Fatty Acid Biomarkers of 15:0, 17:0 and Trans 16:1n-7 and Incident Coronary Heart Disease and Stroke: A Pooling Project of 15 Prospective Cohorts in the Fatty Acids and Outcomes Research Consortium

Introduction: Previous studies have reported inverse associations of circulating and tissue levels of pentadecanoic acid (15:0), heptadecanoic acid (17:0) and trans -palmitoleic acid ( trans 16:1n-7), which have been proposed as potential biomarkers of dairy fat intake, with risk of type-2 diabetes and certain cardiovascular outcomes. Hypothesis: We assessed the hypothesis that circulating and tissue levels of 15:0, 17:0, trans 16:1n-7 are inversely associated with risk of incident coronary heart disease (CHD) and stroke in a global consortium of prospective studies. Methods: We used data from 15 prospective cohorts in the Fatty Acids and Outcomes Research Consortium. We included adults (age≥18 years) who were free of cardiovascular diseases and had blood or adipose tissue measurements of 15:0, 17:0 or trans 16:1n-7. We used a harmonized analysis protocol with each exposure standardized to the interquintile range (IQR): difference between the 10 th and 90 th percentiles of each fatty acid to conduct new individual participant-level analyses. We harmonized covariate definitions across studies to include demographic, lifestyle and health variables, and levels of other fatty acids associated with CHD or stroke. We used inverse-variance meta-analysis to calculate the pooled relative risks (RR) and 95% confidence intervals (CI) for each outcome. We also calculated Spearman correlation coefficients between levels of each fatty acid exposure and potential dietary determinants of their levels (intakes of total, high-fat and low-fat dairy, meat from ruminant animals, fish and dietary fiber) among 6 studies with dietary data. Results and Conclusions: Among 34,187 participants, 5,790 incident CHD and 3,098 stroke cases were documented during a maximum follow-up of 23.3 years. We did not observe significant associations of any of the fatty acid biomarkers with risk of CHD or stroke. The pooled multivariate RR and 95% CI of CHD per IQR were 0.97 (0.92, 1.02) for 15:0, 0.97 (0.92, 1.02) for 17:0, 1.11 (0.97, 1.26) for trans 16:1n-7, and 0.98 (0.92, 1.04) for the sum of the fatty acids. The respective RR and 95% of stroke were 1.01 (0.93, 1.09) for 15:0, 0.91 (0.81, 1.03) for 17:0, 0.99 (0.83, 1.18) for trans 16:1n-7, and 0.93 (0.85, 1.04) for the summed fatty acids. Additionally, we did not observe significant heterogeneity by age, sex, race/ethnicity, world region, baseline hypertension status or lipid compartment. Circulating and tissue levels of 15:0, 17:0 and trans 16:1n-7 were weakly correlated with intakes of total or high-fat dairy (Spearman correlations [ r = 0.05 to 0.37]) but were not correlated with intakes of low-fat dairy, ruminant meat, fish or dietary fiber [ r = -0.08 to 0.09]. In conclusion, circulating and tissue levels of 15:0, 17:0, trans 16:1n-7 were not associated with risk of CHD or stroke. Our study suggests a limited role for these fatty acids in the etiology of cardiovascular disease.