Dietary plant-to-animal protein ratio and risk of cardiovascular disease in 3 prospective cohorts

Dietary guidelines recommend substituting animal protein with plant protein, however, the ideal ratio of plant-to-animal protein (P:A) remains unknown. We aimed to evaluate associations between the P:A ratio and incident cardiovascular disease (CVD), coronary artery disease (CAD), and stroke in 3 cohorts. Multivariable-adjusted Cox proportional hazard models were used to estimate hazard ratios (HRs) for CVD outcomes among 70,918 females in the Nurses’ Health Study (NHS) (1984–2016), 89,205 females in the NHSII (1991–2017) and 42,740 males from the Health Professionals Follow-up Study (1986–2016). The P:A ratio was based on percent energy from plant and animal protein and assessed using food frequency questionnaires every 4 y. During 30 y of follow-up, 16,118 incident CVD cases occurred. In the pooled multivariable-adjusted models, participants had a lower risk of total CVD [HR: 0.81; 95% confidence interval (CI): 0.76, 0.87; P trend < 0.001], CAD (HR: 0.73; 95% CI: 0.67, 0.79; P trend < 0.001), but not stroke (HR: 0.98; 95% CI: 0.88, 1.09; P trend = 0.71), when comparing highest to lowest deciles of the P:A ratio (ratio: ∼0.76 compared with ∼0.24). Dose–response analyses showed evidence of linear and nonlinear relationships for CVD and CAD, with more marked risk reductions early in the dose-response curve. Lower risk of CVD (HR: 0.72; 95% CI: 0.64, 0.82) and CAD (HR: 0.64; 95% CI: 0.55, 0.75) were also observed with higher ratios and protein density (20.8% energy) combined. Substitution analyses indicated that replacing red and processed meat with several plant protein sources showed the greatest cardiovascular benefit. In cohort studies of United States adults, a higher plant-to-animal protein ratio is associated with lower risks of CVD and CAD, but not stroke. Furthermore, a higher ratio combined with higher protein density showed the most cardiovascular benefit.