such factors as HDL-C and LDL-C. The average TG levels in
these tertiles were 78, 118, and 217 mg/dl, suggesting that even TG over
100 conferred excess risk in this population.Error: Reference source not
found

**Crucial to any discussion of lipid treatment for primary and secondary
prevention for CHD is the CHD risk equivalence of diabetes.** Diabetes
is clearly associated with a marked increase in CHD[^30] and likely
explains, to a large degree, the rising rates of CHD in Native
Americans. The rates among Native Americans are now greater than rates
in other community studies.[^31] Haffner and colleagues compared the
7-year incidence of myocardial infarction (fatal and nonfatal) in a
population of Finnish subjects ages 45-65 with and without
diabetes.[^32] The 7 year cumulative incidence of MI in subjects without
diabetes but with prior history of MI was 18.8%; for subjects with
diabetes but no prior MI the rate was 20.2%; for subjects with prior MI
and diabetes the rate was 45%. Thus, the conclusion from this study is
that subjects in this age group with diabetes should be treated as
aggressively from the standpoint of lipid lowering as subjects who have
had a prior MI. In addition, diabetics frequently have silent (and often
unrecognized) ischemic events and increased post-event mortality as well
as higher rates of sudden death compared to non-diabetics.

*Approaches to treatment of evaluation/ treatment of high TG and low
HDL*

Evaluation of patients with high TG and low HDL should be an important
part of the treatment plan. Their fasting glucose should be measured to
rule out diabetes or impaired fasting glucose. Inquiries into use of
other medications (oral estrogens and systemic glucocorticoids in
particular), thyroid function testing, liver function tests, urine
protein testing, and screening for alcohol use should also be
considered. The optimal agent for the initiation of therapy depends on
the overall lipid profile and concomitant disorders. LDL-C should
continue to receive primary consideration for treatment.

*Statins*

Statins lower TG in direct proportion to the amount of LDL‑C lowering
and the baseline TG level.[^33]^,^[^34] The mechanism of TG lowering by
statins is likely the same as that for LDL‑C lowering, that is,
increased removal of TG‑rich particles by the upregulated LDL receptor.

*Resins*

Currently, resins are not recommended if the TG level is borderline or
high as these agents tend to increase VLDL synthesis and further raise
TG levels. Error: Reference source not found

*Fibric acid derivatives*

Fibric acid derivatives bind to a family of nuclear hormone receptors
called the peroxisome proliferator activated receptors (PPARS).[^35] Via
these receptors, fibrates induce expression of lipoprotein lipase and
decrease expression of apo C-III, enhancing clearance of TG rich
particles and VLDL.[^36]^,^[^37] Thus, they are potent TG lowering
medications. They also increase HDL-C via increase in production of the
major HDL‑C apoproteins.[^38]^,^[^39]

Fibrates are excellent medications for treatment of the high TG/low
HDL‑C disorder. They may be considered first line agents in patients
with low LDL‑C or in patients with severe TG elevations (400-1000
mg/dL). Use of fibrates in combination with statins is relatively safe
except for the combination of cerivastatin and gemfibrozil, which has
prompted the recent withdrawal of cerivastatin from the market. A recent
review suggests that the combination of most statins and fibrates
results in a rate of myositis of approximately 1%.Error: Reference
source not found

*Nicotinic acid/Niacin*

The use of niacin in patients with the metabolic syndrome is somewhat
controversial. Niacin lowers LDL-C, raises HDL-C and lowers TG,[^40] but
the concern remains the precipitation of diabetes or worsening of
glycemic control.[^41] Recent data from the ADMIT trial[^42] suggest
that niacin was safe in subjects with diabetes, raised HDL‑C by 29%,
decreased TG by 23% and LDL-C by 8%. Subjects with and without diabetes
had a small increase in average glucose levels. Diabetic subjects on
niacin did not have a change in their hemoglobin A1c (HgbA1c) over the
course of the 48 week study period, but their HgbA1c was slightly higher
at the end of the study (a difference of 0.3%, p=0.04) compared to the
group on placebo.

*Glycemic control*

Patients with diabetes can have marked lowering of TG with improvement
in glycemic control, particularly when the HgbA1C is \> 9.0%. TG
lowering is less dramatic with lowering of HgbA1C less than 9.0%; lipid
lowering agents are generally more beneficial in this group.

***Recommendations***

These recommendations are based on the concept that much of the
cardiovascular disease in Native Americans has as its roots the
metabolic syndrome. Because of the tremendous increases in diabetes and
cardiovascular disease, early recognition and a lower threshold for
intervention may be essential to prevent cardiovascular disease. Because
of the increased risk for the entire population of Native Americans,
interventions should be considered against a backdrop of the larger
intervention of community and individual lifestyle changes. We suggest
that the percent of the population "at risk" for this syndrome, and
particularly diabetics, is large and lipid values should be judged in
that context. For the sake of simplicity and because of the high risk
these patients have of developing diabetes as well as the presence of
these entities within the metabolic syndrome, we have combined patients
with impaired glucose tolerance (IGT) and impaired fasting plasma
glucose (IFG) in with diabetic patients. Patients with diabetes and
pre-existing CHD remain a distinct category owing to the extreme risk of
recurrent events in this group. It should also be noted that diet,
weight loss, and physical activity should be integral parts of
treatment.

  ------------------------------ ---------- ----------- --------- --------
  [Figure 3. HDL‑C/TG            HDL-C                  TG        LDL-C
  Goals.]{.underline}                                             

                                 Male       Female                

  Normal Glucose Tolerance       \> 45      \> 45       \< 200    \< 130

  IGT, IFG, DM without CVD\*,    \> 45      \> 45       \< 150    \< 100
  CHD without DM                                                  

  DM and CVD\*                   \> 45      \> 45       \<        \< 100
                                                        100\*\*   
  ------------------------------ ---------- ----------- --------- --------

*\*CVD includes: CHD, PVD, and/or other known atherosclerotic events*

*\*Some authors felt that less than 150 mg/dl was more reasonable in
this category.*

# **[III. Primary Prevention - Risk Evaluation Methodologies]{.underline}**

### ***Introduction and rationale***

It is often helpful to patients and their providers to have a reasonable
assessment of risk for cardiovascular disease for the individual risk
level identification as well as a motivational tool for patient
compliance. In addition, the level of intervention aggressiveness is
most appropriate if matched to the risk of the individual. In
particular, lipid treatment guidelines are optimally based on overall
risk of cardiac events. The National Cholesterol Education Program
Guidelines I and II recommended that lipid treatment be based on three
broad categories -- those with known coronary artery disease, those with
two or more other cardiac risk factors, and those with one or no other
cardiac risk factor.[^43],[^44] More recently, several investigators and
expert panels have recommended that treatment guidelines be based on not
only the presence but the severity of risk factors with the development
of a graded, quantitative global risk of future cardiac
events.[^45],[^46],[^47]

Experts suggest that the optimal approach is to divide the 10-year risk
of cardiac events into three categories as determined by level of risk:
high risk (greater than 20%), intermediate risk (10%-20%), and lower
risk (less than 10%). To determine 10-year cardiac risk for individuals
without known CVD (i.e. primary prevention), our participants agreed
upon the utilization of the subsequently published NCEP Adult Treatment
Panel III Framingham Risk Point Scores.Error: Reference source not found
Although these are the best data available for this purpose, the data
for this risk assessment were derived from the Framingham, Mass.
community population a number of years ago utilizing a predominantly
white population. This may not accurately reflect the current risks
among a different population with a varying prevalence of risk factors
and disease incidence, such as Native Americans.Error: Reference source
not found In fact, Howard and colleagues have demonstrated that the
standard Framingham risk estimates underestimate the risk among Native
Americans. (Personal communication, B. Howard and E. Lee, 2001)

