# Presentation: 388816

## Cardiovascular Disease in WomenModule II: Risk Factors

## Module II: Risk Factors

**Traditional Risk Factors**
**Evolving Risk Factors**

## Cardiovascular Risk Factors in Women

**Unmodifiable**
- Age
- Family History
**Modifiable**
- Sedentary Lifestyle
- Smoking
- Obesity
- Diabetes
- Hypertension
- Dysplipidemia

**     ****Source: **ATP III 2002

**Notes:**
SLIDE INFORMATION SOURCE:  Third Report of the National Cholesterol Education Program (NCEP) Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III), NIH, NHLBI, 2002.

## Cardiovascular Risk Factors

**Sedentary Lifestyle**

## Modifiable Risk Factors: Sedentary Lifestyle

**30% of women report no leisure time physical activity**
**Exercise is less prevalent among white women ****compared to white men**
**African American and Hispanic women have the lowest prevalence of leisure time physical activity**

**Source: **CDC, U.S. Surgeon General 1996

**Notes:**
SLIDE INFORMATION SOURCE:   U.S. Department of Health and Human Services. Physical activity and health: a Report of the Surgeon General. Atlanta, Georgia: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, 1996. 

## Estimated Percentage of Americans Age 18 and Older Who Report No Leisure-time Physical Activity by Race and Sex

**Source: **U.S. Surgeon General 1996

**Notes:**
SLIDE INFORMATION SOURCE:   U.S. Department of Health and Human Services. Physical activity and health: a Report of the Surgeon General. Atlanta, Georgia: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, 1996. 

## Risk Reduction for CHD Associated with Exercise in Women

**     ****Source: **Adapted from Manson 1999

**Notes:**
SLIDE INFORMATION SOURCE:  Manson JE, et al.  A prospective study of walking as compared with vigorous exercise in the prevention of coronary heart disease in women.  N Engl J Med 1999;341:650-658.

Research has shown that, after controlling for other factors that affect heart disease risk,  women who walk the equivalent of three or more hours per week have a risk of coronary events that is  35% lower than women who walk infrequently(1) .  

(1) Manson JE, et al.  A prospective study of walking as compared with vigorous exercise in the prevention of coronary heart disease in women.  N Engl J Med 1999;341:650-658.

## Cardiovascular Risk Factors

**Smoking**

## Relative Risk of Coronary Events for Smokers Compared to Non-Smokers

**Source: **Adapted from** **Stampfer 2000

**Notes:**
SLIDE INFORMATION SOURCE: Stampfer, MJ, et al.  Primary prevention of coronary heart disease in women through diet and lifestyle.  N Engl J Med 2000; 343:16-22.

In a cohort study of 84,129 U.S. female registered nurses (Nurses’ Health Study), over 40% of coronary events were found to be attributable to smoking.  The relative risk of coronary events for nonsmokers compared to smokers is demonstrated on this slide (1).  A prospective cohort study in Demark showed  a greater relative risk of myocardial infarction for current female smokers (RR=2.24) compared to current male smokers (RR=1.43) (2).

(1) Stampfer, MJ, et al.  Primary prevention of coronary heart disease in women through diet and lifestyle.  N Engl J Med 2000; 343:16-22.
(2) Prescott E, et al.  Smoking and risk of myocardial infarction in women and men: longitudinal population study. BMJ 1998; 316:1043-1047.

## Smoking

- The same treatments benefit both women and men
- Women face different barriers to quitting
- Concomitant depression
- Concerns about weight gain

**      ****Source: **Fiore 2000

**Notes:**
SLIDE INFORMATION SOURCE:  Fiore MC, et al.  Treating tobacco use and dependence.  Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services. Public Health Service. June 2000.

## Five A’s

**Ask**** about tobacco use at every visit**
**Advise**** in a clear and personalized message**
**Assess**** willingness to quit**
**Assist**** to quit**
**Arrange**** follow-up**
**For more information:       www.surgeongeneral.gov/tobacco/treating_tobacco_use.pdf**

**Source:  **Fiore 2000

**Notes:**
SLIDE INFORMATION SOURCE:  Fiore MC, et al.  Treating tobacco use and dependence.  Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services. Public Health Service. June 2000.

