Supplementary Table and Figure.docx

Background: Limited studies have shown a protective effect of very long chain saturated fatty acids （VLSFAs） on healthy aging, diabetes, heart failure and risk factors related to cardiovascular disease (CVD), but the role of VLSFAs on mortality risk is unclear. We aimed to investigate the association of serum docosanoic acid (C22:0) and serum lignoceric acid (C24:0) with all-cause and disease-specific mortality to confirm the effect of VLSFAs on mortality risk in the whole, hyperlipidemia and hypertensive populations. Methods: A total of 4132 individuals of the National Health and Nutrition Examination Survey (NHANES) 2015-2016 were included in this study. Among them, there were 1326 participants in the hyperlipidemia population and 1456 participants in the hypertensive population. We confirmed the mortality information with the National Death Index (NDI). Multiple model calibration was performed using COX regression analysis for known risk factors to explore the association between circulating VLSFAs and all-cause or CVD or coronary heart disease (CHD) mortality. Results: In the whole population, individuals with higher circulating C22:0 and C24:0 as a percentage of total serum fatty acids levels reduced the risk of mortality of all-cause (C22:0: HR=0.409, 95%CI=0.271-0.618; C24:0: HR=0.430, 95%CI=0.283-0.651), CVD (C22:0: HR=0.286, 95%CI=0.134-0.612; C24:0: HR=0.233, 95%CI=0.101-0.538) and CHD (C22:0: HR=0.401, 95%CI=0.187-0.913; C24:0: HR=0.263, 95%CI=0.082-0.846). And similar results to the whole population, individuals with higher circulating C22:0 and C24:0 as a percentage of total serum fatty acids levels in the hyperlipidemia and hypertensive populations were also protective for all cause, CHD and CVD mortality. Conclusion: Our results confirm the protective effect of high levels of circulating VLSFAs (C22:0 and C24:0) on all-cause, CVD and CHD cause of death in the whole, hyperlipidemia and hypertensive populations.