Association between cardiovascular health factors, carotid intima-media thickness and cardiovascular outcomes in primary prevention population for cardiovascular disease

Background: This large-scale study aims to comprehensively examine associations between cardiovascular health (CVH), arterial injury and clinical cardiovascular disease (CVD) events in primary prevention populations, and quantify the potential mediating role of carotid intima-media thickness (cIMT) in Asia population. Methods: A total of 358,650 adults aged 35-75 years without baseline CVD were included from a national cohort in China. CVH factors were assessed via Life's Simple 7 (LS7) metrics. Multilevel regression models were employed to identify cIMT risk factors. Time-to-event analyses for new onset CVD outcomes were conducted using frailty models. Mediation analysis was performed to quantify the proportion of the association between CVH and CVD events mediated through cIMT. Results: Participants in the highest LS7 quartile had a 0.014 mm lower mean-max cIMT and a 12 % lower risk (OR: 0.88, 95 % CI: 0.86-0.90) of elevated cIMT compared to those in the lowest quartile. Each 0.1 mm higher in mean-max cIMT was associated with a 6 % increased risk of CVD (HR: 1.06, 95 % CI: 1.06-1.07). Mediation analysis demonstrated that cIMT mediated a significant but modest portion of the overall CVH-CVD relationship, accounting for 3.64 % (95 % CI: 2.76 %-4.80 %) of the effect. This mediation effect showed notable heterogeneity, being substantially stronger for factors directly affecting arterial structure and in male participants. Conclusions: cIMT serves as a partial mediator in the relationship between CVH and incident CVD. Sex-specific and risk-stratified findings highlight cIMT's potential for personalized CVD prevention.