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The data on primary prevention of coronary heart disease (CHD) are starting to diverge for women and men—and those differences hold important implications for treatment of women, whose deaths from CHD have surpassed those of men since 1984, according to Karol E. Watson, MD, PhD, assistant professor of medicine in the division of cardiology at University of California, Los Angeles (UCLA) and co-director of the UCLA Program in Preventive Cardiology.
Preventive aspirin therapy, for example, has different cardiovascular effects for women and men.
Watson described four major areas where clinical thinking has changed about primary prevention of CHD in women: hormone therapy, risk factors, preventive medications, and lifestyle intervention. She presented a summary of the data at Internal Medicine 2007, the American College of Physicians annual meeting, held April 19–21 in San Diego.
HORMONE THERAPY
Hormone therapy in particular went through a major revolution in 2002, when results from the Women's Health Initiative (WHI) showed that combined estrogen and progestin therapy increased the risk of CHD, stroke, pulmonary embolism, and breast cancer.1 The study of 16,608 women with a mean age of 63 years was terminated 3.3 years early because the risks were deemed to outweigh the benefits, Watson says.
A more recent reanalysis of WHI explored whether the timing of the start of hormone therapy might influence its effect on cardiovascular disease in 24,317 women 50–79 years of age.2 The researchers found an increased risk for stroke in all the women, regardless of age. But overall, hormone therapy may be safe, or even beneficial, in terms of reduced CHD risk if taken in the early postmenopausal years, Watson says.
A summary of WHI estrogen-only results showed that estrogen therapy alone is neutral for heart disease.3 And the Multiple Outcomes of Raloxifene Evaluation (MORE) trial of 10,010 women, which compared 60 mg/day of the osteoporosis prevention drug raloxifene with placebo, found no adverse effect on or benefit to heart disease, but an increase in stroke risk. Women in the MORE trial who received raloxifene also had a reduced risk of invasive breast cancer and vertebral fractures.4
When one conference attendee asked Watson if she would recommend hormone therapy to diabetic patients with early atherosclerotic disease, Watson answered, "I would not make any blanket statements about hormone therapy yet. I think we need a lot more studies."
Much of the current research is looking at whether estrogen means different things to different vessels, Watson says. It may depend on age and the stage of atherosclerosis in the vessel. For example, in a younger woman with a healthy vessel, estrogen may be beneficial, but perhaps not in an older woman with a diseased vessel that has greater chances for plaque disturbance.
RISK, PREVENTION, AND INTERVENTION
Watson notes that the only group for whom cardiac events have increased is women with diabetes. Other conditions related to insulin resistance, such as elevated triglycerides, polycystic ovary syndrome, and metabolic syndrome (a cluster of symptoms including hypertension, glucose intolerance, dyslipidemia, and a large waist size) are greater risks for women compared with men.
For primary prevention, researchers have discovered that aspirin therapy affects men and women differently. The Physicians' Health Study randomized 22,071 men to 325 mg/day aspirin for 5 years and found aspirin significantly reduced the risk of myocardial infarction (MI) and CHD in men.5 The Women's Health Study low-dose aspirin trial randomized 39,876 women to 100 mg aspirin every other day or placebo for an average of 10 years.6
That trial concluded that aspirin lowered the risk of stroke without affecting the risk of MI or death from cardiovascular causes. In the subgroup of women >65 years of age, both stroke and MI were decreased significantly, Watson summarizes. However, she notes the aspirin dose studied is not a dose commonly used in practice. She also adds that "there is no question" that 81 mg/day of aspirin for secondary prevention is good for everyone, and that studies show all diabetes patients do better with aspirin.
For both men and women, research shows antioxidant vitamins do not prevent CHD and may in fact increase cardiovascular and cancer risks, Watson says. Folic acid and vitamins B6 and B12 also do not prevent CHD and show a trend toward increased events.
As for interventions, a study of popular diets such as Atkins, South Beach, Zone, Ornish, and Weight Watchers, which women turn to more than men, "tells us weight loss trumps everything, at least in the short term" in terms of reducing LDL cholesterol, increasing HDL cholesterol, and reducing insulin levels, Watson says. Adherence can lead to modest weight loss, she notes, although most of these popular diets are hard to follow, and the long-term effects of the diets are not known. Diets that lower only total fat probably will not reduce CHD. Diets that lower saturated fats and trans fats but increase monounsaturated and certain polyunsaturated fats (fish oils) decrease CHD risk, Watson says.
She points out that the American Heart Association recently updated its
prevention guidelines for women to reflect the evidence she
presented.7 The
guidelines recommend more exercise and the consumption of oily fish at least
twice a week, but do not recommend hormone replacement therapy, antioxidants,
or folic acid supplements for CHD prevention. Low-dose aspirin therapy is
recommended for women >65 years, but not for younger women. 
References
2. Rossouw JE, Prentice RL, Manson JE, et al.: Postmenopausal hormone
therapy and risk of cardiovascular disease by age and years since menopause.
JAMA 297:1465–1477, 2007.
3. Anderson GL, Limacher M, Assaf AR, et al., for the Women's Health
Initiative Steering Committee: Effects of conjugated equine estrogen in
postmenopausal women with hysterectomy: The Women's Health Initiative
randomized controlled trial. JAMA 291: 1701–1712, 2004.
4. Barrett-Connor E, Mosca L, Collins P, et al.: Effects of raloxifene
on cardiovascular events and breast cancer in postmenopausal women.
N Engl J Med 355:125–137, 2006.
5. Steering Committee of the Physicians' Health Study Research Group: Final report on the aspirin component of the ongoing Physicians' Health Study. N Engl J Med 321:129–135, 1989.[Abstract]
6. Ridker PM, Cook NR, Lee IM, et al.: A randomized trial of low-dose
aspirin in the primary prevention of cardiovascular disease in women.
N Engl J Med 352:1293–1304, 2005.
7. Mosca L, Banka CL, Benjamin CJ, et al.: Evidence-based guidelines
for cardiovascular disease prevention in women: 2007 update.
Circulation 115:1481–1501, 2007.
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