Published Online
on June 16, 2003

A more recent version of this article appeared on July 1, 2003

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Submitted on December 13, 2002
Revised on March 25, 2003
Accepted on April 7, 2003

D-Dimer, Inflammatory Markers, and Lower Extremity Functioning in Patients With and Without Peripheral Arterial Disease

Mary McGrae McDermott MD^*, Philip Greenland MD, David Green MD, PhD, Jack M. Guralnik MD, PhD, Michael H. Criqui MD, MPH, Kiang Liu PhD, Cheeling Chan MS, William H. Pearce MD, Lloyd Taylor MD, Paul M Ridker MD, Joseph R. Schneider MD, PhD, Gary Martin MD, Nader Rifai PhD, Maureen Quann BS, and Myriam Fornage PhD

From the Departments of Medicine (M.M.M., P.G., D.G., G.M., M.Q., P.M.R.), Preventive Medicine (M.M.M., P.G., K.L., C.C.), and Surgery (W.H.P., J.R.S.), Northwestern University's Feinberg School of Medicine, Chicago, Ill; National Institute on Aging (J.M.G.), Bethesda, Md; University of California at San Diego (M.H.C.), San Diego, Calif; Oregon Health and Science University (L.T.), Portland, Ore; Harvard Medical School (P.M.R., N.R.), Boston, Mass; Department of Surgery, Evanston Hospital (J.R.S.), Evanston, Ill; and University of Texas at Houston (M.F.), Houston, Tex.

^* To whom correspondence should be addressed. E-mail: mdm608{at}northwestern.edu.

Background--We determined whether higher levels of D-dimer, C-reactive protein (CRP), fibrinogen, and serum amyloid A are associated independently with functional impairment in patients with and without peripheral arterial disease (PAD).

Methods and Results--Participants were 370 men and women with PAD (ankle brachial index <0.90) and 231 without PAD. Functional outcomes were 6-minute walk distance and 4-meter walking velocity. A summary performance score combined performance in walking speed, standing balance, and time for 5 repeated chair rises into an ordinal score ranging from 0 to 12 (12=best). Adjusting for age, sex, ankle brachial index, comorbidities, and other potential mediators and confounders, D-dimer levels were associated independently and inversely with performance on all 3 functional measures in the entire cohort and among patients with and without PAD, respectively. Adjusting for known and potential confounders, CRP levels were associated independently with 6-minute walk distance and the summary performance score among participants with PAD. No significant associations were observed between CRP and the functional measures among participants without PAD. Fibrinogen and SAA levels were not associated independently with the functional measures.

Conclusions--Higher D-dimer levels are associated with poorer functioning among individuals with and without PAD. Higher CRP levels were associated with poorer 6-minute walk performance and a lower summary performance score among participants with PAD but not among those without PAD. Additional study is needed to determine whether D-dimer and CRP are involved in the pathophysiology of functional impairment or whether they are simply sensitive markers of the extent of systemic atherosclerosis.

Key words: coagulation • fibrinolysis • epidemiology • peripheral vascular disease • claudication

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