Risk factors for peripheral arterial disease incidence in persons with diabetes: The Atherosclerosis Risk in Communities (ARIC) Study

Background: Some risk factors for peripheral arterial disease (PAD) have been identified, but little information is available on PAD risk factors in individuals with diabetes. Methods: Using data from the Atherosclerosis Risk in Communities (ARIC) Study, we assessed the relation of traditional and non-traditional risk factors with the risk of PAD in 1651 participants with diabetes, but not PAD, at baseline. Incident PAD was defined as an ankle-brachial index (ABI) < 0.9 assessed at regular examinations; hospital discharge codes for PAD, amputation, or leg revascularization; or claudication assessed by annual questionnaire. Results: Over a mean of 10.3 years of follow-up, 238 persons developed incident PAD identified, yielding a PAD event rate of 13.9 per 1000 person years. Adjusted for sex, age, race, and center, the risk of developing PAD was increased 1.87-fold (95% confidence interval (95% CI): 1.36-2.57) in persons who were current smokers versus non-smokers, 2.27-fold (95% CI: 1.57-3.26) for baseline coronary heart disease (CHD) versus no baseline CHD, and 1.75-fold (95% CI: 1.18-2.60) for the highest quartile versus lowest quartile of triglycerides. We found no evidence of an association with other blood lipids or hypertension. Compared with the lowest quartiles, comparably-adjusted relative risks for the highest quartiles were 1.60 (95% CI: 1.10-2.33) for waist-to-hip ratio, 2.52 (95% CI: 1.70-3.73) for fibrinogen, 1.70 (95% CI: 1.17-2.47) for factor VIII, 1.73 (95% CI: 1.18-2.54) for von Willebrand factor, 2.15 (95% CI: 1.43-3.24) for white blood cell count, 1.81 (95% CI: 1.19-2.74) for serum creatinine, 0.55 (95% CI: 0.37-0.83) for serum albumin, and 2.73 (95% CI: 1.77-4.22) for carotid intima-media thickness. Persons who had a prior history of diabetes and were taking insulin had a relative risk of 1.97 (95% CI: 1.35-2.87) for future PAD events, compared with those with newly identified diabetes at baseline. In our final multivariable model, current smoking, prevalent CHD, elevated fibrinogen and carotid IMT, and a prior history of diabetes with insulin treatment were independently associated with greater PAD incidence. Conclusion: These markers might be useful to identify individuals with diabetes at particular risk for PAD.