Cardiovascular disease (CVD) remains the leading cause of death in women.1 Identification of risk factors is the first step toward the prevention of CVD. The 2011 Effectiveness-Based Guidelines for the Prevention of Cardiovascular Disease in Women classifies a woman’s risk status as either high risk, at risk, or ideal cardiovascular health.2 The classic high-risk profile includes the presence of any of the following: clinical CVD, cerebrovascular disease, peripheral arterial disease, abdominal aortic aneurysm, end-stage or chronic kidney disease, diabetes mellitus, or a 10-year Framingham-predicted CVD risk of ≥10%.2 The at-risk profile includes having any of the following: cigarette use, systolic blood pressure (SBP) ≥120 mm Hg, diastolic blood pressure (DBP) ≥80 mm Hg, treatment for hypertension, total cholesterol ≥200 mg/dL, high-density-lipoprotein cholesterol (HDL-C) <50 mg/dL, treatment for dyslipidemia, obesity, poor diet, physical inactivity, family history of premature CVD in first-degree relative, metabolic syndrome, advanced subclinical atherosclerosis, poor exercise capacity on treadmill test and/or abnormal heart rate recovery after stopping exercise, systemic autoimmune collagen-vascular disease, history of preeclampsia, gestational diabetes, or pregnancy-induced hypertension.2 Ideal cardiovascular health includes having all of the following without treatment: total cholesterol <200 mg/dL, BP <120/80 mm Hg, fasting blood glucose <100 mg/dL, body mass index (BMI) <25 kg/m2, abstinence from tobacco, physical activity for adults >20 years with ≥150-min/wk moderate intensity or ≥75 min/wk vigorous intensity exercise2 (see Table 2-1).
Risk Status | Class |
---|---|
High risk (≥1 high-risk states) | Clinically manifest CHD Clinically manifest cerebrovascular disease Clinically manifest peripheral arterial disease Abdominal aortic aneurysm End-stage or chronic kidney disease Diabetes mellitus 10-year predicted CVD risk ≥10% |
At risk (≥ major risk factor) | Cigarette smoking SBP ≥120 mm Hg, DBP ≥80 mm Hg, or treated hypertension Total cholesterol ≥200 mg/dL, HDL-C <50 mg/dL, or treated for dyslipidemia Obesity, particularly central adiposity Poor diet Physical inactivity Family history of premature CVD occurring in first-degree relative in men <55 y of age or in women <65 y of age Metabolic syndrome Evidence of advanced subclinical atherosclerosis (eg, coronary calcification, carotid plaque, or thickened IMT) Poor exercise capacity on treadmill test and/or abnormal heart rate recovery after stopping exercise Systemic autoimmune collagen-vascular disease (eg, lupus or rheumatoid arthritis) History of preeclampsia, gestational diabetes, or pregnancy-induced hypertension |
Ideal cardiovascular health (all of these) | Total cholesterol <200 mg/dL (untreated) BP <120/80 mm Hg (untreated) Fasting blood glucose <100 mg/dL (untreated) Body mass index <25 kg/m2 Abstinence from smoking Physical activity at goal for adults >20 y of age: >150 min/wk moderate intensity, ≥75 min/wk vigorous intensity, or combination Healthy (DASH-like) diet |
The second step of the health care provider should be to acknowledge that not only are there sex-specific risk factors for CVD and coronary heart disease (CHD), but also that the same risk factors in men and women do not affect them equally and similarly. Understanding the sex differences in CVD risk may result in a more aggressive patient education and primary prevention of CHD and CVD. This chapter summarizes the CHD and CVD risk factors that are nonmodifiable, modifiable, emerging, and female specific (see Figure 2-1).
