Use of BNP and CRP as Biomarkers in Assessing Cardiovascular Disease:Diagnosis Versus Risk

Abstract

Biomarkers are used in medicine to facilitate diagnosis, assess risk, direct therapy and determine efficacy of treatment. Sensitivity and specificity are essential in order for a biomarker to be useful. Brain natriuretic peptide (BNP) and C-reactive protein (CRP) are considered biomarkers of cardiovascular disease. However, they differ in function, sensitivity and specificity. BNP is released from the myocardium in response to myocardial stretch, a clear cause and effect relationship; therefore, it is useful in the diagnosis of heart failure when patients present with dyspnea of unknown origin and to assess treatment in high risk patients with diagnosed heart failure. Sex and age based reference ranges and partition values are established from clinical trials and from populations screened for the absence of cardiovascular disease. Highly sensitive and reproducible methods are also available to measure CRP. However, although CRP is associated with adverse cardiovascular events, unlike BNP, multiple stimuli increase production of CRP. Therefore, elevation in CRP is not specific to cardiovascular disease. Partition values for CRP and cardiovascular risk based on epidemiological studies predict risk for populations but may not always be useful when used alone to predict individual risk or to direct therapy. Given the non-specific stimuli which affect circulating concentrations of CRP, using CRP to monitor treatment to reduce cardiovascular risk may provide little benefit without understanding or targeting the underlying causes for its elevation.

Vascular Actions of Estrogens: Functional Implications

“…Such measurements do not identify the cell of origin of the cytokine/protein or take into account kinetics of their production, biological half-life, or degradation. Furthermore, in many clinical trials, these measurements represent two time points (before and after intervention) and are related to changes in risk factor profile rather than to measurable physical changes in the vascular wall or disease progression (Stork et al, 2004;Miller et al, 2007b). In contrast, in studies using experimental animals, effects of estrogen on vascular inflammation evaluate structural changes in the vascular wall including infiltration of leukocytes or expression of adhesion molecules or secretion of enzymes, such as matrix metalloproteinases.…”

“…Additional parameters, including endothelial function, are needed for cardiovascular risk stratification in early menopausal women as the standard characterization of risk using parameters of hypertension, plasma lipids, and smoking status (i.e., Framingham Risk Score) does not adequately predict risk in this group of women (Shaw et al, 2006;Lakoski et al, 2007;Miller et al, 2007b;Sherwood et al, 2007). The search for a set of blood biomarkers has not yielded a reliable indicator of early disease (Redberg et al, 2000;Kullo et al, 2003Kullo et al, , 2006.…”

Review on Cardiovascular Risk Prediction

“…Degrading enzymes produced by macrophages and endothelial cells Hemodynamic stress BNP 8 Marker of systolic and diastolic dysfunction [47]. Further details are in the text.…”

Editorial [ Cardiovascular Risk Factor Modification: A sine qua non in the Management of Vascular Surgery Patients ]

“…Other molecular systems and processes implicated in the pathogenesis of vascular diseases include the plasminogen activator system [84], interferon-gamma and stimulated macrophages [85], several prostanoids [86], guanosine-dependent cyclic nucleotide second messenger signaling [87] and several biomarkers (e.g. brain natriuretic peptide) [88]. Establishment of a definite role for these emerging risk factors, molecular systems and processes may improve the therapeutic approach of vascular patients.…”