Sex differences in cardiovascular disease risk and the role of biological aging pace

Abstract Aims This study aims to investigate the role of biological aging pace and quantify its contributions in explaining sex disparities in cardiovascular disease (CVD) risk. Methods and results A population-based study was conducted, including 371 032 participants in the UK Biobank. Two measures of biological aging pace were assessed, including phenotypic age acceleration (PhenoAgeAccel) and telomere length. The chronological age was similar between females [56.1 (8.0) years] and males [56.1 (8.2) years]. Male participants consistently had higher CVD risks than female participants, including any CVD [hazard ratio (HR), 1.66; 95% confidence interval (CI), 1.54–1.80], atrial fibrillation (HR, 1.78; 95% CI, 1.73–1.83), coronary heart disease (HR, 2.11; 95% CI, 2.05–2.18), heart failure (HR, 1.72; 95% CI, 1.65–1.80), and stroke (HR, 1.44; 95% CI, 1.38–1.51). Females had 0.71–2.90 years longer time to CVD than males. Males had a faster biological aging pace of 1.02 (95% CI, 0.99–1.06) years in PhenoAgeAccel than females, with 17.1% explained by unhealthy lifestyles, followed by prevalent chronic diseases (8.6%) and metabolic factors (6.5%). The sex disparities in PhenoAgeAccel significantly explained 65.0% of male-associated any CVD, 64.7% of atrial fibrillation, 68.2% of coronary heart disease, 64.4% of heart failure, and 60.4% of stroke, respectively. Similar findings were observed when using the telomere length for evaluating biological aging pace or controlling for sex hormones. Conclusion Our findings reveal that the biological aging pace might partially explain sex disparities in CVD risk, highlighting the importance of monitoring the biological aging pace to address the huge sex gap and promote sex-specific CVD primary prevention.