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Abstract

More women die of cardiovascular disease than any other cause. Effective primary prevention depends on accurate assessment of risk status. While most risk factors are similar for men and women, risk factors may differ in magnitude between the sexes, and recognition of gender-specific risk factors such as gestational diabetes, hypertensive syndromes of pregnancy and polycystic ovarian syndrome provides opportunities for early intervention and prevention. Obesity, hypertension and hyperlipidemia affect both genders; however, women often postpone addressing these risk factors until later in life. The American Heart Association emphasizes that all women are at cardiovascular risk and should maintain a healthy lifestyle and avoid smoking. Blood pressure, hyperlipidemia and diabetes should be aggressively treated. Current available data regarding proposed preventive drug therapies including daily aspirin, HRT, vitamin D and omega-3 fatty acid supplements will be reviewed.

Keywords

cardiovascular risk factors coronary heart disease gender differences postmenopausal hormone therapy primary cardiovascular prevention women

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Release date: 25th July 2011; Expiration date: 25th July 2012

Learning objectives

Upon completion of this activity, participants should be able to:

Describe specific factors related to cardiovascular disease among women

Identify patient management goals to prevent cardiovascular disease among women

Discuss the current recommendations to counsel women effectively regarding the prevention of cardiovascular disease

Analyze medications to prevent cardiovascular disease among women

Cardiovascular disease (CVD) claims more female lives than cancer, chronic low respiratory diseases, Alzheimer's disease and accidents combined, accounting for approximately one death per min or 421,918 female deaths in the USA in 2007 [1]. Among all ages, at least 38.2 million (or 34%) women in the USA were known to be affected in 2006, and an even larger proportion of women are at risk [2]. Heart disease is the leading cause of death in both men and women aged 65 years and over. The second leading cause of death in women is cancer, followed by stroke [3]. Contrary to popular belief, more women die of CVD than men [4]; in the USA, this has been the case since 1984.

Globally, CVD is the number one cause of morbidity and mortality accounting for many more deaths than malaria, HIV/AIDS and TB [5]. Of the approximately 16.7 million worldwide deaths attributed to CVD, 80% of these occur in low- and middle-income countries [6]. CVD affects both genders at a younger age in these countries, leading to loss of productive years of life with dramatic financial implications for the individual, family, community and country [7]. In South Africa, CVD is the third largest women's disease burden, even in the midst of the HIV/AIDS epidemic [5]. Increasing attention is being directed towards the primary prevention of CVD globally [5 –7]. As our understanding of prevention in women advances, information must be disseminated and measures implemented on a global scale.

In the USA, women from lower income groups, those who lack adequate health insurance, and have fewer years of education, as well as women from some racial and ethnic minority groups, are at higher risk of morbidity and mortality from CVD [8]. The racial gap between black and white people for CVD appears highest in young-to-middle-age (ages 35–64 years), with narrowing over ages 65 years. More than a quarter of cardiovascular mortality of black people occurs under 65 years of age (28%), as compared with 13% of white people in that age group [9].

With the expanding epidemic of diabetes, obesity and the metabolic syndrome, CVD will undoubtedly continue to rise. Among women in the USA, the 2008 estimated prevalence of diabetes was 8.2% (or 10 million), 27% of which are estimated to be undiagnosed (2.7 million). Prediabetes is estimated to affect 33.4 million women (28.8% of all women) [1]. The prevalence of obesity is even higher. An estimated 40.1 million women (35.2%) are obese with a BMI of 30 or higher, compared with 34.9 million men (32.4%). An astounding 71.3 million women (62.3%) have a BMI of 25 or higher [1].

The metabolic syndrome is closely associated with obesity and insulin resistance, affecting 35.1% of men and 32.6% of women, based on National Health and Nutrition Examination Survey (NHANES) 2003–2006 data [3]. An estimated 76 million adults in the USA meet criteria for the metabolic syndrome [10]. Specifically, the Adult Treatment Panel (ATP) III defines the metabolic syndrome as any three of the following: a waist circumference >88 cm, triglycerides ≥150 mg/dl high-density lipoprotein-cholesterol (HDL-C) <50 mg/dl, systolic blood pressure ≥130 mmHg or diastolic blood pressure ≥85 mmHg, a history of hypertension, fasting blood glucose ≥100 mg/dl or a history of diabetes mellitus. A slightly modified definition put forth by the International Diabetes Foundation requires a waist circumference ≥80 cm and any two of the above noted lipid, sugar or blood pressure parameters. The presence of the metabolic syndrome not only increases risk for future diabetes or CVD, but is also an independent predictor of mortality among women with stable coronary artery disease [11].

Age at onset of CVD is approximately 10–15 years later in women than in men. The ATP III defines aged 55 years and older as a risk factor for women, but aged 45 years for men [12]. The reason for this age disparity is unclear, although several factors may play a role. On average, men have HDL-C levels that are 10 mg/dl lower throughout adult life than women. Furthermore, low-density lipoprotein-cholesterol (LDL-C), triglycerides and blood pressure rise at an earlier age in men [12]. Endogenous estrogen may provide protection from coronary disease, but oral estrogens can increase coagulation, inflammation, and increase cardiovascular events, despite being shown to raise HDL-C and lower LDL-C [13].

Risk factors unique to women

Gestational diabetes

Gestational diabetes mellitus (GDM) affects 2–10% of pregnant women in the USA and Europe [14] and is defined as glucose intolerance leading to hyperglycemia that is first recognized during pregnancy. GDM usually resolves postpartum, but up to one third of affected women may continue to have diabetes or impaired glucose metabolism [15,16]. Most women who manifest GDM have preexisting β-cell dysfunction and glucose intolerance, and many will eventually develop Type 2 diabetes [16]. The relative risk of developing diabetes within 5 years of a pregnancy with GDM is 3–20% [16]. The risk of developing diabetes after GDM increases with time, and in one large retrospective study women had a cumulative risk of 25.8% of developing diabetes within 15 years of GDM [17]. Similarly, 18.9% of 21,823 Canadian women with GDM were found to have diabetes by 9 years after the pregnancy [18]. Offspring of mothers affected by GDM may also have an increased risk of obesity and glucose intolerance [19].

