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HbA_1c and Peripheral Arterial Disease in Diabetes

The Atherosclerosis Risk in Communities study

¹ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
² Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, Maryland
³ Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota
⁴ Department of Laboratory Medicine and Pathology, Medical School, University of Minnesota, Minneapolis, Minnesota

Address correspondence and reprint requests to Elizabeth Selvin, PhD, MPH, Department of Epidemiologythe Welch Center for Prevention, EpidemiologyClinical Research, Johns Hopkins Bloomberg School of Public Health, 2024 E. Monument St., Suite 2-600, Baltimore, MD 21205-2223. E-mail: lselvin{at}jhsph.edu

OBJECTIVE—To assess the relation between HbA_1c (A1C) and incident peripheral arterial disease (PAD) in a community-based cohort of diabetic adults from the Atherosclerosis Risk in Communities (ARIC) study. A second aim was to investigate whether the association was stronger for severe, symptomatic disease compared with PAD assessed by low ankle-brachial index (ABI).

RESEARCH DESIGN AND METHODS—This was a prospective cohort study of 1,894 individuals with diabetes using ARIC visit 2 as baseline (1990–1992) with follow-up for incident PAD through 2002. We assessed the relation between A1C and incident PAD, defined by intermittent claudication, PAD-related hospitalization, or a low ABI (<0.9).

RESULTS—During a mean follow-up of 9.8 years, the crude incidence rates were 2.1 per 1,000 person-years for intermittent claudication (n = 41), 2.9 per 1,000 person-years for PAD-related hospitalization (n = 57), and 18.9 per 1,000 person-years for low ABI at visit 3 or 4 (n = 123). The relative risk (RR) (95% CI) of an incident PAD event comparing the second and third tertiles of A1C to the first, respectively, after adjustment for cardiovascular risk factors was strongest for severe, symptomatic forms of disease, e.g., PAD-related hospitalization (RR = 4.56 [1.86–11.18] for the third A1C tertile compared with the first, P trend <0.001) than for low ABI (RR = 1.64 [0.94–2.87], P trend = 0.08).

CONCLUSIONS—We found a positive, graded, and independent association between A1C and PAD risk in diabetic adults. This association was stronger for clinical (symptomatic) PAD, whose manifestations may be related to microvascular insufficiency, than for low ABI. Our results suggest that efforts to improve glycemic control in persons with diabetes may substantially reduce the risk of PAD.

Abbreviations: ABI, ankle-brachial index • ARIC, Atherosclerosis Risk in Communities • PAD, peripheral arterial disease

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