Screening for cardiovascular risk with C-reactive protein
- David A Morrow, MD, MPH
David A Morrow, MD, MPH
- Professor of Medicine
- Harvard Medical School
- Filippo Crea, MD
Filippo Crea, MD
- Professor of Cardiology
- Head, Department of Cardiovascular Medicine and Thoracic Sciences
- Catholic University Rome
- Section Editor
- Juan Carlos Kaski, DSc, MD, DM (Hons), FRCP, FESC, FACC, FAHA
Juan Carlos Kaski, DSc, MD, DM (Hons), FRCP, FESC, FACC, FAHA
- Section Editor — Coronary Heart Disease
- Professor of Cardiovascular Science
- Director, Cardiovascular and Cell Sciences Research Institute
- St. George's, University of London
Atherosclerotic cardiovascular disease (CVD) is common in the general population and is the most common cause of death in the United States as well as in most developed countries. CVD can be subdivided into four major areas:
●Coronary heart disease (CHD) manifesting as myocardial infarction (MI), angina pectoris, congestive heart failure (CHF), and sudden cardiac death
●Cerebrovascular disease manifesting as stroke and transient ischemic attack
●Peripheral artery disease manifesting as intermittent claudication and critical limb ischemia
●Aortic atherosclerosis and thoracic or abdominal aortic aneurysmTo continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Ridker PM. Clinical application of C-reactive protein for cardiovascular disease detection and prevention. Circulation 2003; 107:363.
- Roberts WL, Moulton L, Law TC, et al. Evaluation of nine automated high-sensitivity C-reactive protein methods: implications for clinical and epidemiological applications. Part 2. Clin Chem 2001; 47:418.
- Pearson TA, Mensah GA, Alexander RW, 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.
- Khera A, McGuire DK, Murphy SA, et al. Race and gender differences in C-reactive protein levels. J Am Coll Cardiol 2005; 46:464.
- Anand SS, Razak F, Yi Q, et al. C-reactive protein as a screening test for cardiovascular risk in a multiethnic population. Arterioscler Thromb Vasc Biol 2004; 24:1509.
- Wilson PW, Pencina M, Jacques P, et al. C-reactive protein and reclassification of cardiovascular risk in the Framingham Heart Study. Circ Cardiovasc Qual Outcomes 2008; 1:92.
- Ockene IS, Matthews CE, Rifai N, et al. Variability and classification accuracy of serial high-sensitivity C-reactive protein measurements in healthy adults. Clin Chem 2001; 47:444.
- Bogaty P, Brophy JM, Boyer L, et al. Fluctuating inflammatory markers in patients with stable ischemic heart disease. Arch Intern Med 2005; 165:221.
- Gaskins AJ, Wilchesky M, Mumford SL, et al. Endogenous reproductive hormones and C-reactive protein across the menstrual cycle: the BioCycle Study. Am J Epidemiol 2012; 175:423.
- Bower JK, Lazo M, Juraschek SP, Selvin E. Within-person variability in high-sensitivity C-reactive protein. Arch Intern Med 2012; 172:1519.
- Shah T, Newcombe P, Smeeth L, et al. Ancestry as a determinant of mean population C-reactive protein values: implications for cardiovascular risk prediction. Circ Cardiovasc Genet 2010; 3:436.
- Mackenzie I, Woodhouse J. C-reactive protein concentrations during bacteraemia: A comparison between patients with and without liver dysfunction. Intensive Care Med 2006; 32:1344.
- Jialal I, Stein D, Balis D, et al. Effect of hydroxymethyl glutaryl coenzyme a reductase inhibitor therapy on high sensitive C-reactive protein levels. Circulation 2001; 103:1933.
- Ridker PM, Rifai N, Pfeffer MA, et al. Long-term effects of pravastatin on plasma concentration of C-reactive protein. The Cholesterol and Recurrent Events (CARE) Investigators. Circulation 1999; 100:230.
- Albert MA, Danielson E, Rifai N, et al. Effect of statin therapy on C-reactive protein levels: the pravastatin inflammation/CRP evaluation (PRINCE): a randomized trial and cohort study. JAMA 2001; 286:64.
- Plenge JK, Hernandez TL, Weil KM, et al. Simvastatin lowers C-reactive protein within 14 days: an effect independent of low-density lipoprotein cholesterol reduction. Circulation 2002; 106:1447.
- Sever PS, Poulter NR, Chang CL, et al. Evaluation of C-reactive protein prior to and on-treatment as a predictor of benefit from atorvastatin: observations from the Anglo-Scandinavian Cardiac Outcomes Trial. Eur Heart J 2012; 33:486.
- Cushman M, Legault C, Barrett-Connor E, et al. Effect of postmenopausal hormones on inflammation-sensitive proteins: the Postmenopausal Estrogen/Progestin Interventions (PEPI) Study. Circulation 1999; 100:717.
- Ridker PM, Hennekens CH, Rifai N, et al. Hormone replacement therapy and increased plasma concentration of C-reactive protein. Circulation 1999; 100:713.