In addition to the development of diabetes, GDM increases cardiovascular risk. A Canadian study of 8191 women with GDM and 81,262 women without GDM followed patients for a mean duration of 11.5 years. The hazard ratio for cardiovasular events was 1.71, attenuated to 1.13 after adjustment for development of Type 2 diabetes [20]. A study of women with GDM and a first-degree relative with Type 2 diabetes found that a history of GDM put women at higher risk of CVD independent of the metabolic syndrome or Type 2 diabetes, with an adjusted odds ratio 1.85 [21]. Clearly, women with a history of GDM are at high risk of both future diabetes and CVD. Unfortunately, many women with GDM are not screened for diabetes after delivery [22].

Pregnancy-induced hypertension & preeclampsia

Several studies have demonstrated that hypertensive syndromes during pregnancy confer increased future cardiovascular risk. Preeclampsia and gestational hypertension both increase maternal risk of postpartum hypertension, as well as death from stroke [23]. Preeclampsia increases maternal risk of ischemic heart disease (adjusted hazard ratio: 2.0; 95% CI: 1.5–2.5) [24], diabetes (odds ratio: 3.8; 95% CI: 2.1–2.6) [25], and carries a 1.2-fold higher long-term risk of death (95% CI: 1.02–1.37) [26]. Women who had preeclampsia and a preterm delivery had an 8.12-fold increase in death from cardiovascular causes (95% CI: 4.31–15.33) [26]. A Canadian study [27] of 75,380 women with preeclampsia, gestational hypertension, placental abruption, or placental infarction showed that these women had an increased risk of CVD (defined as hospital admission or revascularization for coronary artery, cerebrovascular, or peripheral artery disease) with an adjusted hazard ratio of 2.0 (95% CI: 1.7–2.2), with an even higher risk in the presence of fetal compromise [27]. In a cohort of 198,252 women affected by preeclampsia, the relative risk of subsequent hypertension was 3.70 (95% CI: 2.70–5.05) after 14.1 years, ischemic heart disease 2.16 (95% CI: 1.86–2.52) after 11.7 years, stroke 1.81 (95% CI: 1.45–2.27) after 10.4 years, and venous thromboembolism 1.79 (95% CI: 1.37–2.33) after 4.7 years [28].

The reasons for such dramatically increased cardiovascular risk are unclear, but prepregnancy risk factors such as obesity, dyslipidemia, and hypertension are likely contributors, rather than an intrinsic factor related to the hypertensive pregnancy itself [29]. Furthermore, women with an adverse risk profile prior to pregnancy are at higher risk of developing hypertensive complications of pregnancy, especially preeclampsia [29]. Offspring of mothers who had gestational hypertension are also at increased risk of developing high blood pressure, although the exact mechanism by which this occurs remains unclear [30]. Regular physical activity throughout pregnancy is advocated as a means of preventing both gestational diabetes mellitus and gestational hypertension [31], although risk factor interventions might also be helpful prior to pregnancy. Clearly, women with hypertension during pregnancy are at increased risk for CVD and should be closely monitered.

Polycystic ovarian syndrome

Polycystic ovarian syndrome (PCOS) is estimated to affect nearly 10% of women at reproductive age, is classically characterized by irregular menses, hirsutism, alopecia, hyper-androgenism and obesity, although variations exist. The pathophysiology is complex, yet centers around hyperinsulinemia; indeed many women with PCOS are similar to women with the metabolic syndrome [32]. Associated risk factors include insulin resistance, hypertension and dyslipidemia. Women with PCOS are at high risk for impaired glucose intolerance (IGT) and diabetes, with a prevalence of 31.1 and 7.5%, respectively, in one population [33]. Among women with PCOS who were not obese (BMI

<27 kg/m²), 10.3% had IGT and 1.5% had diabetes. The odds ratio of IGT in women with PCOS was 2.76 (95% CI: 1.23–26.57) [33].

Women with PCOS may have several cardiovascular risk factors such as insulin resistance [34], low LDL-C [35], central adiposity, hypertension [36], and elevated C-reactive protein (CRP) [37] and homocysteine levels [38]. Left ventricular hypertrophy, increased left atrial size, and diastolic dysfunction are more prevalent with PCOS [39], as well as coronary artery calcium scores [40] and carotid intima media thickening [41].

Awareness of these findings is particularly important since women with PCOS are typically young and may have subclinical disease at an early age. Guidelines for the assessment of cardiovascular risk in PCOS were recently released [42]. This committee recommends women with PCOS and any risk factor be considered at risk, whereas those with Type 2 diabetes, the metabolic syndrome or vascular or renal disease be considered high risk. Risk assessment should include measuring waist circumference at every office visit. If a fasting lipid profile is normal, it should be reassessed every 2 years or sooner in the setting of weight gain. The LDL-C target is <130 mg/dl in women without additional CVD risk factors, and <70–100 mg/dl in high risk women with metabolic syndrome, Type 2 diabetes mellitus or overt vascular or renal disease. Triglyceride levels should be 150 mg/dl or less. Women with a BMI >30 kg/m², age >40 years, history of gestational diabetes or a family history of Type 2 diabetes should undergo a 2-h post 75-g oral glucose tolerance test, generally repeated every 2 years or sooner if new risk factors develop. Goal blood pressure is <120/80 mmHg. To achieve these goals, lifestyle modification is the first-line therapy. Even modest weight loss can have multiple benefits for women with PCOS and should be strongly encouraged. Metformin is currently only recommended in the setting of IGT in conjunction with lifestyle changes, and it is not recommended for the primary prevention of IGT or CVD [42].

Major risk factors

The American Heart Association (AHA) recently published the Effectiveness-Based Guidelines for the Prevention of CVD in Women – 2011 Update [43]. Specific goals and interventions are recommended for patients with CVD risk factors, including hyperlipidemia, hypertension and diabetes.

Hypertension

Optimal blood pressure is <120/80 mmHg and is ideally achieved through lifestyle approaches such as maintaining a healthy weight, exercising regularly, restricting sodium and limiting alcohol, and consuming a diet rich in fresh fruits and vegetables and low-fat dairy products (Class I; Level B). For most women, initiation of pharmacotherapy should be considered when blood pressure is ≥140/90 mmHg. In the setting of chronic kidney disease or diabetes, the goal blood pressure set out in current guidelines is ≤130/80 mmHg [43,44] although some recent data suggests that aggressive lowering of blood pressure in diabetes may not be beneficial [45]. Thiazide diuretics, calcium channel blockers, and angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs) are considered first-line pharmacotherapy. In the setting of prior coronary heart disease (CHD), chronic kidney disease, diabetes or other specific vascular diseases or high-risk features, β-blockers and/or ACE inhibitors/ARBs are indicated, with the addition of thiazide diuretics as needed (Class I: conditions for which there is evidence and/or general agreement that this procedure is useful and effective; Level A: the presence of multiple randomized clinical trials) [43,44].

