Debra R. Judelson

Effectiveness-Based Guidelines for the Prevention of Cardiovascular Disease in Women—2011 Update: A Guideline From the American Heart Association

Substantial progress has been made in the awareness, treatment, and prevention of cardiovascular disease (CVD) in women since the first women-specific clinical recommendations for the prevention of CVD were published by the American Heart Association (AHA) in 1999.1 The myth that heart disease is a “mans disease” has been debunked; the rate of public awareness of CVD as the leading cause of death among US women has increased from 30% in 1997 to 54% in 2009.2 The age-adjusted death rate resulting from coronary heart disease (CHD) in females, which accounts for about half of all CVD deaths in women, was 95.7 per 100 000 females in 2007, a third of what it was in 1980.3,4 Approximately 50% of this decline in CHD deaths has been attributed to reducing major risk factors and the other half to treatment of CHD including secondary preventive therapies.4 Major randomized controlled clinical trials such as the Womens Health Initiative have changed the practice of CVD prevention in women over the past decade.5 The investment in combating this major public health issue for women has been significant, as have the scientific and medical achievements. Despite the gains that have been made, considerable challenges remain. In 2007, CVD still caused ≈1 death per minute among women in the United States.6 These represent 421 918 deaths, more womens lives than were claimed by cancer, chronic lower respiratory disease, Alzheimer disease, and accidents combined.6 Reversing a trend of the past 4 decades, CHD death rates in US women 35 to 54 years of age now actually appear to be increasing, likely because of the effects of the obesity epidemic.4 CVD rates in the United States are significantly higher for black females compared with their white counterparts (286.1/100 000 versus …

Guide to preventive cardiology for women

Coronary heart disease (CHD) is the single leading cause of death and a significant cause of morbidity among American women.1 Risk factors for CHD in women are well documented.2 Compelling data from epidemiological studies and randomized clinical trials show that CHD is largely preventable. Assessment and management of several risk factors for CHD are cost-effective.3 Despite these facts, there are alarming trends in the prevalence and management of risk factors in women.2 Smoking rates are declining less for women than for men. The prevalence of obesity is increasing, and ≈25% of women report no regular sustained physical activity.4 Approximately 52% of women >45 years old have elevated blood pressure, and ≈40% of women >55 years old have elevated serum cholesterol.5 The purpose of this statement is to highlight risk factor management strategies that are appropriate for women with a broad range of CHD risk. A more detailed description, including the scientific basis for these recommendations, is available in the 1997 American Heart Association scientific statement “Cardiovascular Disease in Women.”2 Recently, the Centers for Disease Control and Prevention National Ambulatory Medical Care Survey6 showed clinicians are missing opportunities to prevent CHD. In this study of 29 273 routine office visits, women were counseled less often than men about exercise, nutrition, and weight reduction. In the multicenter Heart and Estrogen/progestin Replacement Study (HERS),7 only 10% of women enrolled with documented CHD had baseline LDL-cholesterol levels below a National Cholesterol Education Program (NCEP) target of 100 mg/dL. A recent national survey showed that women were significantly less likely than men to enroll in cardiac rehabilitation after an acute …

Evidence-based guidelines for cardiovascular disease prevention in women. American Heart Association scientific statement.

Significant advances in our knowledge about interventions to prevent cardiovascular disease (CVD) have occurred since publication of the first female-specific recommendations for preventive cardiology in 1999.1 Despite research-based gains in the treatment of CVD, it remains the leading killer of women in the United States and in most developed areas of the world.2–3⇓ In the United States alone, more than one half million women die of CVD each year, exceeding the number of deaths in men and the next 7 causes of death in women combined. This translates into approximately 1 death every minute.2 Coronary heart disease (CHD) accounts for the majority of CVD deaths in women, disproportionately afflicts racial and ethnic minorities, and is a prime target for prevention.1–2⇓ Because CHD is often fatal, and because nearly two thirds of women who die suddenly have no previously recognized symptoms, it is essential to prevent CHD.2 Other forms of atherosclerotic/thrombotic CVD, such as cerebrovascular disease and peripheral arterial disease, are critically important in women. Strategies known to reduce the burden of CHD may have substantial benefits for the prevention of noncoronary atherosclerosis, although they have been studied less extensively in some of these settings. In the wake of the reports of the Women’s Health Initiative and the Heart and Estrogen/Progestin Replacement Study (HERS), which unexpectedly showed that combination hormone therapy was associated with adverse CVD effects, there is a heightened need to critically review and document strategies to prevent CVD in women.4–7⇓⇓⇓ These studies underscore the importance of evidence-based practice for chronic disease prevention. Optimal translation and implementation of science to improve preventive care should include a rigorous process of evaluation and clear communication about the quantity and quality of evidence used to support clinical recommendations. Recently, there has …

