Although long considered a disease of elderly men, cardiovascular disease is increasingly recognized for its impact on women. In fact, it is now the leading cause of death in women worldwide, and in the United States more women than men die of it.1
Given this epidemic of cardiovascular disease in women, more research is now being dedicated to identifying sex-specific aspects of cardiovascular disease, the better to prevent and treat it.
This review will focus on the most recent information about how prevention, symptoms, and underlying cardiovascular conditions differ in women.
PRIMARY PREVENTION: ONGOING DEBATE
Women who diet, exercise, and abstain from smoking have an 80% lower rate of cardiovascular events than the female population overall.2 However, beyond lifestyle modification and blood pressure control, there is ongoing debate as to the efficacy of our available therapies for preventing cardiovascular disease in women.
Aspirin for primary prevention in women: No benefit?
The use of aspirin to prevent cardiovascular disease in women has long been controversial. Several trials showed a lower rate of myocardial infarction in people using aspirin for primary prevention, but most of the patients in the initial trials were men (Table 1).3
The Women’s Health Study4 assigned 39,876 women age 45 and older to receive either aspirin (100 mg on alternate days) or placebo, and monitored them for more than 10 years for major cardiovascular events (non-fatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes).
The results, published in 2005, showed that the rates of myocardial infarction and cardiovascular death were not significantly lower in the aspirin group, although the rate of ischemic stroke was 24% lower. There were more hemorrhagic strokes in the aspirin group (not statistically significant), and there was significantly more gastrointestinal bleeding. The study showed the relative risk (RR) and 95% confidence interval (CI) for several outcomes in aspirin users were:
- Myocardial infarction—RR 1.02, 95% CI 0.84–1.25, P = .83
- Cardiovascular death—RR 0.95, 95% CI 0.74–1.22, P = .68
- Ischemic stroke—RR 0.76, 95% CI 0.63–0.93, P = .009
- Hemorrhagic stroke—RR 1.24, 95% CI 0.82–1.87, P = .31
- Gastrointestinal bleeding—RR 1.4, 95% CI 1.07–1.83, P = .02.
A later analysis indicated that noncompliance had no effect on these results.5
However, a subgroup analysis of women over age 65 found a significant reduction in the rate of myocardial infarction and in the composite end point of myocardial infarction, stroke, and cardiovascular death, although there was a trend toward a higher rate of gastrointestinal bleeding. The numbers in aspirin users in the subgroup over age 65 were as follows:
- Myocardial infarction—RR 0.66, 95% CI 0.44–0.97, P = .04
- Composite end point—RR 0.74, 95% CI 0.59–0.92, P = .008.
Aspirin was taken every other day and at a higher dose than the 81 mg recommended in the United States, although it is unclear how these differences may have affected the results.
United States Preventive Services Task Force (USPSTF) recommendations. Although the USPSTF currently recommends aspirin for men age 45 to 79 to prevent myocardial infarction, it offers no such recommendation for women, largely because of the results of the Women’s Health Initiative study. However, it does recommend aspirin to prevent ischemic stroke in women age 55 to 79.3 Additionally, aspirin can be considered for prevention of myocardial infarction in women who are over age 65 or at high risk.6
This is based on Women’s Health Study data for women over age 65 showing a number needed to treat of 47 to prevent 1 cardiovascular event, whereas the number needed to harm, defined by a major hemorrhagic event, was 128. In contrast, in women younger than age 65, the number needed to treat was 2,001 and the number needed to harm was 196.4
High-risk features, as defined by the guidelines, are a history of coronary artery disease, cerebrovascular disease, peripheral arterial disease, abdominal aortic aneurysm, diabetes, or chronic kidney disease, or a 10-year predicted risk of cardiovascular disease of more than 10%.
Jardine et al7 reported that aspirin was beneficial in patients with chronic kidney disease. The rates of cardiovascular death, death from any cause, and stroke were significantly lower in patients with a glomerular filtration rate (GFR) less than 45 mL/min if they received aspirin. The rates were also lower in aspirin recipients with a GFR between 46 and 60 mL/min, but the difference was not statistically significant.
Comments. Given the risk of significant gastrointestinal bleeding and a trend toward hemorrhagic stroke with aspirin use,4 it is important to weigh the risks and benefits of aspirin for primary prevention in women.
Our understanding of the reasons for sex differences in the clinical benefits of aspirin for primary prevention is limited at this point. Studies have shown a higher prevalence of platelet reactivity and aspirin resistance in women than in men, suggesting that hormonal differences may play a role.8 There has been mention of using higher doses of aspirin in women to achieve the same level of platelet inhibition as in men. However, studies have shown essentially equal platelet inhibition in both men and women after aspirin administration.9 Therefore, more work needs to be done to better understand the observed sex differences in response to aspirin.