Hyperlipidemia

Hyperlipidemia is also ideally controlled through lifestyle interventions with goal lipid levels of LDL-C <100 mg/dl, HDL-C >50 mg/dl, triglycerides <150 mg/dl, and non-HDL-C (total cholesterol minus HDL-C) <130 mg/dl (Class I; Level B: the presence of a single randomized trial or nonrandomized studies). In addition to lifestyle changes, the AHA Guidelines [43] recommend statin therapy to achieve LDL-C <100 mg/dl in high risk women with known CHD (Class I; Level A) or CVD, diabetes mellitus, or a Framingham risk of >20% (Class I; Level B). A goal of <70 mg/dl is reasonable in women who are very high-risk with CHD, and combination drug therapy may be required (Class IIa: weight of evidence/opinion is in favor of usefulness/efficacy; Level B). For women who fall into the at-risk category, the goal LDL-C levels are: <130 mg/dl in women with multiple risk factors and a 10-year absolute risk of 10–20%, <160 mg/dl with multiple risk factors and 10-year absolute risk <10%, and <190 mg/dl regardless of risk factors (Class I; Level B). Likewise, the ATP III Guidelines recommend a goal LDL-C < 130 mg/dl in women with multiple risk factors, and <100 mg/dl in women with known CHD or a risk of CHD >20% per 10 years [12,46]. Lowering LDL-C is the primary goal, but raising HDL-C or lowering non-HDL-C with niacin or fibrate therapy may benefit high-risk (Class IIb: usefulness/efficacy is less well established by evidence/opinion; Level B) women after LDL-C goal is achieved [43].

Diabetes

Diabetes is a well-recognized risk factor for coronary disease. The Copenhagen Heart Study demonstrated the relative risk of incident myocardial infarction (MI) or stroke was 2–3-fold higher in the setting of diabetes mellitus [47]. In another series, nearly a third of patients presenting with acute MI had undiagnosed diabetes [48]. In addition to diabetes, insulin resistance, hyperinsulinemia and hyperglycemia are associated with increased risk of CVD [49,50]. The AHA Guidelines place women with diabetes in the high-risk category and recommend optimal treatment of other coronary risk factors with goal LDL ideally <70 mg/dl and blood pressure (BP) <130/80 mmHg. The goal hemoglobin A1c is <7%, if this can be achieved without significant hypoglycemia (Class IIa; Level B) [43]. The Atherosclerosis Risk in Communities (ARIC) study recently demonstrated that even levels of glycated hemoglobin >6%, not technically meeting the diagnosis of diabetes, were associated with increased cardiovascular risk [51]. More studies will be needed since aggressive lowering of blood glucose and hypoglycemia can increase all cause mortality and does not necessarily lead to cardiovascular benefit [52].

Risk stratification

The AHA Guidelines recommend classification of female patients as: optimal risk, at risk or high risk (Box 1) [43]. Owing to the high prevalence of CVD in women, all women have a relatively high lifetime risk [53], cited as 39.2% (95% CI: 37.0–41.4) for all women aged 50 years and older, but potentially higher or lower depending on the presence or absence of additional risk factors [54]. In the AHA Guidelines [43,44], high-risk criteria include a history of coronary or cerebrovascular disease, peripheral arterial disease, abdominal aortic aneurysm, end-stage or chronic renal disease, diabetes mellitus or a 10-year Framingham global risk ≥10%. Women who fall into the at-risk category have one or more of the following risk factors: cigarette smoking, hypertension (≥120/80 mmHg or on medications), or dyslipidemia (total cholesterol ≥200 mg/dl, HDL <50 mg/dl, or on medications), poor diet, physical inactivity, obesity (especially central adiposity), family history of premature CVD (under 55 years in males or aged 65 years in females), or history of preeclampsia, gestational diabetes or pregnancy-induced hypertension. Women with subclinical vascular disease, such as coronary calcification, the metabolic syndrome, autoimmune collagen vascular disease (e.g., lupus or rheumatoid arthritis), poor exercise capacity on treadmill test and/or abnormal heart rate recovery after exercise also fall into the at-risk category. Within this category, there may be a wide range of risk for CVD, and the guidelines urge clinicians to take all the risk factors, lifestyle and Framingham risk information into account when determining the goals of therapy. Women at lowest risk or those with ideal cardiovascular health have no risk factors, abstain from tobacco, maintain a healthy lifestyle with sufficient physical exercise (≥150 min/week at moderate intensity or ≥75 min/week at vigorous intensity) and follow a healthy (Dietary Approaches to Stop Hypertension-style) diet. Without medications, their total cholesterol should be <200 mg/dl, BP <120/80 mmHg, fasting blood glucose <100 mg/dl, and BMI <25 kg/m² [43].

The updated AHA Guidelines [43] acknowledge that several 10-year risk prediction equations exist and suggest using either the updated Framingham CVD risk profile [55] or the Reynolds risk score [56]. The original Framingham risk score had been criticized for underestimating CVD risk in women since the score is based on risk of MI or CHD, not accounting for subclinical disease, which is common among women, and for not including family history [57]. The updated Framingham score is sex-specific and provides risk of CVD in general, as well as for specific events (e.g., coronary, cerebrovascular, peripheral arterial disease and heart failure).

The Reynolds risk score includes high-sensitivity CRP and family history, as well as traditional risk factors of age, gender, blood pressure, total and HDL-C, and smoking [56]. This risk prediction tool reclassified 40–50% of women at intermediate risk according to the ATP III (based heavily on Framingham 10-year risk calculations) into higher or lower-risk categories [56], and when applied to the Women's Health Study population, women in the intermediate risk category were accurately reclassified into either higher or lower risk [58]. However, the AHA Guidelines do not endorse routine screening with high-sensitivity CRP, which is required for the Reynolds risk score, since there is no evidence that a reduction in this biomarker leads to improved clinical outcomes [43]. Although other scoring systems have been developed, each appears accurate in populations similar to those in which the score was derived, and more research into risk calculations for young and elderly populations is required [59].

Box 1.

Risk classification: adapted from the 2011 American Health Association Guidelines.