The 5 A’s  are designed to be a brief intervention for engaging patients in conversation about smoking cessation.  
ASK about tobacco use at every opportunity; include in vitals signs; stickers on charts or other reminders for physicians, other healthcare providers, and staff
ADVISE   In a clear, strong message, advise them to quit.  Personalize the message if possible
ASSESS  willingness to quit; this is an important tool to see where they are in the process of change.  How does the patient  view it?
ASSIST to quit;  discuss how others have done it and how you can help them too
ARRANGE  follow up; schedule follow up visits, phone calls(1)  

(1) Fiore MC,et al.  Treating tobacco use and dependence.  Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services. Public Health Service. June 2000.

## Cardiovascular Risk Factors

**Obesity**

## Obesity Trends* Among U.S. AdultsBehavioral Risk Factor Surveillance System

**BRFSS, 1991-2002**

- No Data         <10%           10%–14%	       15%–19%          20%–24%            ≥25%

**(*BMI ≥30, **
**or ~ 30 lbs **
**overweight for **
**5’ 4” woman)**

**Source:  **CDC

## Body Mass Index: Definition

**BMI = weight in kilograms divided by the square of the height in meters (kg/m2)**
**BMI chart showing BMI based on weight in pounds and height in inches available at: **http://www.nhlbi.nih.gov/guidelines/obesity/ob_home.htm

## Body Weight and CHD Mortality Among Women

**P for trend < 0.001**

**      ****Source:  **Adapted from Manson 1995

**Notes:**
SLIDE INFORMATION SOURCE:  Manson JE, et al.  Body weight and mortality among women.  N Engl J Med 1995. 333:677-685.

The participants in this part of the Nurses Health Study were 115,195 women free of diagnosed cardiovascular disease and cancer in 1976,  who were followed until 1992 (1).  This graph demonstrates mortality among non-smoking women at various BMI.
The lowest mortality was seen in women who weighed at least 15% less than the U.S. average, and among those whose weight had been stable since early adulthood (1).

(1) Manson JE, et al.  Body weight and mortality among women.  N Engl J Med 1995. 333:677-685.

## Body Weight and CHD Mortality Among Women

**P for trend < 0.001**

**≥**

**      ****Source:  **Adapted from Manson 1995

**Notes:**
SLIDE INFORMATION SOURCE:  Manson JE, et al.  Body weight and mortality among women.  N Engl J Med 1995. 333:677-685.

The participants in this part of the Nurses Health Study were 115,195 women free of diagnosed cardiovascular disease and cancer in 1976,  who were followed until 1992 (1).  
This graph represents data for non-smokers in the study.  Weight gain of 20 kg or more since the age of 18 confers a greater than 7 times relative risk of CHD mortality.

(1) Manson JE, et al.  Body weight and mortality among women.  N Engl J Med 1995. 333:677-685.

## Adult Treatment Panel III Guidelines

**Sample menus for different ethnic & cultural preferences**
**Assessment tools**
**Counseling tools**
**Adherence tips**
**Patient handouts**

**      ****Source: **ATP III 2002

**Notes:**
SLIDE INFORMATION SOURCE:  Third Report of the National Cholesterol Education Program (NCEP) Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III), NIH, NHLBI, 2002.

The ATP III full report document has several chapters devoted  to suggestions on dietary management (1).  
Some resources in the ATP III document include sample menus for different ethnic and cultural preferences, assessment tools to facilitate counseling women, tips on adherence and patient hand-outs (1).

(1) Third Report of the National Cholesterol Education Program (NCEP) Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III), NIH, NHLBI, 2002.

## Cardiovascular Risk Factors

**Diabetes**

## Diabetes

**Diabetes affects 8.7% of all U.S. women age 20 years ****or older**
**Compared to whites:**
- African Americans, Latinas, American Indians, Asian Americans, and Pacific Islanders have a 1.5-2.3 times greater prevalence of diabetes

**      ****Source: **CDC 2003

**Notes:**
SLIDE INFORMATION SOURCE:  Centers for Disease Control and Prevention, Department of Health and Human Services.  National Diabetes Fact Sheet, 2003.

## Diabetes

**65% of diabetics die of cardiovascular disease**
**Diabetics have death rates from heart disease that are ****2 to 4 times higher than non-diabetics**

**      ****Source: **CDC 2003

**Notes:**
SLIDE INFORMATION SOURCE:  Centers for Disease Control and Prevention, Department of Health and Human Services.  National Diabetes Fact Sheet, 2003.

