Unexplored Sex Differences in Cardiovascular Disease

Paula A. Johnson '80, MD '84, MPH '85, SPH '90
Tony RinaldoTony Rinaldo
By Madeline Drexler

Not long ago, cardiovascular disease was considered an affliction primarily of men. But the fact is that more women than men die from disorders of the heart and blood vessels. Indeed, in the United States, cardiovascular disease, or CVD, claims nearly 460,000 women every year—more than are lost to the next five causes of death combined.

There's more to this story, however. Emerging evidence shows dramatic sex differences not only in risk for CVD, but in the disease's presentation, progression, treatment response, and outcome. For example, women who suffer heart attacks are more likely than men to die from them. They are also more likely to suffer small-vessel disease that eludes traditional diagnostic tests. Perhaps most telling, complications during pregnancy and delivery, such as preeclampsia and preterm birth, are clear indicators of heart disease later in life—for both mother and child.

This evidence suggests that sex differences in CVD may hold precious clues to the underlying biology and early antecedents of the disease—clues that may lead to more effective treatments for all sufferers.

That was the vision of the seminar "Unexplored Sex Differences in Cardiovascular Disease," convened on December 3 and 4, 2008, by the Connors Center for Women's Health and Gender Biology at Brigham and Women's Hospital and Harvard Medical School, and sponsored by the Radcliffe Institute for Advanced Study.

Doctors have long noted clinical differences—whether hormonal, physical, or psychological—between male and female CVD patients, explained cardiologist Paula A. Johnson '80, MD '84, MPH '85, SPH '90, executive director of the Connors Centers. But "very little is known about the underlying differences in biology between men and women, and how those differences are influenced by the environment."

"There's vast unexplored territory to be covered by paying attention to women's reproductive health," added Janet Rich-Edwards '84, SD '95, director of developmental epidemiology at the Connors Center. "With the advent of a life-course approach, we're understanding that the real foundations of chronic disease in maturity occur at much younger ages, and that the potential for intervening and preventing is at these younger ages." Today's refined epidemiologic and diagnostic tools, she said, strengthen the likelihood of improving pregnancy outcomes. "Now we need to marshal the evidence."

To that end, the seminar's 23 invited experts—basic scientists, clinicians, and population health scholars—forged a provocative research proposal, which will be submitted for grant funding this year. The study would examine cardiovascular sex differences and risk factors beginning in utero and continuing through childhood, adolescence, pregnancy, the menopausal transition, and postmenopause.

At the Connors Center, scientists hope to establish a "family cohort" that would enable researchers to track mothers, fathers, and offspring from the point of pregnancy. A long-term study like this could help pinpoint sex differences in the development of CVD risk and suggest early interventions that might alter the trajectory of the disease in individuals.

The seminar's cross-disciplinary approach is unusual in medical research. "Radcliffe is this wonderful place—a kind of neutral place—for bringing together not only investigators across different hospitals and schools at Harvard, but also around the country," said Jill M. Goldstein AM '04, director of research for the Connors Center.

"We tend to operate in different spheres," Rich-Edwards said. "When several people talk across the types of science they do, the conversation generates ideas that would never occur when two scientists talk one-on-one."

Indeed, Paula Johnson sees Radcliffe's convening role as essential to supporting nascent but potentially groundbreaking lines of research. "Radcliffe provides the funding, the space, and the philosophy that bringing groups of people together from different disciplines can be transformational, whether in the arts or in science," she said. "We could not have done it without all three."

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