Ideal cardiovascular health (all of these)

BMI <25 kg/m²

BP <120/80 mmHg, total cholesterol <200 mg/dl and fasting blood glucose <100 mg/dl (without treatment)

Nonsmoker

Physically active (>150 min/week of moderate activities, or >75 min/week of vigorous activity or a combination)

Healthy diet

At risk (≥1 major risk factor)

History of pregnancy-induced hypertension, preeclampsia or gestational diabetes

Metabolic syndrome

Subclinical vascular disease (e.g., coronary calcification)

Poor exercise capacity on the treadmill and/or abnormal heart rate recovery after stopping exercise

Hyperlipidemia (TC ≥200 mg/dl, HDL <50 mg/dl or on medication)

Hypertension

Obesity (especially central adiposity)

Physical inactivity

Poor diet

Smoking

Family history of premature CVD (age <55 years in a male relative and <65 years in a female relative)

Systemic autoimmune collagen–vascular disease

High risk (≥1 high risk state)

Known coronary heart disease

Peripheral arterial disease

Cerebrovascular disease

Diabetes mellitus

End-stage or chronic renal failure

Abdominal aortic aneurysm

10-year predicted CVD risk ≥10%

Preventive strategies

Between 1997 and 2007, mortality from CVD declined by 27.8% in the USA [1], with half the decline owing to better treatment of established disease, the other half attributed to improved management of risk factors [60]. In the Nurses' Health Study of primary prevention, women who adhered to a low-risk lifestyle (defined as a heart healthy diet, daily exercise, maintaining a normal BMI and not smoking) had a very low incidence of coronary events. Notably, only 3% of the women studied fell into this low-risk lifestyle category [61]. Women often delay focus on their own health owing to pressures and responsibilities of caring for parents and children, frequently delaying preventive care measures until after menopause. Unfortunately, early behaviors and long-standing uncontrolled risk factors account for 82% of coronary events [61]. In fact, CVD can even begin in childhood and adolescence, suggesting the importance of prevention and low-risk lifestyles beginning as early in life as possible [62,63].

Nonpharmacological strategies

Cigarette smoking

Smoking cessation should be strongly recommended at every office visit. Sadly, 18.1% of women (20.9 million) and 23.5% of men (26.2 million) are smokers, according to data from 2006 [4]. Counseling, nicotine replacement, pharmacotherapy and referral to a behavioral program or formal smoking cessation program may all be needed.

Physical activity

Physical activity is also indicated for all women regardless of risk. A minimum of 150 min/week of moderate intensity physical activity such as brisk walking, 75 min/week of vigorous exercise, or an equivalent combination of moderate- and vigorous-intensity exercise is recommended [43]. Activity should be spread throughout the week in increments of at least 10 min. Additional exercise (5 h of moderate exercise, 2.5 h of vigorous exercise, or a combination) can lead to increased cardiovascular benefits. At least 2 days/week, women should engage in activities that will strengthen all major muscle groups. For weight loss or weight maintenance, women should accumulate a minimum of 60–90 min of at least moderate physical activity most or all days of the week. The goal BMI is less than 25 kg/m² with a waist circumference less than 35 inches [43]. Several studies have demonstrated the cardiovascular benefits of regular exercise. Among patients with stable angina pectoris, exercise and dietary changes led to reduction in angiographic coronary artery disease and improvement in myocardial perfusion [64]. A study of 113 men with known coronary artery disease found that exercise leading to improvement in physical work capacity resulted in significant retardation of disease progression [65]. Among 73,743 postmenopausal women, brisk walking and vigorous exercise led to substantial reduction in CVD incidence, whereas prolonged sitting led to increased risk [66].

Dietary intake

A healthy diet is one that is rich in fruits and vegetables and low in saturated fat (<7–10% of daily caloric intake) and cholesterol (<300 mg/day). Whole grains and high-fiber foods should be encouraged, as well as fish, especially oily fish, at least twice a week. Diets high in fish, marine omega-3 fatty acids, folate, whole grains, dietary sources of vitamins E, C and β-carotene, fruit, and fiber, as well as moderate alcohol intake are supported by moderate levels of evidence [67]. Salt should be limited to approximately one teaspoon per day (<2.3 g of sodium per day). Trans-fatty acids should be eliminated from the diet if possible or at least limited to <1% of daily caloric intake. Foods with high glycemic index or load are best avoided. Supplementation with omega-3 fatty acids is discussed later. Although not directly relevant for cardiac health, all women of child-bearing age should be encouraged to take folic acid supplementation for the prevention of congenital neural tube defects.

Stress & depression

Stress has been associated with an increased risk of acute MI [68]. Depression is also a known risk factor for CVD, sudden cardiac death and all-cause cardiac mortality, and can also interfere with medical adherence and contribute to unhealthy lifestyle choices [69]. Depression is associated with 15–53% increases in 5-year cardiovascular costs [70], and routine screening has been recommended [71], especially among women with established CHD [44]. Two questions from the Patient Health Questionnaire (PHQ-2) should be asked at a minimum: over the past 2 weeks, has the patient had little interest or pleasure in doing things, or felt down, depressed or hopeless. If the answer to either question is yes, then the full PHQ-9 screening instrument should be completed [71]. Referral or initiation of treatment may be indicated (Class IIa; Level B) [44]. Treatment options include antidepressants, cognitive behavioral therapy and physical activity. For patients with high PHQ-9 scores (i.e., 10 or higher), referral to a qualified professional for evaluation of potential concomitant mental disorders is appropriate.

Breastfeeding

Recent evidence has suggested that breastfeeding confers maternal cardiovascular risk protection. A study from the University of Pittsburgh (PA, USA) [72] showed that women who consistently breastfed each child greater than 3 months had a reduced risk of subclinical CVD as measured by surrogate end points: calcification of the aorta and coronary arteries (using electron-beam computed tomography) and carotid intima-media thickness, adventitial diameter and plaque (using B-mode ultrasonography). Women who had not breast-fed were almost four times more likely to have aortic calcification (odds ratio: 3.85; 95% CI: 1.47–10) and nearly three times more likely to have coronary artery calcification (odd ratio: 2.78; 95% CI: 1.05–7.14) compared with women who had consistently breast-fed (adjusted for socioeconomic status, lifestyle and family history) [72]. There is also some evidence that breastfeeding a full-term child for less than 1 month may be associated with increased risk of Type 2 diabetes [73], but the reasons for this finding remain unclear.

