Dietary Meat, Plasma Metabolites, and Cardiovascular Disease Risk: A Multi-Cohort Study in Sweden

BackgroundHigher meat intake has been associated with adverse health outcomes, including cardiovascular disease (CVD). However, the mechanisms by which meat consumption increases CVD risk remain unclear. We used metabolomics data from a large population-based study to identify plasma metabolites associated with self-reported meat intake and associations with cardiometabolic biomarkers, subclinical CVD markers and incident CVD. MethodsWe investigated the association between self-reported meat intake and 1272 plasma metabolites measured using ultra-high-performance liquid chromatography coupled with mass spectrometry in the SCAPIS (n=8,819; aged 50-64) cohort. Meat-associated metabolites were further analyzed in relation with subclinical CVD markers in the POEM cohort (n=502, all aged 50) and with incident CVD in the EpiHealth cohort (n=2,278; aged 45-75; 107 incident cases over 9.6 years follow-up). Meat intake was assessed through food frequency questionnaire, and categorized into white, unprocessed red, and processed red meat. We analyzed associations between meat intake and metabolites, meat-associated metabolites with cardiometabolic biomarkers, and subclinical CVD markers employing linear regression, adjusting for demographics and lifestyle factors. Cox proportional hazards analysis evaluated the associations between meat-associated metabolites and CVD incident. ResultsAfter correction for multiple testing, we identified 458, 368, and 403 metabolites associated with self-reported white, unprocessed red and processed red meat intake, respectively. Metabolites positively associated with all three meat types were related with higher plasma levels of apolipoprotein A1, C-reactive protein, and increased intima-media thickness, while metabolites negatively associated were related with higher fasting insulin levels. Processed red meat-associated metabolites were related with higher levels of fasting insulin, glycated hemoglobin, and lipoprotein(a) and were inversely related with maximal oxygen consumption. Two metabolites, 1-palmitoyl-2-linoleoyl-GPE (16:0/18:2) (HR: 1.32; 95% CI: 1.08, 1.62) and glutamine degradant (HR: 1.35; 95% CI: 1.07, 1.72), associated with higher intakes of all three meat types were also related with a higher risk of incident CVD. ConclusionThis study identified hundreds of metabolites associated with self-reported intake of different meat types. Processed red meat increasing metabolites were associated with worse glycemic measures and reduced cardiovascular function. These findings may enhance our understanding of the relationship between meat intake and CVD, providing insights into underlying mechanisms. What is New?O_LIOur study provides the most comprehensive analyses of self-reported meat intake and plasma metabolites, identifying hundreds of meat-associated metabolites using a large-scale epidemiological sample. C_LIO_LIWe uncovered novel metabolites associated with white, unprocessed, and processed red meat intake and their association with subclinical markers and incident CVD. C_LI What Are the Clinical Implications?Meat-associated metabolites and their relationships with cardiometabolic biomarkers, subclinical markers, and CVD incident may highlight metabolic responses to meat intake and their potential impact on cardiometabolic health and CVD risk.