C-reactive protein as a risk factor versus risk marker

Purpose of review C-reactive protein (CRP) is consistently associated with cardiovascular disease in prospective and cross-sectional clinical and epidemiological studies. Inflammation is an important mechanism in cardiovascular disease, and the plasma level of CRP is considered to reflect the inflammatory condition of the patient and/or the vessel wall. In addition, there are also a number of indications for a causal role of CRP in cardiovascular disease. Recent findings A number of new publications show potential causal effects of CRP on cardiovascular disease, and evidence from human-CRP transgenic animals also indicates a causal contribution of CRP to cardiovascular disease. On the other hand, a new large prospective study and an updated meta-analysis indicate that the contribution of CRP to cardiovascular disease is less impressive than reported earlier (odds ratio, 1.58; 95% confidence interval, 1.48-1.68). Summary We review here the most recent evidence on mechanisms by which CRP is involved as a causal factor in the precipitation of cardiovascular disease. Evidence for such a role is accumulating.

[1]  N. Cook,et al.  C‐reactive protein gene polymorphisms and the risk of venous thromboembolism: a haplotype‐based analysis , 2004, Journal of thrombosis and haemostasis : JTH.

[2]  Hester S. Tak,et al.  Interindividual variation in the response by fibrinogen, C-reactive protein and interleukin-6 to yellow fever vaccination , 2004, Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis.

[3]  F. Burzotta,et al.  Inflammation as a Possible Link Between Coronary and Carotid Plaque Instability , 2004, Circulation.

[4]  J. Raynes,et al.  FcγRIIa expression with FcγRI results in C‐reactive protein‐ and IgG‐mediated phagocytosis , 2004 .

[5]  Seung‐Jung Park,et al.  C-Reactive Protein Promotes Monocyte Chemoattractant Protein-1–Mediated Chemotaxis Through Upregulating CC Chemokine Receptor 2 Expression in Human Monocytes , 2004, Circulation.

[6]  M. Kutryk,et al.  C-Reactive Protein Attenuates Endothelial Progenitor Cell Survival, Differentiation, and Function: Further Evidence of a Mechanistic Link Between C-Reactive Protein and Cardiovascular Disease , 2004, Circulation.

[7]  J. Gamble,et al.  High-Density Lipoproteins Neutralize C-Reactive Protein Proinflammatory Activity , 2004, Circulation.

[8]  E. Paffen,et al.  C-Reactive Protein Does Not Directly Induce Tissue Factor in Human Monocytes , 2004, Arteriosclerosis, thrombosis, and vascular biology.

[9]  J. Filep,et al.  Conformational Rearrangement in C-Reactive Protein Is Required for Proinflammatory Actions on Human Endothelial Cells , 2004, Circulation.

[10]  Prapat Suriyaphol,et al.  Possible Protective Role for C-Reactive Protein in Atherogenesis: Complement Activation by Modified Lipoproteins Halts Before Detrimental Terminal Sequence , 2004, Circulation.

[11]  Vilmundur Gudnason,et al.  C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease. , 2004, The New England journal of medicine.

[12]  W. Grander,et al.  C‐reactive protein plasma levels but not factor VII activity predict clinical outcome in patients undergoing elective coronary intervention , 2004, Clinical cardiology.

[13]  A. Wierzbicki,et al.  Cardiovascular disease in renal allograft recipients is associated with elevated sialic acid or markers of inflammation , 2004, Clinical transplantation.

[14]  E. Rimm,et al.  C-reactive protein and incident cardiovascular events among men with diabetes. , 2004, Diabetes care.

[15]  C. Meisinger,et al.  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 , 2004, Circulation.

[16]  P. Libby,et al.  Inflammation and atherosclerosis: role of C-reactive protein in risk assessment. , 2004, The American journal of medicine.

[17]  H. Shin,et al.  Association of high sensitivity C-reactive protein with coronary heart disease prediction, but not with carotid atherosclerosis, in patients with hypertension. , 2004, Circulation journal : official journal of the Japanese Circulation Society.

[18]  P. Weiner,et al.  The relation between preprocedural C‐reactive protein levels and early and late complications in patients with acute myocardial infarction undergoing interventional coronary angioplasty , 2004, Clinical cardiology.

