Abstract
OBJECTIVE: Cardiovascular disease, largely driven by atherosclerosis, remains a leading cause of global morbidity and mortality. This study aimed to investigate the associations of dietary intake of total flavonoids and their subclasses with the risk of incident atherosclerosis, post-atherosclerosis cardiovascular disease and all-cause mortality in a large prospective cohort. METHODS: The study included 207,571 adults without baseline atherosclerosis from the UK Biobank. Risk factors were investigated using a three-level stepwise-adjusted Cox proportional hazards model, alongside subgroup analyses and subclass-specific analyses. RESULTS: The prevalence of atherosclerosis showed a decreasing trend with increasing quartiles of total flavonoid intake (Q1: 0.75% vs. Q4: 0.48%, p < 0.001). In the fully adjusted model, participants in the highest quartile (Q4) of total flavonoid intake exhibited a significantly lower risk of atherosclerosis compared to those in the lowest quartile (Q1) (HR = 0.781, 95% CI: 0.634-0.961, p = 0.020). This inverse association persisted across all subgroups, particularly in the age-stratified analysis of individuals aged 55-69 years. Subclass-specific analyses revealed that the protective relationship was primarily driven by flavan-3-ols (HR = 0.660, 95% CI: 0.539-0.807, p < 0.001), anthocyanins (HR = 0.816, 95% CI: 0.685-0.971, p = 0.022), and flavonols (HR = 0.733, 95% CI: 0.608-0.884, p = 0.002). Conversely, total flavonoid intake showed no significant association with cardiovascular disease risk or all-cause mortality following atherosclerosis diagnosis. CONCLUSION: Higher consumption of foods rich in flavonoids-such as apples, berries, and tea-was associated with a lower risk of incident atherosclerosis. This inverse association was particularly pronounced among middle-aged and older adults aged 55 to 69. Therefore, incorporating more of these foods into daily diets may be a potential strategy to support cardiovascular health and reduce the burden of subsequent cardiovascular diseases.