Cardiac Biomarkers: Expert Advice for Clinicians
Cardiac biomarkers have revolutionized the practice of medicine. Current guidelines for the evaluation and risk stratification of patients with acute coronary syndromes include the use of cardiac injury biomarkers along with electrocardiography and cardiac imaging. In patients with dyspnea and those with heart failure, the use of natriuretic peptides has become the standard of care for diagnosis, to guide treatment, and for risk stratification. Cardiac Biomarkers: Expert Advice for Clinicians is an excellent book that summarizes existing and newer cardiac biomarkers in this rapidly evolving field. As such, this book is an outstanding resource for the practicing clinician. The book is edited by Dr Alan Maisel, a cardiologist and world-renowned expert in this field, who has assembled an outstanding group of coauthors.
The book is divided in 5 sections. In Section 1, Markers of Cardiac Risk, the first chapter is an overview of the markers of cardiac risk. It is well written and is an excellent summary of the different types of biomarkers in general and specifically of cardiac biomarkers. In the second chapter, the authors provide an in-depth discussion of the role of oxidized phospholipids and oxidative stress and their role in detection of early cardiovascular risk. Unfortunately, this chapter is a bit esoteric because it contains too much methodological trivia that is likely to be of little relevance to the average practicing clinician. For example, the section on oxidized phospholipids/apolipoprotein B methodology is quite long and too technical. As a practicing clinician, I am not much interested in how to develop a chemiluminescent enzyme-linked immunosorbent assay to detect oxidized phospholipids in humans apolipoprotein B100; despite these shortcomings, the potential importance of the oxidized phospholipids/apolipoprotein B assay as a cardiac biomarker is clearly stated.
Section 2, Markers of Cardiac Ischemia, is well written, quite comprehensive, and probably one of the most important of the book. The first chapter in this section provides an overview of the diagnosis and risk stratification of chest pain syndrome/acute coronary syndrome patients presenting to the emergency department. This chapter provides an outstanding summary of the current state of the art of evaluation of the acute coronary syndrome patient in the emergency department with use of combined cardiac and imaging biomarkers. The next chapter deals with issues related to laboratory assessment and evaluation of biomarkers in general. Although interesting and important, the material discussed in this chapter may be less useful to the average practicing clinician. The chapter on highly sensitive troponin assays by Dr Alan Jaffe, a highly respected expert in the field, is perhaps one of the most interesting chapters in the book because it puts into perspective the potential use of these highly sensitive biomarkers to improve the sensitivity and increase the speed of diagnosing cardiac injury and clarifies some of the confusion in this rapidly evolving field. The hypersensitive troponins are those in which values detected for normal subjects exceed 90% (for current assays, this number is <50%), with the implication that detection in a higher percentage of normal subjects reflects higher sensitivity. Additional technical issues of clinical relevance discussed include the importance of hemolysis in affecting serum values of troponins (for cardiac troponin I, hemolysis can increase values, whereas for cardiac troponin T, values can be decreased) and how antibodies against epitopes used for detection result in lower troponin values; other technical issues of clinical importance are also discussed. A short discussion on the value of troponins in nonischemic heart disease and chronic cardiovascular disease suggests that the potential use of these biomarkers exceed the current use for diagnosis of acute coronary syndromes. The final chapter in this section starts with a relevant discussion on the ischemic cascade and new relevant biomarkers for detection of ischemic injury (heart-type fatty acid binding protein), for inflammation and plaque rupture (high-sensitivity C-reactive protein, myeloperoxidase, and pregnancy-associated protein), and markers of hemodynamic stress (natriuretic peptides and copeptin). Some of these markers, such as heart fatty acid binding protein and copeptin, appear to have a high negative predictive value for ischemia, and thus may be of value in the evaluation of acute coronary syndromes in the emergency department.
In Section 3, Natriuretic Peptides for Heart Failure, important biomarkers are discussed. These biomarkers have been clearly established clinically for the evaluation of patients with heart failure and patients presenting with dyspnea of uncertain origin. Three chapters deal with their use for diagnosis, treatment titration, and risk stratification in different clinical settings, including patients with acute shortness of breath, in hospitalized patients, and in the outpatient setting. These 3 chapters are well written and emphasize the role of the 2 most widely used clinical natriuretic peptides: brain natriuretic peptide and N-terminal prohormone of brain natriuretic peptide. Natriuretic peptides are produced and released to the circulation by cardiomyocytes in response to increased wall stress, a condition that results from pressure or volume overload in systolic or diastolic heart failure. In hospitalized patients, natriuretic peptides have been shown to predict cardiac events, including readmission and mortality.
Section 4, Biomarkers in Cardiorenal Disease, addresses, in particular, biomarkers of renal injury. Many medical and/or interventional procedures performed in cardiac patients have the potential to result in renal damage, and thus it is important to prevent and recognize these early. The definition, epidemiology, pathophysiology, diagnosis, prevention, and treatment of cardiorenal syndromes is presented in the first chapter of this section. The second chapter deals with traditional renal biomarkers, such as blood urea nitrogen, creatinine clearance, and urine output, and newer biomarkers, such as neutrophil gelatinase-associated lipocalin, cystatin C, interleukin-18, and kidney injury molecule-1. Despite the importance of this topic, this section is somewhat peripheral to the main focus of this book on cardiac biomarkers. As stated by the authors, the use of novel “kidney biomarkers … have not added much incremental value for clinical decision making.”
The book concludes with Section 5, Looking Towards the Future, in which the most promising cardiac biomarkers are discussed in 4 chapters. Adrenomedullin is a promising marker for the evaluation of patients with dyspnea. Galectin-3 is a marker of myocardial fibrosis that may be important in a number of diseases, including heart failure with preserved ejection fraction, in which a specific treatment is lacking and a marker of disease severity may enhance clinical management. A more general discussion of all fibrosis-related markers, such as n-terminal propeptide of type II collagen, c-terminal telopeptide of type I collagen, tissue inhibitor of metalloproteinase 1, and matrix metalloproteinase 2, would have been beneficial because this is a relatively unknown topic. ST-2 is a marker of inflammation and possibly also myocardial remodeling and progression of heart failure. In the last chapter, copeptin is discussed as a biomarker of potential use in myocardial infarction and as a guide to therapy for those being treated with vasopressin antagonists for heart failure.
I enjoyed reading this most outstanding book, and I certainly agree with its stated purpose in the introduction that it will “make a good doctor better.” Dr Maisel and his coauthors deserve to be congratulated for achieving this aim.
Victor G. Davila-Roman, MD, FACC, FASE
Washington University School of Medicine
St. Louis, MO
- © 2012 American Heart Association, Inc.