A more accurate global risk score for Native Americans is being
developed using Strong Heart Study and other study data. In particular,
this risk score may incorporate additional markers, such as insulin
resistance, triglyceride levels, obesity, and/or physical inactivity,
which may be more relevant for Native Americans. Until this information
is available, a global risk score evaluation based on the Framingham
data will give us a useful estimate (although likely an underestimate)
of the risk of individual patients and may help providers more
appropriately treat cardiac risk factors and help public health workers
tailor interventions. Below are assessment tools utilized by the
National Cholesterol Education Panel ATP III.[^48]

## **Estimating 10-Year Risk for Men and Women**

Risk assessment for determining the 10-year risk for developing CHD is
carried out using Framingham risk scoring (Figure 4 for men and Figure 5
for women). The risk factors included in the Framingham calculation of
10-year risk are: age, total cholesterol, HDL cholesterol, systolic
blood pressure, treatment for hypertension, and cigarette smoking.
The first step is to calculate the number of points for each risk
factor. For initial assessment, values for total cholesterol and HDL
cholesterol are required. Because of a larger database, Framingham
estimates are more robust for total cholesterol than for LDL
cholesterol. Note, however, that the LDL cholesterol level remains the
primary target of therapy. Total cholesterol and HDL cholesterol values
should be the average of at least two measurements obtained from
lipoprotein analysis. The blood pressure value used is that obtained at
the time of assessment, regardless of whether the person is on
anti-hypertensive therapy. However, if the person is on
anti-hypertensive treatment, an extra point is added beyond points for
the blood pressure reading because treated hypertension carries residual
risk. The average of several blood pressure measurements, as recommended
by the Joint National Committee (JNC), is needed for an accurate measure
of baseline blood pressure. The designation "smoker" means any cigarette
smoking in the past month. The total risk score sums the points for each
risk factor. The 10-year risk for myocardial infarction and coronary
death (hard CHD) is estimated from total points.

Figure 4. Estimate of 10-Year Risk for Men (Framingham Point Scores)

  ----------------- -----------------------------------------------------
  **Age**           **Points**

  **20-34**         **-9**

  **35-39**         **-4**

  **40-44**         **0**

  **45-49**         **3**

  **50-54**         **6**

  **55-59**         **8**

  **60-64**         **10**

  **65-69**         **11**

  **70-74**         **12**

  **75-79**         **13**
  ----------------- -----------------------------------------------------

  ------------------------- ----------- ----------- ----------- ----------- -----------
  **Total Cholesterol**     **Points    **Points    **Points    **Points    **Points
                            at\         at\         at\         at\         at\
                            Age 20-39** Age 40-49** Age 50-59** Age 60-69** Age 70-79**

  **\<160**                 **0**       **0**       **0**       **0**       **0**

  **160-199**               **4**       **3**       **2**       **1**       **0**

  **200-239**               **7**       **5**       **3**       **1**       **0**

  **240-279**               **9**       **6**       **4**       **2**       **1**

  **[\>]{.underline}280**   **11**      **8**       **5**       **3**       **1**
  ------------------------- ----------- ----------- ----------- ----------- -----------

  --------------- ----------- ----------- ----------- ----------- -----------
                  **Points    **Points    **Points    **Points    **Points
                  at\         at\         at\         at\         at\
                  Age 20-39** Age 40-49** Age 50-59** Age 60-69** Age 70-79**

  **Nonsmoker**   **0**       **0**       **0**       **0**       **0**

  **Smoker**      **8**       **5**       **3**       **1**       **1**
  --------------- ----------- ----------- ----------- ----------- -----------

  ---------------------------------- ------------------------------------
  **HDL**                            **Points**

  **[\>]{.underline}60**             **-1**

  **50-59**                          **0**

  **40-49**                          **1**

  **\<40**                           **2**
  ---------------------------------- ------------------------------------

  ------------------------- ----------------------- -----------------------
  **Systolic BP**           **If Untreated**        **If Treated**

  **\<120**                 **0**                   **0**

  **120-129**               **0**                   **1**

  **130-139**               **1**                   **2**

  **140-159**               **1**                   **2**

  **[\>]{.underline}160**   **2**                   **3**
  ------------------------- ----------------------- -----------------------

  ----------------- ----------------- ------------------------ ------------------------
  **Point Total**   **10-Year Risk    **Point Total**          **10-Year Risk (%)**
                    (%)**                                      

  **\<0**           **\<1**           **9**                    **5**

  **0**             **1**             **10**                   **6**

  **1**             **1**             **11**                   **8**

  **2**             **1**             **12**                   **10**

  **3**             **1**             **13**                   **12**

  **4**             **1**             **14**                   **16**

  **5**             **2**             **15**                   **20**

  **6**             **2**             **16**                   **25**

  **7**             **3**             **[\>]{.underline}17**   **[\>]{.underline}30**

  **8**             **4**                                      
  ----------------- ----------------- ------------------------ ------------------------

FIGURE 5. Estimate of 10-Year Risk for Women (Framingham Point Scores)

  ------------------------------------ ----------------------------------
  **Age**                              **Points**

  20-34                                -7

  35-39                                -3

  40-44                                0

  45-49                                3

  50-54                                6

  55-59                                8

  60-64                                10

  65-69                                12

  70-74                                14

  75-79                                16
  ------------------------------------ ----------------------------------

  --------------------- ----------- ----------- ----------- ----------- -----------
  **Total Cholesterol** **Points    **Points    **Points    **Points    **Points
                        at\         at\         at\         at\         at\
                        Age 20-39** Age 40-49** Age 50-59** Age 60-69** Age 70-79**

  \<160                 0           0           0           0           0

  160-199               4           3           2           1           1

  200-239               8           6           4           2           1

  240-279               11          8           5           3           2

  [\>]{.underline}280   13          10          7           4           2
  --------------------- ----------- ----------- ----------- ----------- -----------

  --------------- ----------- ----------- ----------- ----------- -----------
                  **Points    **Points    **Points    **Points    **Points
                  at\         at\         at\         at\         at\
                  Age 20-39** Age 40-49** Age 50-59** Age 60-69** Age 70-79**

  **Nonsmoker**   0           0           0           0           0

  **Smoker**      9           7           4           2           1
  --------------- ----------- ----------- ----------- ----------- -----------

  ---------------------------------- ------------------------------------
  **HDL**                            **Points**

  [\>]{.underline}60                 -1

  50-59                              0

  40-49                              1

  \<40                               2
  ---------------------------------- ------------------------------------

  ----------------------- ----------------------- -----------------------
  **Systolic BP**         **If Untreated**        **If Treated**

  \<120                   0                       0

  120-129                 1                       3

  130-139                 2                       4

  140-159                 3                       5

  [\>]{.underline}160     4                       6
  ----------------------- ----------------------- -----------------------

  ----------------- ----------------- -------------------- --------------------
  **Point Total**   **10-Year Risk    **Point Total**      **10-Year Risk (%)**
                    (%)**                                  

  \<9               \<1               18                   6

  9                 1                 19                   8

  10                1                 20                   11

  11                1                 21                   14

  12                1                 22                   17

  13                2                 23                   22

  14                2                 24                   27

  15                3                 [\>]{.underline}25   [\>]{.underline}30

  16                4                                      

  17                5                                      
  ----------------- ----------------- -------------------- --------------------

## **Recommendations**

1.  Risk assessment evaluations should be based on 10-year global risk
    of cardiovascular events, categorizing patients into high (\>20%),
    intermediate (10%-20%), and lower risk (\<10%), currently utilizing
    the Framingham risk scoring. Due to the underestimation of risk
    utilizing these methods, risk factor counting methods will be
    primarily utilized for determining appropriate lipid interventions
    in Native Americans.