## Coronary Disease Mortality and Diabetes in Women

**     ****Source: **Adapted from Krolewski 1991

**Notes:**
 SLIDE INFORMATION SOURCE:  Krolewski AS, et al.  Evolving natural history of coronary artery disease in diabetes mellitus.  Am J Med 1991.  90(2A): 56S-61S.

This graph represents results from a study of 116,000 subjects, aged 30-55, who were followed for 8 years (1).
The risk of nonfatal and fatal CHD was >6 fold that of women without diabetes (1).
 Risks for all forms of CVD are elevated in type 1 and type 2 diabetics(2).
Diabetics with CHD are more likely  to die than non-diabetics with CHD(2).

(1) Krolewski AS, et al.  Evolving natural history of coronary artery disease in diabetes mellitus.  Am J Med 1991.  90(2A): 56S-61S.
(2) Third Report of the National Cholesterol Education Program (NCEP) Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III), NIH, NHLBI, 2002.

## Race/Ethnicity and Diabetes

**At high risk:**
- Latinas
- American Indians
- African Americans
- Asian Americans
- Pacific Islanders

**      ****Source: **American Diabetes Association 2001

**Notes:**
SLIDE SOURCE:  American Diabetes Association.  Screening for Diabetes. Diabetes Care 2001; 24 Suppl 1:521-4; www.diabetes.org accessed on March 8, 2005.

Women of color are at particularly high risk for type 2 diabetes(1). Recommendations for screening for type 2 diabetes can be found at the web site of the American Diabetes Association. 

(1) www.diabetes.org accessed on March 8, 2005

## Definition of Metabolic Syndrome in Women

**Abdominal obesity - waist circumference > 35 in. **
**High triglycerides ≥ 150mg/dL**
**Low HDL cholesterol < 50mg/dL**
**Elevated BP ≥ 130/85mm Hg**
**Fasting glucose ≥ 100mg/dL**

**      ****Source: **AHA/NHLBI 2005

**Notes:**
SLIDE INFORMATION SOURCE: Grundy SM, et al.  Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute scientific statement.  Circulation 2005, accessed at www.circulationaha.org on October 25, 2005.
The metabolic syndrome is characterized by a constellation of risk factors in one individual.  This syndrome increases the risk for CHD at any given LDL-cholesterol level (1).
The definition of metabolic syndrome remains controversial.  This is the AHA/NHLBI definition.   Patients are diagnosed with metabolic syndrome when three of five criteria are met.  Patients receiving drug treatment for elevated triglycerides, reduced HDL, hypertension, or high glucose meet the threshhold for each criteria.  A cutoff of 31 inches waist circumference for Asian American women should be used(1) 

(1) Grundy SM, et al.  Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute scientific statement.  Circulation 2005, accessed at www.circulationaha.org on October 25, 2005.

## Cardiovascular Risk Factors

**Hypertension**

## Treatable Risk Factors: Hypertension

**32% of women in the United States have hypertension**
**Hypertension is more prevalent among older women than older men**
**Death from CHD  progresses increasingly and ****linearly as blood pressure increases**
**For every 20 mmHg systolic or 10 mmHg diagnostic increase in blood pressure, risk of death from CHD doubles**

**Source:  **American Heart Association 2004, JNC 7 2004

**Notes:**
SLIDE INFORMATION SOURCE:  American Heart Association.  Heart Disease and Stroke Statistics 2004.  The Seventh Report of the Joint National Committee on Prevention, Evaluation, and Treatment of High Blood Pressure.  U.S. Department of Health and Human Services.  National Institutes of Health.  National Heart, Lung, and Blood Institute, NIH Publication No. 04-5230, 2004.