[19]  S. Devaraj,et al.  Effect of C-reactive protein on chemokine expression in human aortic endothelial cells. , 2004, Journal of molecular and cellular cardiology.

[20]  Richard D. Weisel,et al.  C-Reactive Protein Upregulates Complement-Inhibitory Factors in Endothelial Cells , 2004, Circulation.

[21]  K. Kitamura,et al.  Effects of C-reactive protein on atherogenic mediators and adrenomedullin in human coronary artery endothelial and smooth muscle cells. , 2004, Biochemical and biophysical research communications.

[22]  Lan Li,et al.  C-Reactive Protein Accelerates the Progression of Atherosclerosis in Apolipoprotein E–Deficient Mice , 2004, Circulation.

[23]  J. Whittaker,et al.  Polymorphism at the C-reactive protein locus influences gene expression and predisposes to systemic lupus erythematosus. , 2003, Human molecular genetics.

[24]  T. Spector,et al.  Genetic effects on baseline values of C-reactive protein and serum amyloid a protein: a comparison of monozygotic and dizygotic twins. , 2004, Clinical chemistry.

[25]  S. Rubin,et al.  Inflammatory Markers and Onset of Cardiovascular Events: Results From the Health ABC Study , 2003, Circulation.

[26]  S. Humphries,et al.  Human CRP Gene Polymorphism Influences CRP Levels: Implications for the Prediction and Pathogenesis of Coronary Heart Disease , 2003, Arteriosclerosis, thrombosis, and vascular biology.

[27]  S. Devaraj,et al.  C-Reactive Protein Decreases Prostacyclin Release From Human Aortic Endothelial Cells , 2003, Circulation.

[28]  E. Edelman,et al.  Increased Thrombosis After Arterial Injury in Human C-Reactive Protein–Transgenic Mice , 2003, Circulation.

[29]  Mark B Pepys,et al.  C-reactive protein: a critical update. , 2003, The Journal of clinical investigation.

[30]  G. Lip,et al.  Effects of C-reactive protein on the release of von Willebrand factor, E-selectin, thrombomodulin and intercellular adhesion molecule-1 from human umbilical vein endothelial cells , 2003, Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis.

[31]  S. Verma,et al.  C-Reactive Protein Upregulates Angiotensin Type 1 Receptors in Vascular Smooth Muscle , 2003, Circulation.

[32]  Gary L Myers,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. , 2003, Circulation.

[33]  S. Devaraj,et al.  C-Reactive Protein Increases Plasminogen Activator Inhibitor-1 Expression and Activity in Human Aortic Endothelial Cells: Implications for the Metabolic Syndrome and Atherothrombosis , 2003, Circulation.

[34]  S. Meri,et al.  Binding of C-reactive protein to modified low-density-lipoprotein particles: identification of cholesterol as a novel ligand for C-reactive protein. , 2002, The Biochemical journal.

[35]  J. Witztum,et al.  C-reactive protein binds to both oxidized LDL and apoptotic cells through recognition of a common ligand: Phosphorylcholine of oxidized phospholipids , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[36]  Sridevi Devaraj,et al.  Demonstration That C-Reactive Protein Decreases eNOS Expression and Bioactivity in Human Aortic Endothelial Cells , 2002, Circulation.

[37]  Ren-Ke Li,et al.  A Self-Fulfilling Prophecy: C-Reactive Protein Attenuates Nitric Oxide Production and Inhibits Angiogenesis , 2002, Circulation.

[38]  M. Eren,et al.  Age-Dependent Spontaneous Coronary Arterial Thrombosis in Transgenic Mice That Express a Stable Form of Human Plasminogen Activator Inhibitor-1 , 2002, Circulation.

[39]  P. Ridker,et al.  Polymorphism in the human C-reactive protein (CRP) gene, plasma concentrations of CRP, and the risk of future arterial thrombosis. , 2002, Atherosclerosis.

[40]  S. Verma,et al.  Endothelin Antagonism and Interleukin-6 Inhibition Attenuate the Proatherogenic Effects of C-Reactive Protein , 2002, Circulation.

[41]  M. Lathrop,et al.  Genotype at a promoter polymorphism of the interleukin-6 gene is associated with baseline levels of plasma C-reactive protein. , 2002, Cardiovascular research.