- Pradhan AD, Manson JE, Rossouw JE, 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.
- Langer RD, Pradhan AD, Lewis CE, et al. Baseline associations between postmenopausal hormone therapy and inflammatory, haemostatic, and lipid biomarkers of coronary heart disease. The Women's Health Initiative Observational Study. Thromb Haemost 2005; 93:1108.
- Kervinen H, Palosuo T, Manninen V, et al. Joint effects of C-reactive protein and other risk factors on acute coronary events. Am Heart J 2001; 141:580.
- Ridker PM. High-sensitivity C-reactive protein: potential adjunct for global risk assessment in the primary prevention of cardiovascular disease. Circulation 2001; 103:1813.
- Koenig W, Löwel H, Baumert J, Meisinger C. C-reactive protein modulates risk prediction based on the Framingham Score: implications for future risk assessment: results from a large cohort study in southern Germany. Circulation 2004; 109:1349.
- Ridker PM, Wilson PW, Grundy SM. Should C-reactive protein be added to metabolic syndrome and to assessment of global cardiovascular risk? Circulation 2004; 109:2818.
- Ridker PM, Cushman M, Stampfer MJ, et al. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med 1997; 336:973.
- Ridker PM, Cushman M, Stampfer MJ, et al. Plasma concentration of C-reactive protein and risk of developing peripheral vascular disease. Circulation 1998; 97:425.
- Ridker PM, Glynn RJ, Hennekens CH. C-reactive protein adds to the predictive value of total and HDL cholesterol in determining risk of first myocardial infarction. Circulation 1998; 97:2007.
- Koenig W, Sund M, Fröhlich M, et al. C-Reactive protein, a sensitive marker of inflammation, predicts future risk of coronary heart disease in initially healthy middle-aged men: results from the MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) Augsburg Cohort Study, 1984 to 1992. Circulation 1999; 99:237.
- Mendall MA, Strachan DP, Butland BK, et al. C-reactive protein: relation to total mortality, cardiovascular mortality and cardiovascular risk factors in men. Eur Heart J 2000; 21:1584.
- Pai JK, Pischon T, Ma J, et al. Inflammatory markers and the risk of coronary heart disease in men and women. N Engl J Med 2004; 351:2599.
- Yeboah J, McClelland RL, Polonsky TS, et al. Comparison of novel risk markers for improvement in cardiovascular risk assessment in intermediate-risk individuals. JAMA 2012; 308:788.
- Albert CM, Ma J, Rifai N, et al. Prospective study of C-reactive protein, homocysteine, and plasma lipid levels as predictors of sudden cardiac death. Circulation 2002; 105:2595.
- Sesso HD, Buring JE, Rifai N, et al. C-reactive protein and the risk of developing hypertension. JAMA 2003; 290:2945.
- Ridker PM, Buring JE, Shih J, et al. Prospective study of C-reactive protein and the risk of future cardiovascular events among apparently healthy women. Circulation 1998; 98:731.
- Ridker PM, Hennekens CH, Buring JE, 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.
- Ridker PM, Rifai N, Rose L, et al. 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.
- Cushman M, Arnold AM, Psaty BM, et al. C-reactive protein and the 10-year incidence of coronary heart disease in older men and women: the cardiovascular health study. Circulation 2005; 112:25.
- Sattar N, Murray HM, Welsh P, et al. Are markers of inflammation more strongly associated with risk for fatal than for nonfatal vascular events? PLoS Med 2009; 6:e1000099.
- Sattar N, Murray HM, McConnachie A, et al. C-reactive protein and prediction of coronary heart disease and global vascular events in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER). Circulation 2007; 115:981.
- Garcia-Moll X, Zouridakis E, Cole D, Kaski JC. C-reactive protein in patients with chronic stable angina: differences in baseline serum concentration between women and men. Eur Heart J 2000; 21:1598.
- Rifai N, Buring JE, Lee IM, et al. Is C-reactive protein specific for vascular disease in women? Ann Intern Med 2002; 136:529.
- Ridker PM, Cook N. Clinical usefulness of very high and very low levels of C-reactive protein across the full range of Framingham Risk Scores. Circulation 2004; 109:1955.
- Zimmermann J, Herrlinger S, Pruy A, et al. Inflammation enhances cardiovascular risk and mortality in hemodialysis patients. Kidney Int 1999; 55:648.
- Kanwar M, Hashem M, Rosman H, et al. Usefulness of clinical evaluation, troponins, and C-reactive protein in predicting mortality among stable hemodialysis patients. Am J Cardiol 2006; 98:1283.
- Sakkinen P, Abbott RD, Curb JD, et al. C-reactive protein and myocardial infarction. J Clin Epidemiol 2002; 55:445.
- Best LG, Zhang Y, Lee ET, et al. C-reactive protein as a predictor of cardiovascular risk in a population with a high prevalence of diabetes: the Strong Heart Study. Circulation 2005; 112:1289.
- Sung KC, Ryu S, Chang Y, et al. C-reactive protein and risk of cardiovascular and all-cause mortality in 268 803 East Asians. Eur Heart J 2014; 35:1809.