## Lifestyle Approaches to Hypertension in Women

** ****Source: **JNC VII 2004, Sacks 2001

**Maintain ideal body weight**
- Weight loss of as little as 10 lbs reduces blood pressure
**DASH eating plan **
- Even without weight loss, a diet rich in fruits, vegetables, and low fat dairy products can reduce blood pressure
**Sodium restriction to 2400 mg/d**
- Further restriction to 1500 mg/d may be beneficial, especially in African American patients
**Increase physical activity**
**	****        ****	**
**Limit alcohol to one drink per day**
- Alcohol raises blood pressure
- One drink = 12 oz beer, 5 oz wine, or 1.5 oz liquor

**Notes:**
SLIDE SOURCE:  The Seventh Report of the Joint National Committee on Prevention, Evaluation, and Treatment of High Blood Pressure.  U.S. Department of Health and Human Services.  National Institutes of Health.  National Heart, Lung, and Blood Institute, NIH Publication No. 04-5230, 2004, Sacks FM, et al.  Effects on blood pressure of reduced dietary sodium and the dietary approaches to stop hypertension (DASH) diet. N Eng J Med 2001 344:3-10.

## JNC 7 Report

**Classification of blood pressure**
**Treatment algorithms**
**Lifestyle strategies**
**Antihypertensive drug choices**
**Special indications and situations**
**Resistant hypertension**

**Source: **NIH 2004

**Notes:**
SLIDE SOURCE:  The Seventh Report of the Joint National Committee on Prevention, Evaluation, and Treatment of High Blood Pressure.  U.S. Department of Health and Human Services.  National Institutes of Health.  National Heart, Lung, and Blood Institute, NIH Publication No. 04-5230, 2004.

The JNC 7 report serves as a reference for the treatment of hypertension.  It covers lifestyle strategies(including detailed diet information), drug choices and special indications and situations, such as what medications work best in different populations(1). 

(1) The Seventh Report of the Joint National Committee on Prevention, Evaluation, and Treatment of High Blood Pressure.  U.S. Department of Health and Human Services.  National Institutes of Health.  National Heart, Lung, and Blood Institute, NIH Publication No. 04-5230, 2004.

## Age-adjusted Prevalence of Hypertension Among Women in the United States

**Source:**

**Notes:**
SLIDE INFORMATION SOURCE:  Fields FE,  et al.  The burden of adult hypertension in the United States 1999 to 2000: a rising tide.  Hypertension 2004. 44:398-404.

Data from the NHANES survey from 1999-2000 revealed that among whites, blacks, and  Mexican-Americans, blacks had the highest prevalence of hypertension(1).  
Although young men have a higher prevalence of hypertension than young women, the number of women with hypertension increases progressively with age.  Women have higher values relative to men after age 54 years.  By the age of 75 years, 16% more women than men have hypertension (1).

(1) Fields FE, et al.  The burden of adult hypertension in the United States 1999 to 2000: a rising tide.  Hypertension 2004. 44:398-404.

## Prevalence of High Blood Pressure by Age and Race 

**Source: **Data from National Vital Statistics System, Health, United States, 1996-97

**Notes:**
Slide Information Source: National Vital Statistics System, Health, United States, 1996-97

African Americans are more likely to have high blood pressure than Caucasians and this occurs at earlier ages (1).

(1) National Vital Statistics System, Health, United States, 1996-97

## African Americans and Hypertension

**Compared to whites**
- African Americans develop hypertension earlier in life
- African Americans have much higher average blood pressures
- African Americans have a 1.5 times greater risk of heart disease death

**Source:  **American Heart Association 2004

**Notes:**
SLIDE INFORMATION SOURCE:  American Heart Association.  Heart Disease and Stroke Statistics 2004.

In all ethnic groups, the etiology of hypertension is multifactorial, and may include the contributions of a variety of factors including diet, stress, cardiovascular reactivity, body weight, nephron number, and  hormonal systems(1). 
In the Hypertension Detection and Follow-up Program, when medications and provider services were free of charge, African Americans benefited more than whites (1).
The low sodium DASH eating plan was associated with greater reductions in BP in African Americans than in other demographic subgroups(1).

(1)  The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. U.S. Department of Health and Human Services, National Institutes of Health, National Heart, Lung, and Blood Institute., NIH Publication 04-5230, 2004.

## Age-Adjusted 16-Year Incidence of End Stage Renal Disease by Diastolic Blood Pressure and Race (MRFIT data)

**Source: **Klag 1997

**P**
**e**
**r**
**c**
**e**
**n**
**t**

**Diastolic Blood Pressure**

**Notes:**
SLIDE INFORMATION SOURCE:  Klag MJ,  et al.  End-stage renal disease in African American and white men. 16-year MRFIT findings. JAMA 1997; 277:1293.

