Representativeness of Peripheral Artery Disease Randomized Clinical Trials Supporting Current Guidelines.

Women, older adults, and racial/ethnic minorities are differentially affected by lower extremity peripheral artery disease (PAD), yet their representation in randomized controlled trials (RCTs) on which current PAD guidelines are based is not known. We therefore evaluated whether RCTs supporting most recent American Heart Association/American College of Cardiology lower extremity PAD guidelines proportionately represent the spectrum of demographic groups affected by PAD. All PAD-specific RCTs cited in the guidelines were included. From 409 references, 78 RCTs were included, representing 101,359 patients. Pooled proportion of women enrolled was 33% (95% confidence interval 29% to 37%) versus 57.5% in US PAD epidemiologic studies. Pooled mean age of all trial participants was 67.4 ± 0.8 years, in comparison with global estimates of PAD, in which 29.4% of the global population with PAD is >70 years old. Race/ethnicity distribution was reported in 27% of studies (21 of 78). In conclusion, in trials supporting current PAD guidelines, women and older adults patients are underrepresented, and different race and ethnic groups are underreported across the spectrum of studies. Underrepresentation of these groups differentially affected by PAD may limit the generalizability of the evidence supporting PAD guidelines.

Non-esterified fatty acids and risk of peripheral artery disease in older adults: The cardiovascular health study.

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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.