Biomarkers in cardiovascular disease: integrating pathophysiology into clinical practice.

Biomarkers play an important role in the diagnosis, prognostic assessment, and management of patients with suspected acute coronary syndromes (ACS). Specific biomarkers identify different components of the pathophysiology of ACS: troponins are prototype markers of myocyte necrosis, natriuretic peptides reflect neurohormonal activation and hemodynamic stress, soluble CD40 ligand is an indicator of platelet activation, and C-reactive protein, myeloperoxidase, and monocyte chemoattractant protein-1 reflect various inflammatory processes. When combined, multiple biomarkers reflecting different pathophysiologic processes appear to enhance risk stratification, as compared with using individual markers alone. Advances in proteomic technology promise to identify additional novel biomarkers that facilitate diagnosis, risk stratification, and selection of therapies in ACS. In the future, it is hoped that multiple biomarker panels will form the basis of an individualized approach to the treatment of ACS, in which therapy is tailored to individual biomarker profiles.

[1]  R. Califf,et al.  Prognostic value of serial B-type natriuretic peptide testing during follow-up of patients with unstable coronary artery disease. , 2005, JAMA.

[2]  A. Khera,et al.  Relation of coronary atherosclerosis determined by electron beam computed tomography and plasma levels of n-terminal pro-brain natriuretic peptide in a multiethnic population-based sample (the Dallas Heart Study). , 2005, The American journal of cardiology.

[3]  A. Khera,et al.  Race and gender differences in C-reactive protein levels. , 2005, Journal of the American College of Cardiology.

[4]  G. Guyatt,et al.  Capability of ischemia-modified albumin to predict serious cardiac outcomes in the short term among patients with potential acute coronary syndrome , 2005, Canadian Medical Association Journal.

[5]  A. Jeremias,et al.  Narrative Review: Alternative Causes for Elevated Cardiac Troponin Levels when Acute Coronary Syndromes Are Excluded , 2005, Annals of Internal Medicine.

[6]  Fred S Apple,et al.  Future biomarkers for detection of ischemia and risk stratification in acute coronary syndrome. , 2005, Clinical chemistry.

[7]  A. Dobson,et al.  How well does B-type natriuretic peptide predict death and cardiac events in patients with heart failure: systematic review , 2005, BMJ : British Medical Journal.

[8]  François Mach,et al.  Inflammation and Atherosclerosis , 2004, Herz.

[9]  M. Sabatine,et al.  Acute changes in circulating natriuretic peptide levels in relation to myocardial ischemia. , 2004, Journal of the American College of Cardiology.

[10]  A. Khera,et al.  Association among plasma levels of monocyte chemoattractant protein-1, traditional cardiovascular risk factors, and subclinical atherosclerosis. , 2004, Journal of the American College of Cardiology.

[11]  A. García-Méndez,et al.  Proteomic analysis of plasma from patients during an acute coronary syndrome. , 2004, Journal of the American College of Cardiology.

[12]  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.

[13]  W. Aronow,et al.  Prevalence of increased cardiac troponin I levels in patients with and without acute pulmonary embolism and relation of increased cardiac troponin I levels with in-hospital mortality in patients with acute pulmonary embolism. , 2004, The American journal of cardiology.

[14]  P O Collinson,et al.  Role of “Ischemia Modified Albumin”, a new biochemical marker of myocardial ischaemia, in the early diagnosis of acute coronary syndromes , 2004, Emergency Medicine Journal.

[15]  E. Topol,et al.  Prognostic value of myeloperoxidase in patients with chest pain. , 2003, The New England journal of medicine.

[16]  C. Heeschen,et al.  Myeloperoxidase Serum Levels Predict Risk in Patients With Acute Coronary Syndromes , 2003, Circulation.

[17]  P. Libby,et al.  Soluble CD40L: Risk Prediction After Acute Coronary Syndromes , 2003, Circulation.

