Higher adherence to (poly)phenol-rich diet is associated with lower CVD risk in the TwinsUK cohort

Background: Previous studies have reported inverse associations between total (poly)phenol intake or specific subclasses of (poly)phenols, estimated from dietary questionnaires, and cardiovascular disease (CVD) risk. However, no studies have examined (poly)phenol-rich dietary patterns and their corresponding urinary metabolite profiles in relation to CVD risk. This study investigated the associations between a (poly)phenol-rich dietary score (PPS-D), its urinary metabolic signature (PPS-M), and longitudinal CVD risk in the TwinsUK cohort. Methods: We included 3110 participants (followed up for 11.20 ± 7.03 years) from TwinsUK who completed the EPIC-Norfolk Food Frequency Questionnaire with longitudinal data. A subset of 200 participants provided spot urine samples, in which 114 (poly)phenol metabolites were quantified using ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) to objectively measure (poly)phenol exposure. Associations between the PPS-D or PPS-M and CVD risk scores (ASCVD risk score and HeartScore), and biomarkers of CVD risk (blood pressure and lipid profile) were assessed using linear mixed models, adjusting for covariates and multiple testing (FDR < 0.05). Results: PPS-D was negatively associated with ASCVD risk score (stdBeta: − 0.05 (− 0.07, − 0.04)) and Heartscore (stdBeta: − 0.03 (− 0.04, − 0.01)) (FDR-adjusted p < 0.01) in the overall population (n = 3,110). In the subgroup with urinary metabolites (n = 200), such significant associations were partially replicated through metabolites of flavonoids, phenolic acids, and tyrosols that significantly negatively associated with the ASCVD risk score, HeartScore, diastolic blood pressure (DBP), and positively with high-density lipoprotein cholesterol (HDL-C). In addition, a higher PPS-M was correlated with elevated HDL-C and lower blood pressure, ASCVD risk score, and HeartScore. Conclusions: Higher adherence to a (poly)phenol-rich diet is associated with lower CVD risk, with consistent associations observed through urinary metabolite profiles, highlighting the long-term cardiovascular benefits of (poly)phenol consumption, particularly flavonoids and phenolic acids.