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Stroke more common first CVD event in women
ANAHEIM, Calif. — CHD is the most common first CVD event in men, but stroke is more often the first manifestation of CVD in women. The reasons for this difference, however, remain unclear, according to a presenter at the American Heart Association Scientific Sessions.
“Looking at known curves for the cumulative incidence of CVD in men and women aged 55 years and older from the Rotterdam study, women have an onset of CVD about 7 to 10 years later than men, but less well-known are the differences in first CVD manifestations,” said Kathryn M. Rexrode, MD, MPH, chief of the division of women’s health at Brigham and Women’s Hospital and associate professor of medicine at Harvard Medical School.
Sex differences in stroke rates
According to data from the Rotterdam study, the frequency of CHD, cerebrovascular disease and HF remain parallel as men age, but women clearly exhibit a different pattern, Rexrode said. Instead, at about age 73 years, the incidence of stroke begins exceeding that of CHD in women. Moreover, although it is not until age 85 years that women have the same absolute incidence rate of stroke as men, the stroke curve accelerates steeply thereafter.
Rexrode also cited information from a study of 1.9 million patients in England in which a similar pattern emerged. Across every 10-year age category from age 30 to 80 years, the percentage of CHD as the initial CVD presentation was higher in men than women, whereas the percentage of stroke as the initial CVD presentation was higher for women than men. This trend was also reflected when all ages were combined, she said.
As stroke is the fifth leading cause of death in men, the fourth leading cause of death in women and the third leading cause of death in women who are black, Hispanic or Asian/Pacific Islanders, the outcomes of stroke are concerning. Furthermore, the case fatality rate is high — about 24% at 1 month and 42% at 1 year, according to Rexrode.
In terms of stroke-related death, the percentages remain higher in women than men. In Europe, even among adults younger than 75 years, the rates of CVD death were similar between men and women, but more women than men died from stroke (11% vs. 8%), according to Rexrode.
Several disturbing trends have also emerged, she said. Data from the Greater Cincinnati/Northern Kentucky Stroke study showed a clear decrease in incidence of stroke from 1993 to 2010 in men, but in women, there was no significant trend over time.
“In fact, rates of stroke increased among women between 2005 and 2010, with absolute incidence rates exceeding that of men in 2010,” Rexrode said. “As we look at aging of the population, it becomes even more dramatic. In projections of rates from 2000 to 2050, we can see that with aging of the population, the projected number of deaths from stroke is ballooning.”
Sex differences in risk factors
Unfortunately, Rexrode said, physicians and researchers lack a conclusive explanation as to why women more commonly experience stroke as a first CVD event. However, researchers have identified some potential factors.
For instance, she highlighted data from the Rotterdam study indicating differences in atherosclerosis by location and sex. They showed that atherosclerosis is more common in the coronary arteries in men than women, at a ratio of about 8:1, but this difference was smaller in the carotid arteries, at a ratio of 3:1 for men to women.
“Clearly, there is a difference in manifestations of atherosclerosis in coronary vs. cerebrovascular distributions,” Rexrode said during her presentation. “This is a call to understand biologically what risk factors might have different effects on atherosclerosis in different vascular beds in men than women.”
The AHA/American Stroke Association guidelines for the prevention of stroke in women, published in 2014, focused on three sex-specific risk factors based on the observation of the escalating stroke risk in women, particularly in older women, as well as disease prevalence.
One point of focus is hypertension. Before age 65 years, hypertension is more common in men, but after menopause, this trend appears to shift so that after age 65 years, the prevalence of hypertension in women exceeds that of men, according to Rexrode.
“Of note and concern, though, is the fact that hypertension control for women older than 65 appears to be inferior to men,” she said. “It should also be emphasized that nonwhite women have consistently worse hypertension control rates, so there are, again, disparities in race and ethnicity.”
Although the risk for stroke conferred by hypertension is relatively similar in men, women have higher rates of hypertension as well as worse control, which magnifies the effect, Rexrode said. Moreover, she said hypertension is a stronger risk factor for stroke than CHD, and this higher prevalence of hypertension might contribute to the higher frequency of stroke in women. These data underscore the need for more hypertension control in women as well as further study on whether lower BP targets, such as those proposed in the SPRINT trial, also reduce risk in women, Rexrode said, noting that the trial had relatively low enrollment of women.
Atrial fibrillation is another area of potential discordance, according to Rexrode. The rates of AF have been escalating rapidly, especially in older patients, and the rate of ischemic stroke in patients with AF is higher in women than men. Data from 2014 have also shown a steep upward tick in total stroke hospitalizations in women with AF. The use of anticoagulation, however, appears to be higher in men than women, despite the higher risk associated with AF and stroke in women.
One point of encouragement, though, is that with changes in AF treatment guidelines and the availability of direct oral anticoagulants, there has been some decrease in stroke hospitalizations among women who undergo anticoagulation. The problem is, Rexrode said, getting women on anticoagulation.
Role of metabolomics
Another reason for the difference in stroke frequency between men and women may relate to the increasing rates of obesity and, consequently, diabetes, Rexrode said. Data have shown that the prevalence of obesity has consistently been higher in women than men during the past few decades and that the risk for stroke is higher in women with diabetes than in men with diabetes.
These differences led Rexrode and colleagues to evaluate metabolomics as a potential explanation. They measured metabolomics profiles in more than 2,300 women in the Women’s Health Initiative. The researchers identified eight metabolites that were linked to increased CHD risk, including one that was significantly linked to elevated risk for CVD, as well as subsequent increased odds for stroke, in women.
“Attention to BP control, anticoagulation in women with AF and prevention and treatment of diabetes are key to reducing stroke in women,” Rexrode said. “Further research is needed to understand the underlying vascular biologic mechanisms for differences relative to CHD and stroke incidence in men and women, and clinical trials should account for the higher relative proportion of incident stroke than CHD in women than men.” – by Melissa Foster
Reference:
Rexrode KM. VA.CVS.742. Vascular Disease as a Women's Health Concern. Presented at: American Heart Association Scientific Sessions; Nov. 11-15, 2017; Anaheim, Calif.
Disclosures: Rexrode reports no relevant financial disclosures.