Metabolic health, obesity and 9-year incidence of peripheral arterial disease: The D.E.S.I.R. study

Objective: To determine which metabolic and cardiovascular risk factors are associated with the change in ankle brachial pressure index and incident peripheral arterial disease over 9 years, and whether these associations differ between healthy weight and overweight & obese individuals. Methods: Metabolic factors, change in ankle brachial pressure index and incidence of peripheral arterial disease (ankle brachial pressure index <0.90) over 9-years were determined in 2139 healthy weight and 1453 overweight & obese participants from the D.E.S.I.R. study. Results: Fasting glucose, insulin, HDL-cholesterol, systolic blood pressure and pulse pressure were all directly associated with the incidence of peripheral arterial disease, however BMI and the metabolic syndrome were not. There was some evidence that the associations of fasting insulin (P_{heterogeneity}=0.06), insulin resistance (P_{heterogeneity}=0.08) and β-cell function (P_{heterogeneity}=0.004) with change in ankle brachial pressure index, differed between healthy weight and overweight & obese subjects. Principal components analysis identified a classical metabolic syndrome cluster, and an alternative clustering of metabolic factors that was characterised by high pulse pressure, high HDL-cholesterol and low triglycerides. This alternative cluster of cardiovascular and metabolic risk factors was associated with reductions in ankle brachial pressure index and an increased incidence of peripheral arterial disease (both P<0.0001). Conclusions: Overweight & obesity do not increase the risk of developing peripheral arterial disease. We identified an alternative cluster of metabolic factors that is strongly associated with reductions in ankle brachial pressure index and an increased incidence of peripheral arterial disease.