Preventive drug therapies

Statins

Statin therapy is considered first-line therapy for lipid lowering and primary prevention. In a subgroup analysis of the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial, statins were effective for the primary prevention of cardiovascular events among older women [74]. JUPITER enrolled 6801 women ≥60 years old and 11,001 men ≥50 years old without prior CHD, diabetes mellitus, or stroke who had LDL-C <130 mg/dl and high-sensitivity CRP ≥2.0 mg/l, and randomized them to receive rosuvastatin 20 mg daily versus placebo [75]. The study was stopped early after median follow-up of only 2 years because of overall benefit to the study population receiving the statin. In the subgroup analysis of women, there was a statistically significant relative risk reduction in women for the primary end point of myocardial infarction, stroke, hospitalization for unstable angina, arterial revascularization, or cardiovascular death (hazard ratio: 0.54; p = 0.002), which was similar to the reduction in men (hazard ratio: 0.58; p < 0.001) [75].

By contrast, two prior studies of statins for primary prevention with reported sex-specific outcomes failed to demonstrate a benefit [76,77]. The Primary Prevention of Acute Coronary Events With Lovastatin in Men and Women With Average Cholesterol Levels; Results of AirForce/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) and the Usefulness of Pravastatin in Primary Prevention of Cardiovascular Events in Women: Analysis of the Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese (MEGA) study enrolled fewer patients (997 and

5356 women, respectively) compared with the 6801 women enrolled in JUPITER, and may not have been sufficiently powered to show significant benefit. Furthermore, JUPITER may have demonstrated benefit from statin therapy since women were older on average. All women were aged 60 years and over, with a median age of 68. AFCAPS/TexCAPS enrolled women aged 55–73 years, with a mean age of 62–63 years. MEGA enrolled women ages 40–70 years with a mean age of 60. Of note, MEGA revealed a more marked benefit among women age 60 years and older, but this did not reach statistical significance. Lastly, the degree of LDL-C lowering in JUPITER was greater than in AFCAPS/TexCAPS and in MEGA (47% reduction vs 25% and 20%, respectively) [78]. Since JUPITER enrolled women with LDL-C less than 130 mg/dl without known CVD and found benefit with the use of statin therapy, earlier use of statins may be indicated; however, additional studies are required and the role of serum CRP continues to be debated. Statin therapy has been suggested for postmenopausal women with at least one traditional risk factor, especially a family history of premature CVD, and particularly among women over 60 years of age with one additional risk factor [78]. The 2011 AHA Guidelines (Box 2) state that statin therapy can be considered for women over the age of 60 years with an estimated CHD risk >10% and a high sensitivity CRP >2 mg/l (in the absence of an acute inflammatory process) after lifestyle modification (Class IIb; Level B) [43].

Aspirin

Aspirin for secondary prevention is strongly recommended [79], however, its routine use for primary prevention has been called into question. Furthermore, there appears to be a gender difference in the benefit of aspirin for primary prevention [80 –82]. A recent meta-analysis of six primary prevention trials found the cardiovascular benefit of aspirin is frequently outweighed by the risks of bleeding [83]. In this study, there was a 12% proportional reduction in serious vascular events (0.51% aspirin vs 0.57% control per year; p = 0.0001), primarily owing to a reduction in nonfatal MI. There was no significant reduction in stroke or vascular mortality. Aspirin increased the incidence of major gastrointestinal and extracranial bleeding (0.10 vs 0.07% per year; p < 0.0001). Of note, the populations included in this study were predominantly not on statin therapy, which is known to reduce CVD without the added risk of bleeding. In this analysis, no significant gender differences were observed.

In the Women's Health Study [81], nearly 40,000 women aged 45 years and over were randomized to take 100 mg of aspirin on alternating days with no significant overall benefit. There was a 17% reduction in risk of stroke (RR: 0.83; 95% CI: 0.69–0.99; p = 0.04) with a 24% reduction in risk of ischemic stroke (relative risk: 0.76; 95% CI: 0.63–0.93; p = 0.009) and a nonsignificant increase in risk of hemorrhagic stroke (RR: 1.24; 95% CI: 0.82–1.87; p = 0.31). There was no significant difference in the relative risk of MI, although 90% of the subjects were under the age of 65 years, and the predominant vascular event in this age group is stroke. The AHA guidelines for the prevention of CVD in women state that aspirin (75–325 mg) should be used in women with known CHD (Class I; Level A), and is reasonable in women with diabetes mellitus unless contraindicated (Class IIa; Level B) [43]. For all other women, low-dose aspirin (81 mg daily or 100 mg every other day) can be useful for ischemic stroke and MI prevention in women aged 65 years or older with controlled blood pressure (Class IIa; Level B), and clinicians must ensure potential benefits outweigh the individual's risk of gastrointestinal bleeding or hemorrhagic stroke [43]. The guidelines also state aspirin may be reasonable for ischemic stroke prevention alone for those younger than 65 years (Class IIb; Level B), but this is not recommended by the Joint British Societies [84]. Unfortunately, risk of bleeding often coincides with CHD risk factors, especially age, making this determination challenging, and patients may wish to be involved in this discussion. Since the absolute risk of CVD is much lower among patients being treated for primary prevention, some clinicians prefer to be more cautious and reserve aspirin therapy only for those who will clearly benefit, such as those with established disease. Further studies are awaited, including aspirin in reducing events in the elderly (ASPREE) and aspirin to reduce risk of initial vascular events (ARRIVE). To help determine the efficacy of aspirin among patients with diabetes, we await the results of a study of cardiovascular events in diabetes (ASCEND) and aspirin and simvastatin combination for cardiovascular events prevention trial in diabetes (ACCEPT-D).

Postmenopausal HRT

Early observational and epidemiologic studies suggested that estrogen HRT was beneficial for the primary prevention of CVD in women, particularly those at highest risk for CVD [85]. Low levels of estrogen correlated with angiographic coronary artery disease [86]. However, the first randomized, blinded, placebo-controlled trial of HRT for secondary prevention, the Heart and Estrogen/progestin Replacement Study (HERS), found no benefit among 1380 women randomized to the active treatment arm [87]. Likewise, the Women's Health Initiative showed no benefit

Box 2.

Preventive strategies: adapted from the 2011 American Health Association Guidelines.