2.  Development of a global risk score specific for the Native American
    population based on the data from the Strong Heart Study, with
    assessment of the value of a separate global risk score for patients
    with diabetes mellitus. As this becomes available, this will replace
    the Framingham risk assessment for Native Americans.

3.  Lipid levels and risk evaluation in the general adult population
    should be done at least once every 5 years. For diabetics, lipid
    levels and risk evaluation should be performed at least annually.
    More frequent evaluations may be necessary based on clinical
    considerations such as use of lipid lowering therapy and intervening
    change in clinical status.

4.  All non-diabetic patients greater than 45 years of age with
    cardiovascular risk factors and without contraindications should be
    on aspirin 81--325 mg/day. Diabetic patients over 30 years of age
    should be on 162--325 mg daily, unless contraindicated, due to the
    increased thrombotic tendencies associated with diabetes.

[IV. Cardiovascular Health Promotion Programs]{.underline}

**Introduction and rationale**

CHD is the leading cause of death in American Indians/Alaska Natives
(AI/AN), with rates exceeding other US populations.Error: Reference
source not found Since cardiovascular morbidity and mortality are
related to CHD risk factors, it has been postulated that by targeting
and aggressively treating patients to modify or control risk factors,
the result would lead to long-term reduction of CHD rates in American
Indians.Error: Reference source not found,[^49],[^50],[^51] Healthy
People 2010 specifically supports this concept with a goal to "improve
cardiovascular health and quality of life through prevention, detection,
and treatment of CHD risk factors".[^52]

# **Recommendations**

# *Reinventing the approach to risk management* 

It has been shown that physician directed multidisciplinary programs,
where CHD risks were managed by clinical pharmacists, registered nurses
or advance practice nurses, were more effective than individual
physician management.[^53],[^54],[^55],[^56],[^57] In the AI/AN
population, effective risk management has been demonstrated by the
clinical pharmacy specialist/dietitian team.Error: Reference source not
found,[^58] The success of these programs is related to variables such
as number of visits with the providers, time spent with the patient at
each visit, amount of patient education provided, and aggressive
risk/goal oriented management.

An optimal intervention includes the development and implementation and
of effective health promotion programs that are multidisciplinary in
nature, where patients have their CHD risks "team managed". These
programs should involve physicians and mid-level providers (clinical
pharmacy specialists, nurse practitioners, clinical nurse specialists,
and/or physician assistants) utilizing medical staff approved protocols
with appropriate peer review performed by the designated physician
consultant. This team should include a dietitian and appropriate
ancillary staff (diabetes educator, exercise physiologist, etc.). It is
essential for the medial staff to actively endorse cardiovascular health
promotion programs, including team approaches with medical staff
guidance, and provide a referral base. The support of tribal leadership,
the health board, community health representatives, and the service unit
administration are also essential to the success of these programs.

# *Practitioner training and certification*

It is essential that mid-level providers be certified and current in
risk reduction practice for the team concept to be effective. The Indian
Health Service should support the establishment of a certificate program
specifically designed to train and update practitioners. Minimally this
program will cover the following topics: American Indian cultural,
psychological and social values, motivational interviewing, exercise
physiology, medical nutrition therapy, weight loss, tobacco cessation,
diabetes, hypertension and dyslipidemias using available national
consensus clinical practice guidelines. When initiating strategies,
certification allows team consensus on cardiovascular health goals,
identification, and treatment of high-risk patients.

##### **[V. Effective Lifestyle Modifications in a Cultural Context]{.underline}**

# 

## ***Introduction and rationale***

# Healthy lifestyles incorporating regular physical activity and balanced nutrition are essential to the health of Native Americans. Along with weight reduction, improved glycemic and blood pressure control, and an increase in HDL cholesterol will be seen.Error: Reference source not found Through dietary and lifestyle modification one can significantly improve dyslipidemia, minimizing the need for pharmacotherapy or significantly reduce the dosage needed to reach LDL-C goals.[^59] LDL-C response to dietary intervention is variable but generally quite modest in Caucasian populations, typically with a 3 to 15% reduction reported.Error: Reference source not found^,^[^60] However, The Native American Cardiovascular Risk Reduction Program found a 12 to 23% LDL-C reduction through diet and exercise in their population.Error: Reference source not found The American Heart Association (AHA) has established and revised specific well supported recommendations that emphasize weight management, regular physical activity, and "individualized dietary recommendations, involving medical nutrition therapy for specific subgroups."[^61] The new 2000 AHA Dietary Guidelines have replaced the previously used AHA Step 1 and Step 2 diets. The American Diabetes Association has also suggested lifestyle modifications that are widely accepted. In addition, the Diabetes Prevention Program has recently released their results revealing a striking 58% reduction in the onset of type 2 diabetes mellitus with diet and lifestyle interventions, when compared to an untreated control group. These results were seen in a mixed U.S. population group, including Native Americans, selected for the presence of impaired glucose tolerance as a marker of high risk for the development of type 2 diabetes mellitus.[^62]

# These recommendations are relevant to Native Americans. However, they need to be tailored to the specific traditions and culture of Native American communities. For maximal benefit and compliance, goal implementation should be developed around the strong sense of culture and family. The future health of the individual patient and his family both would greatly improve through family directed lifestyle modifications. Particular attention focusing on educational approaches in the school system would further reinforce these guidelines. The cultural aspects of health care for Native Americans have many advantages that can be mobilized to encourage lifestyle modification. In general, a teamwork approach is more acceptable and encouraged. The broad team of health care professionals, should include dietitians, pharmacists, nurses, physicians, physical therapists, certified diabetes educators, and ancillary heath care staff. Well-validated materials and programs promoting diet and lifestyle modifications for the general US population are available and should be appropriately adapted for local use in the Native American population. Consistency within and between patient-based and community-based education is desirable. This teamwork should strive to achieve community acceptance and should utilize Tribally elected officials and other Tribal leaders. Well-established programs directed at lifestyle modifications exist within Native communities and should be utilized. 

## ***Recommendations***

## *Nutrition*

Patients with dyslipidemia should be referred to a Registered Dietitian
for Medical Nutrition Therapy. The 2000 AHA Dietary GuidelinesError:
Reference source not found should be followed while accommodating the
local diets. Some specific recommendations that should be consistent
across the Indian health care system are as follows:

1.  Reduce intake of total fat, saturated fat and trans fatty acids.

2.  Reduce the total caloric intake, especially empty calories from
    simple sugars. In this vein, a general reduction in sugar based
    beverages is essential, and non-calorie containing beverages with
    specific attention to water should be emphasized.

3.  Increase the intake of dietary fiber and complex carbohydrates
    (whole grains), fruits and vegetables.

4.  Hospitals and community facilities should set examples. Some
    specific examples are providing healthier options in vending
    machines and at tribal and community events. Providing lower-fat
    dairy products and healthy meals for patients, staff and visitors
    should be considered.

