Risk curves split by age 35 years, driven by earlier coronary disease in men, long-term data shows.
Cardiovascular disease strikes men years earlier than women, with the risk gap opening by the mid-30s and persisting through midlife, according to a large prospective cohort study that followed young adults for more than three decades.
The findings came from the Coronary Artery Risk Development in Young Adults – a large US study that has tracked cardiovascular health and outcomes since the mid-1980s.
In an analysis published in the Journal of the American Heart Association, researchers reported that men developed cardiovascular disease (CVD) substantially earlier than women, a pattern driven almost entirely by earlier onset of coronary heart disease (CHD) and largely unchanged by contemporary shifts in cardiometabolic risk factors.
“These findings highlight that established sex differences in CVD risk in a contemporary cohort are largely due to earlier onset of CHD, which may inform the need for strategies to address atherosclerosis more intensively in men,” they wrote.
“Further, these data demonstrate that the fourth decade of life is a critical life period where CVD rates begin to diverge between men and women and may warrant more intensive screening and detection of subclinical CVD to guide intensification of preventive measures.”
The study followed 5112 adults who were aged 18 to 30 years when recruited in 1985–1986 and who were free of cardiovascular disease at baseline. Participants self-reported gender (male, female) at study enrolment. The breakdown was 2785 female participants and 2327 males.
Participants were observed for a median of 34.1 years, with near-complete follow-up for vital status and adjudicated cardiovascular outcomes through to August 2020.
Over this period, 387 cardiovascular events occurred, including myocardial infarction, stroke, heart failure and coronary revascularisation procedures.
Men experienced a significantly higher cumulative incidence of overall cardiovascular disease than women and reached a 5% incidence threshold an average of seven years earlier, at 50.5 years compared with 57.5 years in women.
The sex gap was even more pronounced for coronary heart disease, the most common cardiovascular subtype, with men reaching a 2% cumulative incidence more than 10 years earlier than women.
By age 50 years, coronary heart disease incidence in men was nearly three times that observed in women.
In contrast, stroke incidence did not differ between sexes, with men and women reaching comparable cumulative incidence at similar ages.
Heart failure showed a more modest sex difference, with similar onset through early midlife and divergence only at older ages, suggesting that premature cardiovascular disease disparities were not uniform across subtypes.
To better characterise when risk trajectories begin to separate, researchers examined rolling 10-year cardiovascular event rates across adulthood.
This showed that absolute and relative differences between men and women first became statistically apparent at an index age of 35 years and persisted through middle age.
Among participants free of cardiovascular disease at age 50, the 10-year event rate was 6.0% for men compared with 3.3% for women, highlighting a sustained excess burden in men well before traditional “high-risk” ages.
Importantly, the observed sex differences were not meaningfully explained by differences in cardiovascular health behaviours or clinical risk factors.
Adjustment for measures of blood pressure, lipids, body mass index, smoking, diet and physical activity only modestly attenuated the excess risk in men.
Systolic blood pressure accounted for the largest reduction, yet overall cardiovascular health scores explained less than 3% of the male–female difference, suggesting that traditional risk factors do not fully capture the mechanisms underlying earlier disease onset in men.
The authors said their findings challenged assumptions that changing patterns of obesity, diabetes and smoking have narrowed sex-based gaps in cardiovascular disease.
They also said that young adulthood was identified as a critical but underutilised window for prevention, particularly for men, who were less likely than women to engage with preventive health care in early adult life.
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The researchers noted the study’s strengths, including a large, prospective biracial cohort with rigorously adjudicated cardiovascular events and standardised, repeatedly measured cardiovascular health data.
Key limitations were the young age of participants and focus on premature CVD, which led to low event numbers and prevented detailed or separate analyses of fatal and nonfatal and specific CVD subtypes.
The study also could not assess whether sex differences persisted into older age, particularly after menopause. Sleep was not included because it was measured only in later exams. Residual confounding was possible, and findings may not generalise beyond black and white populations.
“The limited attenuation of sex differences after adjustment for cardiovascular health suggests a broader need to understand onset of premature CVD in men and the need to initiate risk assessment, subclinical CVD detection, and risk reduction strategies in the critical young adult life period,” the researchers concluded.
