Sex Differences in Cardiovascular Disease and Unique Pregnancy-Associated Risk Factors in Women

Abstract

Cardiovascular disease is the leading cause of mortality in women. Beyond conventional cardiovascular risk factors, women additionally face sex-specific cardiovascular disease risk factors, which include a history of adverse pregnancy outcomes. Adverse pregnancy outcomes include the hypertensive disorders of pregnancy, gestational diabetes mellitus, preterm delivery, and small-for-gestational age delivery. Here, we review sex differences in cardiovascular disease with an emphasis on pregnancy-associated risk factors and discuss implications for the prevention and treatment of cardiovascular disease in women. Adverse pregnancy outcomes, especially the hypertensive disorders of pregnancy, have been linked to diverse cardiovascular conditions, accelerated cardiovascular aging, and multimorbidity. Chronic hypertension appears to be a key mediator of accelerated cardiovascular disease risk in women with hypertensive disorders of pregnancy. Recent genetic analyses suggest a shared genetic predisposition between adverse cardiometabolic traits and development of hypertension in pregnancy. Mechanisms linking gestational diabetes, preterm delivery, small-for-gestational age delivery, and infertility to cardiovascular disease are less well understood. The mechanisms linking adverse pregnancy outcomes to future cardiovascular disease remain incompletely understood. Further research is needed to better understand this relationship and the implications of adverse pregnancy outcomes for cardiovascular disease prevention.