5.  Individual and community education should emphasize easily
    understandable materials and techniques. For example, one teaching
    aide uses a pie chart to represent a dinner plate in which half of
    the plate is filled with vegetables and fruit, one quarter with a
    starchy food, and the remaining quarter with lean protein.[^63]

6.  Contact the Indian Health Service and the National Diabetes Program
    for educational materials.[^64]

## *Physical activity*

Guidelines for physical activity from both the Surgeon General and the
AHA should be followed with an emphasis upon lifestyle
modifications.Error: Reference source not found,[^65] Any individual
with known disease will need physician written approval before beginning
an exercise program and, ideally, all high risk individuals should have
physician consultation prior to exercise program initiation as
well.[^66] If no contraindications exist, the level of physical activity
should be assessed and goals tailored towards a gradual increase working
up to 30 to 60 minutes of activity on most, if not all, days per
week.[^67] The physical activity sessions can also be broken up during
the day to equal the total 30 to 60 minutes. In particular, these
changes should be directed at lifelong changes and should begin as early
in life as possible. In addition, emphasis should be placed on
increasing routine non-strenuous physical activity, such as stair
climbing and walking, throughout the day. Physical Education throughout
school should be required from kindergarten to completion of high
school, while involvement in competitive and recreational sports should
be encouraged. Finally, identification and resumption of traditional
fitness activities should be highly promoted.

### *Tobacco cessation* 

Prevention and cessation of tobacco is critical to effective health
promotion. All people who abuse tobacco must be counseled to stop. The
level of addiction and readiness to quit should also be assessed.
Medications for assistance in cessation are effective, and should be
encouraged as a routine part of smoking cessation efforts. If available,
refer to a smoking cessation program. Tobacco prevention and cessation
education efforts should begin with children and adolescents. Finally,
while specific efforts for smoking cessation may be directed at the
individual, community efforts should be continuously emphasized. We
encourage that all public buildings be smoke free and economic
dependence on the sale of tobacco should be de-emphasized.

#### *Obesity prevention and treatment*

The Body Mass Index (BMI) should be used to identify obesity and guide
its treatment. BMI ≥ 25.0 but [\<]{.underline} 29.9 is defined as
overweight, BMI [\>]{.underline} 30 but [\<]{.underline} 40 is defined
as obese, and BMI [\>]{.underline} 40.0 is defining as extreme
obesity.[^68] In addition to BMI, the presence of other comorbidities to
obesity needs to be assessed. Accurate measurements of height are
required. Waist circumference measurements should be made initially and
repeated if significant change in weight is noted. Waist circumference
over 40" for men or over 35" for women greatly increases the adverse
impact of obesity on health. An assessment of depression should also be
performed in all obese patients, with appropriate medication initiation
and referral to mental health.

All patients with a BMI ≥30.0 or BMI ≥25.0 with other risk factors or
comorbidities should be offered a formal weight management program.
Initial weight loss goal should begin with a 10% reduction of total body
weight in a 6- month time frame.Error: Reference source not found A
reasonable target weight loss goal of 1 to 2 pounds per week is set.
Emphasis should include an increase in physical activity and a reduction
of total calories. Referral to a Registered Dietitian and/or a Certified
Lifestyle and Weight Management Consultant is essential to assist in the
implementation of these changes.

+-----------+----------------------------+----------------------------+
| [Figure   |                            |                            |
| 6.        |                            |                            |
| Nu        |                            |                            |
| tritional |                            |                            |
| R         |                            |                            |
| ecommenda |                            |                            |
| tions]{.u |                            |                            |
| nderline} |                            |                            |
+-----------+----------------------------+----------------------------+
| Modality  | National Recommendations   | Indian Health              |
|           |                            | Supplementation            |
+-----------+----------------------------+----------------------------+
| Diet      | These recommendations are  | Refer patients at risk to  |
|           | appropriate for all        | a Registered Dietitian for |
|           | individuals \> 2 years of  | Medical Nutrition Therapy  |
|           | age                        |                            |
|           |                            | -   Encourage whole wheat  |
|           | -   6 or more servings a   |     flour in homemade      |
|           |     day of a variety of    |     breads and tortillas;  |
|           |     grain products,        |     oatmeal; enriched      |
|           |     including whole        |     whole grain cereals;   |
|           |     grains.                |     and brown rice.        |
|           |                            |                            |
|           | -   5 or more servings a   | -   Encourage use of whole |
|           |     day of a variety of    |     pieces of fruit        |
|           |     fruits and vegetables. |     instead of juice,      |
|           |                            |     encourage vegetables   |
|           | ```{=html}                 |     and salad at lunch and |
|           | <!-- -->                   |     dinner meals.          |
|           | ```                        |                            |
|           | -   2 -- 4 servings a day  | -   Use low-fat dairy      |
|           |     of nonfat or low-fat   |     products for those     |
|           |     milk and nonfat or     |     over 2 years of age,   |
|           |     low-fat dairy          |     and include low-fat or |
|           |     products.              |     non-fat dairy products |
|           |                            |     in schools.            |
|           | -   Limit to 6 ounces a    |                            |
|           |     day of fish, skinless  | -   Encourage low-fat      |
|           |     poultry or lean meat.  |     preparation techniques |
|           |     Include at least 2     |     for meat, poultry and  |
|           |     servings of fish per   |     fish. (Baking,         |
|           |     week.                  |     broiling, roasting,    |
|           |                            |     grilling).             |
|           | ```{=html}                 |                            |
|           | <!-- -->                   | -   Remove skin from       |
|           | ```                        |     poultry and trim off   |
|           | -   Limit intake of sugars |     visible fat from meat. |
|           |     (and refined           |                            |
|           |     carbohydrates) --      | -   Encourage less         |
|           |     particularly in        |     frequent usage and     |
|           |     insulin resistance,    |     smaller portions of    |
|           |     glucose intolerance,   |     high fat meats such as |
|           |     and                    |     bacon, sausage, salt   |
|           |     hypertriglyceridemia.  |     pork, potted meat,     |
|           |                            |     Spam, Vienna sausage.  |
|           | -   Limit saturated fat to |                            |
|           |     \< 10% calories and    | ```{=html}                 |
|           |     limit trans-fatty      | <!-- -->                   |
|           |     acids. Substitute      | ```                        |
|           |     mono- and              | -   Encourage increased    |
|           |     poly-unsaturated fats  |     water intake and       |
|           |     and increase omega 3   |     limited                |
|           |     fatty acids.           |     sugar-sweetened        |
|           |                            |     beverages such as soda |
|           |                            |     pop, fruit punches,    |
|           |                            |     Kool-Aid; Gatorade.    |
|           |                            |                            |
|           |                            | -   Limit intake of sweets |
|           |                            |     and candy. Serve fruit |
|           |                            |     as dessert.            |
|           |                            |                            |
|           |                            | -   Encourage use of oil,  |
|           |                            |     preferably canola or   |
|           |                            |     olive oil in place of  |
|           |                            |     lard, shortening,      |
|           |                            |     margarine and butter.  |
|           |                            |                            |
|           |                            | -   Encourage use of fatty |
|           |                            |     fish (sardines,        |
|           |                            |     mackerel, herring,     |
|           |                            |     salmon, tuna) twice    |
|           |                            |     weekly, and small      |
|           |                            |     portions of nuts and   |
|           |                            |     seeds                  |
+-----------+----------------------------+----------------------------+
| Physical  | -   Contraindications      | -   Require physical       |
| activity  |     should be assessed     |     education in schools   |
|           |                            |                            |
|           | -   Assess current level   | -   Encourage              |
|           |     of physical activity   |     identification and     |
|           |                            |     resumption of          |
|           | -   Short range goal:      |     traditional fitness    |
|           |     increase level of      |     activities             |
|           |     physical activity      |                            |
|           |                            | -   Provide tribal         |
|           | -   Long range goal: 30 -- |     physical activity      |
|           |     60 minutes on most if  |     facilities             |
|           |     not all days of the    |                            |
|           |     week                   |                            |
+-----------+----------------------------+----------------------------+
| Obesity   | -   Begin formal weight    | -   BMI should be used to  |
|           |     reduction program if   |     assess weight status   |
|           |     BMI ≥ 30 or ≥ 25 with  |                            |
|           |     comorbidities          | -   Weight should be       |
|           |                            |     documented at all      |
|           |                            |     regular clinic visits  |
|           |                            |                            |
|           |                            | -   Measure waist          |
|           |                            |     circumference          |
|           |                            |     initially and upon     |
|           |                            |     significant weight     |
|           |                            |     change.                |
+-----------+----------------------------+----------------------------+
| Tobacco   | -   Assess level of        | -   Routinely document     |
| Use       |     nicotine addiction     |     tobacco use in health  |
|           |                            |     record. Refer to       |
|           | -   Assess readiness to    |     smoking cessation      |
|           |     quit                   |     program                |
|           |                            |                            |
|           | -   Pharmacotherapy with   |                            |
|           |     \> 10 cigarettes/day   |                            |
+-----------+----------------------------+----------------------------+

