Familial factors, diet, and risk of cardiovascular disease: a cohort analysis of the UK Biobank

Background: Both diet and familial factors have a major role in the development of cardiovascular disease (CVD). However, it remains unclear whether familial predisposition to CVD modifies the association between dietary factors and CVD. Objectives: The aim was to assess whether the association between diet and CVD varies with familial predisposition to CVD. Methods: In this prospective cohort of the UK Biobank, 462,155 CVD-free participants were included in 2006-2010 and followed for CVD incidence until 2020. Food intake was measured using a short food-frequency questionnaire. Familial predisposition was measured by self-reported family history of CVD and by polygenic risk score (PRS) for CVD based on summary statistics of independent genome-wide association studies. Results: During a median follow-up of 11.2 y, 46,164 incident CVD cases were identified. A moderately higher risk of CVD was associated with more frequent processed-meat consumption. with an adjusted HR of 1.07 (95% CI: 1.03, 1.11; highest vs. lowest level). Conversely, intakes of fish, cheese, vegetables, and fruit were each associated with reduced CVD risk [HR (95% CI): 0.92 (0.89. 0.96). 0.90 (0.86. 0.94), 0.98 (0.95, 1.00), and 0.93 (0.89, 0.96), respectively]. Stratification analyses by family history of CVD and by PRS for CVD revealed an inverse association between CVD and intakes of fish and cheese, for both subgroups with and without a familial predisposition to CVD. Notably, while the association between processed-meat intake and CVD was restricted to individuals with a familial predisposition to CVD [e.g., HR: 1.11 (1.05, 1.16) and 1.03 (0.97, 1.10) for with and without a family history, respectively, P-interaction < 0.001], the risk reduction of CVD associated with vegetable and fruit intake was only noted among participants without a CVD familial predisposition [e.g., HR for fruit consumption: 1.00 (0.97, 1.03) and 0.91 (0.87, 0.95), respectively, P < 0.001]. Conclusions: Familial factors modify the association between diet and CVD, underscoring the need for personalized dietary guidelines for CVD prevention.