ObjectivesA low-saturated fat diet has been suggested to reduce serum cholesterol and thereby presumably lower the risk of atherosclerotic cardiovascular disease (CVD). We compared associations of a low-saturated fat diet vs a plant-centered diet with lower serum low-density lipoprotein cholesterol (LDL-C) concentration and risk of incident CVD, coronary heart disease (CHD), and stroke. MethodsWe followed 4,887 Black and White men and women in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort, ages 18–30 years and free of CVD at baseline from 1985–86 (exam year 0) to 2018 (year 32). The A Priori Diet Quality Score (APDQS), a measure of plant-centered diet quality, was assessed in an interviewer-administered diet history at years 0, 7, and 20. Higher APDQS implies higher intake of nutritionally-rich plant foods with less high-fat meats and unhealthy plant foods. Low-saturated fat diet was judged by lower the Keys score, based on saturated fat, polyunsaturated fat, and dietary cholesterol intake. Linear and proportional hazards regression models were used, the latter with time-varying average APDQS and CVD outcomes, both adjusted for age, sex, race, education, energy intake, physical activity, smoking, and parental history of CVD (CVD outcome only). ResultsHigher APDQS had higher dietary fiber and lower total and saturated fat. Keys score and APDQS 7-year changes correlated similarly with lower concurrent LDL-C change. During the 32 year follow-up, we documented 280,135, and 92 incident cases of CVD, CHD, and stroke, respectively. LDL-C predicted CVD and CHD, but not stroke. APDQS, but not Keys score, was associated with a lower risk of each CVD outcome. Multivariable-adjusted HRs per 1-SD increment for the APDQS were 0.81 (95% CI: 0.68 – 0.96) for CVD, 0.78 (95% CI: 0.61 – 1.00) for CHD, and 0.71 (95% CI: 0.52 – 0.98) for stroke. The primary results for APDQS and for LDL-C were not substantially altered in mutually adjusted models. ConclusionsBoth a plant-centered and a low-saturated fat diet were associated with lower LDL-C. A plant-centered diet and LDL-C, but not a low-saturated fat diet, were associated with long-term CVD risk. Our findings imply that dietary strategies aimed solely to lower saturated fat may be less effective in reducing CVD burden than recommendations for a plant-centered diet. Funding SourcesHFHL, MnDRIVE, NHLBI.