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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N. S. Jenny, R. P. Tracy, M. S. Ogg, L. A. Luong, L. H. Kuller, A. M. Arnold, A. R. Sharrett, and S. E. Humphries In the Elderly, Interleukin-6 Plasma Levels and the -174G>C Polymorphism Are Associated With the Development of Cardiovascular Disease Arterioscler Thromb Vasc Biol, December 1, 2002; 22(12): 2066 - 2071. [Abstract] [Full Text] [PDF]
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 I. M. van der Meer, M. P.M. de Maat, A. E. Hak, A. J. Kiliaan, A. I. del Sol, D. A.M. van der Kuip, R. L.G. Nijhuis, A. Hofman, and J. C.M. Witteman C-Reactive Protein Predicts Progression of Atherosclerosis Measured at Various Sites in the Arterial Tree: The Rotterdam Study Stroke, December 1, 2002; 33(12): 2750 - 2755. [Abstract] [Full Text] [PDF]
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M. Schillinger, M. Exner, W. Mlekusch, H. Rumpold, R. Ahmadi, S. Sabeti, M. Haumer, O. Wagner, and E. Minar Vascular Inflammation and Percutaneous Transluminal Angioplasty of the Femoropopliteal Artery: Association with Restenosis Radiology, October 1, 2002; 225(1): 21 - 26. [Abstract] [Full Text] [PDF]
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A. Papafili, M. R. Hill, D. J. Brull, R. J. McAnulty, R. P. Marshall, S. E. Humphries, and G. J. Laurent Common Promoter Variant in Cyclooxygenase-2 Represses Gene Expression: Evidence of Role in Acute-Phase Inflammatory Response Arterioscler Thromb Vasc Biol, October 1, 2002; 22(10): 1631 - 1636. [Abstract] [Full Text] [PDF]
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A. D. Blann, P. M. Ridker, and G. Y.H. Lip Inflammation, Cell Adhesion Molecules, and Stroke: Tools in Pathophysiology and Epidemiology? Stroke, September 1, 2002; 33(9): 2141 - 2143. [Full Text] [PDF]
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A. D. Pradhan, N. Rifai, and P. M. Ridker Soluble Intercellular Adhesion Molecule-1, Soluble Vascular Adhesion Molecule-1, and the Development of Symptomatic Peripheral Arterial Disease in Men Circulation, August 13, 2002; 106(7): 820 - 825. [Abstract] [Full Text] [PDF]
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A. R. Brasier, A. Recinos III, and M. S. Eledrisi Vascular Inflammation and the Renin-Angiotensin System Arterioscler Thromb Vasc Biol, August 1, 2002; 22(8): 1257 - 1266. [Abstract] [Full Text] [PDF]
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D. L. Bhatt and E. J. Topol Need to Test the Arterial Inflammation Hypothesis Circulation, July 2, 2002; 106(1): 136 - 140. [Full Text] [PDF]
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J.-J. Li, H. Jiang, C.-X. Huang, C.-H. Fang, Q.-Z. Tang, H. Xia, J. Liu, and G.-S. Li Elevated Level of Plasma C-reactive Protein in Patients with Unstable Angina: Its Relations with Coronary Stenosis and Lipid Profile Angiology, May 1, 2002; 53(3): 265 - 272. [Abstract] [PDF]
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 C. Monaco, E. Andreakos, S. Young, M. Feldmann, and E. Paleolog T cell-mediated signaling to vascular endothelium: induction of cytokines, chemokines, and tissue factor J. Leukoc. Biol., April 1, 2002; 71(4): 659 - 668. [Abstract] [Full Text] [PDF]
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E. van Exel, J. Gussekloo, A.J.M. de Craen, A. Bootsma-van der Wiel, M. Frolich, and R.G.J. Westendorp Inflammation and Stroke: The Leiden 85-Plus Study Stroke, April 1, 2002; 33(4): 1135 - 1138. [Abstract] [Full Text] [PDF]
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P. Tarkkinen, T. Palenius, and T. Lovgren Ultrarapid, Ultrasensitive One-Step Kinetic Immunoassay for C-Reactive Protein (CRP) in Whole Blood Samples: Measurement of the Entire CRP Concentration Range with a Single Sample Dilution Clin. Chem., February 1, 2002; 48(2): 269 - 277. [Abstract] [Full Text] [PDF]
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A. M. O'Hare, C.-y. Hsu, P. Bacchetti, and K. L. Johansen Peripheral Vascular Disease Risk Factors among Patients Undergoing Hemodialysis J. Am. Soc. Nephrol., February 1, 2002; 13(2): 497 - 503. [Abstract] [Full Text] [PDF]
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D J Grainger and H W L Bethell High titres of serum antinuclear antibodies, mostly directed against nucleolar antigens, are associated with the presence of coronary atherosclerosis Ann Rheum Dis, February 1, 2002; 61(2): 110 - 114. [Abstract] [Full Text] [PDF]
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R. Schindler, R. Senf, and U. Frei Influencing the inflammatory response of haemodialysis patients by cytokine elimination using large-pore membranes Nephrol. Dial. Transplant., January 1, 2002; 17(1): 17 - 19. [Full Text] [PDF]
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R. Blackburn, P. Giral, E. Bruckert, J.-M. Andre, S. Gonbert, M. Bernard, M. J. Chapman, and G. Turpin Elevated C-Reactive Protein Constitutes an Independent Predictor of Advanced Carotid Plaques in Dyslipidemic Subjects Arterioscler Thromb Vasc Biol, December 1, 2001; 21(12): 1962 - 1968. [Abstract] [Full Text] [PDF]
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A. O'Hare and K. Johansen Lower-Extremity Peripheral Arterial Disease among Patients with End-Stage Renal Disease J. Am. Soc. Nephrol., December 1, 2001; 12(12): 2838 - 2847. [Abstract] [Full Text] [PDF]
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N. S. Rost, P. A. Wolf, C. S. Kase, M. Kelly-Hayes, H. Silbershatz, J. M. Massaro, R. B. D'Agostino, C. Franzblau, and P. W.F. Wilson Plasma Concentration of C-Reactive Protein and Risk of Ischemic Stroke and Transient Ischemic Attack: The Framingham Study Stroke, November 1, 2001; 32(11): 2575 - 2579. [Abstract] [Full Text] [PDF]
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 G. J. Blake and P. M. Ridker Novel Clinical Markers of Vascular Wall Inflammation Circ. Res., October 26, 2001; 89(9): 763 - 771. [Abstract] [Full Text] [PDF]
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A. Yildirir, S. L. Tokgozoglu, I. Haznedaroglu, I. Sinici, G. Kabakci, K. Ovunc, S. Aksoyek, A. Oto, F. Ozmen, S. Kirazli, et al. Extent of Coronary Atherosclerosis and Homocysteine Affect Endothelial Markers Angiology, September 1, 2001; 52(9): 589 - 596. [Abstract] [PDF]
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