Genomics impact the risk of developing CVD. The Framingham Heart Study demonstrated an association between the family history of CHD and the risk of developing CHD.3 This study revealed that having a single parent die from CHD resulted in a 30% increased risk of developing CHD.3 This effect was more pronounced in women compared to men, although this finding may be influenced by a sampling bias. On average, the age of parental death was younger in the women compared to the men, and additional age-adjusted parental death studies have shown slightly lower rates of CVD in women compared to men.3,4 Nonetheless, family history of premature heart disease, defined as heart disease in a first-degree relative in a woman <65 years or man <55 years, is considered a risk factor for heart disease development (see Figure 2-2).4 The 2010 ACCF/AHA (American College of Cardiology Foundation/American Heart Association) Guideline for Assessment of Cardiovascular Risk in Asymptomatic Adults recommends that family history of atherothrombotic CVD should be obtained for cardiovascular risk assessment in all asymptomatic adults.5
FIGURE 2-2
Offspring participants were stratified into quintiles of predicted risk of cardiovascular disease based on factors: offspring age, systolic blood pressure, total cholesterol to high-density lipoprotein cholesterol ratio, body mass index, diabetes, current smoking, and use of antihypertensive therapy. The risk of CVD based on family history and presence of risk factors are depicted. Study description: Cohort study of 2302 men and women followed an average of 30 years.
Reproduced with permission from Lloyd-Jones DM, et al. Parental cardiovascular disease as a risk factor for cardiovascular disease in middle-aged adults: a prospective study of parents and offspring. JAMA. 2004;291:2204-2211.
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African American and Mexican American women have higher risk for CVD compared to Caucasian women largely due to increased prevalence of hypertension, central obesity, and diabetes.6,7 The average age-adjusted CHD incidence per 1000 person-years in a National Heart, Lung, and Blood Institute study was 4 for Caucasian women and 4.9 for African American women.8 After adjusting for risk factors, rates of CVD in African American women are similar to Caucasian women (see Figure 2-3).9 However, disparities in CHD and CVD persist with African American women having the highest morbidity and mortality.10,11 Some of this may be accounted for by inequality in racial distribution of medical management and advanced interventions as detailed in the Institute of Medicine Unequal Treatment report.11
FIGURE 2-3
Lifetime risk of death from cardiovascular disease among African American and Caucasian women at 55 years of age, according to the aggregate burden of risk factors and adjusted for competing risks of death. Optimal indicates nonsmoker, absence of diabetes, total cholesterol <180 mg/dL, untreated systolic blood pressure (SBP) <120 mm Hg, and diastolic blood pressure (DBP) <80 mm Hg; nonoptimal indicates nonsmoker, absence of diabetes, total cholesterol level 180-199 mg/dL, untreated SBP 120-139 mm Hg, or untreated DBP 80-89 mm Hg. Elevated risk indicates nonsmoker, absence of diabetes, total cholesterol level 200-239 mg/dL, untreated SBP 140-159 mm Hg, or untreated DBP 90-99 mm Hg. Major risk factors indicate current smoker, diabetes, treated hypercholesterolemia, untreated total cholesterol level at least 240 mg/dL, treated hypertension, SBP at least 160 mm Hg, or untreated DBP at least 100 mm Hg. Study description: Meta-analysis of 18 cohort studies involving 257,284 African American and Caucasian men and women.
Reproduced with permission from Berry JD, et al. Lifetime risks of cardiovascular disease. N Engl J Med. 2012;366:321-329.