African Americans at all levels of blood pressure are more likely than whites  to go on to end stage renal disease(1).
ESRD confers a high risk of CHD events(2).

(1) Klag MJ, et al.  End-stage renal disease in African American and white men. 16-year MRFIT findings. JAMA 1997; 277:1293.
(2) Mosca L, et al.  Evidence-based guidelines for cardiovascular disease prevention in women. Circulation 200;. 1109:672-693.

## DASH Eating Plan

**7****–****8 servings of grains, grain products daily**
**4****–****5 servings of vegetables daily**
**4****–****5 servings of fruits daily**
**2****–****3 servings of low-fat or nonfat dairy foods daily**
**≤ ****2 servings of meats, poultry, fish daily**
**4****–****5 servings of nuts, seeds, legumes weekly**
**Limited intake of fats, sweets**

**Source: **NHLBI 1998

**Notes:**
SLIDE INFORMATION SOURCE:  Facts about the DASH eating plan. Bethesda, Md: National Heart, Lung, and Blood Institute 1998. NIH publication no. 03-4082.

In a multicenter randomized trial of 412 participants,  the DASH diet resulted in significantly lower systolic and diastolic blood pressure at high and intermediate levels of sodium intake (approximately 3500 mg and 2500 mg per day).  A combination of the DASH diet and a sodium intake of approximately 1500 mg daily lowered mean systolic blood pressure by 11.5 mm Hg compared to a control diet with a sodium intake comparable to the average intake in the U.S. (3500 mg) (1). 
The DASH diet is most effective when combined with low sodium intake (approximately 1500 mg per day).

(1).  Sacks FM, et al.  Effects on blood pressure of reduced dietary sodium and the dietary approaches to stop hypertension (DASH) diet. N Eng J Med 2001; 344: 3-10.

## DASH Diet with Low Sodium Intake in Hypertensive Individuals Compared to Control Diet with Average U.S. Sodium Intake

**    ****African American      Non-African American**

*** P<.001 from baseline**

- *

**Source:  **Sacks 2001

- *

**Notes:**
SLIDE INFORMATION SOURCE:  Sacks FM, et al.  Effects on blood pressure of reduced dietary sodium and the dietary approaches to stop hypertension (DASH) diet. N Eng J Med  2001; 344: 3-10.

The DASH diet combined with low sodium intake is particularly effective in reducing blood pressure in African Americans(1).

(1) Sacks FM, et al.  Effects on blood pressure of reduced dietary sodium and the dietary approaches to stop hypertension (DASH) diet. N Eng J Med 2001; 344: 3-10.

## Cardiovascular Risk Factors

**Dyslipidemia**

## Approximate and Cumulative LDL Cholesterol Reduction Achievable By Dietary Modification

**Dietary Component ****	****	****Dietary Change ****	****Approximate ****	****	****	****	****	****	****                          LDL Reduction**
**Major**
- Saturated fat			<7% of calories		8-10%
- Dietary cholesterol		<200 mg/day		3-5%
- Weight reduction		Lose 10 lbs		5-8%
**Other LDL-lowering options**
- Viscous fiber			5-10 g/day		3-5%
- Plant/sterol			2g/day			6-15%
-     stanol esters
**	**
**Cumulative estimate****	****	****	****	****	****20-30%****	**

**      ****Source: **Adapted from ATP III 2002

**Notes:**
SLIDE SOURCE: Third Report of the National Cholesterol Education Program (NCEP) Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III), NIH, NHLBI, 2002.

Dietary interventions have the potential to significantly lower LDL cholesterol (1). 

(1) Third Report of the National Cholesterol Education Program (NCEP) Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III), NIH, NHLBI, 2002.

## ATP III Full Report

**      ****Source: **ATP III 2002

**How to choose a statin**
**Dosing regimens**
**How to monitor when combining drugs**
**Side effect management**
**Reprintable nutritional hand-outs**
**Menu samples for different cultures**
**Adherence strategies/barrier reduction**

## Treatable Risk Factors: The Epidemiology of Cholesterol Levels and Subfractions

**Low HDL more important in women than men**
- For every 1 mg/dL increase in HDL 3% decrease in CHD risk for women and 2% decrease in CHD risk for men
**Total cholesterol/HDL ratio very predictive of CHD risk in women**
**Triglyceride elevation associated with greater atherogenic significance in women than in men**

**      ****Source: **Maron 2000

**Notes:**
SLIDE INFORMATION SOURCE:  Maron DJ.  The epidemiology of low levels of high-density lipoprotein cholesterol in patients with and without coronary artery disease.  Am J Cardiol 2000. 86:11L-14L.