[18]  J. Kaski,et al.  Relation of ischemia-modified albumin (IMA) levels following elective angioplasty for stable angina pectoris to duration of balloon-induced myocardial ischemia. , 2003, The American journal of cardiology.

[19]  M. Drazner,et al.  B-type natriuretic peptide in cardiovascular disease , 2003, The Lancet.

[20]  C. Herzog,et al.  Cardiac troponin T and C-reactive protein for predicting prognosis, coronary atherosclerosis, and cardiomyopathy in patients undergoing long-term hemodialysis. , 2003, JAMA.

[21]  H. Joller-jemelka,et al.  Troponin as a risk factor for mortality in critically ill patients without acute coronary syndromes. , 2003, Journal of the American College of Cardiology.

[22]  P. Collinson,et al.  Ischemia Modified Albumin Is a Sensitive Marker of Myocardial Ischemia After Percutaneous Coronary Intervention , 2003, Circulation.

[23]  E. Antman,et al.  The search for a biomarker of cardiac ischemia. , 2003, Clinical chemistry.

[24]  M. Sabatine,et al.  Evaluation of B-type natriuretic peptide for risk assessment in unstable angina/non-ST-elevation myocardial infarction: B-type natriuretic peptide and prognosis in TACTICS-TIMI 18. , 2003, Journal of the American College of Cardiology.

[25]  C. Heeschen,et al.  Soluble CD40 ligand in acute coronary syndromes. , 2003, The New England journal of medicine.

[26]  R. Califf,et al.  Clinical study: acute coronary syndrome/myocardial infarctionTroponin and C-reactive protein have different relations to subsequent mortality and myocardial infarction after acute coronary syndrome: A GUSTO-IV substudy , 2003 .

[27]  E. Antman,et al.  Association Between Plasma Levels of Monocyte Chemoattractant Protein-1 and Long-Term Clinical Outcomes in Patients With Acute Coronary Syndromes , 2003, Circulation.

[28]  Fred S Apple,et al.  Predictive Value of Cardiac Troponin I and T for Subsequent Death in End-Stage Renal Disease , 2002, Circulation.

[29]  J. Herlitz,et al.  N-Terminal Pro-B-Type Natriuretic Peptide and Long-Term Mortality in Acute Coronary Syndromes , 2002, Circulation.

[30]  Patrick André,et al.  Platelet-derived CD40L: the switch-hitting player of cardiovascular disease. , 2002, Circulation.

[31]  B. Lindahl,et al.  N-terminal pro brain natriuretic peptide on admission for early risk stratification of patients with chest pain and no ST-segment elevation. , 2002, Journal of the American College of Cardiology.

[32]  Alan S Maisel,et al.  Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure. , 2002, The New England journal of medicine.

[33]  C. Cannon,et al.  Elevations in Troponin T and I Are Associated With Abnormal Tissue Level Perfusion: A TACTICS-TIMI 18 Substudy , 2002, Circulation.

[34]  Michael R. Müller,et al.  Simvastatin Reduces Expression of Cytokines Interleukin-6, Interleukin-8, and Monocyte Chemoattractant Protein-1 in Circulating Monocytes From Hypercholesterolemic Patients , 2002, Arteriosclerosis, thrombosis, and vascular biology.

[35]  R. Califf,et al.  Troponin T levels in patients with acute coronary syndromes, with or without renal dysfunction. , 2002, The New England journal of medicine.

[36]  R. Masters,et al.  Natriuretic Peptide System Gene Expression in Human Coronary Arteries , 2002, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[37]  N. Weissman,et al.  Intravascular ultrasound findings in patients with acute coronary syndromes with and without elevated troponin I level. , 2002, The American journal of cardiology.

[38]  Nader Rifai,et al.  Multimarker Approach to Risk Stratification in Non-ST Elevation Acute Coronary Syndromes: Simultaneous Assessment of Troponin I, C-Reactive Protein, and B-Type Natriuretic Peptide , 2002, Circulation.

