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. 2006 Dec 5;28(9):408–412. doi: 10.1002/clc.4960280905

High‐sensitivity C‐reactive protein as a risk assessment tool for cardiovascular disease

Edward T H Yeh 1,✉
PMCID: PMC6654463  PMID: 16250263

Abstract

Almost half of first cardiovascular events occur in individuals with no known risk factors. Attempts in the last decade to predict cardiovascular risk more accurately have led to the emergence of a novel risk factor, C‐reactive protein (CRP), which has proved to be as good a risk predictor as low‐density lipoprotein cholesterol. C‐reactive protein is an index of inflammation that is now believed to promote directly all stages of atherosclerosis, including plaque rupture. As measured by high‐sensitivity assays, high‐sensitivity CRP (hs‐CRP) also independently predicts recurrent events in patients with known coronary artery diseases. Recent evidence implicates hs‐CRP, and thus inflammation, in the metabolic syndrome and diabetes mellitus, particularly in women. As a clinical tool for cardiovascular risk assessment, hs‐CRP testing enhances information provided by lipid screening or global risk assessment. Statin therapy and other interventions can lower hs‐CRP. Whether or not such reductions can prevent cardiovascular events is under investigation.

Keywords: cardiovascular risk assessment, C‐reactive protein, inflammation, metabolic syndrome, statins

