Total Flavonoid Intake, Plasma atherosclerosis index, and Risk of Incident ASCVD: A Prospective Cohort Study from the UK Biobank

<title>Abstract</title> <p>Background The association between flavonoid intake, plasma atherosclerosis index (AIP), and new-onset atherosclerotic cardiovascular disease (ASCVD) remains unclear; therefore, this study investigated these associations and their utility in risk stratification. Methods This prospective cohort study included 124,541 UK Biobank participants without ASCVD at baseline. AIP was calculated as log10 (triglycerides/HDL-C). Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident ASCVD. Restricted cubic spline analysis assessed the dose-response association between AIP and ASCVD. Exploratory mediation analysis was performed to evaluate AIP as a potential mediator. Results Adjusted mean AIP decreased progressively across quartiles of total flavonoid intake, from 0.103 in Q1 to 0.066 in Q4 (P for trend &lt; 0.001). AIP was strongly associated with incident ASCVD; each 1-SD increase in AIP was associated with a 19.8% higher risk of ASCVD (HR = 1.198, 95% CI: 1.164–1.233). Participants in the highest quartile of total flavonoid intake had a modestly lower risk of ASCVD than those in the lowest quartile (HR = 0.923, 95% CI: 0.853–0.998). Mediation analysis suggested a small indirect effect through AIP, with an estimated proportion mediated of 11.3%. Conclusions Higher total flavonoid intake was associated with lower AIP and a modestly lower risk of ASCVD. AIP may represent a potential but limited lipid-related pathway linking flavonoid intake to ASCVD risk.</p>