on March 29, 2004
Circulation. 2004
Published online before print March 29, 2004, doi: 10.1161/01.CIR.0000125690.80303.A8
Published online before print March 29, 2004, doi: 10.1161/01.CIR.0000125690.80303.A8
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on December 15, 2003
From the Donald W. Reynolds Center for Cardiovascular Research and the Center for Cardiovascular Disease Prevention, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass. * To whom correspondence should be addressed. E-mail: pridker{at}partners.org.
Background--High-sensitivity C-reactive protein (hsCRP) is a strong independent risk factor for cardiovascular events, and levels of hsCRP of <1, 1 to <3, and Methods and Results--Baseline levels of hsCRP were evaluated among 27 939 apparently healthy women who were followed up for myocardial infarction, stroke, coronary revascularization, or cardiovascular death. Crude and Framingham Risk Score (FRS)-adjusted relative risks (RRs) of incident cardiovascular events were calculated across a full range of hsCRP levels. Cardiovascular risks increased linearly from the very lowest (referent) to the very highest levels of hsCRP. Crude RRs for those with baseline hsCRP levels of <0.5, 0.5 to <1.0, 1.0 to <2.0, 2.0 to <3.0, 3.0 to <4.0, 4.0 to <5.0, 5.0 to <10.0, 10.0 to <20.0, and Conclusions--Both very low (<0.5 mg/L) and very high (>10 mg/L) levels of hsCRP provide important prognostic information on cardiovascular risk. hsCRP is clinically useful for risk prediction across a full range of values and across a full range of FRS.
Revised on February 3, 2004
Accepted on February 3, 2004
Clinical Usefulness of Very High and Very Low Levels of C-Reactive Protein Across the Full Range of Framingham Risk Scores
Paul M Ridker MD, MPH* and Nancy Cook ScD
3 mg/L have been suggested to define low-, moderate-, and high-risk groups. However, the positive predictive value of very low (<0.5 mg/L) and very high levels of hsCRP (>10.0 mg/L) is uncertain.20.0 mg/L were 1.0, 2.2, 2.5, 3.1, 3.7, 4.2, 4.9, 6.3, and 7.6, respectively (P for trend <0.001). After adjustment for FRS, these risks were 1.0, 1.6, 1.6, 1.7, 1.9, 2.2, 2.3, 2.8, and 3.1 (P for trend <0.001). All risk estimates remained significant in analyses stratified by FRS and after control for diabetes. Of the total cohort, 15.1% had hsCRP <0.50 mg/L, and 5.4% had hsCRP >10.0 mg/L.
Key words: risk factors • prevention • epidemiology • inflammation • C-reactive protein
This article has been cited by other articles:
 |
|
 |
|
  J.-M. Dayer and E. Choy Therapeutic targets in rheumatoid arthritis: the interleukin-6 receptor Rheumatology, October 23, 2009; (2009) kep329v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. I. Buckley, R. Fu, M. Freeman, K. Rogers, and M. Helfand 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, October 6, 2009; 151(7): 483 - 495. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Helfand, D. I. Buckley, M. Freeman, R. Fu, K. Rogers, C. Fleming, and L. L. Humphrey Emerging Risk Factors for Coronary Heart Disease: A Summary of Systematic Reviews Conducted for the U.S. Preventive Services Task Force Ann Intern Med, October 6, 2009; 151(7): 496 - 507. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Cushman, L. A. McClure, V. J. Howard, N. S. Jenny, S. G. Lakoski, and G. Howard Implications of Increased C-Reactive Protein for Cardiovascular Risk Stratification in Black and White Men and Women in the US Clin. Chem., September 1, 2009; 55(9): 1627 - 1636. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Abedini, I. Holme, W. Marz, G. Weihrauch, B. Fellstrom, A. Jardine, E. Cole, B. Maes, H.