**[VI. Public Health and Community Education]{.underline}**

***Introduction and rationale***

Community education for dyslipidemia in Native American communities is
an essential aspect of an overall effort to reduce the rising tide of
CVD in Native Americans. Such education must be addressed at several
levels to insure an appropriate and effective campaign. Native
communities exist on several levels including national, regional, tribal
and local. Education and involvement at each of these levels may provide
different but equally important influences on the goal of reducing
dyslipidemia. Clearly, without community leadership and direction as
well as enthusiastic support, any intervention in this regard will be
unsuccessful.

***Recommendations***

*National Native American Community Involvement*

The inclusion of national Native American leaders and organizations is
vital. Their endorsement and collaboration with local communities will
help insure thorough coverage and acceptance of these guidelines by
Indian communities throughout the U.S. These may include such groups as
the Association of American Indian Physicians, the National Indian
Health Board, the National Indian Council on Aging, and the National
Congress of American Indians. These respected organizations and others
may help underscore the vital need for local communities to act. Also
national publications such as *Indian Country Today* could be helpful in
this regard.

*Local Community Level Involvement*

Community level education is greatly enhanced by the inclusion and
support of local leaders. Participants at this conference felt it vital
to include all positive role models and leaders in this activity. A key
first step is the identification of champions within the community.
These may include tribal leaders, tribal council members, traditional
healers/ medicine people, community health representatives, local health
board members, educators, athletes, entertainers, etc. Individual
communities should identify those in the community who are most
influential and enthusiastic about such activities and encourage their
involvement. Obviously, it is not necessary for these leaders to be
members of the medical community.

Local community success requires the integration of local traditional
and community beliefs and values that support the goals of the
educational program. This fosters community ownership of the program and
will increase relevance to the community. Our work group has identified
the following issues as central on the local level.

1.  Emphasize proactive/positive message of wellness through lifestyle,
    diet, etc. Messages should be simple. Special emphasis on the
    benefits of dyslipidemia therapies (lifestyle and medication) should
    be prominent. Focus on the potential benefits for both present and
    future generations.

2.  Use of traditional media plays an important role, even in extremely
    rural communities and may include local publications, handouts,
    brochures, posters, billboards, as well as public service
    announcements on local radio.

3.  Utilize patient role models as examples of treatment successes along
    with patient support groups for those with established CHD/CVD to
    provide culturally appropriate education in multiple venues (i.e.,
    schools, clinics, etc.).

4.  Identify unique potential settings where community education can
    occur. Take advantage of existing activities and organizations
    within the community. These may include schools, health
    fairs/walks/races etc., WIC, Indian Centers, HeadStart, churches,
    clinics, and rodeos. Urban settings may include large employers
    (such as casinos), social gathering places, powwows, fairs, and
    clinics among others.

*Professional Education and Organization*

The participants at this conference recognize that appropriate therapy
for dyslipidemia is as dependent upon health provider education and
motivation as it is upon that of the client. Providers have a unique
opportunity to intervene both therapeutically and educationally at each
patient encounter. Providers must be considered an integral part of the
community, both as role models for healthy lifestyles and as
participants in the educational process.

In communities with established medical facilities, we recommend the
consideration of one health care professional with special interest in
cardiovascular risk reduction being specified. This individual could be
considered the **dyslipidemia coordinator** (DC), analogous to the
diabetes coordinator position already established at many IHS
facilities. This individual should work closely with the diabetes
coordinator, or even function concurently as the diabetes coordinator at
smaller facilities, to provide direct patient and provider information
regarding dyslipidemia and its therapy. Consideration of the
establishment of dyslipidemia clinics should be made, coordinated by the
DC. This would serve to underscore the importance of the issue both to
patients and other providers and improve the follow-up of patients
already on therapy or requiring initiation of therapy. The DC's interest
and expertise in dyslipidemia should be widely disseminated within the
community to ensure that individual providers and patients have a
resource for questions and concerns.

In addition, consideration of the liberalization of lipid testing is
recommended. RNs, NPs, PAs, and pharmacists are all in a unique
situation to identify patients at high cardiovascular risk and may
assure that adequate lipid screening is occurring. In addition, these
health care professionals can assist to ensure adequate follow-up of
patients currently on therapy and provide patient education on risk
factor reduction.

*Program Evaluation*

Periodic evaluation of the educational program efficacy should be
performed. This may be both formal and informal, and include at least a
semi-annual assessment of rates of lipid profile and risk factor
assessment as well as intervention. Both provider and patient feedback
should be sought to assure continuous quality improvement.

On a broader level, comparison to current data from the Diabetes Audit
will allow reassessment of the status of lipid evaluations within
participating service units.

# **[VII. Secondary Prevention]{.underline}**

## ***Introduction and rationale***

Lipid lowering therapy in patients with known coronary artery disease
(CAD) is termed "secondary prevention."[^69],[^70],[^71] This concept
refers to the observation that the presence of CAD in a patient confers
a very high risk of subsequent coronary events and CAD mortality.
Indeed, men and women with proven CAD have a 5- to 7-fold increased risk
of developing subsequent myocardial infarction (MI) or coronary death,
with a greater than 20% ten-year risk for subsequent CHD event.Error:
Reference source not found Native American patients are similarly
afflicted, and CAD prevalence in American Indians now exceeds rates in
other U.S. populations, possibly related to the high prevalence of type
2 diabetes mellitus (DM2).Error: Reference source not found

Previously, coronary atherosclerosis was considered to be a relentless
progressive disease, where disability and death from CAD were
inevitable. This was especially true for DM2 patients who experienced
acute MI.[^72],[^73],Error: Reference source not found However, numerous
multi-center, randomized clinical trials have proven conclusively that
lowering elevated low density lipoprotein cholesterol (LDL-C) levels in
patients with established CAD sharply reduces the risk of future MI,
revascularization procedures, death from CAD, stroke and death from all
causes.Error: Reference source not found,[^74],[^75] The benefit of
cholesterol lowering therapy has been shown to extend even to patients
with "average" cholesterol levels.Error: Reference source not
found,[^76] Most patients with CAD demonstrate one or more of the
various abnormalities of cholesterol metabolism.

Other clinical atherosclerotic syndromes (cerebrovascular disease,
carotid artery disease, peripheral arterial disease, and aortic
aneurysm) identify patients at high risk for subsequent MI and CAD death
as well.Error: Reference source not found,Error: Reference source not
found Hence these patients, even without known CAD, are considered
equally eligible for "secondary prevention" lipid therapy as CHD risk
equivalents.

Diabetes has been a risk factor for CAD for many years; however recent
reviews have clarified the extent of increased risk. [^77] Patients with
DM2, without known CAD have a risk of MI and CAD death equal to or
greater than non-diabetic patients with recent MI.Error: Reference
source not found Over 80% of deaths in diabetics are due to MI, stroke,
or peripheral atherosclerosis.

