Association between healthy plant-based diet-lifestyle (hPDI-Lifestyle) score and incidence of coronary heart disease, and effect modification by genetic predisposition: a prospective analysis in a population-based cohort

Background: Healthy plant-based diet has been shown to benefit cardiovascular health and prevent coronary heart disease (CHD). However, association in combination with other ideal health behaviours on CHD prevention has been understudied. Furthermore, limited attention has been given to potential interactions with genetic CHD predisposition, which may add personalized health behaviour recommendations. We evaluated the association between healthy lifestyle and CHD incidence and investigated potential effect modification with genetically determined CHD risk. Methods: We analysed 7764 participants (mean age 63, 60.1% women) from the population-based Rotterdam Study. The degree of adherence to the healthy lifestyle was quantified by a healthy plant-based diet-lifestyle (hPDI-Lifestyle) score. Multivariable Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95%-confidence intervals (CIs) for CHD according to the hPDI-Lifestyle score, stratified by polygenic risk score of coronary artery disease. Findings: We documented 918 CHD cases during 116,324 person-years of follow-up. Ideal adherence to the hPDI-Lifestyle was associated with a 20% lower CHD risk among participants at low genetic risk (HR 0.80, 95% CI 0.71-0.90), and a 44% lower CHD risk among those at high genetic risk (HR 0.56, 95% CI 0.49-0.64) compared with participants at high genetic risk but with poor adherence to the hPDI-Lifestyle (p for interaction <0.001). Interpretation: Our findings support recommendations to adopt a healthful plant-based diet in combination with lifestyle (non-smoking, adequate physical activity and moderate sleep duration) for personalized CHD prevention. Potential differences by genetic predisposition of lifestyle on CHD prevention warrants further investigations. Funding: This work was supported by the Erasmus Medical Centre and Erasmus University, Rotterdam, Netherlands.