Abstract
C-reactive protein (CRP) is produced by the macrophages in the liver and adipocytes and is integrated in the acute-phase response pathway. Being a nonspecific marker of inflammation, it increases in response to inflammation. The results of recent studies that have analyzed the role of CRP have not yet influenced current clinical practice. When used in combination with other established biomarkers for the prediction of the first major cardiovascular event or death, CRP does not improve the risk stratification obtained with the current guidelines. The reduction of CRP levels itself or as a statin-related pleiotropic effect has been assessed in different scenarios, including the acute phase of myocardial infarction; secondary prevention of cardiovascular diseases; special patient populations, such as diabetic patients; and finally in a primary prevention study (JUPITER [Justification for the Use of statins in primary Prevention: an Intervention Trial Evaluating Rosuvastatin]). Risk stratification in all the examined scenarios was related to serum LDL-C levels; in other words, the degree of cardiovascular risk was always lipid dependent.
Similar content being viewed by others
References
Libby P. Inflammation in atherosclerosis. Nature 2002; 420: 864–8.
Roselló-Leti E, Rivera M, Martínez-Dolz L, et al. Inflammatory activation and left ventricular mass in essential hypertension. Am J Hypertens 2009; 22:444–50.
Burke AP, Russel PT, Kolodgie F, et al. Elevated C-reactive protein values and atherosclerosis in sudden coronary death: association with different pathologies. Circulation 2002; 105: 2019–23.
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: 1387–97.
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: 973–9.
Ridker PM, Wilson P, Grundy SM. Should C-reactive protein be added to metabolic syndrome and to assessment of global cardiovascular risk? Circulation 2004; 109: 2818–25.
Ridker PM, Paynter NP, Rifai N, et al. C-reactive protein and parental history improve global cardiovascular risk prediction: the Reynolds Risk Score for men. Circulation 2008; 118: 2243–51.
Ridker PM, Buring JE, Rifai N, et al. Development and validation of improved algorithms for the assessment of global cardiovascular risk in women: The Reynolds Risk Score. JAMA 2007; 297: 611–9.
Zethelius B, Berglund L, Sundström J, et al. Use of multiple biomarkers to improve the prediction of death from cardiovascular causes. N Engl J Med 2008; 358: 2107–16.
Libby P. Role of inflammation in atherosclerosis associated with rheumatoid arthritis. Am J Med 2008; 121: S21–31.
González-Gay MA, González-Juanatey C, Martín J. Rheumatoid arthritis: a disease associated with accelerated atherogenesis. Semin Arthritis Rheum 2005; 35: 8–17.
Ridker PM, Cannon CP, Morrow D, et al. C-reactive protein levels and outcomes after statin therapy. N Engl J Med 2005; 352: 20–8.
Kuch B, von Scheidt W, Kling B, et al. Differential impact of admission C-reactive protein levels on 28-day mortality risk in patients with ST-elevation versus non-ST-elevation myocardial infarction (from the Monitoring Trends and Determinants on Cardiovascular Diseases [MONICA]/Cooperative Health Research in the Region of Augsburg [KORA] Augsburg Myocardial Infarction Registry. Am J Cardiol 2008; 102: 1125–30.
Altman DG, Andersen PK. Calculating the number needed to treat for trials where the outcome is time to an event. BMJ 1999; 319: 1492–5.
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: 2195–207.
Pearson TA, Mensah GA, Alexander 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.
Libby P, Ridker PM. Novel inflammation markers of coronary risk: theory vs practice. Circulation 1999; 100: 1148–50.
Ridker PM, Rifai N, Clearfield M, et al. 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: 1959–65.
Robinson JG, Smith B, Maheshwari N, et al. Pleiotropic effects of statins: benefit beyond cholesterol reduction? A meta-regression analysis. J Am Coll Cardiol 2005; 46: 1855–62.
O’Keefe JH, Cordain L, Harris WH, et al. Optimal low-density lipoprotein is 50 to 70mg/dL lower: lower is better and physiologically normal. Am J Col Cardiol 2004; 43: 2142–6.
Taglieri N, Fernandez-Berges DJ, Koenig W, et al; for the SIESTA Investigators. Plasma cystanin C for prediction of 1-year cardiac events in Mediterranean patients with non-ST elevation acute coronary syndrome. Artherosclerosis 2009 Sep 20 [E-pub ahead of print].
Zacho J, Tybjaerg-Hansen A, Jensen JS, et al. Genetically elevated C-reactive protein and ischemic vascular disease. N Engl J Med 2008; 359: 1897–908.
Wang TJ, Gona P, Larson MG, et al. Multiple biomarkers for the prediction of first major cardiovascular events and death. N Engl J Med 2006; 355: 2631–9.
Acknowledgments
Funding for the preparation of this manuscript was provided by Rovi Farmaceuticals. Medical writing assistance was provided by Sofia Perea, PhD on behalf of Wolters Kluwer Pharma Solutions. The authors do not report any conflicts of interest.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Martínez, V.B., González-Juanatey, J.R. Markers of Inflammation and Cardiovascular Disease. Am J Cardiovasc Drugs 9 (Suppl 1), 3–7 (2009). https://doi.org/10.2165/1153161-S0-000000000-00000
Published:
Issue Date:
DOI: https://doi.org/10.2165/1153161-S0-000000000-00000