Omega‐6 Polyunsaturated Fatty Acids and Peripheral Artery Disease: An Individual Participant‐Level Analysis of 9 International Prospective Studies
13 affiliations
- 1University of Minnesota
- 2University of Southern California Keck School of Medicine
- 3University of Illinois
- 4Fatty Acid Research Institute
- 5University of Eastern Finland
- 6University of Washington
- 7Tufts University
- 8Tufts Medical Center
- 9The New York Academy of Medicine
- 10University of Cambridge, Cambridge Biomedical Campus
- 11Karolinska Institutet
- 12University of South Dakota
- 13University of Texas Southwestern Medical Center
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.
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BibTeX
@article{nomura2026omega6,
title = {{Omega‐6 Polyunsaturated Fatty Acids and Peripheral Artery Disease: An Individual Participant‐Level Analysis of 9 International Prospective Studies}},
author = {Sarah O. Nomura and Natalie L. Weir and Weihua Guan and Amy B. Karger and Parveen K. Garg and Lina Thiel and Nathan Tintle and Jyrki K. Virtanen and Rozenn N. Lemaitre and Brenton Swenson and Bruce M. Psaty and Dariush Mozaffarian and David Siscovick and Fumiaki Imamura and Karin Leander and Federica Laguzz and William S. Harris and Nita G. Forouhi and Nicholas J. Wareham and Jing Cao and James S. Pankow and Michael Y. Tsai and the Fatty Acids and Outcomes Research Consortium (FORCE)},
journal = {Journal of the American Heart Association},
year = {2026},
month = oct,
doi = {10.1161/jaha.126.049223},
url = {https://www.ahajournals.org/doi/10.1161/JAHA.126.049223},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Omega‐6 Polyunsaturated Fatty Acids and Peripheral Artery Disease: An Individual Participant‐Level Analysis of 9 International Prospective Studies
AU - Sarah O. Nomura
AU - Natalie L. Weir
AU - Weihua Guan
AU - Amy B. Karger
AU - Parveen K. Garg
AU - Lina Thiel
AU - Nathan Tintle
AU - Jyrki K. Virtanen
AU - Rozenn N. Lemaitre
AU - Brenton Swenson
AU - Bruce M. Psaty
AU - Dariush Mozaffarian
AU - David Siscovick
AU - Fumiaki Imamura
AU - Karin Leander
AU - Federica Laguzz
AU - William S. Harris
AU - Nita G. Forouhi
AU - Nicholas J. Wareham
AU - Jing Cao
AU - James S. Pankow
AU - Michael Y. Tsai
AU - the Fatty Acids and Outcomes Research Consortium (FORCE)
PY - 2026
DA - 2026/10/20
JO - Journal of the American Heart Association
DO - 10.1161/jaha.126.049223
UR - https://www.ahajournals.org/doi/10.1161/JAHA.126.049223
AB - 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.
SN - 2047-9980
ER -