Cardiovascular disease (CVD) is the leading cause of death and disability in American women. Since 1984, more women have died of cardiovascular disease than men. More than 200,000 of these deaths are due to coronary heart disease.1 In two-thirds of these women, sudden death was the presenting symptom and studies2 show that 90% of them had at least one of the modifiable risk factors (e.g. hypertension, smoking, or diabetes). Not only is there a gender disparity in CVD deaths, there are also racial disparities. CVD death rates are higher in African-American women compared with white women. There is also a greater prevalence of hypertension, obesity, and diabetes in African-American and Hispanic women.
Over the last 10 years there has been an increase in public awareness of cardiovascular disease in women, yet there still remains a gap between a woman’s awareness of cardiovascular disease and her actual risk. In the 2006 American Heart Association survey,3 57% of the women surveyed were aware of heart disease as the leading cause of death in women, compared with 30% in 1997. There is still little evidence that women personalize this awareness, as only 21% of women identify heart disease or heart attack as a woman’s greatest health problem. Unfortunately, there is a disparity in awareness among African-American and Hispanic women. Only 15% of African-American women and 6% of Hispanic women believe that they are at risk for CVD. This disparity needs to be improved, as these women have a high prevalence of risk factors such as diabetes, obesity, sedentary lifestyle, and hypertension.
With increased awareness comes confusion. Women felt that the media contributed to the confusion about diet, hormone therapy, and the use of aspirin and antioxidant vitamin supplements to reduce risk for heart disease. Women between the ages of 25 and 45 years were more likely to find the information confusing compared with women between the ages of 45 and 65 years. This is an important gap to narrow, as the CVD risk starts early. Autopsy studies in young women showed the development of atherosclerosis related to risks such as smoking and obesity.4 There is also a lack of awareness that women’s symptoms can be atypical for heart attack. Lack of recognition of these symptoms could delay emergency treatment for acute coronary syndrome. All of these factors contribute to women’s excessive death due to and risk of CVD. The burden of preventing CVD should not rest solely on women.
The women in the 2006 survey responded that their physicians discussed women at risk; it is also the responsibility of healthcare providers. Less than half of the women recalled their physician discussing preventive strategies for heart disease with them. In a study of lipid-lowering therapy in high-risk women in a managed care setting, it was found that only 33% received the recommended lipid-lowering therapy based on National Cholesterol Education Panel (NECP) guidelines.5 Physicians have identified lack of insurance reimbursement as a barrier to counseling patients on lifestyle interventions to prevent cardiovascular disease.6
The recent evidence-based guidelines in women7 differed from previous guidelines in recommending that CVD screening for women begin at age 20, and use the Framingham Risk Score (FRS)8 for the prescription of lipid therapy. The change was based on limitations of the FRS for women. The FRS overestimates and underestimates CVD risk in non-white women, focuses on short-term absolute risk, and omits family history, a factor that increases a woman’s risk for CVD 2.3-fold. Women can be at low risk according to FRS for CVD yet have subclinical CVD such as coronary artery calcification.9
Instead, new guidelines7 classify women as high-risk, at-risk, or optimal-risk. High-risk women are those with established coronary heart disease, cerebrovascular disease, and peripheral vascular disease. It also includes women who are diabetic or have end-stage chronic kidney disease or aortic aneurysms. At-risk women have one or more of the already established modifiable risk factors such as smoking, family history, hypertension, and dyslipidemia; subclinical CVD such as coronary artery calcification; metabolic syndrome; and poor exercise tolerance on treadmill testing. Optimal-risk women are those women with a healthy lifestyle without risk factors. Shaw et al.10 identified gender-related variability in prevalence and outcome in cardiovascular risk factors. Men and women share cardiovascular risk factors; although there are more male smokers and more hypertensive men, there is an excess of young female smokers and elderly hypertensive women. Men have higher low-density lipoprotein (LDL) cholesterol levels until their fifties compared with women, until women reach menopause, when their LDL cholesterol levels rise.
Women have higher high-density lipoprotein (HDL) cholesterol levels compared with men throughout their life, though at menopause women do have a slight decline in HDL cholesterol. HDL is a greater predictor of fatal ischemic heart disease in women compared with in men. Hypertriglyceridemia is a more potent risk factor for ischemic heart disease in women compared with in men, at 76 and 32%, respectively.11
Metabolic syndrome is a greater predictor of subclinical atherosclerotic disease than obesity alone. The Wise investigators showed that women with metabolic syndrome had a four-fold increase in CVD risk compared with those women with a normal metabolic status.12 Diabetic women have a two-fold increase in CVD risk compared with non-diabetic women.10
Novel risk markers such as highly sensitive C-reactive protein (hsCRP) may have a role in helping further stratify women at intermediate cardiovascular risk. Ridker and colleagues have shown that elevated CRP increases CVD in women who have normal cholesterol.13 Recently, the Reynolds score14 has been validated in women aged 45 and older, and hsCRP was added to CVD risk factors such as smoking, diabetes, and parental history of CVD, total cholesterol, and HDL cholesterol. The Reynolds Risk Score reclassified 40–50% of the women who were at intermediate risk in the FRS to higher or lower risk categories. One of the limitations of the Reynolds score is that it has been predominantly validated in Caucasian women at midlife. Therefore, we do not yet know if it is valid in other populations of women.