[39]  R. Hynes,et al.  CD40L stabilizes arterial thrombi by a β3 integrin–dependent mechanism , 2002, Nature Medicine.

[40]  E. Antman,et al.  Prognostic value of N-terminal pro-atrial and pro-brain natriuretic peptide in patients with acute coronary syndromes. , 2002, The American journal of cardiology.

[41]  P. Libby,et al.  CD40 Signaling and Plaque Instability , 2001, Circulation research.

[42]  W. Daniel,et al.  Patients with acute coronary syndromes express enhanced CD40 ligand/CD154 on platelets , 2001, Heart.

[43]  E. Braunwald,et al.  Ability of minor elevations of troponins I and T to predict benefit from an early invasive strategy in patients with unstable angina and non-ST elevation myocardial infarction: results from a randomized trial. , 2001, JAMA.

[44]  E J Topol,et al.  Association between myeloperoxidase levels and risk of coronary artery disease. , 2001, JAMA.

[45]  M. Sabatine,et al.  The prognostic value of B-type natriuretic peptide in patients with acute coronary syndromes. , 2001, The New England journal of medicine.

[46]  A. Go,et al.  The prognostic value of troponin in patients with non-ST elevation acute coronary syndromes: a meta-analysis. , 2001, Journal of the American College of Cardiology.

[47]  F. Hetzel,et al.  Reduced albumin-cobalt binding with transient myocardial ischemia after elective percutaneous transluminal coronary angioplasty: a preliminary comparison to creatine kinase-MB, myoglobin, and troponin I. , 2001, American heart journal.

[48]  Wendy R. Sanhai,et al.  Characteristics of an Albumin Cobalt Binding Test for assessment of acute coronary syndrome patients: a multicenter study. , 2001, Clinical chemistry.

[49]  A. Aljada,et al.  Suppression of nuclear factor-kappaB and stimulation of inhibitor kappaB by troglitazone: evidence for an anti-inflammatory effect and a potential antiatherosclerotic effect in the obese. , 2001, The Journal of clinical endocrinology and metabolism.

[50]  L. Wallentin,et al.  Comparison between strategies using creatine kinase-MB(mass), myoglobin, and troponin T in the early detection or exclusion of acute myocardial infarction in patients with chest pain and a nondiagnostic electrocardiogram. , 2000, The American journal of cardiology.

[51]  E. Antman,et al.  Cardiac troponin I for stratification of early outcomes and the efficacy of enoxaparin in unstable angina: a TIMI-11B substudy. , 2000, Journal of the American College of Cardiology.

[52]  A. Siegbahn,et al.  Markers of myocardial damage and inflammation in relation to long-term mortality in unstable coronary artery disease. FRISC Study Group. Fragmin during Instability in Coronary Artery Disease. , 2000, The New England journal of medicine.

[53]  M. Ohyanagi,et al.  Transient increase in plasma brain (b‐type) natriuretic peptide after percutaneous transluminal coronary angioplasty , 2000, Clinical cardiology.

[54]  Hugo A. Katus,et al.  Myocardial infarction redefined--a consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. , 2000, European heart journal.

[55]  P. Ridker,et al.  C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. , 2000, The New England journal of medicine.

[56]  G. Wagner,et al.  Very early diagnosis and risk stratification of patients admitted with suspected acute myocardial infarction by the combined evaluation of a single serum value of cardiac troponin-T, myoglobin, and creatine kinase MB(mass) , 2000, European heart journal.

[57]  Y. L. Chen,et al.  Red wine inhibits monocyte chemotactic protein-1 expression and modestly reduces neointimal hyperplasia after balloon injury in cholesterol-Fed rabbits. , 1999, Circulation.

[58]  H. White,et al.  Troponin concentrations for stratification of patients with acute coronary syndromes in relation to therapeutic efficacy of tirofiban , 1999, The Lancet.

