Platelet hyperreactivity in women from families with premature atherosclerosis

This study was designed to determine whether sex differences in platelet function exist in families with premature atherosclerosis. Compared with men, women have a greater risk of death and recurrent events following myocardial infarction and coronary artery bypass graft surgery. The reasons for this sex discrepancy are unknown. Because blood platelets play a central role in the formation of pathologic thrombi at sites of ruptured atheromatous plaques, we postulated that sex differences in platelet function exist that may be partly responsible for the sex difference in coronary artery disease (CAD) outcomes.

We compared platelet reactivity in 400 asymptomatic men and women with family histories of premature CAD. Subjects were participants in the Johns Hopkins Sibling Study, a prospective investigation of coronary risk factors in asymptomatic, apparently healthy siblings of people with documented CAD.

The platelets from women bound more fibrinogen in response to low and high concentrations of adenosine diphosphate. This sex difference was greater in whites than in African Americans. Age did not have an impact on these findings, although platelets from women 48 to 59 years old tended to bind less fibrinogen than those younger than 48 years. Female platelets also demonstrated greater spontaneous aggregation compared with male platelets, and women had higher levels of plasma thromboxane than men did. These differences were independent of smoking, hypertension, diabetes, hypercholesterolemia, or aspirin use.

In asymptomatic individuals with family histories of premature CAD, platelets from women are more reactive than platelets from men. This observation cannot be explained by differences in cardiac risk factors.