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Age is a powerful predictor of CVD, and specifically CHD. The prevalence of CVD increases with age for both sexes, but CHD events lag at least 10 years in women compared to men.7 For men, there is a linear increase of CHD prevalence with age, in contrast with the more exponential increase with age in women, where the risk of heart disease in a woman is 1 in 8 for women aged 45 to 64 years, but 1 in 3 for women aged 65 years or older.7
International evaluations of the impact of tobacco usage for both men and women have revealed similar risks for CHD.12,13 However, there is data showing that in women who use tobacco, the risk for CHD is 25% greater than men for the age group of 60 to 69 years.12 The INTERHEART study suggests that the odds of a woman or man with tobacco usage compared to one without tobacco usage has a 3 times higher risk of developing a myocardial infarction (see Figure 2-4).13 Furthermore, the overall effects of tobacco usage may be more harmful to women than to men. Female smokers have been reported to die 14.5 years earlier than female nonsmokers, whereas male smokers have been reported to die 13.2 years earlier than male nonsmokers.14 Education and increased public awareness have assisted in the plight against tobacco usage, particularly among pregnant women.15 For unclear reasons, the benefit of tobacco cessation has been slightly greater in women than in men with odds of developing a myocardial infarction after tobacco cessation 1½ times higher in men than in women.13
FIGURE 2-4
Risk factors for myocardial infarction in women and men: insights from the INTERHEART study. The odds ratio of a myocardial infarction based upon risk factors in men and women are depicted. Study description: Global case-control study including 27,098 participants from 52 countries, of which 6787 were women.
Reproduced with permission from Anand SS, et al. Risk factors for myocardial infarction in women and men: insights from the INTERHEART study. Eur Heart J. 2008;29:932-940.
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The prevalence of hypertension overall was similar in women and men based on the 2009 to 2010 NHANES data, but varies by age.7,16 Based on the NHANES data, before the age of 45, more men than women have hypertension.7 As women age, the risk of developing hypertension rises significantly, approaching the level of men from age 45 to 64 and exceeding the rates in men after age 65.7 During the child-bearing years, women who take oral contraceptive medication are 2 to 3 times more likely to develop hypertension than women who do not take oral contraceptive medications, especially if they are obese.7,17 Normotensive women who take oral contraceptive medications develop on average 7 to 8 mm Hg increase in systolic blood pressure.18 In postmenopausal women, risks are heightened with a 10-year incidence of CVD of 3.63% for normotensive women, 7.11% for prehypertensive (systolic blood pressure 120-139 mm Hg or diastolic blood pressure 80-89 mm Hg) women, and 14.16% for hypertensive women19 (see Figure 2-5). Different target goals will likely be identified in the future installment (eighth report) of the Joint National Committee (JNC) on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Improving the public’s awareness, prevention, and appropriate treatment would go far in reducing the burden of CHD and CVD.
FIGURE 2-5
Cumulative hazard of cardiovascular events by the seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. The cumulative hazard of cardiovascular events including myocardial infarction, stroke, hospitalized heart failure, or cardiovascular death is depicted based upon blood pressure levels. Normotensive represents systolic blood pressure <120 mm Hg and diastolic blood pressure <80 mm Hg. Prehypertensive represents systolic blood pressure 120-139 mm Hg or diastolic blood pressure 80-89 mm Hg. Hypertensive represents systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg. Study description: Cohort study of Women’s Health Initiative with 60,785 postmenopausal women followed for 7.7 years.
Adapted with permission from Hsia, J et al. Prehypertension and cardiovascular disease risk in the Women’s Health Initiative. Circulation. 2007;115:855-860.