Lifestyle interventions: Class I recommendations

Smoking cessation

Physical activity

– Minimum of 150 min/week of moderate-intensity activity, or 75 min/week of vigorous-intensity activity, or a combination

– Additional cardiovascular benefit can be obtained from higher levels of physical activity: 300 min/week of moderate-intensity activity, 150 min/week of vigorous activity, or a combination

– Muscle-strengthening activities should be included at least 2 days/week

Weight maintenance/reduction

– At least 60–90 min of moderate activity most days of the week

– Goal BMI <25 kg/m² and a waist circumference <35 inches

Dietary intake

– Rich in fruits and vegetables

– Whole grain and high-fiber foods

– Fish, especially oily fish, at least twice weekly

– Limit saturated fat, cholesterol, alcohol, sodium and sugar

– Avoid trans-fatty acid consumption

Cardiac rehabilitation

– For women with a recent acute coronary syndrome or coronary intervention, new-onset or chronic angina, recent cerebrovascular event, peripheral arterial disease or current/prior symptoms of heart failure and an LVEF <35%

Lifestyle interventions: Class II recommendation

Omega-3 fatty acid supplementation can be considered for women with hyperlipidemia and/or hypertriglyceridemia, either in the form of fish or capsules (e.g., EPA 1800 mg/day). EPA and DHA are the active ingredients

Blood pressure: Class I recommendations

Optimal BP (<120/80 mmHg) should be encouraged through lifestyle approaches:

– Weight management, physical activity, alcohol moderation and a diet high in fresh fruits, vegetables, low-fat dairy products and low in sodium

Medical treatment is indicated for BP ≥140/90 mmHg (or ≥130/80 mmHg in the setting of chronic kidney disease or diabetes)

– Thiazide diuretics should be part of the drug regimen unless there are compelling reasons for other medications

– High-risk women should be treated with β-blockers and/or ACE inhibitors/ARBs, with addition of other drugs such as thiazides to achieve BP goals

– Note that ACE inhibitors are contraindicated in pregnancy

Dyslipidemia: Class I recommendations

Goal lipids: LDL <100 mg/dl, HDL >50 mg/dl, triglycerides <150 mg/dl, non-HDL <130 mg/dl, ideally achieved through lifestyle interventions

LDL-lowering drug therapy is indicated (in addition to lifestyle therapy) for:

– LDL ≥190 mg/dl

– LDL ≥160 mg/dl with multiple risk factors (even if 10-year risk is <10%)

– LDL ≥130 mg/dl with multiple risk factors and a 10-year absolute risk of 10–20%

– LDL ≥100 mg/dl with known CVD, diabetes mellitus or 10-year absolute risk >20%

Dyslipidemia: Class II recommendations

Treatment to LDL <70 mg/dl is reasonable in very-high-risk women with CHD; more than one medication may be required

After lifestyle modification, statin therapy can be considered for primary prevention in women over age 60 with an estimated CVD risk >10% and a high sensitivity CRP >2 mg/l (in the absence of an acute inflammatory process)

Niacin or fibrates can be used to raise HDL after LDL goal is reached in high-risk women

Diabetes mellitus: Class II recommendation

Goal HbA1c is <7% if this can be achieved without significant hypoglycemia. Lifestyle therapy and medications may be needed

of estrogen plus progestin for the primary prevention of CHD [88]. In this study, postmenopausal women (n = 16,608) age 50–79 years were randomly assigned to receive conjugated equine estrogens (0.625 mg per day) plus medroxyprogesterone acetate (2.5 mg per day) or placebo. The trial was prematurely terminated after mean follow-up of 5.2 years (instead of 8.5 years) based on evidence that overall risk of estrogen plus progestin exceeded the benefits, with a hazard ratio for CHD of 1.24 (nominal 95% CI: 1.00–1.54; 95% CI after adjustment for sequential monitoring: 0.97–91.60), with the highest risk occurring in the first year of treatment (hazard ratio: 1.81; 95% CI: 1.09–3.01) [88]. The estrogen-only treatment arm of the Women's Health Initiative (WHI) also had no benefit for CHD prevention [89]. A second multicenter trial of HRT among postmenopausal women (the WISDOM trial) was terminated early after the results of the WHI trial. After a median of 1-year of follow-up, there was an excess risk of venous thromboembolism and cardiovascular events [90]. Additional studies of both unopposed estrogen and combined HRT in postmenopausal women have found no benefit for primary prevention of CHD, with increased risk of stroke and venous thromboembolism [89,91,92]. A follow-up analysis of the WHI suggested that younger postmenopausal women taking HRT may have a reduced risk of CHD, but this did not reach statistical significance [93].

Although use of HRT for primary prevention of CVD in women fell quickly out of favor after the WHI trial, and is not currently recommended by the AHA [44], there is ongoing controversy with respect to other formulations and timing of HRT. Different preparations of HRT may have different cardiovascular effects [94]. For example, unlike oral estrogen, transdermal estrogen does not increase CRP and triglyceride levels, or other markers of inflammation and thrombosis (i.e., reduced fibrinogen, factor VII and antithrombin III) [95 –99]. Transdermal estrogen may also have beneficial effects on blood pressure [98]. The Estrogen and Thromboembolism Risk (ESTHER) trial [100] found that transdermal estrogen and micronized progesterone and pregnane derivatives did not confer increased risk of venous thromboembolism as compared with oral estrogens and norpregnane progesterone derivatives.

The timing hypothesis refers to observations that younger women may derive greater benefit from HRT than women who are older and several years into menopause [93,101,102]. Although these data are not sufficiently robust to support the initiation of HRT for the primary prevention of CVD they provide reassurance that short-term use for relief of vasomotor symptoms is likely safe [103]. The Kronos Early Estrogen Prevention Study (KEEPS) trial is underway to determine whether earlier initiation of estrogen would reduce CVD [104]. For now, HRT is not recommended for primary or secondary prevention of CVD, nor is the use of selective estrogen-receptor modulators (Class III: conditions for which there is evidence and/or general agreement that the procedure is not useful/effective and in some cases may be harmful; Level A) [44], which can also increase the risk of venous thromboembolism [105]. In addition, women with a history of venous thromboembolism or coronary disease should be actively discouraged from taking HRT. Of note, the US FDA has issued a warning about non-FDA compounds marketed as bioidentical hormones that have not been shown to be safe or effective.