## Treatable Risk Factors: Cholesterol Level and Subfractions

**LDL>160 mg/dL associated with 3.3-fold elevation in risk for women less than 65 years old**
**LDL pattern of small, dense particles (more atherogenic) present in 25% of population, but less frequently seen ****in women**
**Menopausal transition associated with increasing proportion of this subfraction**

**Source:  **Keil 2000, Carr 2000, Hokanson 1996

**Notes:**
SLIDE INFORMATION SOURCES:  Keil U.  Coronary artery disease: the role of lipids, hypertension, and smoking.  Basic Res Cardiol 2000. 95: I/52-I/58;   Carr MC,  et al. Changes in LDL density across the menopausal transition. J Investig Med 2000. 48: 245-250., Hokanson JE, Austin MA, Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: a meta-analysis of population-based prospective studies. J Cardiovasc Risk 1996. 3: 213-219.

## Relative Risk of Various Factors for CHD for Women and Men

**Relative Risk**

**1.5**

**1.5**

**1.4**

**1.1**

**1.9**

**2.4**

**1.3**

**1.4**

**1.6**

**1.8**

**0**

**0.5**

**1**

**1.5**

**2**

**2.5**

**HTN**

**CHOL**

**DM**

**Obesity**

**Smoking**

**Men**

**Women**

**Relative Risk of Various Factors for CHD for Women and Men**

**Notes:**
SLIDE  SOURCE:  Coronary heart disease incidence, by sex—United States, 1971-1987.  MMWR 1992. 41:526-529.

Diabetes, obesity, and smoking present a greater relative risk for women vs. men, whereas cholesterol elevation appears to be more significant for men than for women(1).

(1) Coronary heart disease incidence, by sex—United States, 1971-1987.  MMWR 1992. 41:526-529.

## Emerging Risk Factors for CHD

**Pro-inflammatory markers**
- C-reactive protein (hs-CRP)
- Fibrinogen
**Hyperhomocyst(e)inemia**

**      ****Source: **ATP III 2002

**Notes:**
SLIDE INFORMATION SOURCE:  Third Report of the National Cholesterol Education Program (NCEP) Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III), NIH, NHLBI, 2002.

## Relative Risk of Cardiovascular Events According to Baseline Levels of hs-CRP in Healthy Postmenopausal Women

**P for trend < 0.001**

**Source:  **Ridker 2000

**Notes:**
SLIDE INFORMATION SOURCE:  Ridker PM, et al.  C-reactive protein and other markers of inflammation in the predication of cardiovascular disease in women.  N Engl J Med 2000. 342:836-843.

C-reactive protein is a serum inflammatory marker.  Currently, high sensitivity (hs) C-reactive protein appears to be the most reliable inflammatory marker(1).
Ridker et al. demonstrated a strong correlation between risk of CV events and increased level of hs-CRP.  This marker has been shown to distinguish between women at high risk and at low risk, even in women with LDL less than 130 mg/dL.(2).
The extent to which hs-CRP measurement provides additional benefit in terms of CHD risk screening and CHD prevention is uncertain.  Routine measurement of hs-CPR is not recommended (1).

(1) Third Report of the National Cholesterol Education Program (NCEP) Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III), NIH, NHLBI, 2002.
(2) Ridker PM, et al.  C-reactive protein and other markers of inflammation in the predication of cardiovascular disease in women.  N Engl J Med 2000. 342:836-843.
.

## Fibrinogen Levels and CHD Risk in Women

***Adjusted for age, smoking, BMI, systolic blood pressure, total cholesterol, HDL, triglycerides, and educational level**

****** ****2.8**

**>2.8, ******** 3.1**

**>3.1, ******** 3.6**

**>3.6**

**      ****Source: **Eriksson 1999

**P for trend <0.0001**** **

**Notes:**
SLIDE INFORMATION SOURCE:  Eriksson M, et al.  Relationship between plasma fibrinogen and coronary heart disease in women.  Arterioscler Thromb Vasc Biol 1999; 19:67-72.