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Diabetes remains a strong risk factor with rising prevalence, affecting 10.8% of US women >20 years of age as of 2010.20 Diabetes is considered a cardiovascular disease equivalent, given the high risk for the development of CVD. The presence of diabetes is a relatively greater risk factor for CHD in women compared with men, increasing a woman’s risk of CHD by 3- to 7-fold with only a 2- to 3-fold increase in diabetic men.21 Despite advances in care from 1971 to 2000, NHANES reveals that mortality in women with diabetes has doubled compared to women without diabetes whereas the mortality in men with diabetes compared to men without diabetes has declined by 43%.7
Cholesterol levels in women do not follow the same trends as in men. Dyslipidemia is common in women, and more than half of American women have a total cholesterol >200 mg/dL and 36% of them have an LDL cholesterol >130 mg/dL.7,22 In patients with dyslipidemia, evidence has shown that women on average are 3.5 years older than men with higher total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) and with lower triglyceride (TG) and TC to HDL-C ratio compared to men.23 For women, adverse changes in the lipid profile accompany menopause and include increased levels of total cholesterol, LDL-C, and triglycerides and decreased levels of HDL-C, but it remains unclear how much lipid changes are related to aging as opposed to menopause-related hormonal changes.24,25,26
HDL-C is a predictor of CVD in both sexes, but is relatively more predictive in women. The Framingham study showed that in men with the lowest quartile for HDL-C (HDL <36 mg/dL), there was a 70% greater risk of myocardial infarction compared with those in the highest HDL-C quartile (HDL >53 mg/dL). However, this risk was even stronger for women with low HDL-C. Women in the lowest HDL-C quartile (HDL <46 mg/dL) had 6 to 7 times the rate of coronary events compared with those in the highest HDL-C quartile (HDL >67 mg/dL), even after adjustment for other risk factors.27 For women, HDL-C levels average around 10 mg/dL higher than in men throughout their lives.27 This is reflected in the Effectiveness-Based Guidelines for the Prevention of Cardiovascular Disease in Women 2011 Update guidelines and the Adult Treatment Panel III (ATP III) guidelines, as desired HDL-C is recommended to be 50 mg/dL in women as opposed to 40 mg/dL in men.27
When deciding upon the best management approach for lipid control in women, we direct the provider to the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (NCEP ATP) guideline, which should be updated in the near future.
Physical inactivity is a large contributor to CHD, accounting for 12.2% global burden of CHD.7 Despite education about the effects of physical inactivity, it continues to worsen. From 2001 to 2006, the proportion of women who exercised >12 bouts a month decreased from 49% to 43.3%.7 The reliance of self-assessment of activity levels may be insufficient particularly in women. In one study, the women overestimated 138% higher physical activity than actually measured compared to men who overestimated 44% higher physical activity than actually measured.7 Women and men do not have an equal risk of CHD based on activity levels and corresponding central obesity and waist circumference13,28 (see Figure 2-4). The Hazard Ratio of future CHD for individuals with inactivity (sedentary job and no recreational physical activity) and increased waist circumference compared to individuals with high activity levels (sedentary job with >1 hour recreational physical activity per day, standing job with >0.5 hours recreational physical activity, physical job with at least some recreational physical activity, or heavy manual job) and decreased waist circumference is 4-fold higher in women and 1.75-fold higher in men.28 (see Table 2-2) The benefit of physical activity conversely may be higher in women than in men. In a study with young adults followed through middle-age, women with high activity levels gained 6.1 kg less in weight and 3.8 cm less in waist circumference than women with little physical activity, while the corresponding data in men with high activity levels were a gain of 2.6 kg less and 3.1 cm less when compared to men with little physical activity.7
Active | Moderately Active | Moderately Inactive | Inactive | |
---|---|---|---|---|
Men Waist <91.0 cm (<35.8 in) Waist 91.0-97.9 cm (35.8-38.5 in) Waist >98.0 cm (>38.6 in) | 1.00 1.39(1.01-1.93) 1.71(1.26-2.33) | 1.04(0.75-1.45) 1.58(1.16-2.15) 2.32(1.74-3.10) | 1.08(0.77-1.51) 1.50(1.10-2.05) 2.25(1.71-2.98) | 2.18(1.62-2.93) 2.05(1.54-2.72) 3.04(2.35-3.94) |
Women Waist <76.0 cm (29.9 in) Waist 76.0-84.9 cm (29.9-33.4 in) Waist >85.0 cm (>33.5 in) | 1.00 4.51(2.17-9.37) 5.34(2.53-11.3) | 2.70(1.29-5.66) 4.09(2.00-8.38) 6.34(3.14-12.79) | 2.58(1.24-5.36) 4.37(2.19-8.73) 9.44(4.81-18.56) | 4.48(2.18-9.19) 9.35(4.75-18.4) 11.38(5.83-22.20) |
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