Improving Risk Stratification for Cardiovascular Disease
Improving Risk Stratification for Cardiovascular Disease
Identifying people at high risk of cardiovascular events is the cornerstone of cardiovascular disease prevention and a major challenge for healthcare worldwide. Recently, both inflammatory and oxidative markers have been shown to improve cardiovascular risk prediction models in a wide range of patients. Here, we evaluate a recent publication investigating the value of inflammatory and oxidative markers for the prediction of cardiovascular mortality in patients with stable coronary artery disease. This study shows that the use of multiple markers may increase the predictive power of traditional risk models. The findings are discussed in the context of cardiovascular risk prediction in general.
In this article, we shall discuss the importance and goals of primary and secondary prevention of atherosclerotic complications and evaluate a recent paper examining the combined value of C-reactive protein (CRP) and myeloperoxidase (MPO) in predicting cardiovascular mortality among patients with stable coronary artery disease (CAD). Identifying individuals at high risk of cardiovascular disease is the cornerstone of cardiovascular disease prevention and a major public health challenge worldwide. The Framingham risk score is one of the best validated risk algorithms currently available and has shown excellent discriminative power in predicting cardiovascular events using traditional risk factors including sex, age, diabetes mellitus, systolic blood pressure, smoking, and LDL- and HDL-cholesterol. Apart from these established risk factors, our more recently acquired understanding of the pathogenesis of atherosclerosis and cardiovascular disease suggests that inflammation and oxidative stress also play a crucial role in the development of atherosclerosis and its clinical manifestations, such as myocardial infarction and stroke. However, these recent advances have not been translated into routine clinical practice, where the mainstay of treatment is still lipid-targeted therapy. Biomarker risk prediction is rapidly evolving, and recently, numerous reports on the relationship between various inflammatory and oxidative biomarkers have shown them to be associated with cardiovascular risk, both in apparently healthy individuals and in patients with prevalent coronary heart disease. Among the range of biomarkers proposed for diagnostic use, oxidized LDL (oxLDL), MPO, lipoprotein-associated phospholipase A2, pentraxin-3, cytokines such as IL-6, proteases such as matrix metalloproteinase-9, and CRP have received considerable attention.
Myeloperoxidase is a heme-containing peroxidase abundantly expressed in neutrophil leukocytes. Enzymatically active MPO is a key contributor to the oxygen-dependent microbicidal activity of phagocytes. In addition, excessive generation of MPO-derived oxidants has been linked to tissue damage in many diseases, especially those characterized by acute or chronic inflammation. Furthermore, MPO affects various processes involved in cell signaling and cell–cell interactions, and is, as such, capable of modulating inflammatory responses. Recent epidemiological studies have shown associations between MPO and the risk of cardiovascular disease, both in apparently healthy people and in patients with prevalent CAD. In addition, MPO activity can result in nitration of protein tyrosine residues, yielding nitrotyrosine, an independent risk factor of CAD.
Abstract and Introduction
Abstract
Identifying people at high risk of cardiovascular events is the cornerstone of cardiovascular disease prevention and a major challenge for healthcare worldwide. Recently, both inflammatory and oxidative markers have been shown to improve cardiovascular risk prediction models in a wide range of patients. Here, we evaluate a recent publication investigating the value of inflammatory and oxidative markers for the prediction of cardiovascular mortality in patients with stable coronary artery disease. This study shows that the use of multiple markers may increase the predictive power of traditional risk models. The findings are discussed in the context of cardiovascular risk prediction in general.
Introduction
In this article, we shall discuss the importance and goals of primary and secondary prevention of atherosclerotic complications and evaluate a recent paper examining the combined value of C-reactive protein (CRP) and myeloperoxidase (MPO) in predicting cardiovascular mortality among patients with stable coronary artery disease (CAD). Identifying individuals at high risk of cardiovascular disease is the cornerstone of cardiovascular disease prevention and a major public health challenge worldwide. The Framingham risk score is one of the best validated risk algorithms currently available and has shown excellent discriminative power in predicting cardiovascular events using traditional risk factors including sex, age, diabetes mellitus, systolic blood pressure, smoking, and LDL- and HDL-cholesterol. Apart from these established risk factors, our more recently acquired understanding of the pathogenesis of atherosclerosis and cardiovascular disease suggests that inflammation and oxidative stress also play a crucial role in the development of atherosclerosis and its clinical manifestations, such as myocardial infarction and stroke. However, these recent advances have not been translated into routine clinical practice, where the mainstay of treatment is still lipid-targeted therapy. Biomarker risk prediction is rapidly evolving, and recently, numerous reports on the relationship between various inflammatory and oxidative biomarkers have shown them to be associated with cardiovascular risk, both in apparently healthy individuals and in patients with prevalent coronary heart disease. Among the range of biomarkers proposed for diagnostic use, oxidized LDL (oxLDL), MPO, lipoprotein-associated phospholipase A2, pentraxin-3, cytokines such as IL-6, proteases such as matrix metalloproteinase-9, and CRP have received considerable attention.
Myeloperoxidase is a heme-containing peroxidase abundantly expressed in neutrophil leukocytes. Enzymatically active MPO is a key contributor to the oxygen-dependent microbicidal activity of phagocytes. In addition, excessive generation of MPO-derived oxidants has been linked to tissue damage in many diseases, especially those characterized by acute or chronic inflammation. Furthermore, MPO affects various processes involved in cell signaling and cell–cell interactions, and is, as such, capable of modulating inflammatory responses. Recent epidemiological studies have shown associations between MPO and the risk of cardiovascular disease, both in apparently healthy people and in patients with prevalent CAD. In addition, MPO activity can result in nitration of protein tyrosine residues, yielding nitrotyrosine, an independent risk factor of CAD.
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