Advertisement

C-reactive protein levels and coronary artery disease incidence and mortality in apparently healthy men and women: The EPIC-Norfolk prospective population study 1993–2003

      Abstract

      Introduction

      Measurement of C-reactive protein (CRP) levels has been proposed as a useful marker to improve the prediction of future coronary artery disease (CAD) risk, but this notion has been challenged recently.

      Methods and results

      We performed a prospective case–control study among apparently healthy men and women. The odds ratio (OR) for future CAD incidence was 2.49 (95% CI = 2.02–3.08, p for linearity <0.0001) unadjusted, and 1.66 (95% CI = 1.31–2.12, p for linearity <0.0001), after adjustment for classical cardiovascular risk factors, for top versus bottom quartile of the CRP distribution. Notably, the risk factor adjusted predictive value was substantially stronger for fatal CAD (OR = 2.92, 95% CI = 1.83–4.67, p for linearity <0.0001) than for non-fatal CAD (OR = 1.25, 95% CI = 0.93–1.66, p for linearity = 0.06). CRP levels were among the strongest predictors of CAD incidence and mortality. CRP levels remained a statistically significant predictor of future CAD, even after adjustment for the Framingham risk score.

      Conclusions

      In this British cohort with risk factor levels representative of a contemporary Western population, CRP concentration was among the strongest predictors of CAD incidence and mortality. We suggest that current guidelines on CRP measurement in clinical practice should be based on contemporary and representative populations.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Atherosclerosis
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Bickel C.
        • Rupprecht H.J.
        • Blankenberg S.
        • et al.
        • AtheroGene Investigators
        Relation of markers of inflammation (C-reactive protein, fibrinogen, von Willebrand factor, and leukocyte count) and statin therapy to long-term mortality in patients with angiographically proven coronary artery disease.
        Am J Cardiol. 2002; 89: 901-908
        • Haverkate F.
        • Thompson S.G.
        • Pyke S.D.
        • Gallimore J.R.
        • Pepys M.B.
        Production of C-reactive protein and risk of coronary events in stable and unstable angina.
        Lancet. 1997; 349: 462-466
        • Toss H.
        • Lindahl B.
        • Siegbahn A.
        • Wallentin L
        • FRISC Study Group
        Prognostic influence of increased fibrinogen and C-reactive protein levels in unstable coronary artery disease.
        Circulation. 1997; 96: 4204-4210
        • Ridker P.M.
        • Cushman M.
        • Stampfer M.J.
        • Tracy R.P.
        • Hennekens C.H.
        Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men.
        N Engl J Med. 1997; 336: 973-979
        • Ridker P.M.
        • Hennekens C.H.
        • Buring J.E.
        • Rifai N.
        C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women.
        N Engl J Med. 2000; 342: 836-843
        • Pradhan A.D.
        • Manson J.E.
        • Rossouw J.E.
        • et al.
        Inflammatory biomarkers, hormone replacement therapy, and incident coronary heart disease: prospective analysis from the Women's Health Initiative observational study.
        JAMA. 2002; 288: 980-987
        • Pearson T.A.
        • Mensah G.A.
        • Alexander R.W.
        • et al.
        Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association.
        Circulation. 2003; 107: 499-511
        • Danesh J.
        • Wheeler J.G.
        • Hirschfield G.M.
        • et al.
        C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease.
        N Engl J Med. 2004; 350: 1387-1397
        • Glynn R.J.
        • Cook N.R.
        C-reactive protein and coronary heart disease.
        N Engl J Med. 2004; 351: 295
        • Libby P.
        • Willerson J.T.
        • Braunwald E.
        C-reactive protein and coronary heart disease.
        N Engl J Med. 2004; 351: 295-296
        • Foody J.M.
        • Gotto A.M.
        • Wenger N.
        C-reactive protein and coronary heart disease.
        N Engl J Med. 2004; 351: 296
        • Ridker P.M.
        • Koenig W.
        • Fuster V.
        C-reactive protein and coronary heart disease.
        N Engl J Med. 2004; 351: 296-297
        • Danesh J.
        • Pepys M.B.
        • Gudnason V.
        C-reactive protein and coronary heart disease.
        N Engl J Med. 2004; 351: 297
        • Greenland S.
        • Schlesselman J.J.
        • Criqui M.H.
        The fallacy of employing standardized regression coefficients and correlations as measures of effects.
        Am J Epidemiol. 1986; 123: 203-208
        • Day N.E.
        • Oakes S.
        • Luben R.
        • et al.
