- •Higher non-esterified fatty acids (NEFAs) were significantly associated with incident clinical peripheral artery disease (PAD) over a long-term follow-up.
- •NEFAs may have a relationship with downstream consequences of progressive atherosclerosis.
- •NEFAs may represent part of the link between oxidative stress and resulting health outcomes like PAD.
- •This is the first study to longitudinally examine the association between NEFAs and PAD.
Background and aims
Non-esterified fatty acids have been implicated in the pathogenesis of diabetes and cardiovascular disease. No longitudinal study has assessed their effects on peripheral artery disease (PAD). We determined the relationships between NEFAs and incident clinical PAD and abnormal ankle-brachial index (ABI) in a population-based cohort of older persons.
We evaluated 4575 community living participants aged >65 years who underwent measurement of circulating NEFAs in fasting specimens and ABI in 1992–1993. Participants were assessed annually for clinical PAD until 2015 and underwent repeat ABI in 1998–1999. We used Cox proportional hazards regression to model the associations between NEFAs and risk of clinical PAD and logistic regression to model the associations of NEFAs with incident abnormal ABI.
Mean age was 74.8 years, 59% were female, and 17% were Black. NEFAs were associated with higher risk of clinical PAD in unadjusted and adjusted models. The adjusted hazard ratios for incident clinical PAD were 1.51 (95%CI = 1.06–2.13, p = 0.02) across extreme tertiles, and 1.14 (95%CI = 0.99–1.31, p = 0.08) per standard deviation higher NEFA. The corresponding odds ratios for abnormal ABI were 0.95 (95%CI = 0.69–1.32, p = 0.76) across extreme tertiles, and 1.03 (95%CI = 0.89–1.20, p = 0.68) per standard deviation higher NEFA. Relationships appeared similar irrespective of sex, race, or pre-existing cardiovascular disease, but were stronger later than earlier in follow-up.
Higher serum levels of NEFAs are significantly associated with increased likelihood of clinical PAD over long-term follow-up but not with 6-year decline in ABI. NEFAs may offer a potential target for intervention against clinical PAD.
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Published online: January 29, 2023
Accepted: January 24, 2023
Received in revised form: January 7, 2023
Received: March 27, 2022
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