Omega‐6 Polyunsaturated Fatty Acids and Peripheral Artery Disease: An Individual Participant‐Level Analysis of 9 International Prospective Studies

Background Omega‐6 polyunsaturated fatty acids (PUFAs) have previously been associated with several peripheral artery disease (PAD) risk factors. We studied the association between individual omega‐6 PUFAs and incident PAD in a multicohort analysis. Methods This study was conducted among participants from 9 cohorts (N=137 704; PAD cases=2014) in the FORCE (Fatty Acids and Outcomes Research Consortium) who were free of clinical PAD at baseline. Omega‐6 PUFAs were measured at baseline and with a median follow‐up of 14 years. Cox proportional hazards regression analyses were conducted in individual cohorts to evaluate associations of omega‐6 PUFAs (continuous cohort‐standardized interquintile ranges [difference between the medians of the 10th and 90th omega‐6 PUFAs percentiles] and cohort‐specific quintiles) with incident clinical PAD adjusting for prespecified covariates. Inverse‐variance weighted meta‐analysis was used to calculate the combined hazard ratios (HRs) and 95% CIs. Results Linoleic acid (LA) was measured in all 9 cohorts, arachidonic acid in 8 (N=33 541; PAD cases=1766), dihomo‐γ‐LA and γ‐LA in 7 (N=29 861; PAD cases=1686), and eicosadienoic acid in 6 (N=27 538; PAD cases=1435). Only LA was associated with a lower risk of incident PAD (quintile 5 versus quintile 1: HR, 0.75 [95% CI, 0.64–0.89]; P =0.0009). Results did not differ in a statistically significant manner by age, sex, diabetes status, or smoking status. Conclusions Results suggest that the omega‐6 PUFA LA may be protective against PAD, and other omega‐6 PUFAs are not associated with PAD incidence. This is further evidence that omega‐6 PUFA—disease relationships should be evaluated by individual fatty acids rather than grouped as total omega‐6 PUFAs.