Diabetes is not only a metabolic disease, but also a vascular disease.
Thus, in accord with National Cholesterol Education Program (NCEP)Error:
Reference source not found,Error: Reference source not found, American
Heart Association (AHA),Error: Reference source not found,Error:
Reference source not found and American Diabetes Association (ADA)
guidelines,Error: Reference source not found all patients with DM2 are
treated with "secondary prevention" diet and drug intensity. The various
clinical syndromes which indicate "secondary prevention" therapy are
listed in Figure 7.

Additionally, certain clinical coronary syndromes identify those at very
high risk for recurrent MI and CAD death. These include patients with
recent acute coronary syndromes (acute MI or unstable angina), patients
with both symptomatic coronary ischemia and congestive heart failure
(CHF), and diabetic patients with known CAD, even if asymptomatic post
CABG or PTCA.Error: Reference source not found,Error: Reference source
not found,[^78] Those at highest risk for CAD death are listed in Figure
8.

In summary, the intensity of lipid therapy depends on the patient's
clinical risk status, and those patients at higher risk should receive
the more aggressive
interventions.[^79]^,Error:\ Reference\ source\ not\ found,Error:\ Reference\ source\ not\ found^

#### ***Recommendations***

#### *Lipid testing and hyperlipidemia*

For the diagnosis and management of patients needing secondary
prevention a complete lipid profile is required, including total
cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides.Error:
Reference source not found A "direct LDL-C" should be strongly
considered for patients with diabetes, triglycerides over 250 mg/dL, or
for those individuals in whom a fasting sample would be difficult to
obtain.Error: Reference source not found Ideally a lipid panel should be
drawn in the fasting state, although total and HDL cholesterol can be
tested accurately in the post-prandial state. Patients with acute
coronary syndromes may have a lipid profile drawn on hospital admission
within 4 hours of admission. After that, lipid values pseudo-normalize,
but can be accurately repeated 8 to 12 weeks later. A review of previous
lipid values and repeat testing of lipids is encouraged. Diagnosis of
hyperlipidemia and dyslipidemia should follow NCEP guidelines.Error:
Reference source not found In addition, fasting glucose and hemoglobin
A1C should be ordered, as well as a TSH, a complete metabolic profile,
and a urinalysis to complete the patient's risk profile.

#### *General therapy goals*

The goals for cholesterol lowering for patients needing secondary
prevention are listed in Figure 9. Although the primary effort is LDL-C
lowering, all parts of the cholesterol profile should be treated to
"normal" if possible.Error: Reference source not
found^,Error:\ Reference\ source\ not\ found,Error:\ Reference\ source\ not\ found,Error:\ Reference\ source\ not\ found,^[^80]
These profile goals and specific diet, lifestyle, and drugs must be
adjusted to individual patient characteristics.

\*Some authors felt that less than or equal to 150 mg/dl was more
reasonable in those with DM and CVD.

#### *Diet and lifestyle efforts*

All secondary prevention patients should be referred to a registered
dietician for medical nutrition therapy to improve lipid levels and/or
lower the risk of MI and CAD death. Diet instruction should include AHA
2000 Dietary Guidelines diet, emphasizing a decrease in saturated fat
(\< 7% of calories), trans-fatty acids and dietary cholesterol.Error:
Reference source not found Stricter dietary restriction of fat is often
difficult to achieve and produces diminishing benefits. The recently
described Lyon "Mediterranean" diet, which emphasizes an increased
intake of monounsaturated fat, is an alternative. In post-MI patients,
lipid profiles were not affected by this diet, but its use was
associated with a dramatic fall in subsequent cardiac events.[^81] In
addition, this diet can improve glycemic control and assist in reducing
elevated triglycerides. Because of the saturated fat and caloric
density, "fast foods" are particularly discouraged.

All patients with a BMI greater than or equal to 25 should be offered a
formal weight management program. Initial weight loss goal should begin
with a 10% reduction of total body weight in a 6-month time frame.^66^ A
reasonable target weight loss goal of 1 to 2 pounds per week is set.
Emphasis should include an increase in physical activity and a reduction
of total calories. A registered dietitian and/or a Certified Lifestyle
and

Weight Management Consultant is essential to assist in the
implementation of these changes.

Guidelines for physical activity from both the Surgeon General and the
AHA should be followed with an emphasis upon lifestyle
modifications.^60,80^ With physician approval, and if no
contraindications exist, the level of physical activity should be
assessed and goals tailored towards a gradual increase, working up to 30
to 60 minutes of activity on most, if not all, days. Elderly patients or
those with conditions such as arthritis or diabetic foot conditions can
often do limited exercises, yoga, or other similarly low-level
activities. Diet and physical activity efforts are most effective if
both are pursued simultaneously.[^82]

*Drug therapy planning*

Most patients receiving secondary prevention will require diet and drug
therapy to lower their risk of future CAD events. It has been shown
repeatedly that in CAD patients, treatment of even relatively normal
levels of cholesterol reduces the future risk of CAD morbidity and
mortality.Error: Reference source not
found^,Error:\ Reference\ source\ not\ found,Error:\ Reference\ source\ not\ found^
Drug therapy follows the current NCEP, AHA, and ADA guidelines.Error:
Reference source not
found^,Error:\ Reference\ source\ not\ found,Error:\ Reference\ source\ not\ found^
Lipid goals are shown in Figure 9, in descending order of importance,
and suggested drug therapy is outlined in Figure 10.

While any of the lipid drug groups (statins, fibrates, niacin, and bile
acid binding agents) may be utilized, statins are preferred considering
their profound benefits evident in clinical trials.Error: Reference
source not
found^,Error:\ Reference\ source\ not\ found,Error:\ Reference\ source\ not\ found,^[^83]
Benefit has been demonstrated for men as well as for women, for
diabetics and non-diabetics,Error: Reference source not found^,^[^84]
and the elderly as well as middle aged patients.Error: Reference source
not found Fortunately, these drugs are also remarkably safe. Although
relatively expensive, the use of statins in secondary prevention has
been shown to be very cost beneficial, and in the highest risk groups,
cost saving.Error: Reference source not found^,^[^85] The use of
combination therapies of cholesterol lowering drugs in patients with
severe dyslipidemia, especially combined dyslipidemia and diabetic
dyslipidemia, is often required to normalize lipids and achieve maximal
clinical benefit.[^86] First generation statins (lovastatin,
pravastatin, and simvastatin) may be used with fibrates or niacin; this
combination therapy is associated with a small but definite risk of
myositis, rhabdomyolysis and hepatitis, and should be done cautiously,
with frequent blood testing (LFTs), or with consultation. [^87] Niacin
has recently been shown to be usable in type 2 diabetics if close
attention to glycemic status is observed.Error: Reference source not
found

-   Because of the profound effects statins have on cholesterol as well
    as on endothelial function and plaque biology, all patients at
    "higher risk" (see Figure 8) should be considered for statin
    therapy, even if LDL-C is less than 100 mg/dL or lipid levels are
    not available.[^88],[^89],[^90],[^91],[^92] The starting dose should
    be proportional to the level of LDL cholesterol elevation.
    Prescribing a clinically effective dose is more important than the
    specific statin chosen. A summary of lipid therapy is shown in
    Figure 10.