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References

  • 1. Ridker PM, Rifai N, Rose L, Buring JE, Cook NR: 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 [DOI] [PubMed] [Google Scholar]
  • 2. Braunwald E: Shattuck Lecture—cardiovascular medicine at the turn of the millennium: Triumphs, concerns, and opportunities. N Engl J Med 1997; 337: 1360–1369 [DOI] [PubMed] [Google Scholar]
  • 3. 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: 836–843 [DOI] [PubMed] [Google Scholar]
  • 4. Ross R: Atherosclerosis: An inflammatory disease. N Engl J Med 1999; 340: 115–126 [DOI] [PubMed] [Google Scholar]
  • 5. Libby P, Ridker PM, Maseri A: Inflammation and atherosclerosis. Circulation 2002; 105: 1135–1143 [DOI] [PubMed] [Google Scholar]
  • 6. Albert CM, Ma J, Rifai N, Stampfer MJ, Ridker PM: Prospective study of C‐reactive protein, homocysteine, and plasma lipid levels as predictors of sudden cardiac death. Circulation 2002; 105: 2595–2599 [DOI] [PubMed] [Google Scholar]
  • 7. Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH: Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med 1997; 336: 973–979 [DOI] [PubMed] [Google Scholar]
  • 8. Liuzzo G, Biasucci LM, Gallimore JR, Grillo RL, Rebuzzi AG, Pepys MB, Maseri A: The prognostic value of C‐reactive protein and serum amyloid A protein in severe unstable angina. N Engl J Med 1994; 331: 417–424 [DOI] [PubMed] [Google Scholar]
  • 9. 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: 391–397 [DOI] [PubMed] [Google Scholar]
  • 10. Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM: C‐reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. J Am Med Assoc 2001; 286: 327–334 [DOI] [PubMed] [Google Scholar]
  • 11. Venugopal SK, Devaraj S, Yuhanna I, Shaul P, Jialal I: Demonstration that C‐reactive protein decreases eNOS expression and bioactivity in human aortic endothelial cells. Circulation 2002; 106: 1439–1441 [DOI] [PubMed] [Google Scholar]
  • 12. Yeh ETH, Palusinski RP: C‐reactive protein: The pawn has been promoted to queen. Curr Atheroscler Rep 2003; 5: 101–105 [DOI] [PubMed] [Google Scholar]
  • 13. Yeh ETH, Willerson JT: Coming of age of C‐reactive protein: Using inflammation markers in cardiology. Circulation 2003; 107: 370–372 [DOI] [PubMed] [Google Scholar]
  • 14. Pearson TA, Mensah GA, Alexander RW, Anderson JL, Cannon RO III, Criqui M, Fadl YY, Fortmann SP, Hong Y, Myers GL, Rifai N, Smith SC Jr, Taubert K, Tracy RP, Vinicor F: 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: 449–511 [DOI] [PubMed] [Google Scholar]
  • 15. Crea F, Monaco C, Lanza GA, Maggi E, Ginnetti F, Cianflone D, Niccoli G, Cook T, Bellomo G, Kjekshus J: Inflammatory predictors of mortality in the Scandinavian Simvastatin Survival Study. Clin Cardiol 2002; 25: 461–466 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16. Nissen SE, Tuzcu EM, Schoenhagen P, Crowe T, Sasiela WJ, Tsai J, Orazem J, Magorien RD, O'Shaughnessy C, Ganz P, for the Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) Investigators : Statin therapy, LDL cholesterol, C‐reactive protein, and coronary artery disease. N Engl J Med 2005; 352: 29–38 [DOI] [PubMed] [Google Scholar]
  • 17. Ridker PM, Cannon CP, Morrow D, Rifai N, Rose LM, McCabe CH, Pfeffer MA, Braunwald D, for the Pravastatin or Atorvastatin Evaluation and Infection Therapy—Thrombolysis in Myocardial Infarction 22 (PROVE IT—TIMI 22) Investigators : C‐reactive protein levels and outcomes after statin therapy. N Engl J Med 2005; 352: 20–28 [DOI] [PubMed] [Google Scholar]
  • 18. Curb JD, Abbott RD, Rodriquez BL, Sakkinen P, Popper JS, Yano K, Tracy RP: C‐reactive protein and the future risk of thromboembolic stroke in healthy men. Circulation 2003; 107: 2016–2020 [DOI] [PubMed] [Google Scholar]
  • 19. Rost NS, Wolf PA, Kase CS, Kelly‐Hayes M, Silbershatz H, Massaro JM, D'Agostino RB, Franzblau C, Wilson PWF: Plasma concentration of C‐reactive protein and risk of ischemic stroke and transient ischemic attack: The Framingham Study. Stroke 2001; 32: 2575–2579 [DOI] [PubMed] [Google Scholar]
  • 20. 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: 1955–1959 [DOI] [PubMed] [Google Scholar]
  • 21. Pasceri V, Willerson JT, Yeh ETH: Direct proinflammatory effect of C‐reactive protein on human endothelial cells. Circulation 2000; 102: 2165–2168 [DOI] [PubMed] [Google Scholar]
  • 22. Pasceri V, Chang J, Willerson JT, Yeh ETH: Modulation of C‐reactive protein‐mediated monocyte chemoattractant protein‐1 induction in human endothelial cells by antiatherosclerosis drugs. Circulation 2001; 103: 2531–2534 [DOI] [PubMed] [Google Scholar]
  • 23. Zwaka TP, Homback V, Torzewski J: C‐reactive protein‐mediated low‐density lipoprotein uptake by macrophages: Implications for atherosclerosis. Circulation 2001; 103: 1194–1197 [DOI] [PubMed] [Google Scholar]
  • 24. Calabrò P, Willerson JT, Yeh ETH: Inflammatory cytokines stimulated C‐reactive protein production by human coronary artery smooth muscle cells. Circulation 2003; 108: 1930–1932 [DOI] [PubMed] [Google Scholar]
  • 25. Ridker PM, Wilson PWF, Grundy SM: Should C‐reactive protein be added to metabolic syndrome and to assessment of global cardiovascular risk? Circulation 2004; 109: 2818–2825 [DOI] [PubMed] [Google Scholar]
  • 26. Calabrò P, Chang DW, Willerson JT, Yeh ETH: Production of C‐reactive protein in response to inflammatory cytokines by human adipocytes (abstr 549). Circulation 2004; 110 (suppl III): III‐116 [Google Scholar]
  • 27. Freeman DJ, Norrie J, Caslake MJ, Gaw A, Ford I, Lowe GDO, O'Reilly DSJ, Packard CJ, Sattar N, for the West of Scotland Coronary Prevention Study Group : 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: 1596–1600 [DOI] [PubMed] [Google Scholar]
  • 28. Han TS, Sattar N, Williams K, Gonzalez‐Villalpando C, Lean MEJ, Haffner SM: Prospective study of C‐reactive protein in relation to the development of diabetes and metabolic syndrome in the Mexico City Diabetes Study. Diabetes Care 2002; 25: 2016–2021 [DOI] [PubMed] [Google Scholar]
  • 29. Rutter MK, Meigs JB, Sullivan LM, D' Agostino RB Sr, Wilson PWF: C‐reactive protein, the metabolic syndrome, and prediction of cardiovascular events in the Framingham Offspring Study. Circulation 2004; 110: 380–385 [DOI] [PubMed] [Google Scholar]
  • 30. Ridker PM: Clinical application of C‐reactive protein for cardiovascular disease detection and prevention. Circulation 2003; 107: 363–369 [DOI] [PubMed] [Google Scholar]
  • 31. Ridker PM, Rifai N, Pfeffer MA, Sacks FM, Moyé LA, Goldman S, Flaker GC, Braunwald E, for the Cholesterol and Recurrent Events (CARE) Investigators : Inflammation, pravastatin, and the risk of coronary events after myocardial infarction in patients with average cholesterol levels. Circulation 1998; 98: 839–844 [DOI] [PubMed] [Google Scholar]
  • 32. Ridker PM, Rifai N, Clearfield M, Downs JR, Weis SE, Miles JS, Gotto AM Jr, for the Air Force/Texas Coronary Atherosclerosis Prevention Study Investigators : Measurement of C‐reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events. N Engl J Med 2001; 344: 1959–1965 [DOI] [PubMed] [Google Scholar]
  • 33. Ridker PM, on behalf of the JUPITER Study Group : Rosuvastatin in the primary prevention of cardiovascular disease among patients with low levels of low‐density lipoprotein cholesterol and elevated high‐sensitivity C‐reactive protein: Rationale and design of the JUPITER trial. Circulation 2003; 108: 2292–2297 [DOI] [PubMed] [Google Scholar]

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