-H. Neumayer, C. Gronhagen-Riska, et al. Inflammation in Renal Transplantation Clin. J. Am. Soc. Nephrol., July 1, 2009; 4(7): 1246 - 1254. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. W McDade, J. N Rutherford, L. Adair, and C. Kuzawa Population differences in associations between C-reactive protein concentration and adiposity: comparison of young adults in the Philippines and the United States Am. J. Clinical Nutrition, April 1, 2009; 89(4): 1237 - 1245. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H.F. Rudd, K. S. Myers, S. Bansilal, J. Machac, M. Woodward, V. Fuster, M. E. Farkouh, and Z. A. Fayad Relationships Among Regional Arterial Inflammation, Calcification, Risk Factors, and Biomarkers: A Prospective Fluorodeoxyglucose Positron-Emission Tomography/Computed Tomography Imaging Study Circ Cardiovasc Imaging, March 1, 2009; 2(2): 107 - 115. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. Harbord, D. A. Lawlor, G. D. Smith, M. R. Bubb, H. Morita, R. Nagai, J. Zacho, A. Tybjaerg-Hansen, and B. G. Nordestgaard Genetically Elevated C-Reactive Protein and Vascular Disease N. Engl. J. Med., February 26, 2009; 360(9): 933 - 935. [Full Text] [PDF]
|
|
|
|
 |
|
 S. Devaraj, J.-M. Yun, C. Duncan-Staley, and I. Jialal C-reactive protein induces M-CSF release and macrophage proliferation J. Leukoc. Biol., February 1, 2009; 85(2): 262 - 267. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Shemesh, K. G. Rowley, A. J. Jenkins, J. D. Best, and K. O'Dea C-Reactive Protein Concentrations Are Very High and More Stable over Time Than the Traditional Vascular Risk Factors Total Cholesterol and Systolic Blood Pressure in an Australian Aboriginal Cohort Clin. Chem., February 1, 2009; 55(2): 336 - 341. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. S. Spatz, M. E. Canavan, and M. M. Desai From Here to JUPITER: Identifying New Patients for Statin Therapy Using Data From the 1999-2004 National Health and Nutrition Examination Survey Circ Cardiovasc Qual Outcomes, January 1, 2009; 2(1): 41 - 48. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Lamarche Review of the Effect of Dairy Products on Non-Lipid Risk Factors for Cardiovascular Disease J. Am. Coll. Nutr., December 1, 2008; 27(6): 741S - 746S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. W. McDade, J. N. Rutherford, L. Adair, and C. Kuzawa Adiposity and Pathogen Exposure Predict C-Reactive Protein in Filipino Women J. Nutr., December 1, 2008; 138(12): 2442 - 2447. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Pepe and H. E. Janes Gauging the Performance of SNPs, Biomarkers, and Clinical Factors for Predicting Risk of Breast Cancer J Natl Cancer Inst, July 16, 2008; 100(14): 978 - 979. [Full Text] [PDF]
|
|
|
|
 |
|
 P. M Ridker The Time for Cardiovascular Inflammation Reduction Trials Has Arrived: How Low to Go for hsCRP? Arterioscler Thromb Vasc Biol, July 1, 2008; 28(7): 1222 - 1224. [Full Text] [PDF]
|
|
|
|
 |
|
 U. Singh, M. R. Dasu, P. G. Yancey, A. Afify, S. Devaraj, and I. Jialal Human C-reactive protein promotes oxidized low density lipoprotein uptake and matrix metalloproteinase-9 release in Wistar rats J. Lipid Res., May 1, 2008; 49(5): 1015 - 1023. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Tasali and M. S. M. Ip Obstructive Sleep Apnea and Metabolic Syndrome: Alterations in Glucose Metabolism and Inflammation Proceedings of the ATS, February 15, 2008; 5(2): 207 - 217. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Martin-Fuentes, F. Civeira, D. Recalde, A. L. Garcia-Otin, E. Jarauta, I. Marzo, and A. Cenarro Individual Variation of Scavenger Receptor Expression in Human Macrophages with Oxidized Low-Density Lipoprotein Is Associated with a Differential Inflammatory Response J. Immunol., September 1, 2007; 179(5): 3242 - 3248. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Weiss Fat distribution and storage: how much, where, and how? Eur. J. Endocrinol., August 1, 2007; 157(suppl_1): S39 - S45. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Cicala, G. de Simone, M. J. Roman, L. G. Best, E. T. Lee, W. Wang, T. K. Welty, J. M. Galloway, B. V. Howard, and R. B. Devereux Prevalence and Prognostic Significance of Wall-Motion Abnormalities in Adults Without Clinically Recognized Cardiovascular Disease: The Strong Heart Study Circulation, July 10, 2007; 116(2): 143 - 150. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. M. Ridker C-Reactive Protein and the Prediction of Cardiovascular Events Among Those at Intermediate Risk: Moving an Inflammatory Hypothesis Toward Consensus J. Am. Coll. Cardiol., May 29, 2007; 49(21): 2129 - 2138. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Bisoendial, J. J. P. Kastelein, S. L. M. Peters, J. H. M. Levels, R. Birjmohun, J. I. Rotmans, D. Hartman, J. C. M. Meijers, M. Levi, and E. S. G. Stroes Effects of CRP infusion on endothelial function and coagulation in normocholesterolemic and hypercholesterolemic subjects J. Lipid Res., April 1, 2007; 48(4): 952 - 960. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Cappabianca, D. Paparella, G. Visicchio, G. Capone, G. Lionetti, F. Numis, P. Ferrara, C. D'Agostino, and L. de Luca Tupputi Schinosa Preoperative C-Reactive Protein Predicts Mid-Term Outcome After Cardiac Surgery Ann. Thorac. Surg., December 1, 2006; 82(6): 2170 - 2178. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Luther, J. V. Gainer, L. J. Murphey, C. Yu, D. E. Vaughan, J. D. Morrow, and N. J. Brown Angiotensin II Induces Interleukin-6 in Humans Through a Mineralocorticoid Receptor-Dependent Mechanism Hypertension, December 1, 2006; 48(6): 1050 - 1057. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Oda The metabolic syndrome (emperor) wears no clothes: response to kahn. Diabetes Care, November 1, 2006; 29(11): 2566 - 2566. [Full Text] [PDF]
|
|
|
|
|
|
P. Libby and P. M. Ridker Inflammation and Atherothrombosis: From Population Biology and Bench Research to Clinical Practice J. Am. Coll. Cardiol., October 27, 2006; 48(9_Suppl_A): A33 - A46. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Cavusoglu, C. Ruwende, V. Chopra, S. Yanamadala, C. Eng, L. T. Clark, D. J. Pinsky, and J. D. Marmur Adiponectin is an independent predictor of all-cause mortality, cardiac mortality, and myocardial infarction in patients presenting with chest pain Eur. Heart J., October 1, 2006; 27(19): 2300 - 2309. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. K. Figaro, S. B. Kritchevsky, H. E. Resnick, R. I. Shorr, J. Butler, A. Shintani, B. W. Penninx, E. M. Simonsick, B. H. Goodpaster, A. B. Newman, et al. Diabetes, Inflammation, and Functional Decline in Older Adults: Findings from the Health, Aging and Body Composition (ABC) study. Diabetes Care, September 1, 2006; 29(9): 2039 - 2045. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Devaraj, B. Davis, S. I. Simon, and I. Jialal CRP promotes monocyte-endothelial cell adhesion via Fc{gamma} receptors in human aortic endothelial cells under static and shear flow conditions Am J Physiol Heart Circ Physiol, September 1, 2006; 291(3): H1170 - H1176. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. B. Muhlestein, H. T. May, J. R. Jensen, B. D. Horne, R. B. Lanman, F. Lavasani, R. L. Wolfert, R. R. Pearson, H. D. Yannicelli, and J. L. Anderson The Reduction of Inflammatory Biomarkers by Statin, Fibrate, and Combination Therapy Among Diabetic Patients With Mixed Dyslipidemia: The DIACOR (Diabetes and Combined Lipid Therapy Regimen) Study J. Am. Coll. Cardiol., July 18, 2006; 48(2): 396 - 401. