High-Sensitivity C-Reactive Protein and Cardiovascular Disease
The role of inflammation in the propagation of atherosclerosis and susceptibility to cardiovascular (CV) events is well established. Of the wide array of inflammatory biomarkers that have been studied, high-sensitivity C-reactive protein (hsCRP) has received the most attention for its use in screening and risk reclassification and as a predictor of clinical response to statin therapy. Although CRP is involved in the immunologic process that triggers vascular remodeling and plaque deposition and is associated with increased CV disease (CVD) risk, definitive randomized evidence for its role as a causative factor in atherothrombosis is lacking. Whether measurement of hsCRP levels provides consistent, clinically meaningful incremental predictive value in risk prediction and reclassification beyond conventional factors remains debated. Despite publication of guidelines on the use of hsCRP in CVD risk prediction by several leading professional organizations, there is a lack of clear consensus regarding the optimal clinical use of hsCRP. This article reviews 4 distinct points from the literature to better understand the current state and application of hsCRP in clinical practice: 1) the biology of hsCRP and its role in atherosclerosis; 2) the epidemiological association of hsCRP with CVD; 3) the quality of hsCRP as a biomarker of risk; and 4) the use of hsCRP as a tool to initiate or tailor statin therapy. Furthermore, we highlight recommendations from societies and important considerations when using hsCRP to guide treatment decisions in the primary prevention setting.
Inflammation is central to the initiation and progression of atherothrombosis and to triggering cardiovascular disease (CVD) events. Advances in vascular biology have established the interaction of the innate immune system with atherosclerosis. Clinical studies have linked chronic inflammation to future CV events, and emerging biomarkers of inflammation have been postulated to improve identification of at-risk asymptomatic patients.
Conventional risk factors in the Framingham risk score (FRS), such as age, male sex, hypercholesterolemia, hypertension, and smoking, account for most of the risk of coronary heart disease (CHD) and have been the bedrock of risk assessment for decades. However, approximately one-third of individuals with 0 or 1 risk factor develop CHD and up to 40% of individuals with cholesterol levels below the population average die from CHD. Furthermore, many CV events occur in patients treated with statin therapy. As such, a wide array of biomarkers—high-sensitivity assays detecting low levels of C-reactive protein (CRP), genetic polymorphism arrays, and direct imaging of subclinical atherosclerosis with coronary artery calcium (CAC) or carotid intima-media thickness—have been investigated for refinement of risk assessment and preventive therapy allocation (Fig. 1).
(Enlarge Image)
Figure 1.
Utility of Biomarkers in the Lifelong Prevention of Cardiovascular Disease
A dynamic set of genetic, circulating, and imaging biomarkers may be used in the lifelong prevention of atherosclerosis. Genetic and serum biomarkers may be useful in detecting those with early risk factor exposure and genetic predisposition (A) Imaging biomarkers may be useful in detecting subclinical disease. (B) Circulating biomarkers may be most informative in detecting earlier stages of atherosclerosis before the presence of cardiovascular disease, although high-sensitivity C-reactive protein has been shown to predict coronary heart disease in patients with unstable angina (C). Figure illustration by Craig Skaggs.
This paper reviews 4 distinct points from the literature to better understand the current state and application of high-sensitivity C-reactive protein (hsCRP) in clinical practice: 1) the biology of CRP and its role in atherosclerosis; 2) the epidemiological association of hsCRP with CVD; 3) the quality of hsCRP level as a biomarker of risk; and 4) the use of hsCRP as a tool to initiate or tailor statin therapy. Furthermore, we highlight recommendations from societies and important considerations when using hsCRP to guide treatment decisions in primary prevention.
Abstract and Introduction
Abstract
The role of inflammation in the propagation of atherosclerosis and susceptibility to cardiovascular (CV) events is well established. Of the wide array of inflammatory biomarkers that have been studied, high-sensitivity C-reactive protein (hsCRP) has received the most attention for its use in screening and risk reclassification and as a predictor of clinical response to statin therapy. Although CRP is involved in the immunologic process that triggers vascular remodeling and plaque deposition and is associated with increased CV disease (CVD) risk, definitive randomized evidence for its role as a causative factor in atherothrombosis is lacking. Whether measurement of hsCRP levels provides consistent, clinically meaningful incremental predictive value in risk prediction and reclassification beyond conventional factors remains debated. Despite publication of guidelines on the use of hsCRP in CVD risk prediction by several leading professional organizations, there is a lack of clear consensus regarding the optimal clinical use of hsCRP. This article reviews 4 distinct points from the literature to better understand the current state and application of hsCRP in clinical practice: 1) the biology of hsCRP and its role in atherosclerosis; 2) the epidemiological association of hsCRP with CVD; 3) the quality of hsCRP as a biomarker of risk; and 4) the use of hsCRP as a tool to initiate or tailor statin therapy. Furthermore, we highlight recommendations from societies and important considerations when using hsCRP to guide treatment decisions in the primary prevention setting.
Introduction
Inflammation is central to the initiation and progression of atherothrombosis and to triggering cardiovascular disease (CVD) events. Advances in vascular biology have established the interaction of the innate immune system with atherosclerosis. Clinical studies have linked chronic inflammation to future CV events, and emerging biomarkers of inflammation have been postulated to improve identification of at-risk asymptomatic patients.
Conventional risk factors in the Framingham risk score (FRS), such as age, male sex, hypercholesterolemia, hypertension, and smoking, account for most of the risk of coronary heart disease (CHD) and have been the bedrock of risk assessment for decades. However, approximately one-third of individuals with 0 or 1 risk factor develop CHD and up to 40% of individuals with cholesterol levels below the population average die from CHD. Furthermore, many CV events occur in patients treated with statin therapy. As such, a wide array of biomarkers—high-sensitivity assays detecting low levels of C-reactive protein (CRP), genetic polymorphism arrays, and direct imaging of subclinical atherosclerosis with coronary artery calcium (CAC) or carotid intima-media thickness—have been investigated for refinement of risk assessment and preventive therapy allocation (Fig. 1).
(Enlarge Image)
Figure 1.
Utility of Biomarkers in the Lifelong Prevention of Cardiovascular Disease
A dynamic set of genetic, circulating, and imaging biomarkers may be used in the lifelong prevention of atherosclerosis. Genetic and serum biomarkers may be useful in detecting those with early risk factor exposure and genetic predisposition (A) Imaging biomarkers may be useful in detecting subclinical disease. (B) Circulating biomarkers may be most informative in detecting earlier stages of atherosclerosis before the presence of cardiovascular disease, although high-sensitivity C-reactive protein has been shown to predict coronary heart disease in patients with unstable angina (C). Figure illustration by Craig Skaggs.
This paper reviews 4 distinct points from the literature to better understand the current state and application of high-sensitivity C-reactive protein (hsCRP) in clinical practice: 1) the biology of CRP and its role in atherosclerosis; 2) the epidemiological association of hsCRP with CVD; 3) the quality of hsCRP level as a biomarker of risk; and 4) the use of hsCRP as a tool to initiate or tailor statin therapy. Furthermore, we highlight recommendations from societies and important considerations when using hsCRP to guide treatment decisions in primary prevention.
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