Metabolic syndrome and incident peripheral artery disease - the Multi-Ethnic Study of Atherosclerosis

•Among 4817 men and women in the MESA cohort, 29% had metabolic syndrome at baseline.•Metabolic syndrome was associated with higher risk of peripheral artery disease.•Metabolic syndrome conferred a 1.78-fold increased risk of peripheral artery disease.•Individual metabolic syndrome components did not predict peripheral artery disease.•Inflammation did not explain the higher risk associated with metabolic syndrome.

ObjectiveWe evaluated whether metabolic syndrome (MetS) is associated with an increased incidence of lower extremity peripheral artery disease (PAD) in community dwelling people free of clinical cardiovascular disease at baseline. We assessed whether higher levels of inflammatory biomarkers may mediate the association of MetS with incident PAD.MethodsMetS was defined at baseline as the presence of three or more of the following components: elevated waist circumference, triglycerides ≥150 mg/dL, reduced high-density lipoprotein (HDL) cholesterol, blood pressure ≥130/85 mm Hg or taking blood pressure medication, and fasting glucose ≥100 mg/dL and <126 mg/dL. People with diabetes were excluded. Incident New PAD was defined among people with a normal ankle brachial index (ABI) at baseline (i.e. baseline ABI of 0.90 to 1.40) and consisted of one of the following outcomes during 3-year follow-up: ABI decline to < 0.90 combined with a decline ≥0.15 or medical record confirmed PAD outcome. Multivariable Poisson regression was used to estimate the association between MetS and incident PAD.ResultsAmong 4817 participants without PAD at baseline, 1382 (29%) had MetS. Adjusting for age, sex, race, smoking, physical activity, low-density lipoprotein cholesterol, baseline ABI, and other confounders, 23/1382 (1.7%) people with MetS developed PAD vs. 30/3435 (0.87%) people without MetS (risk ratio = 1.78 [95% Confidence Interval (CI), 1.04 to 2.82], P = 0.031). Adjusting for C-reactive protein, fibrinogen, or interleukin-6 did not attenuate this association.ConclusionPeople free of clinical cardiovascular disease with MetS are at increased risk for PAD. Our findings suggest that this association is not mediated by inflammation.