Omega-3 fatty acids

Although omega-3 fatty acid supplementation and diets high in fish oil have been extensively studied, there is no strong evidence of a cardiovascular benefit. A meta-analysis by Hooper et al. demonstrated no significant reduction in mortality or cardiovascular events among subjects taking omega-3 supplements [106]. Another meta-analysis found that participants who reported fish consumption compared with little to no fish consumption had a relative risk of 0.83 (95% CI: 0.76–70.90; p < 0.005) for fatal CHD and a relative risk of 0.86 (95% CI: 0.81–80.92; p < 0.005) for total CHD [107]. A meta-regression analysis of fish oil supplementation (median dose 3.7 g/day) modestly lowered blood pressure, particularly among individuals over the age of 45 years or with pre-existing blood pressure 140/90 mmHg or higher [108]. Although the literature is somewhat inconsistent, a systematic review of the literature by Wang et al. also reported an overall benefit from omega-3 fatty acid intake from fish or supplements in reducing all-cause mortality, and cardiac and sudden death, with stronger evidence for secondary prevention [109]. Another meta-analysis reported that modest fish consumption of 250 mg/day of n-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) was sufficient for primary prevention [110]. Relatively few risks are associated with fish oil, although women of childbearing age and nursing mothers are advised to avoid seafood high in methylmercury, and to limit consumption to two servings per week [110]. Questions remain regarding the optimal dose and duration of omega-3 fatty acid supplementation, as well as the ratio of omega-6 to omega-3 intake.

Currently, omega-3 fatty acids in capsule form (e.g. eicasapentaenoic acid 1800 mg/day) or in the form of fish may be considered for women with hypercholesterolemia and/or hypertriglyceridemia for primary and secondary prevention (Class IIb; Level B recommendation) [43].

Vitamin D

Based largely on observational data, vitamin D deficiency (25-hydroxyvitamin D <20 ng/ml) has been associated with increased risk of CVD, defined as self-reported angina, myocardial infarction or stroke [111], as well as other cardiovascular risk factors such as hypertension, diabetes mellitus, intima-media thickness and coronary calcification [112,113]. In a recent meta-analysis of ten randomized trials, there was no significant reduction in blood pressure among individuals treated with supplemental vitamin D [114]. Another meta - analysis showed a nonsignificant trend toward CVD reduction among patients treated with moderate to high doses of vitamin D (RR: 0.90; CI: 0.77–1.05), but no benefit with combination vitamin D and calcium supplementation (RR: 1.04; CI: 0.92–1.18) [115]. Recently, the Institute of Medicine concluded that current data are inconclusive, inconsistent and insufficient to support the use of vitamin D or calcium for prevention of CVD [116], although individuals with vitamin D deficiency may benefit from supplementation for other reasons, such as prevention of osteoporosis.

Other supplements

Antioxidant supplementation with vitamin E, C or β-carotene has not been found to prevent CVD [117 –120] and should not be used for such purposes (Class III; Level A) [44]. Long-term use of vitamin E supplements may even lead to increased risk of heart failure [121] and to underutilization of other medications with proven efficacy [120]. Folic acid is also not indicated for CVD, but is recommended for all women of childbearing age for the prevention of neural tube defects in babies.

Awareness

Women's awareness of CVD and risk factors was assessed by Mosca et al. using a nationally representative survey of 1008 women [122]. They reported that the overall awareness of CVD as the leading cause of death had nearly doubled in 2006 as compared with 1997 (55 vs 30%). White women had greater awareness than black and Hispanic women (62 vs 38 and 34%, respectively). Awareness was independently correlated with increased physical activity and weight loss. Less than 50% of the women were aware of healthy levels of risk factors. Barriers to heart health included confusion in the media, belief that health is determined by a higher power, and caretaking responsibilities [122]. Women are 55% less likely than men to participate in cardiac rehabilitation after MI, an intervention that is associated with reduced mortality and recurrent MI [123]. These findings are certainly related to a significant lack of awareness in the medical field. Among physicians surveyed in 2004, fewer than one in five were aware that more women die of CVD than men [124].

Guidelines into practice

The most important barrier to improving women's health may be the lack of access that many women face, particularly those who are uninsured, underinsured or unaware of the importance of cardiovascular health and prevention. The Well-Integrated Screening and Evaluation for Women Across the Nation (WISEWOMAN) program, funded by the US CDC, is one example of programs designed to increase women's access to healthcare for primary prevention of disease. Massachusetts implemented a WISEWOMAN program that aimed to reduce cardiovascular risk among women aged 50 years and older who were uninsured or underinsured [125]. Baseline screening of 1443 patients collected data regarding blood pressure, total cholesterol, diet and physical activity. Patients were randomized to minimal intervention or enhanced intervention, which involved one-on-one nutritional and physical activity counseling and group activities, such as walking groups and nutrition classes. At 12-month follow-up, there was a significant reduction in blood pressure among both intervention groups who underwent screening (7 and 9%; p < 0.05), and a significantly greater percentage of women in the enhanced intervention group were physically active (18 vs 6%; p < 0.05). Similar projects were held in Arizona and North Carolina [126] and involved multiple outreach strategies to reach underserved women and promote cardiovascular health, as well as breast and cervical cancer screening. Community health workers were also integral to the projects, particularly among Hispanic communities in Arizona. Increased physical activity and improved nutrition were emphasized. In several states, the WISEWOMAN project has used a variety of unique interventions to empower underserved women to successfully quit smoking [201]. Projects such as this, which target high-risk and underserved women, are essential for achieving the goals set out by the AHA Guidelines [43]. The HEART for Women Act is currently progressing through US Congress and aims to: raise awareness among women and their healthcare providers; provide gender and race-specific information for clinicians and researchers; and improve screening of low-income women at risk for heart disease by expanding WISEWOMAN programs to all 50 states (currently available in 20 states).

Conclusion

Although awareness of CVD in women is increasing, more attention is required to determine the most effective means of primary prevention. Guidelines for prevention in women are inherently limited since women remain under-represented in clinical trials and gender-specific analyses have been reported in only 31–50% of major publications about CVD over the past 10 years [127,128]. Several risk factors are unique to women and should be elicited during clinic visits for appropriate risk stratification. Many comorbidities such as obesity, diabetes mellitus, hyperlipidemia and hypertension affect both genders. The optimal medications and therapeutic goals in managing these chronic diseases continue to be active areas of investigation. Drugs for primary prevention such as aspirin and HRT have been called into question, despite strong support for these interventions in prior decades. As our medical understanding of primary prevention continues to evolve, information must be disseminated to underserved women in the USA and abroad.