- Ridker PM, Buring JE, Cook NR, Rifai N. C-reactive protein, the metabolic syndrome, and risk of incident cardiovascular events: an 8-year follow-up of 14 719 initially healthy American women. Circulation 2003; 107:391.
- Freeman DJ, Norrie J, Caslake MJ, et al. C-reactive protein is an independent predictor of risk for the development of diabetes in the West of Scotland Coronary Prevention Study. Diabetes 2002; 51:1596.
- Rutter MK, Meigs JB, Sullivan LM, et al. C-reactive protein, the metabolic syndrome, and prediction of cardiovascular events in the Framingham Offspring Study. Circulation 2004; 110:380.
- Rohde LE, Hennekens CH, Ridker PM. Survey of C-reactive protein and cardiovascular risk factors in apparently healthy men. Am J Cardiol 1999; 84:1018.
- Danesh J, Wheeler JG, Hirschfield GM, 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.
- Ridker PM, Buring JE, Rifai N, Cook NR. Development and validation of improved algorithms for the assessment of global cardiovascular risk in women: the Reynolds Risk Score. JAMA 2007; 297:611.
- Sondermeijer BM, Boekholdt SM, Rana JS, et al. Clinical implications of JUPITER in a contemporary European population: the EPIC-Norfolk prospective population study. Eur Heart J 2013; 34:1350.
- Emerging Risk Factors Collaboration, Kaptoge S, Di Angelantonio E, et al. C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis. Lancet 2010; 375:132.
- Buckley DI, Fu R, Freeman M, et al. C-reactive protein as a risk factor for coronary heart disease: a systematic review and meta-analyses for the U.S. Preventive Services Task Force. Ann Intern Med 2009; 151:483.
- Emerging Risk Factors Collaboration, Kaptoge S, Di Angelantonio E, et al. C-reactive protein, fibrinogen, and cardiovascular disease prediction. N Engl J Med 2012; 367:1310.
- Miller M, Zhan M, Havas S. High attributable risk of elevated C-reactive protein level to conventional coronary heart disease risk factors: the Third National Health and Nutrition Examination Survey. Arch Intern Med 2005; 165:2063.
- Folsom AR, Chambless LE, Ballantyne CM, et al. An assessment of incremental coronary risk prediction using C-reactive protein and other novel risk markers: the atherosclerosis risk in communities study. Arch Intern Med 2006; 166:1368.
- Wilson PW, Nam BH, Pencina M, et al. C-reactive protein and risk of cardiovascular disease in men and women from the Framingham Heart Study. Arch Intern Med 2005; 165:2473.
- Hingorani AD, Sofat R, Morris RW, et al. Is it important to measure or reduce C-reactive protein in people at risk of cardiovascular disease? Eur Heart J 2012; 33:2258.
- U.S. Preventive Services Task Force. Using nontraditional risk factors in coronary heart disease risk assessment: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2009; 151:474.
- Helfand M, Buckley DI, Freeman M, et al. Emerging risk factors for coronary heart disease: a summary of systematic reviews conducted for the U.S. Preventive Services Task Force. Ann Intern Med 2009; 151:496.
- Genest J, McPherson R, Frohlich J, et al. 2009 Canadian Cardiovascular Society/Canadian guidelines for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease in the adult - 2009 recommendations. Can J Cardiol 2009; 25:567.
- Ridker PM, Danielson E, Fonseca FA, et al. Reduction in C-reactive protein and LDL cholesterol and cardiovascular event rates after initiation of rosuvastatin: a prospective study of the JUPITER trial. Lancet 2009; 373:1175.
- Mosca L. C-reactive protein--to screen or not to screen? N Engl J Med 2002; 347:1615.
- Kushner I, Sehgal AR. Is high-sensitivity C-reactive protein an effective screening test for cardiovascular risk? Arch Intern Med 2002; 162:867.
- Laaksonen DE, Niskanen L, Nyyssönen K, et al. C-reactive protein in the prediction of cardiovascular and overall mortality in middle-aged men: a population-based cohort study. Eur Heart J 2005; 26:1783.
- Smith SC Jr, Milani RV, Arnett DK, et al. Atherosclerotic Vascular Disease Conference: Writing Group II: risk factors. Circulation 2004; 109:2613.
- Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 2008; 359:2195.
- CRP ASSAYS
- Test characteristics
- Clinical context
- - Definition of normal
- - Variability within an individual patient
- - Variability within ethnic groups
- - Specificity
- - Comorbid illness
- - Effect of medications
- Cardiovascular medications
- Menopausal hormone therapy
- ASSOCIATION OF CRP WITH CARDIOVASCULAR RISK
- Prediction of incident CVD events
- - General population
- - Elderly
- - Women
- - Renal dysfunction
- - Ethnicity
- Association with established risk factors
- Is CRP an independent risk indicator?
- RECOMMENDATIONS OF OTHERS
- OUR APPROACH
- SUMMARY AND RECOMMENDATIONS