The updated American Heart Association (AHA) guidelines for women set a framework for practicing physicians in all disciplines to evaluate and treat CVD risk factors in women. The guidelines cover both the primary and secondary prevention of cardiovascular disease. Lifestyle changes, such as smoking cessation, diet, and exercise, are recommended to all women. The dietary recommendations are consistent with previous AHA recommendations.15 The recommended diet contains fruits, vegetables, wholegrains, high fiber, and oily fish at least twice a week. Saturated fat should be less than 10% of daily caloric intake for primary prevention and less than 7% of total intake for secondary prevention. All women should reduce transfat intake to less than 1% of calories daily. At least 30 minutes of brisk activity is recommended daily and 60–90 minutes is recommended for losing and sustaining weight loss. When counseling patients on exercise, it is important to stress moderate physical activity at regular intervals for the greatest gain in CVD prevention.16
It is also important to give patients reasonable expectations when using diet and exercise as part of a lipid-lowering program. In studies of middle-aged women, the average reduction in LDL cholesterol is 14.5mg/dl.17 This may be adequate for those women with mildly elevated cholesterol, but may require the addition of pharmaceutical intervention for those with moderate to high levels of cholesterol depending on their level of risk. HDL cholesterol increases with increasing levels of aerobic activity in women;18 however, in middle-aged women it may take up to a year to make significant increases.20
Optimal cholesterol levels are LDL <100mg/dl, HDL >50mg/dl, triglycerides <150mg/dl, and non-HDL cholesterol of <130mg/dl. Pharmaceutical therapy with statin drugs is recommended at an LDL cholesterol >100mg/dl level to all women at high risk for congenital heart disease (CHD) to achieve an LDL cholesterol <100mg/dl, 130mg/dl for those women at intermediate Framingham risk, and at a level of 160mg/dl if the 10-year FRS is <10% and LDL of 190mg/dl in low-risk women. Although women have been under-represented in the majority of lipid-lowering trials, meta-analyses have shown similar cardiovascular benefits in men and women. It is important to remember that statins cannot be used during pregnancy, and prior to starting a woman of childbearing age on a statin pregnancy testing should be performed. HDL is a secondary target for treatment, and niacin or fibrate therapy is recommended in high-risk women after the LDL target is achieved. Omega 3 fish oil is recommended (850–1000mg) for women with CHD, with higher does recommended for those women with hypertriglyceridemia.
Optimal blood pressure is <120/80. The guidelines recommended antihypertensive therapy at blood-pressure levels of 140/90 in non-diabetic women and initiation of pharmaceutical therapy at blood pressures greater than 130/80 for those women with diabetes or chronic kidney disease. Thiazide diuretics are recommended as first-line therapy, unless the woman is at high risk, where initial therapy would be an angiotensin-converting enzyme (ACE)-inhibitor/angiotensin receptor-blocker, or beta-blocker.
Aspirin recommendations for women have been updated based on the Women’s Health study and other studies.21,22 A dose range of 75–325mg is recommended for high-risk women. Aspirin therapy (81–100mg) is recommended for the primary prevention of CHD and stroke in women over the age of 65. Aspirin therapy is also recommended for stroke prophylaxis for healthy women under the age of 65, if the benefit of ischemic stoke outweighs the risk.
Although the recommendations for CVD prevention are comprehensive and recommend early screening, these guidelines are limited in terms of accounting for concerns of women of childbearing age. Most of the evidence-based data for risk factor modification are based on interventions in women at midlife. Recent research also indicates that there may be risk markers in women of childbearing age that predict later-life heart disease. Women who have pre-eclampsia, hypertension of pregnancy, and other maternal-placental syndromes may have a two- to eight-fold increased CVD risk.23–25 Although the mechanism is not yet known, insulin resistance has been a proposed mechanism for these conditions and CVD risk in women.
Lifestyle interventions are important for women of all ages. One concern is that the guidelines may result in more aggressive use of pharmaceutical therapy in women in whom the data are not as strong for benefit.26 The greatest investment a woman can make in her heart health is prevention. As clinicians, it is important that we individualize the guidelines to the needs of our patients, instituting lifestyle changes early, with pharmacotherapy initiated for those women at high risk or with already established CHD. Future research should focus on identifying risk earlier and setting guidelines for risk-factor evaluation and intervention for women throughout their lifecycle, from the childbearing years through menopause.