Future perspective

Several therapies have appeared initially promising for CVD prevention, but have not withstood rigorous study. Aspirin, HRT and ezetimibe will continue to be tested in large populations. The evidence for vitamin supplements has been unimpressive, and although a ‘miracle pill’ with few side effects is appealing, such a discovery is unlikely. Rather, it is more likely that further attention to lifestyle, including regular exercise, weight management and healthy eating will be needed in order to reverse the rapidly rising epidemic of obesity, diabetes and CVD. The role of stress may be a currently overlooked contributor to atherosclerosis in women. Additional research in HRT may offer different formulations and combinations that provide less risk to women, particularly as we learn more about genetic variability in estrogen receptors and response to therapy. As medical knowledge of genetics advances, women may be more accurately classified into risk categories. Assessment of risk in asymptomatic patients may be aided by novel risk markers and testing [129], which continue to be the subject of extensive study. Guidelines for optimal management of hyperlipidemia, hypertension and diabetes may be too stringent owing to the presence of J-shaped curves of many biological parameters. Less strict goals may reduce the risk of hypoglycemia or hypotension, and allow patients to be treated with fewer drugs and have more time to discuss lifestyle interventions with their physicians.

Executive summary

Cardiovascular disease (CVD) is the number one cause of death in women, with ethnic minorities disproportionately affected.

In the USA, more women die of CVD than men.

Globally, CVD is the number one cause of morbidity and mortality, with the heaviest burden in low- and middle-income countries.

Risk factors

Women are significantly affected by diabetes, obesity and metabolic syndrome, all of which increase the risk of CVD.

Age at onset of CVD is about 10–15 years later in women than in men age. Age 55 years and older is a risk factor for women.

Gestational diabetes mellitus, gestational hypertension and preeclampsia all increase future risk of CVD.

Polycystic ovarian syndrome causes insulin resistance, leading to several cardiovascular risk factors as well as subclinical disease.

Hypertension

Optimal blood pressure is <120/80 mmHg and is ideally achieved through lifestyle approaches.

Pharmacotherapy should be considered when blood pressure is ≥140/90 mmHg or ≥130/80 mmHg in chronic kidney disease or diabetes, although recent data suggests these criteria may be too aggressive.

Hyperlipidemia

Optimal lipid levels are low densitiy lipoprotein-cholesterol <100 mg/dl, high-density lipoprotein-cholersterol >50 mg/dl, triglycerides <150 mg/dl, and non-high-density lipoprotein-cholesterol (total cholesterol minus high-density lipoprotein-cholesterol) <130 mg/dl, ideally achieved through lifestyle interventions.

When pharmacological therapy is indicated, statins are considered first-line agents for lipid lowering, primary and secondary prevention.

Diabetes

Diabetes is an important risk factor for coronary disease in women; treatment should be centered around a goal hemoglobin A1c <7%.

Risk stratification

The 2011 American Heart Association (AHA) Guidelines for CVD Prevention in Women classifies women as: high risk, at risk or ideal cardiovascular health.

The updated sex-specific Framingham risk score and the Reynolds risk score (which includes high-sensitivity CRP and family history) are both appropriate for women, but routine screening of high-sensitivity CRP is not recommended.

Preventive strategies: nonpharmacological

A low-risk lifestyle can effectively lower the risk of CVD and is recommended in all women from an early age.

Current smoking rate for women over 18 years of age is 18%, and all women should be counseled to quit.

Physical activity should include a minimum of 150 min/week of moderate-intensity activity, 75 min/week of vigorous exercise or an equivalent combination.

The goal BMI is less than 25 kg/m² with a waist circumference less than 35 inches.

Stress and depression are risk factors for CVD and should be treated when appropriate.

Breastfeeding confers maternal cardiovascular risk protection, based on a study that demonstrated a reduction in subclinical CVD among women who had consistently breast-fed each child for more than 3 months.

Preventive strategies: pharmacological

Aspirin

– Aspirin is effective for secondary prevention of CVD, but is not effective in the primary prevention of myocardial infarction in women under age 65 years.

– Aspirin may reduce the risk of ischemic stroke in women over age 45 years, but it also increases the risk of bleeding, necessitating careful consideration of the risk:benefit ratio.

Postmenopausal HRT

Estrogen HRT should not be used for primary prevention of CVD in women.

Further research into safer formulations and timing of HRT that may have cardiovascular benefit is ongoing.

Awareness

Although women's awareness of CVD as the leading cause of death has improved, overall understanding remains low at 55%, with even lower levels of awareness of risk factors.

Access to care is an important barrier to improving women's health. Public health programs in the USA that focus on underserved women have led to notable improvements in smoking cessation, physical activity and nutrition.

Conclusion

Awareness of CVD in women is increasing, but more attention to primary prevention is required.

Comorbidities such as obesity, diabetes mellitus, hyperlipidemia and hypertension affect both genders, but several risk factors are unique to women, including polycystic ovarian syndrome, hypertensive syndromes of pregnancy and gestational diabetes.

The optimal medications and therapeutic goals in managing these chronic diseases continue to be active areas of investigation.

Aspirin and HRT are not indicated for primary prevention of coronary disease in women.

Special attention should be given to the prevention of CVD among underserved women in the USA and abroad.

Footnotes

CME Author

Charles P Vega, Associate Professor; Residency Director, Department of Family Medicine, University of California, Irvine, USA

Disclosure: Charles P Vega has disclosed no relevant financial relationships.

Authors and Disclosures

Melinda B Davis, Department of Internal Medicine, Division of Cardiology, University of Michigan Health System, Ann Arbor, Michigan.

Disclosure: Melinda B Davis has disclosed no relevant financial relationships.

Claire S Duvernoy, Chief, Cardiology Section, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan.

Director, Women's Heart Program, Associate Professor of Medicine, University of Michigan, Ann Arbor, Michigan.

Disclosure: Claire S Duvernoy has disclosed no relevant financial relationships.

Editor

Elisa Manzotti, Editorial Director, Future Science Group, London, UK.

Disclosure: Elisa Manzotti has disclosed no relevant financial relationships.

How to stay heart healthy in 2011: considerations for the primary prevention of cardiovascular disease in women

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How to Stay Heart Healthy in 2011: Considerations for the Primary Prevention of Cardiovascular Disease in Women

Abstract

Keywords

Risk factors unique to women

Gestational diabetes

Pregnancy-induced hypertension & preeclampsia

Polycystic ovarian syndrome

Major risk factors

Hypertension

Hyperlipidemia

Diabetes

Risk stratification

Preventive strategies

Nonpharmacological strategies

Cigarette smoking

Physical activity

Dietary intake

Stress & depression

Breastfeeding

Preventive drug therapies

Statins

Aspirin

Postmenopausal HRT

Omega-3 fatty acids

Vitamin D

Other supplements

Awareness

Guidelines into practice

Conclusion

Future perspective

Footnotes

How to stay heart healthy in 2011: considerations for the primary prevention of cardiovascular disease in women

References