        EPIC-Norfolk: study design and characteristics of the cohort, European Prospective Investigation of Cancer.
        Br J Cancer. 1999; 80: 95-103
        • Boekholdt S.M.
        • Peters R.J.
        • Day N.E.
        • et al.
        Macrophage migration inhibitory factor and the risk of myocardial infarction or death due to coronary artery disease in adults without prior myocardial infarction or stroke: the EPIC-Norfolk prospective population study.
        Am J Med. 2004; 117: 390-397
        • Boekholdt S.M.
        • Peters R.J.
        • Hack C.E.
        • et al.
        IL-8 plasma concentrations and the risk of future coronary artery disease in apparently healthy men and women, The EPIC-Norfolk prospective population study.
        Arterioscler Thromb Vasc Biol. 2004; 24: 1-7
        • Boekholdt S.M.
        • Kuivenhoven J.A.
        • Wareham N.J.
        • et al.
        Plasma levels of cholesteryl ester transfer protein and the risk of future coronary artery disease in apparently healthy men and women, the prospective EPIC (European Prospective Investigation into Cancer and nutrition)-Norfolk population study.
        Circulation. 2004; 110: 1418-1423
        • Friedewald W.T.
        • Levy R.I.
        • Fredrickson D.S.
        Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge.
        Clin Chem. 1972; 18: 499-502
        • Bruins P.
        • te Velthuis H.
        • Yazdanbakhsh A.P.
        • et al.
        Activation of the complement system during and after cardiopulmonary bypass surgery: postsurgery activation involves C-reactive protein and is associated with postoperative arrhythmia.
        Circulation. 1997; 96: 3542-3548
        • Ridker P.M.
        • Rifai N.
        • Rose L.
        • Buring J.E.
        • Cook N.R.
        Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events.
        N Engl J Med. 2002; 347: 1557-1565
        • Wilson P.W.
        • D’Agostino R.B.
        • Levy D.
        • et al.
        Prediction of coronary heart disease using risk factor categories.
        Circulation. 1998; 97: 1837-1847
        • Day N.
        • Oakes S.
        • Luben R.
        • et al.
        EPIC-Norfolk: study design and characteristics of the cohort, European prospective investigation of Cancer.
        Br J Cancer. 1999; 80: 95-103
        • Cermak J.
        • Key N.S.
        • Bach R.R.
        • et al.
        C-reactive protein induces human peripheral blood monocytes to synthesize tissue factor.
        Blood. 1993; 82: 513-520
        • Danenberg H.D.
        • Szalai A.J.
        • Swaminathan R.V.
        • et al.
        Increased thrombosis after arterial injury in human C-reactive protein-transgenic mice.
        Circulation. 2003; 108: 512-515
        • Bisoendial R.J.
        • Kastelein J.J.
        • Levels J.H.
        • Zwaginga J.J.
        • van den Bogaard B.
        • Reitsma P.H.
        • et al.
        Activation of inflammation and coagulation after infusion of C-reactive protein in humans.
        Circ Res. 2005; 96: 714-716
        • Zwaka T.P.
        • Hombach V.
        • Torzewski J.
        C-reactive protein-mediated low density lipoprotein uptake by macrophages: implications for atherosclerosis.
        Circulation. 2001; 103: 1194-1197
        • Pasceri V.
        • Willerson J.T.
        • Yeh E.T.
        Direct proinflammatory effect of C-reactive protein on human endothelial cells.
        Circulation. 2000; 102: 2165-2168
        • Engstrom G.
        • Hedblad B.
        • Stavenow L.
        • et al.
        Fatality of future coronary events is related to inflammation-sensitive plasma proteins: a population-based prospective cohort study.
        Circulation. 2004; 110: 27-31
        • Griselli M.
        • Herbert J.
        • Hutchinson W.L.
        • et al.
        C-reactive protein and complement are important mediators of tissue damage in acute myocardial infarction.
        J Exp Med. 1999; 190: 1733-1740
        • Barrett T.D.
        • Hennan J.K.
        • Marks R.M.
        • Lucchesi B.R.
        C-reactive-protein-associated increase in myocardial infarct size after ischemia/reperfusion.
        J Pharmacol Exp Ther. 2002; 303: 1007-1013
        • Lagrand W.K.
        • Visser C.A.
        • Hermens W.T.
        • et al.
        C-reactive protein as a cardiovascular risk factor: more than an epiphenomenon?.
        Circulation. 1999; 100: 96-102
        • Nijmeijer R.
        • Lagrand W.K.
        • Lubbers Y.T.
        • et al.
        C-reactive protein activates complement in infarcted human myocardium.
        Am J Pathol. 2003; 163: 269-275
        • Nijmeijer R.
        • Lagrand W.K.
        • Visser C.A.
        • et al.
        CRP, a major culprit in complement-mediated tissue damage in acute myocardial infarction?.
        Int Immunopharmacol. 2001; 1: 403-414