+--------+------+-------+-------+-----+-------+-------+-------------+
| FIGURE |      |       |       |     |       |       |             |
| 10.    |      |       |       |     |       |       |             |
| Lipid  |      |       |       |     |       |       |             |
| T      |      |       |       |     |       |       |             |
| herapy |      |       |       |     |       |       |             |
| S      |      |       |       |     |       |       |             |
| ummary |      |       |       |     |       |       |             |
| for    |      |       |       |     |       |       |             |
| Sec    |      |       |       |     |       |       |             |
| ondary |      |       |       |     |       |       |             |
| Preve  |      |       |       |     |       |       |             |
| ntion. |      |       |       |     |       |       |             |
+--------+------+-------+-------+-----+-------+-------+-------------+
| LDL-C  | L    |       |       | LD  |       |       | HDL \< 35   |
| \< 100 | DL-C |       |       | L-C |       |       | mg/dL       |
| mg/dL  | 100  |       |       | \>  |       |       |             |
|        | --   |       |       | 130 |       |       |             |
|        | 130  |       |       | mg  |       |       |             |
|        | m    |       |       | /dL |       |       |             |
|        | g/dL |       |       |     |       |       |             |
|        |      |       |       | Add |       |       |             |
|        | Add  |       |       | d   |       |       |             |
|        | drug |       |       | rug |       |       |             |
|        | the  |       |       | t   |       |       |             |
|        | rapy |       |       | her |       |       |             |
|        | to   |       |       | apy |       |       |             |
|        | diet |       |       | to  |       |       |             |
|        | and  |       |       | d   |       |       |             |
|        | phys |       |       | iet |       |       |             |
|        | ical |       |       | and |       |       |             |
|        | acti |       |       | ph  |       |       |             |
|        | vity |       |       | ysi |       |       |             |
|        | as   |       |       | cal |       |       |             |
|        | foll |       |       | ac  |       |       |             |
|        | ows: |       |       | tiv |       |       |             |
|        |      |       |       | ity |       |       |             |
|        |      |       |       | as  |       |       |             |
|        |      |       |       | fo  |       |       |             |
|        |      |       |       | llo |       |       |             |
|        |      |       |       | ws: |       |       |             |
+--------+------+-------+-------+-----+-------+-------+-------------+
| Diet   | TG\  | TG    | TG    | T   | TG    | TG    | Emphasize   |
| and    | <200 | 200   | \>400 | G\< | 200   | \>400 | weight loss |
| ph     | m    | --    | mg/dL | 200 | --    | mg/dL | and         |
| ysical | g/dL | 400   |       | mg  | 400   |       | physical    |
| act    |      | mg/dL |       | /dL | mg/dL |       | activity.   |
| ivity. |      |       |       |     |       |       |             |
|        |      |       |       |     |       |       | Advise      |
| Co     |      |       |       |     |       |       | smoking     |
| nsider |      |       |       |     |       |       | cessation.  |
| low    |      |       |       |     |       |       |             |
| dose   |      |       |       |     |       |       | Consider    |
| s      |      |       |       |     |       |       | niavcin,    |
| tatin. |      |       |       |     |       |       | ffibrates   |
|        |      |       |       |     |       |       | or statins  |
|        |      |       |       |     |       |       | as          |
|        |      |       |       |     |       |       | necessary   |
|        |      |       |       |     |       |       | based on    |
|        |      |       |       |     |       |       | remainder   |
|        |      |       |       |     |       |       | of profile. |
+--------+------+-------+-------+-----+-------+-------+-------------+
|        | Sta  | S     | Fibr  | St  | Sta   | Fibr  |             |
|        | tin. | tatin | ates. | ati | tins. | ates. |             |
|        |      | or    |       | ns. |       |       |             |
|        | C    | Fib   | May   |     | May   | May   |             |
|        | ould | rates | co    |     | be    | be    |             |
|        | also | or    | mbine |     | com   | combi |             |
|        | use  | com   | with  |     | bined | ned\* |             |
|        | Re   | bo\*, | St    |     | with  | with  |             |
|        | sin. | if    | atins |     | Fibra | St    |             |
|        |      | ne    | if    |     | tes\* | atins |             |
|        |      | eded. | need  |     | (or   | if    |             |
|        |      |       | ed\*. |     | ni    | neces |             |
|        |      | Could |       |     | acin) | sary. |             |
|        |      | also  | Could |     | if    |       |             |
|        |      | con   | also  |     | nece  |       |             |
|        |      | sider | con   |     | ssary |       |             |
|        |      | Ni    | sider |     |       |       |             |
|        |      | acin. | Ni    |     |       |       |             |
|        |      |       | acin. |     |       |       |             |
+--------+------+-------+-------+-----+-------+-------+-------------+

\*with appropriate monitoring, especially liver function tests.

*Secondary prevention and ischemia*

Patients considered eligible for secondary prevention should be
evaluated for ischemia and left ventricular (LV) dysfunction. Statin
therapy has been shown to decrease ischemia, probably by improving
endothelial function.Error: Reference source not
found^,Error:\ Reference\ source\ not\ found^ Revascularization should
be considered for patients with severe symptoms, evidence of severe
ischemia, especially when multi-vessel disease or LV dysfunction is
evident. Those at highest risk are diabetic patients after an MI.Error:
Reference source not found^,Error:\ Reference\ source\ not\ found^
Asymptomatic patients, even after CABG, should still receive lipid
therapy to prevent native and coronary graft atherosclerosis.Error:
Reference source not found^,Error:\ Reference\ source\ not\ found^
Again, this is especially important for patients with diabetes.Error:
Reference source not
found^,Error:\ Reference\ source\ not\ found,Error:\ Reference\ source\ not\ found,^[^93]

*Non-lipid drug therapy*

Patients indicated for secondary prevention often have indications for
non-lipid lowering drugs, including those in Figure 11.

*Cultural considerations*

Coronary atherosclerosis and dyslipidemia are difficult concepts for
physicians and others in the medical field to master; Native American
patients may also have trouble with these clinical issues. Extensive
time must be taken for discussion of the clinical concepts and should
include the rationale for treatment and therapy goals, in understandable
terms. Native-speaking health educators, dietitians, pharmacists and
other professionals, as well as key family members, should always be
included when possible. Diet and lifestyle advice is much more effective
when concepts are carefully explained, especially by native speakers.
Describing the goal of dietary, physical and drug therapy to return
one's bodily function to normal and emphasizing the positive and hopeful
results cannot be overemphasized, especially in asymptomatic
individuals. For instance, many individuals may not be particularly
willing to "exercise," but are very willing to daily herd sheep, or
daily walk to a relative's house or to the post office. Adherence to
drug therapy often wanes over time and may be affected by any number of
patient issues. A discussion of medication side effects and adherence as
well as potential drug-drug interactions (especially use of macrolide
antibiotics) should accompany each clinic visit. The development of a
warm, caring relationship based on respect for the patient and his or
her cultural milieu may in the end be as important as designing optimal
drug therapy and achieving optimal goal lipids.

# **[VIII. Compliance Development and Recommendations for Counseling]{.underline}**

**Introduction and rationale**

Successful treatment of dyslipidemia in Native American individuals
requires the development of an interpersonal trust between the provider
and the patient as well as similar beliefs related to the importance and
effect of the goal. Successful outcomes will result if a variety of
methods are used to enhance patient adherence, tailored to the
individual. Specific recommendations for individuals should be developed
as a provider-patient team, paying particular heed to their beliefs,
values and culture.

These guidelines are meant to serve as a framework for a consistent set
of standards and an approach to the management of dyslipidemia in local
Indian Health facilities, but efforts should be undertaken by local
providers to tailor these recommendations according to the local culture
and belief systems as well as the availability of resources and the
needs of the community.