Fibrinogen is a hemostatic factor associated with CHD risk (1).
A high fibrinogen level is associated with increased risk of coronary events, independent of cholesterol level (1).
Measurement of fibrinogen is not recommended as part of routine assessment of CHD risk.  Clinical trials of specific therapeutic interventions have not yet been carried out(1).

(1) Third Report of the National Cholesterol Education Program (NCEP) Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III), NIH, NHLBI, 2002.

## Hyperhomocysteinemia and CVD Risk

**Source:  **Adapted from Welch 1998

**Notes:**
SLIDE INFORMATION SOURCE:  Welch GN and Loscalzo J.  Homocysteine and Atherothrombosis. N Engl J Med 1998; 338:1042-1050.

Elevations of serum homocysteine have been correlated with CHD risk(1).
Multiple mechanisms have been proposed to support this correlation(2).
Recent institution of folate fortification of food in the U.S. has lowered average levels of homocysteine in the U.S. population(1).
Because the strength of association between homocysteine levels and CHD is not as strong as for other risk factors, and because there is a lack of clinical trial data that lowering homocysteine with folate and B vitamins reduce CHD risk, routine measurement of homocysteine is not currently recommended(1). 

(1)  Third Report of the National Cholesterol Education Program (NCEP) Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III), NIH, NHLBI, 2002.
 (2)  Welch GN and Loscalzo J.  Homocysteine and Atherothrombosis. N Engl J Med 1998; 338:1042-1050.

## Relative Risk of Cardiovascular Events According to Baseline Levels of Homocysteine in Healthy Postmenopausal Women

**P for trend = 0.02 (not significant)**

- μ

- μ

- μ

- μ

**Source:  **Ridker 2000

**Notes:**
SLIDE INFORMATION SOURCE:  Ridker PM, et al.  C-reactive protein and other markers of inflammation in the predication of cardiovascular disease in women.  N Engl J Med 2000; 342:836-843.

In a study of 28,263 women with no history of cardiovascular disease,  the correlation between plasma levels of homocysteine and risk of cardiovascular events was not statistically significant(1).
Because of associations between homocysteine levels and cardiovascular events in some studies, folic acid supplementation in persons with CHD has been studied in randomized trials.  The results have been mixed, with some trials demonstrating benefit, and others failing to show benefit(2).

(1)  Ridker PM, et al.  C-reactive protein and other markers of inflammation in the predication of cardiovascular disease in women.  N Engl J Med 2000; 342:836-843.
(2)  Leim A, et al.  Secondary prevention with folic acid: effects on clinical outcomes. J Am Coll Cardiol 2003; 41:2105-2113.

## Psychosocial Stressors in Women with CHD: The Stockholm Female Coronary Risk Study

**Among women who were married or cohabitating with ****a male partner, marital stress was associated with nearly 3-fold increased risk of recurrent CHD events**
**Living alone and work stress did not significantly increase recurrent CHD events**

**      ****Source: **Orth-Gomer 2000

**Notes:**
SLIDE INFORMATION SOURCE:  Orth-Gomer K, et al.  Marital stress worsens prognosis in women with coronary heart disease. JAMA 2000; 283:3008-3014.

## Depression and CHD: Results from the Women’s Health Initiative Study

**Depression is an independent predictor of CHD death among women with no history of CHD**

**      ****Source: **Wassertheil-Smoller 2004

- Final May 2006

**Notes:**
SLIDE INFORMATION SOURCE:  Wassertheil-Smoller S, et al. Depression and cardiovascular sequelae in postmenopausal women. The Women's Health Initiative (WHI).  Arch Intern Med. 2004; 164:289-98. 
Recently, an arm of the Women’s Health Initiative reported findings on depression in 93,676  women with no baseline history of CHD.  After an average of 4.1 years of follow-up, depression was an independent predictor of CHD death and all-cause mortality after adjustment for age, race, education, income, DM, HTN, smoking, body mass index, physical activity and increased cholesterol(1).
Whether identification and treatment of depression will lower CHD  risk is unknown(1). 

(1) Wassertheil-Smoller S, et al. Depression and cardiovascular sequelae in postmenopausal women. The Women's Health Initiative (WHI).  Arch Intern Med. 2004; 164:289-98.