Dietary intake of plant- and animal-derived protein and incident cardiovascular diseases: the pan-European EPIC-CVD case-cohort study

Background Epidemiological evidence suggests that a potential association between dietary protein intake and cardiovascular disease (CVD) may depend on the protein source, i.e. plant- or animal- derived, but past research was limited and inconclusive. Objective To evaluate the association of dietary plant- or animal-derived protein consumption with risk of CVD, and its components coronary heart disease (CHD) and stroke. Methods This analysis in the European Prospective Investigation into Cancer and Nutrition (EPIC)-CVD case-cohort study included 16244 incident CVD cases (10784 CHD and 6423 stroke cases) and 15141 subcohort members from seven European countries. We investigated the association of estimated dietary protein intake with CVD, CHD and stroke (total, fatal and non-fatal) using multivariable-adjusted Prentice-weighted Cox regression. We estimated isocaloric substitutions of replacing fats and carbohydrates with plant- or animal-derived protein and replacing food-specific animal protein with plant protein. Multiplicative interactions between dietary protein and pre-specified variables were tested. Results Neither plant- nor animal-derived protein intake was associated with incident CVD, CHD or stroke in adjusted analyses without or with macronutrient-specified substitution analyses. Higher plant-derived protein intake was associated with 22% lower total stroke incidence among never smokers (HR 0.78, 95%CI: 0.62, 0.99), but not among current smokers (HR 1.08, 95%CI: 0.83, 1.40, p-interaction=0.004). Moreover, higher plant-derived protein (per 3% total energy) when replacing red meat protein (HR 0.52, 95%CI: 0.31, 0.88), processed meat protein (HR 0.39, 95%CI:0.17, 0.90) and dairy protein (HR 0.54, 95%CI:0.30, 0.98) was associated with lower incidence of fatal stroke. Conclusion Plant- or animal-derived protein intake was not associated with overall CVD. However, the association of plant-derived protein consumption with lower total stroke incidence among non-smokers, and with lower incidence of fatal stroke highlights the importance of investigating CVD sub-types and potential interactions. These observations warrant further investigation in diverse populations with varying macronutrient intakes and dietary patterns.