Abstract Body: Background Evidence from observational studies and randomized trials suggest a favorable role of omega-3 fatty acids on cardiovascular outcomes. However, whether omega-3 fatty acids may reduce the incidence of peripheral artery disease (PAD) is not known.
Aims We prospectively evaluated blood and adipose tissue levels of alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), and the sum of EPA and DHA, with respect to incident PAD.
Methods We included 11 prospective studies from a global consortium up to May 2023 with measurements of ALA, EPA, DPA, or DHA (as a % of total fatty acids) in blood or adipose tissue among adults (age≥18), who were free of coronary artery disease, stroke, and PAD at baseline, and assessed incident PAD events. Each cohort conducted de novo individual-level analyses with a prespecified analytical plan and harmonized definitions for exposures, outcomes, covariates (including demographics, cardiovascular risk factors, medication use, and omega-6 fatty acid levels), and subgroups. Pooled hazard ratios (HRs) were calculated using inverse-variance weighted meta-analysis.
Results Among 142,316 participants from North America, Europe, and Australia followed for a weighted median of 13.7 years (range of median follow-up: 9.8 to 26.2 years), 1,842 incident cases of PAD were ascertained. In multivariable-adjusted pooled analysis, very long-chain EPA, DPA, DHA, and EPA+DHA each associated with lower PAD incidence, with HRs (95% CI) per interquintile range of 0.79 (0.69, 0.91), 0.80 (0.68, 0.95), 0.74 (0.64, 0.85), and 0.79 (0.69, 0.90), respectively (P<0.01 for each) (Figure 1). Long-chain ALA was not associated with PAD, 1.14 (0.98, 1.33). Heterogeneity between studies was low to moderate (I^2\ ranging from 0% to 57%). Results were broadly consistent in prespecified subgroups by age, sex, smoking status, prevalent diabetes, and biomarker lipid fraction.
Conclusion In this large international consortium, objective levels of very long-chain, but not long-chain, omega-3 fatty acids inversely associated with incident PAD. Our data suggest a protective role for very long-chain omega-3 fatty acids in the development of PAD, supporting the need for further mechanistic studies and appropriately powered randomized controlled trials.