(P23-041-23) Associations of Circulating Fatty Acid Profiles With Total, Cardiovascular Disease, and Cancer Mortality

Objectives: Evidence on biomarkers of circulating fatty acids (FAs) and mortality was limited and inconsistent. We aimed to evaluate associations of circulating specific FAs with total, cardiovascular disease (CVD) and cancer mortality.

Methods: A total of 117,871 participants enrolled in the UK Biobank from 2006 to 2010 were followed up until the end of 2020. Plasma concentrations of saturated (SFAs), monounsaturated (MUFAs) and polyunsaturated (PUFAs) FAs were measured by a high-throughput NMR-based metabolic biomarker profiling platform. Cox proportional hazards regression models were conducted to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality.

Results: Over a median of 11.9 years of follow-up, 7805 deaths occurred. Plasma SFAs were positively associated with risk of total mortality (P trend=0.038) while plasma PUFAs were inversely associated (P trend < 0.001). Multivariable-adjusted HRs (95% CIs) comparing extreme quartiles were 1.10 (1.00 to 1.21) for SFAs, 0.89 (0.78 to 1.02) for MUFAs, 0.71 (0.61 to 0.84) for PUFAs, 0.87 (0.76 to 1.00) for n-6 PUFAs, and 0.67 (0.62 to 0.73) for n-3 PUFAs. Circulating levels of PUFAs, linoleic acid (LA) and n-3 PUFAs were associated with lower CVD mortality. Moreover, plasma n-3 PUFAs were related to lower cancer mortality. Serum levels of C-reactive protein and triglyceride had significant mediation effects on the associations of plasma n-3 PUFAs with total and CVD mortality. Additionally, the inverse association of plasma PUFAs with CVD mortality only existed among FA desaturase rs174547 TT carriers.

Conclusions: Circulating SFAs were associated with higher total mortality, whereas PUFAs and LA were related to lower total and CVD mortality. Circulating n-3 PUFAs were associated with reduced total, CVD, and cancer mortality. Our findings emphasize the maintenance of a healthy plasma FA profile for the prevention of premature death.

Funding Sources: This research was supported by the National Natural Science Foundation of China.