Background: The cardio-protective effects of flavonoids are still controversial; many studies referred to the benefits of specific foods, such as soy, cocoa, tea. A population-based cohort of middle-aged adults, coming from a semi-rural area where the consumption of those foods is almost negligible, was studied.

Aims: The primary objective was establishing if flavonoid intake was inversely associated with the cardiovascular (CV) risk evaluated after 12-year follow-up; the associations between flavonoid intake and CV incidence and mortality and all-cause mortality were also evaluated.

Methods: In 2001-2003, a cohort of 1,658 individuals completed a validated food-frequency questionnaire. Anthropometric, laboratory measurements, medical history and the vital status were collected at baseline and during 2014. The CV risk was estimated with the Framingham risk score.

Results: Individuals with the lowest tertile of flavonoid intake showed a worse metabolic pattern and less healthy lifestyle habits. The 2014 CV risk score and the increase in the risk score from baseline were significantly higher with the lowest intake of total and all subclasses of flavonoids, but isoflavones, in a multiple regression model. During follow-up, 125 CV events and 220 deaths (84 of which due to CV causes) occurred. CV non-fatal events were less frequent in individuals with higher flavonoid intake (HR = 0.64; 95%CI 0.42-1.00 and HR = 0.46; 95%CI 0.28-0.75 for the second and third tertiles, respectively) in Cox-regression models, after multiple adjustments. All subclasses of flavonoids, but flavones and isoflavones, were inversely correlated with incident CV events, with HRs ranging from 0.42 (flavan-3-ols) to 0.56 (anthocyanidins). Being in the third tertile of flavan-3-ols (HR = 0.68; 95% CI 0.48-0.96), anthocyanidins (HR = 0.66; 95% CI 0.46-0.95) and flavanones (HR = 0.59; 95% CI 0.40-0.85) was inversely associated with all-cause mortality. Total and subclasses of flavonoids were not significantly associated with the risk of CV mortality.

Conclusions: Flavonoid intake was inversely associated with CV risk, CV non-fatal events and all-cause mortality in a cohort with a low consumption of soy, tea and cocoa, which are typically viewed as the foods responsible for flavonoid-related benefits.