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From the Divisions of Preventive Medicine (P.M.R, C.H.H.), Cardiovascular
Disease (P.M.R.), and Channing Laboratory (M.J.S.), Department of Medicine,
Brigham and Women's Hospital, and the Department of Ambulatory Care and
Prevention (C.H.H.), Harvard Medical School, Boston, Mass; the Departments of
Epidemiology (M.J.S., C.H.H.) and Nutrition (M.J.S.), Harvard School of Public
Health, Boston, Mass; and the Laboratory for Clinical Biochemistry Research,
University of Vermont (M.C., R.P.T.), Burlington.
Correspondence to Dr Paul M Ridker, Brigham and Women's Hospital, 900 Commonwealth Ave E, Boston, MA 02115-1204. E-mail pmridker{at}bics.bwh.harvard.edu
Background—Among apparently healthy
men, elevated levels of C-reactive protein (CRP), a marker for systemic
inflammation, predict risk of myocardial infarction and thromboembolic
stroke. Whether increased levels of CRP are also associated with the
development of symptomatic peripheral
arterial disease (PAD) is unknown.
Methods and Results—Using a prospective, nested, case-control
design, we measured baseline levels of CRP in 144 apparently healthy
men participating in the Physicians' Health Study who subsequently
developed symptomatic PAD (intermittent claudication or
need for revascularization) and in an equal number
of control subjects matched on the basis of age and smoking habit who
remained free of vascular disease during a follow-up period of 60
months. Median CRP levels at baseline were significantly higher among
those who subsequently developed PAD (1.34 versus 0.99 mg/L;
P=.04). Furthermore, the risks of developing PAD
increased significantly with each increasing quartile of baseline CRP
concentration such that relative risks of PAD from lowest (referent) to
highest quartile of CRP were 1.0, 1.3, 2.0, and 2.1
(Ptrend=.02). Compared with those with no
clinical evidence of disease, the subgroup of case patients who
required revascularization had the highest baseline
CRP levels (median=1.75 mg/L; P=.04); relative risks
from lowest to highest quartile of CRP for this end point were 1.0,
1.8, 3.8, and 4.1 (Ptrend=.02). Risk
estimates were similar after additional control for body mass index,
hypercholesterolemia, hypertension, diabetes,
and a family history of premature atherosclerosis.
Conclusions—These prospective data indicate that among apparently
healthy men, baseline levels of CRP predict future risk of developing
symptomatic PAD and thus provide further support for the
hypothesis that chronic inflammation is important in the pathogenesis
of atherothrombosis.
© 1998 American Heart Association, Inc.
Brief Rapid Communications
Plasma Concentration of C-Reactive Protein and Risk of Developing Peripheral Vascular Disease
Key Words: C-reactive protein • inflammation • claudication • arteries • atherosclerosis • risk factors
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