Free fatty acids and mortality among adults in the United States: a report from US National Health and Nutrition Examination Survey (NHANES)

Abstract Introduction Free fatty acids (FFAs) serve as vital energy sources in multiple body tissues and they have been associated with elevated cardiovascular disease risk and mortality. There is a scarcity of prospective studies examining the associations between specific FFAs and long-term health outcomes. Purpose To examine the correlation between different FFAs types and all-cause or cardiovascular mortality in a large, nationally representative sample of adults in the United States (US), and examine how different concentrations and types of FFAs may mediate this association. Methods This cohort study included 3719 and 3900 participants in the unsaturated fatty acids (USFAs) and saturated fatty acids (SFAs) populations, respectively, who participated in the US National Health and Nutrition Examination Survey (NHANES) from 2011-2014. Multiple model calibration was performed using univariate and multivariate cox regression analysis to explore the associations between circulating FFAs and all-cause or cardiovascular mortality. Results The UFAs (myristoleic acid (14:1 n-5), palmitoleic acid (16:1 n-7), cis-vaccenic acid (18:1 n-7), nervonic acid (24:1 n-9), eicosatrienoic acid (20:3 n-9), docosatetraenoic acid (22:4 n-6), and docosapentaenoic acid (22:5 n-6)) were associated with an elevated risk of all-cause mortality ((hazard ratio (HR) 1.02 [1.006-1.034]; P=0.004), (HR 1.001 [1.001–1.002]; P＜ 0.001), (HR 1.006 [1.003–1.009]; P＜ 0.001), (HR 1.007 [1.002–1.012]; P = 0.003), (HR 1.027 [1.009–1.046]; P= 0.003), (HR 1.024 [1.012–1.036]; P＜ 0.001) and (HR 1.019 [1.006–1.032]; P = 0.005), respectively), whereas docosahexaenoic acid (22:6 n-3) was linked to a lower risk (HR 0.998 [0.996–0.999]; P = 0.007). Among SFAs, palmitic acid 16:0 was associated with a higher all-cause risk (HR 1.00 [1.00–1.00]; P = 0.022), while tricosanoic acid (23:0) and lignoceric acid (24:0) were associated with lower risks (HR 0.975 [0.959–0.991]; P = 0.002) and (HR 0.992 [0.984–0.999]; P = 0.036). Kaplan–Meier survival curves according to FFAs quartiles shown the highest risk for all-cause mortality was observed in the group with the highest concentration, except serum 23:0. The association between FFAs concentration and cardiovascular mortality in the multivariate analysis indicated that only 22:6 n-3 (HR 0.997 [0.994-1.000]; P=0.035) had a lower risk of cardiovascular mortality in the USFAs group, while none of the SFAs was found to be associated with cardiovascular mortality. While, the relationship between 22:6 n-3, and cardiovascular mortality was characterized by neither a linear nor nonlinear association (P-linear = 0.215; P-nonlinear = 0.260). Conclusion In this cohort of US adults, the types and concentrations of FFAs exhibited significant associations with risk of all-cause mortality. Achieving optimal concentrations of specific FFAs effectively lowered this risk of all-cause mortality, but this benefit was not observed in regards to cardiovascular mortality.FFA and all-cause mortality