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