Published Online
on May 30, 2006

A more recent version of this article appeared on June 6, 2006

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Submitted on December 15, 2005
Revised on March 11, 2006
Accepted on March 30, 2006

Risk Factors for Progression of Peripheral Arterial Disease in Large and Small Vessels

Victor Aboyans MD, PhD^*, Michael H. Criqui MD, MPH, Julie O. Denenberg MA, James D. Knoke PhD, Paul M Ridker MD, MPH, and Arnost Fronek MD, PhD

From the Department of Family and Preventive Medicine, University of California, San Diego (V.A., M.H.C., J.O.D., J.D.K.); Department of Thoracic and Cardiovascular Surgery and Vascular Medicine, Dupuytren University Hospital, Limoges, France (V.A.); Center of Cardiovascular Prevention, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass (P.M.R.); and Department of Surgery and Bio-Engineering, University of California, San Diego, La Jolla (A.F.).

^* To whom correspondence should be addressed. E-mail: vaboyans{at}ucsd.edu.

Background--Data on the natural history of peripheral arterial disease (PAD) are scarce and are focused primarily on clinical symptoms. Using noninvasive tests, we assessed the role of traditional and novel risk factors on PAD progression. We hypothesized that the risk factors for large-vessel PAD (LV-PAD) progression might differ from small-vessel PAD (SV-PAD).

Methods and Results--Between 1990 and 1994, patients seen during the prior 10 years in our vascular laboratories were invited for a new vascular examination. The first assessment provided baseline data, with follow-up data obtained at this study. The highest decile of decline was considered major progression, which was a -0.30 ankle brachial index decrease for LV-PAD and a -0.27 toe brachial index decrease for SV-PAD progression. In addition to traditional risk factors, the roles of high-sensitivity C-reactive protein, serum amyloid-A, lipoprotein(a), and homocysteine were assessed. Over the average follow-up interval of 4.6±2.5 years, the 403 patients showed a significant ankle brachial index and toe brachial index deterioration. In multivariable analysis, current smoking, ratio of total to HDL cholesterol, lipoprotein(a), and high-sensitivity C-reactive protein were related to LV-PAD progression, whereas only diabetes was associated with SV-PAD progression.

Conclusions--Risk factors contribute differentially to the progression of LV-PAD and SV-PAD. Cigarette smoking, lipids, and inflammation contribute to LV-PAD progression, whereas diabetes was the only significant predictor of SV-PAD progression.

Key words: diabetes mellitus • inflammation • lipoproteins • peripheral vascular disease • smoking

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