[59]  K. Forfang,et al.  Enhanced levels of soluble and membrane-bound CD40 ligand in patients with unstable angina. Possible reflection of T lymphocyte and platelet involvement in the pathogenesis of acute coronary syndromes. , 1999, Circulation.

[60]  N. Maeda,et al.  Absence of CC chemokine receptor-2 reduces atherosclerosis in apolipoprotein E-deficient mice. , 1999, Atherosclerosis.

[61]  J. Kelley,et al.  Human endothelium as a source of multifunctional cytokines: molecular regulation and possible role in human disease. , 1999, Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research.

[62]  J. Egido,et al.  ACE inhibitor quinapril reduces the arterial expression of NF-kappaB-dependent proinflammatory factors but not of collagen I in a rabbit model of atherosclerosis. , 1998, The American journal of pathology.

[63]  P. Libby,et al.  Absence of monocyte chemoattractant protein-1 reduces atherosclerosis in low density lipoprotein receptor-deficient mice. , 1998, Molecular cell.

[64]  E. Antman,et al.  C-Reactive Protein Is a Potent Predictor of Mortality Independently of and in Combination With Troponin T in Acute Coronary Syndromes: A TIMI 11A Substudy , 1998 .

[65]  J. Kjekshus,et al.  Elevated circulating levels of C-C chemokines in patients with congestive heart failure. , 1998, Circulation.

[66]  Reinhold Förster,et al.  CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells , 1998, Nature.

[67]  A. Siegbahn,et al.  Platelet-derived growth factor-BB and monocyte chemotactic protein-1 induce human peripheral blood monocytes to express tissue factor. , 1996, Thrombosis research.

[68]  R. T. Lie,et al.  Plasma brain natriuretic peptide as an indicator of left ventricular systolic function and long-term survival after acute myocardial infarction. Comparison with plasma atrial natriuretic peptide and N-terminal proatrial natriuretic peptide. , 1996, Circulation.

[69]  R. D. de Winter,et al.  Value of myoglobin, troponin T, and CK-MBmass in ruling out an acute myocardial infarction in the emergency room. , 1995, Circulation.

[70]  I. Hassinen,et al.  Hypoxia stimulates release of ANP and BNP from perfused rat ventricular myocardium. , 1994, The American journal of physiology.

[71]  K. Nakao,et al.  Increased Plasma Levels of Brain Natriuretic Peptide in Patients With Acute Myocardial Infarction , 1993, Circulation.

[72]  S. Coughlin,et al.  Monocyte chemoattractant protein-1 in human atheromatous plaques. , 1991, The Journal of clinical investigation.

[73]  D. Steinberg,et al.  Expression of monocyte chemoattractant protein 1 in macrophage-rich areas of human and rabbit atherosclerotic lesions. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[74]  J. Lemos,et al.  Natriuretic Peptides in Acute and Chronic Coronary Artery Disease , 2006 .

[75]  K. Lewandrowski,et al.  Ischemia-modified albumin improves the usefulness of standard cardiac biomarkers for the diagnosis of myocardial ischemia in the emergency department setting. , 2005, American journal of clinical pathology.

[76]  A. Siegbahn,et al.  N-terminal pro-brain natriuretic peptide in relation to inflammation, myocardial necrosis, and the effect of an invasive strategy in unstable coronary artery disease. , 2003, Journal of the American College of Cardiology.

[77]  Ose,et al.  Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events* , 2002 .

[78]  E. Antman,et al.  C-reactive protein is a potent predictor of mortality independently of and in combination with troponin T in acute coronary syndromes: a TIMI 11A substudy. Thrombolysis in Myocardial Infarction. , 1998, Journal of the American College of Cardiology.

[79]  K. Kangawa,et al.  Plasma brain natriuretic peptide is a biochemical marker for the prediction of progressive ventricular remodeling after acute myocardial infarction. , 1998, American heart journal.

[80]  N. Arakawa,et al.  Relationship between plasma level of brain natriuretic peptide and myocardial infarct size. , 1994, Cardiology.