[42]  G. Cooper,et al.  Association between baseline levels of C-reactive protein (CRP) and a dinucleotide repeat polymorphism in the intron of the CRP gene , 2002, Genes and Immunity.

[43]  James T. Willerson,et al.  Modulation of C-Reactive Protein–Mediated Monocyte Chemoattractant Protein-1 Induction in Human Endothelial Cells by Anti-Atherosclerosis Drugs , 2001 .

[44]  P. Ridker,et al.  High-sensitivity C-reactive protein: potential adjunct for global risk assessment in the primary prevention of cardiovascular disease. , 2001, Circulation.

[45]  V. Hombach,et al.  C-Reactive Protein–Mediated Low Density Lipoprotein Uptake by Macrophages: Implications for Atherosclerosis , 2001, Circulation.

[46]  J. Pankow,et al.  Familial and genetic determinants of systemic markers of inflammation: the NHLBI family heart study. , 2001, Atherosclerosis.

[47]  James T. Willerson,et al.  Direct Proinflammatory Effect of C-Reactive Protein on Human Endothelial Cells , 2000, Circulation.

[48]  W. Koenig,et al.  C-Reactive Protein in the Arterial Intima: Role of C-Reactive Protein Receptor–Dependent Monocyte Recruitment in Atherogenesis , 2000, Arteriosclerosis, thrombosis, and vascular biology.

[49]  C. Geczy,et al.  C-reactive Protein : Relationship with Age, Sex, and Hormone Replacement Treatment and Lipopolysaccharide Potentiate Monocyte Tissue Factor Induction by Γ Interferon- Interferon-␥ and Lipopolysaccharide Potentiate Monocyte Tissue Factor Induction by C-reactive Protein Relationship with Age, Sex, and , 2022 .

[50]  J. Radosevich,et al.  Immunohistochemical localization of modified C-reactive protein antigen in normal vascular tissue. , 2000, The American journal of the medical sciences.

[51]  M. Pepys,et al.  C-Reactive Protein and Complement Are Important Mediators of Tissue Damage in Acute Myocardial Infarction , 1999, The Journal of experimental medicine.

[52]  T. Böhm,et al.  Enhanced inflammatory response to coronary angioplasty in patients with severe unstable angina. , 1999, Circulation.

[53]  S. Bhakdi,et al.  Complement and atherogenesis: binding of CRP to degraded, nonoxidized LDL enhances complement activation. , 1999, Arteriosclerosis, thrombosis, and vascular biology.

[54]  K. Williams,et al.  Atherosclerosis--an inflammatory disease. , 1999, The New England journal of medicine.

[55]  J. Volanakis,et al.  C-Reactive Protein: Structural Biology and Host Defense Function , 1999, Clinical chemistry and laboratory medicine.

[56]  R. Ross,et al.  Atherosclerosis is an inflammatory disease. , 1998, American heart journal.

[57]  W. Koenig,et al.  C-reactive protein frequently colocalizes with the terminal complement complex in the intima of early atherosclerotic lesions of human coronary arteries. , 1998, Arteriosclerosis, thrombosis, and vascular biology.

[58]  R Peto,et al.  Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease: meta-analyses of prospective studies. , 1998, JAMA.

[59]  J. Waltenberger,et al.  Processes in atherogenesis: complement activation. , 1997, Atherosclerosis.

[60]  S. Thompson,et al.  Production of C-reactive protein and risk of coronary events in stable and unstable angina , 1997, The Lancet.

[61]  J. Volanakis,et al.  Role of complement in C-reactive-protein-mediated protection of mice from Streptococcus pneumoniae , 1996, Infection and immunity.

[62]  I. T. Ten Berge,et al.  CRP-mediated activation of complement in vivo: assessment by measuring circulating complement-C-reactive protein complexes. , 1996, Journal of immunology.

[63]  Harry,et al.  C-reactive protein induces human peripheral blood monocytes to synthesize tissue factor. , 1993, Blood.

[64]  M. Pepys.  C-REACTIVE PROTEIN FIFTY YEARS ON , 1981, The Lancet.

[65]  J. Huxley.  The second biological revolution. , 1946, Lancet.