Is the Estrogen Controversy Over? Deconstructing the Women's Health Initiative Study: A Critical Evaluation of the Evidence

Abstract: The Womens Health Initiative (WHI) hormone trials have been widely interpreted as demonstrating that combined menopausal hormone therapy (HT) fails to protect against—and may increase—cardiovascular disease (CVD), stroke, and dementia in menopausal women, regardless of whether initiated early in the menopause or later. This conclusion does not agree with results of large epidemiological studies showing protection by HT and by estrogen replacement alone (ET) against CVD and dementia. One possible reason for this inconsistency is that the epidemiologic data are confounded by “healthy user bias.” Another possible explanation is that most women in the observational studies initiated ET or HT at or near the menopausal transition, at which point there is little or no arterial injury, whereas, in the WHI studies, older women, averaging approximately 12 years postmenopausal, many of whom would have had significant asymptomatic atherosclerosis, were treated. Substantial data demonstrate atheropreventive effects of estrogen before vascular damage occurs, whereas adverse effects of oral estrogen on thrombosis and inflammation may predominate once complex atheromas are present. Similarly, the excess of dementia observed in older WHI women treated with oral conjugated estrogen could be due to cerebral thromboses (multi‐infarct dementia). Given the uncertain relevance of the WHI (and other published randomized clinical trials) to initiation of HT in perimenopausal women, and its subsequent continuation for atheroprevention, new trials will be needed to resolve whether early intervention with estrogen may prevent CVD and/or dementia. The Kronos Early Estrogen Prevention Study (KEEPS), which began in mid‐2005, is a randomized, controlled multicenter trial of HT in recently menopausal women. It will examine surrogate end points as well as risk factors for atherosclerosis.

Is the WHI relevant to HRT started in the perimenopause

The Women’s Health Initiative (WHI) hormone replacement therapy (HRT) estrogen plus progestin (E+P) and estrogen-only arms are part of a large NIH-sponsored randomized controlled trial (RCT). Both arms were terminated prematurely after 5 and 8 yr, respectively. The E+P arm showed non-statistically significant increased incidences of cardiovascular events and breast cancer, whereas the E-only arm did not. Both arms showed an increased rate of thromboembolic events and stroke. Both arms showed protection against fractures and with protection against colon cancer only in the E+P arm. These results have been widely generalized as indicating a negative risk/benefit ratio for HRT in menopausal women.The WHI results are at odds with results of large epidemiological studies that showed protection against cardiovascular disease. Although the latter data are, in part, confounded by a “healthy user bias,” much of the inconsistency may be explained by the fact that women in the latter studies initiated HRT at the menopausal transition, whereas the WHI trial was conducted in older women (mean age 63.3), who were, on average, approx 12 yr postmenopausal. In addition, older trials included women on either unopposed estrogen therapy (ERT) or cyclic HRT regimens.Whatever other forces may have been at work, observational and experimental evidence supports the conclusion that estrogen’s atheropreventive effects predominate early, in the absence of vulnerable plaque to be ruptured or thrombotic episodes propagated by narrowed lumens and intravascular turbulence. On the contrary, age-related adverse effects of HRT may prevail once complex atheromas and luminal narrowing/irregularity are established. It is known that prevalence of subclinical “at-risk” atherosclerotic lesions increases in women during the first 5–10 yr after menopause. Furthermore, animal and clinical evidence supports the use of lower doses of estrogen than were employed in the WHI in older/longer postmenopausal women.Therefore, we suggest that conclusions from the WHI should be strictly limited to the WHI Writing Group’s own published interpretation that initiation of daily continuous treatment with combined oral conjugated equine estrogens (0.625 mg) and medroxyprogesterone acetate (2.5 mg) or 0.625 mg conjugated equine estrogen, alone, in older postmenopausal women is inadvisable for prevention of heart disease. Other conclusions on the use of such regimens are moot, since they are not appropriate clinical treatments. The allowance of “age creep” to generalize these conclusions to subjects not studied in adequate power by the WHI is neither scientifically correct nor appropriate for the development of clinical practice guidelines.Because of the limitations on the interpretation of the WHI, new RCTs are needed to resolve these questions. These RCTs should be designed to resolve whether estrogen treatment started during the menopausal transition is cardioprotective. Meanwhile, decisions of whether to initiate HRT for peri-menopausal women or to maintain it in women on long-term HRT started for estrogen-deficiency symptoms in the perimenopause should continue to be individualized based on consideration of all available data.