Sex Differences in Age of Onset of Premature Cardiovascular Disease and Subtypes: The Coronary Artery Risk Development in Young Adults Study

Background: Historical data indicate men develop coronary heart disease (CHD) 10 years before women. However, whether this sex gap persists in a contemporary sample amid changing cardiometabolic risk profiles, and whether differences exist for other cardiovascular disease (CVD) subtypes (ie, stroke, heart failure), is not known. Methods: Data are from the CARDIA (Coronary Artery Risk Development in Young Adults) study, a prospective multicenter cohort study. US adults aged 18 to 30 years enrolled in 1985 to 1986 and were followed through August 2020. Sex differences in the cumulative incidence functions of premature CVD (onset <65 years), overall and for each subtype (CHD, heart failure, stroke), were compared using Gray’s test. Results: Among 5112 participants (54.5% female, 51.6% Black) with a mean age of 24.8 years (SD: 3.7) at enrollment and a median follow‐up of 34.1 years (interquartile range, 33.8–35.7), men had a significantly higher cumulative incidence of CVD, CHD, and heart failure ( P <0.05 for all), with no difference in stroke ( P =0.63). Men reached 5% incidence of CVD 7.0 years earlier than women (50.5 versus 57.5 years, P <0.001). CHD was the most frequent CVD subtype, and men reached 2% incidence 10.1 years earlier than women ( P <0.001). Men and women reached 2% stroke and 1% heart failure incidence at similar ages. Ten‐year CVD event rates diverged at an index age of 35. Conclusions: Men developed CVD earlier than women, with the greatest difference observed for CHD. Sex differences in CVD risk emerged at age 35, persisted through midlife, and were not attenuated by accounting for cardiovascular health.