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Hausleiter, T. Meyer, M. Hadamitzky, A. Kastrati, S. Martinoff, and A. Schomig Prevalence of Noncalcified Coronary Plaques by 64-Slice Computed Tomography in Patients With an Intermediate Risk for Significant Coronary Artery Disease J. Am. Coll. Cardiol., July 18, 2006; 48(2): 312 - 318. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Lloyd-Jones, K. Liu, L. Tian, and P. Greenland Narrative Review: Assessment of C-Reactive Protein in Risk Prediction for Cardiovascular Disease Ann Intern Med, July 4, 2006; 145(1): 35 - 42. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Tanne, M. Benderly, U. Goldbourt, M. Haim, A. Tenenbaum, E. Z. Fisman, Z. Matas, Y. Adler, R. Zimmlichman, and S. Behar C-Reactive Protein as a Predictor of Incident Ischemic Stroke Among Patients With Preexisting Cardiovascular Disease Stroke, July 1, 2006; 37(7): 1720 - 1724. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. A Ryan-Borchers, J. S. Park, B. P Chew, M. K McGuire, L. R Fournier, and K. A Beerman Soy isoflavones modulate immune function in healthy postmenopausal women Am. J. Clinical Nutrition, May 1, 2006; 83(5): 1118 - 1125. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Montaner, I. Fernandez-Cadenas, C. A. Molina, M. Ribo, R. Huertas, A. Rosell, A. Penalba, L. Ortega, P. Chacon, and J. Alvarez-Sabin Poststroke C-Reactive Protein Is a Powerful Prognostic Tool Among Candidates for Thrombolysis Stroke, May 1, 2006; 37(5): 1205 - 1210. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Matsushita, H. Yatsuya, K. Tamakoshi, K. Wada, R. Otsuka, S. Takefuji, K. Sugiura, T. Kondo, T. Murohara, and H. Toyoshima Comparison of Circulating Adiponectin and Proinflammatory Markers Regarding Their Association With Metabolic Syndrome in Japanese Men Arterioscler Thromb Vasc Biol, April 1, 2006; 26(4): 871 - 876. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Grundy Metabolic Syndrome: Connecting and Reconciling Cardiovascular and Diabetes Worlds J. Am. Coll. Cardiol., March 21, 2006; 47(6): 1093 - 1100. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Eldrup, H. Sillesen, E. Prescott, and B. G. Nordestgaard Ankle brachial index, C-reactive protein, and central augmentation index to identify individuals with severe atherosclerosis Eur. Heart J., February 1, 2006; 27(3): 316 - 322. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. W. F. Wilson, B.-H. Nam, M. Pencina, R. B. D'Agostino Sr, E. J. Benjamin, and C. J. O'Donnell C-Reactive Protein and Risk of Cardiovascular Disease in Men and Women From the Framingham Heart Study Arch Intern Med, November 28, 2005; 165(21): 2473 - 2478. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. S. Ginsburg, M. P. Donahue, and L. K. Newby Prospects for Personalized Cardiovascular Medicine: The Impact of Genomics J. Am. Coll. Cardiol., November 1, 2005; 46(9): 1615 - 1627. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Singh, S. Devaraj, and I. Jialal C-Reactive Protein Decreases Tissue Plasminogen Activator Activity in Human Aortic Endothelial Cells: Evidence that C-Reactive Protein Is a Procoagulant Arterioscler Thromb Vasc Biol, October 1, 2005; 25(10): 2216 - 2221. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. B. Clearfield C-Reactive Protein: A New Risk Assessment Tool for Cardiovascular Disease J Am Osteopath Assoc, September 1, 2005; 105(9): 409 - 416. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. G. Best, Y. Zhang, E. T. Lee, J.-L. Yeh, L. Cowan, V. Palmieri, M. Roman, R. B. Devereux, R. R. Fabsitz, R. P. Tracy, 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, August 30, 2005; 112(9): 1289 - 1295. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Cushman, A. M. Arnold, B. M. Psaty, T. A. Manolio, L. H. Kuller, G. L. Burke, J. F. Polak, and R. P. Tracy C-Reactive Protein and the 10-Year Incidence of Coronary Heart Disease in Older Men and Women: The Cardiovascular Health Study Circulation, July 5, 2005; 112(1): 25 - 31. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M. Okin, M. J. Roman, L. G. Best, E. T. Lee, J. M. Galloway, B. V. Howard, and R. B. Devereux C-Reactive Protein and Electrocardiographic ST-Segment Depression Additively Predict Mortality: The Strong Heart Study J. Am. Coll. Cardiol., June 7, 2005; 45(11): 1787 - 1793. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. W. Zieske, R. P. Tracy, C. A. McMahan, E. E. Herderick, S. Homma, G. T. Malcom, H. C. McGill Jr, J. P. Strong, and for the Pathobiological Determinants of Atheroscle Elevated Serum C-Reactive Protein Levels and Advanced Atherosclerosis in Youth Arterioscler Thromb Vasc Biol, June 1, 2005; 25(6): 1237 - 1243. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.R. Langenfeld, T. Forst, C. Hohberg, P. Kann, G. Lubben, T. Konrad, S.D. Fullert, C. Sachara, and A. Pfutzner Pioglitazone Decreases Carotid Intima-Media Thickness Independently of Glycemic Control in Patients With Type 2 Diabetes Mellitus: Results From a Controlled Randomized Study Circulation, May 17, 2005; 111(19): 2525 - 2531. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. H. Berg and P. E. Scherer Adipose Tissue, Inflammation, and Cardiovascular Disease Circ. Res., May 13, 2005; 96(9): 939 - 949. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Cohen, D. Singh, P. Greenland, D. M. Lloyd-Jones, A. J. Moss, B. L. Jaber, N. E. Madias, P. M Ridker, C. P. Cannon, and E. Braunwald C-Reactive Protein Levels and Outcomes after Statin Therapy N. Engl. J. Med., April 14, 2005; 352(15): 1603 - 1605. [Full Text] [PDF]
|
|
|
|
|
|
J. Genius, T. Dong-Si, A. P. Grau, and C. Lichy Postacute C-Reactive Protein Levels Are Elevated in Cervical Artery Dissection Stroke, April 1, 2005; 36(4): e42 - e44. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Cushman Leukocyte Count in Vascular Risk Prediction Arch Intern Med, March 14, 2005; 165(5): 487 - 488. [Full Text] [PDF]
|
|
|
|
|
|
P. M Ridker, C. P. Cannon, D. Morrow, N. Rifai, L. M. Rose, C. H. McCabe, M. A. Pfeffer, E. Braunwald, and the Pravastatin or Atorvastatin Evaluation and Inf C-Reactive Protein Levels and Outcomes after Statin Therapy N. Engl. J. Med., January 6, 2005; 352(1): 20 - 28. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. K. Pai, T. Pischon, J. Ma, J. E. Manson, S. E. Hankinson, K. Joshipura, G. C. Curhan, N. Rifai, C. C. Cannuscio, M. J. Stampfer, et al. Inflammatory Markers and the Risk of Coronary Heart Disease in Men and Women N. Engl. J. Med., December 16, 2004; 351(25): 2599 - 2610. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. R. Moreno and V. Fuster The year in atherothrombosis J. Am. Coll. Cardiol., December 7, 2004; 44(11): 2099 - 2110. [Full Text] [PDF]
|
|
|
|
|
|
S. S. Levinson, J. J. Miller, and R. J. Elin Poor Predictive Value of High-Sensitivity C-Reactive Protein Indicates Need for Reassessment Clin. Chem., October 1, 2004; 50(10): 1733 - 1735. [Full Text] [PDF]
|
|
|
|
|
|
P. M Ridker, P. W.F. Wilson, and S. M. Grundy Should C-Reactive Protein Be Added to Metabolic Syndrome and to Assessment of Global Cardiovascular Risk? Circulation, June 15, 2004; 109(23): 2818 - 2825. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 CRP Predicts Risk at Every Level Journal Watch Cardiology, May 21, 2004; 2004(521): 2 - 2. [Full Text]
|
|