The relationship between serum Omega-6 fatty acids and cardiovascular disease mortality: A competing risks and multivariate Mendelian randomization analysis

Background & aims

The impact of serum Omega-6 fatty acids on cardiovascular health is debated, with evidence supporting both protective and harmful effects. To investigate the association between serum Omega-6 fatty acid and mortality from all causes and cardiovascular disease (CVD), utilizing advanced statistical methodologies including competing risk models and multivariate Mendelian randomization.

Methods

Data of 5070 participants from National Health and Nutrition Examination Survey (NHANES) in 2011–2014 wave were analyzed, with follow-up data on mortality sourced from the National Death Index. Serum Omega-6 fatty acids level was measured at baseline. Cox proportional hazards regression and competing risks models was used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) for all-cause and CVD mortality by baseline Omega-6 fatty acids level. Restricted cubic splines were used to explore the nonlinearity. Mendelian randomization to assess the causal relationships between Omega-6 levels and mortality.

Results

438 all-cause deaths and 137 CVD deaths were observed during an 83 months median follow-up. Restricted cubic spline analysis demonstrated a U-shaped correlation between baseline serum Omega-6 fatty acid levels with all-cause and CVD mortality risks. Subgroup analysis indicated that for the low-level Omega-6 fatty acid participants, the hazard ratios were 0.68 (95 % CI, 0.55–0.85) for all-cause mortality and 0.62 (95 % CI, 0.40–0.95) for CVD mortality. Conversely, for the high-level participants, the hazard ratios were 1.14 (95 % CI, 1.01–1.28) for all-cause mortality and 1.23 (95 % CI, 1.05–1.44) for CVD mortality. Both univariate and multivariate Mendelian randomization analyses confirmed a positive causal relationship between higher serum Omega-6 fatty acid levels and increased CVD mortality risk.

Conclusions

The findings suggest a U-shaped relationship between serum Omega-6 fatty acid levels and mortality risks, with elevated levels linked causally to increased CVD mortality. These results underscore the need for balanced dietary Omega-6 fatty acid intake to optimize cardiovascular health.