Abstract
Background: Biomarker levels of very long-chain saturated fatty acids (VLCSFAs) have been found to be favorably associated with cardiovascular risk factors including lower risk of diabetes and reduced triglycerides. Few studies have examined the association between VLCSFAs and coronary heart disease (CHD). Aims: To assess the association of circulating arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0) with incident total, fatal, and nonfatal CHD. Methods: We used data from the Fatty Acids and Outcomes Research Consortium consisting of 15 prospective cohorts worldwide which included adults (age≥18 years) who were free of cardiovascular disease and had blood measurements of 20:0, 22:0, and 24:0 at baseline. A study protocol with standardized definitions of exposures, disease outcomes, and covariates was developed, for which each cohort conducted individual participant-level analysis. Cohort-specific associations were pooled using inverse variance-weighted meta-analysis to calculate the overall relative risk (RR) per interquintile range (difference between the 90 th and 10 th percentiles) and 95% confidence interval (CI). Results: Among 33,083 participants, 6,165 cases of total CHD were ascertained. The overall pooled RR and 95% CI were 0.96 (0.89, 1.02) for 20:0, 1.01 (0.92, 1.11) for 22:0, 0.94 (0.86, 1.02) for 24:0, and 0.96 (0.89, 1.04) for 20:0 + 22:0 + 24:0 ( Figure 1 ). However, we noted heterogeneity by lipid compartments, with significant inverse associations for higher 22:0 [0.77 (0.62, 0.96)], 24:0 [0.61 (0.49, 0.77)], and 20:0 + 22:0 + 24:0 [0.73 (0.60, 0.89)] in the total plasma/serum compartment but not in the phospholipid compartment. Similar associations were observed for fatal and nonfatal CHD and when using a random-effects model. Conclusion: Higher circulating VLCSFAs were not associated with total CHD in a global consortium of prospective studies. The finding of an inverse association with total CHD for VLCSFAs in the total plasma/serum compartment warrants further research.
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