Higher Habitual Flavonoid Intake Is Associated with Lower Atherosclerotic Cardiovascular Disease Hospitalizations

Abstract

Background: Flavonoids, compounds found in plant-based foods and beverages, may ameliorate vascular damage and atherosclerosis. We therefore investigated the association between flavonoid intake and atherosclerotic cardiovascular disease (ASCVD) hospitalizations. Methods: Baseline data from 53552 participants of the Danish Diet, Cancer and Health Study without ASCVD, recruited from 1993-1997, were cross-linked with Danish nationwide registries. Associations between flavonoid intake (calculated from food frequency questionnaires using the Phenol-Explorer database) and ASCVD hospitalizations, (ischemic heart disease (IHD), ischemic stroke, or peripheral arterial disease (PAD)), were examined. Hazard ratios were obtained using restricted cubic splines based on Cox proportional hazards models. Findings: After a median [IQR] follow-up time of 21 [15-22] years, 8773 participants were admitted to hospital for ASCVD. Non-linear associations were observed, plateauing at intakes of approximately 1000 mg/day of total flavonoids. Compared to an intake of 175 mg/d, 1000 mg/d was associated with a 14% lower risk of ASCVD [HR:0·86 (0·81, 0·91)] and, more specifically, a 9% lower risk of IHD [HR:0·91 (0·85, 0·98)], a 9% lower risk of ischemic stroke [HR:0·91 (0·82, 1·01)], and a 32% lower risk of PAD [HR:0·68 (0·60, 0·78)]. This association was stronger in smokers compared to non-smokers as well as in high (>20 g/d) versus low-moderate (<20 g/d) alcohol consumers. Interpretation: If confirmed, ensuring the adequate consumption of flavonoid-rich foods, particularly in subpopulations at risk of atherosclerosis, such as smokers and high alcohol consumers, may mitigate ASCVD risk. Funding Statement: The Danish Diet, Cancer, and Health Study was funded by the Danish Cancer Society. FD is funded by The Danish Heart Foundation (Grant number 17-R115-A7443-22062) and Gangstedfonden (Grant number A35136), Denmark. NPB is funded by a National Health and Medical Research Council Early Career Fellowship (Grant number APP1159914), Australia. The salary of JMH is supported by a National Health and Medical Research Council of Australia Senior Research Fellowship, Australia (Grant number APP1116937). Declaration of Interests: The authors have no conflicts of interest to declare. Ethics Approval Statement: In Denmark, register studies do not require approval from an ethics committee. This study was approved by the Danish Data Protection Agency (Ref no 2012-58-0004 I-Suite nr: 6357, VD2018-117).