Association of plasma fatty acid profile with trajectory of multimorbidity and mortality: A community-based longitudinal study

Abstract Background Plasma fatty acids have been linked to various chronic diseases and mortality, but the extent to which fatty acids are associated with the trajectory of multimorbidity remains unclear. We investigated the association of fatty acid profile with multimorbidity trajectories and event-free survival. Methods Within the UK Biobank, 138,685 chronic disease-free participants were followed for up to 16 years. 17 plasma fatty acids were measured by nuclear magnetic resonance. A comprehensive healthy fatty acid score (HFAS) was constructed using LASSO regression. Incidence of chronic diseases and death were ascertained through linkages to medical and death records. Event-free survival was defined as survival without chronic diseases or death. Data were analyzed using a linear mixed-effects model, Cox regression, and Laplace regression. Results High HFAS was associated with lower risk of chronic diseases/death (hazard ratio [HR]: 0.907, 95% confidence interval [CI]: 0.888-0.925) and prolonged event-free survival time by 0.636 (95% CI: 0.500-0.774) years compared to low HFAS. High HFAS was also associated with a slower accumulation trajectory of multimorbidity (β: -0.042, 95% CI: -0.045 to -0.038). There was a significant multiplicative interaction between moderate-to-high HFAS and healthy lifestyle on chronic disease/death (P for interaction = 0.002) and multimorbidity accumulation trajectories (P for interaction<0.001). Conclusions A healthier plasma fatty acid metabolic profile is associated with a slower accumulation of multimorbidity and prolonged event-free survival time. A healthy lifestyle may strengthen the protective association of HFAS with the risk of chronic diseases/death and the accumulation trajectory of multimorbidity.