***Recommendations***

Treating patients with dyslipidemia should involve a holistic approach.
Providers need to treat the whole patient with attention to physical,
mental, cultural, and spiritual dimensions. Patient education and
treatment strategies should be developed which take in to account
patients learning styles, traditions, values and personal goals. Efforts
should be made to empower patients and encourage self-management. Goals
for lifestyle change should be developed with the patient. Providers
should be attentive to cultural, psychosocial and socioeconomic issues
that may present barriers to achieving these goals.

Any approach to treating dyslipidemia should be undertaken with
compassion, respect, understanding and hope. Successful management of
dyslipidemia in AI/AN individuals has the potential to help prevent
tremendous morbidity and mortality from cardiovascular disease in AI/AN
communities. However, no intervention or lifestyle change has a chance
of succeeding without the active participation of the patient in a plan
that fits his or her beliefs and goals.

**[IX. Hypertensive Therapeutic Interventions]{.underline}**

***Introduction and
rationale***[^94]***,***[^95]***,***[^96]***,***[^97]***,***[^98]***,***[^99]***,***[^100]***,***[^101]

The importance of hypertension control can not be overstated, especially
in those with other cardiac risk factors, most notably diabetes
mellitus. Progression of diabetic renal disease and cardiovascular
disease are inextricably linked with blood pressure. Microalbuminuria is
an early predictor of both progressive renal injury and cardiovascular
disease. Elevations in blood pressure, though not necessarily to
hypertensive levels, are detectable along with a drop in glomerular
filtration rate well before the serum creatinine changes. \"Normal\"
blood pressure can be associated with progression of renal disease.
Deaths of ESRD patients are attributed predominantly to cardiovascular
complications. Results from the UKPDS show that "tight" blood pressure
control reduces cardiovascular risk to a greater degree than "tight"
glucose control.

Several long-term studies have demonstrated that anti-hypertensive
therapy is beneficial in early and late stages of diabetic nephropathy.
In untreated hypertensives GFR declines approximately 1 ml/min/month;
anti-hypertensive treatment slows the rate of decline by about
two-thirds. Anti-hypertensive therapy reduces proteinuria, presumably by
lowering glomerular capillary pressure. Angiotensin converting enzyme
inhibitors lower glomerular capillary pressure by dilation of the
efferent arteriole. These agents have been shown to ameliorate the renal
injury even when systemic blood pressure is not effected. In
hypertensives, ACE inhibitors provide a significant additional benefit
when compared to other anti-hypertensives with the same level of blood
pressure control. A recent NIH-sponsored management conference
recommended that ACE inhibitors be initiated in diabetic patients with
any one of the following: hypertension (\>140/90), creatinine\>1.5, or
proteinuria \> 300 mg/day. There is evidence that treatment of
normotensive Type II patients with microalbuminuria may benefit from
treatment with ACE inhibitors.

Not only are conventional drugs being replaced with ACE inhibitors, but
recently published studies justify a lower therapeutic goal for blood
pressure than the traditional 140/90. The MDRD (Modification of Diet in
Renal Disease) study showed that maintaining a mean arterial pressure of
90 mm (equivalent to 125/75) slows progression of renal disease to a
greater degree than higher BP levels in persons with more than 1g/day of
proteinuria. Benefit is greatest in patients with more severe disease. A
recent National Kidney Foundation consensus statement describes an
approach to controlling blood pressure in patients with diabetes and
kidney disease with the goal of reducing progression of blood kidney
disease and cardiovascular disease.

***Recommendations***

The consensus statement synthesizes evidence in the literature into a
cost-effective algorithm, which provides maximum renal and
cardiovascular protection to the diabetic patient. Key elements are: 1)
Blood pressure goal of \<130/80 in diabetics and 140/90 for
non-diabetics, 2) Use of ACE inhibitor as initial drug (with a diuretic
if renal dysfunction), with a beta-blocker generally as second line if
without contraindication or specific indications for another agent, 3)
Necessity to use multiple drugs (including diuretics early) in diabetics
if initial blood pressure is \>15/10 mm Hg above goal.

[Figure 12. Blood Pressure Goals and Treatment Regimen]{.underline}

# **[Appendix A: Primary References used during Conference Sessions]{.underline}**

# 

# ***General Session***

-   Expert Panel. Summary of the Second Report of the NCEP Expert Panel
    on Detection, Evaluation, and Treatment of High Blood Cholesterol in
    Adults (ATP II). JAMA 1993;269(23):3015-3023.

-   American Diabetes Association. Management of Dyslipidemia in Adults
    with Diabetes. Diabetes Care 2000;23(Suppl 1):S57-S60.

-   Howard BV et al. Rising Tide of Cardiovascular Disease in American
    Indians: The Strong Heart Study. Circulation 1999;99(2389-2395).

-   Howard BV et al. Coronary Heart Disease Prevalence and Its Relation
    to Risk Factors in American Indians: The Strong Heart Study. Am J
    Epidemiology 1995;142:254-268.

-   Krauss RM et al. AHA Dietary Guidelines: Revision 2000: A Statement
    for Healthcare Professionals From the Nutrition Committee of the
    American Heart Association. Circulation 2000;102:2284-2299.

-   Smith SC et al. Prevention Conference V: Executive Summary.
    Circulation 2000;101:111-116.

-   Grundy SM et al. Prevention Conference V: Medical Office Assessment.
    Circulation 2000;101:111-116.

-   Handout: Cost Effectiveness of Lipid Lowering Therapy (Summary). CC
    Lamer, PharmD.

-   Grundy SM et al. Diabetes and Cardiovascular Disease: A Statement
    for Healthcare Professionals from the American Heart Association.
    Circulation 1999;100:1134-46.

# 

# ***Elevated LDL-C***

-   BV Howard et al. LDL Cholesterol as a Strong Predictor of Coronary
    Heart Disease in Diabetic Individuals with Insulin Resistance and
    Low LDL. Arterioscler Thromb Vasc Biol 2000;20:830-835.

***Low HDL and High Triglycerides: The Metabolic Syndrome***

-   Ballantyne CM et al. Hyperlipidemia: Diagnostic and Therapeutic
    Pespectives. J Clin Endocrinology and Metabolism
    2000;85(6):2089-112.

# 

# ***Risk Evaluation Methodologies***

-   Wilson PWF et al. Prediction of Coronary Heart Disease Using Risk
    Factor Categories. Circulation 1998;97:1837-1847.

-   D'Agostino RB et al. Primary and subsequent coronary risk appraisal:
    New results from The Framingham Study. Am Heart J 2000;139:272-281.

# ***Cardiovascular Health Promotion Programs***

-   Burden R et al. Management of dyslipidemias: Establishing a clinic
    run by clinical pharmacy specialists. IHS Provider 1998;23(2):17-20.

```{=html}
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```
-   Burden RW et al. An innovative software program approach directly
    links Microsoft Excel and Microsoft Access to the IHS RPMS databases
    for clinical epidemiological evaluation. IHS Provider
    1998;23(12):165-66.

# ***Hypertensive Therapeutic Interventions***

-   Bakris GL et al. Preserving Renal Function in Adults With
    Hypertension and Diabetes: A Consensus Approach. Am J of Kidney
    Diseases 2000;36(3):646-661.

# ***Public Health and Community Education***

-   Luepker RV et al. Effect of a Community Intervention on Patient
    Delay and Emergency Medical Service Use in Acute Coronary Heart
    Disease: The REACT Trial. JAMA 2000;284:60-67.

# 

# ***Secondary prevention***

-   Balady GJ et al. Core Components of Cardiac Rehabilitation/Secondary
    Prevention Programs. Circulation 2000;102:1069-1073.

-   Horne BD et al. Statin Therapy, Lipid Levels, C-Reactive Protein and
    the Survival of Patients With Angiographically Severe Coronary
    Artery Disease. JACC 2000;36:1774-1780.

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