Comparative Analysis of Biomarkers
Abstract & Commentary
By Michael H. Crawford, MD Professor of Medicine, and Chief of Clinical Cardiology, at the University of California, San Francisco. Dr. Crawford is on the speaker's bureau for Pfizer.
Synopsis: Although levels of various inflammatory biomarkers are significantly related to future cardiovascular risk, their incremental predictive value is modest.
Source: Blankenberg S, et al. Comparative Impact of Multiple Biomarkers and N-Terminal Pro-Brain Natriuretic Peptide in the Context of Conventional Risk Factors for the Prediction of Recurrent Cardiovascular Events in the Heart Outcomes Prevention Evaluation (HOPE) Study. Circulation. 2006;114:201-208.
Traditional clinical risk factors explain about 90% of the risk for acute myocardial infarction (MI). Newer biomarkers may account for the other 10%, but little comparative data are available. Thus, Blankenberg and colleagues from the HOPE study sought to access the incremental value of 11 biomarkers: C-reactive protein, fibrinogen; interleukin 1, 6, 18; tumor necrosis factor 1, 2; soluble vascular cell adhesion molecule; soluble intercellular adhesion molecule; microalbuminuria; and Nt-proBNP as compared to simple clinical risk factors for the prediction of cardiovascular events in the 3119 HOPE participants. HOPE was a study of ramipril and vitamin E in patients with known vascular disease, but with preserved left ventricular function. The primary end point was MI, stroke, or cardiovascular death, which occurred in 501 patients over 4.5 years of follow-up. In age- and sex- adjusted analyses, the strongest predictors of the primary end point were traditional clinical risk factors. For example, current smoking [hazard ratio (HR) 1.79], diabetes (1.48) and LDL/HDL cholesterol ratio (1.24) al P < .0001. Only Nt-proBNP added incremental information above the standard risk factors. Inflammatory markers such as CRP provided little additional predictive value above clinical risk factors. Blankenberg et al concluded that a model using traditional clinical risk factors and Nt-proBNP was the most predictive of major cardiovascular events in a vascular disease population.
Commentary
Although all the biomarkers studied were predictive of events individually, BNP had the highest individual HR (1.72), and was higher than many clinical risk factors such as diabetes and LDL/HDL ratio. Also, BNP was the only one that added predictive power to traditional clinical risk factors. Other studies have shown that BNP is a powerful predictor of cardiovascular events in heart failure, acute coronary syndrome, stable angina, and apparently health individuals. The reason for its power is unclear. Perhaps it identifies early diastolic or systolic heart failure, or identifies those with multiple risk factors or more advanced disease.
One weakness of this analysis is that it was not adjusted for left ventricular ejection fraction. However, severe heart failure patients were eliminated. Another limitation of this study is that it was done in vascular disease (including coronary) patients. In this group, left ventricular dysfunction may be more common. However, the results were not influenced by randomization to ramipril, which suggests some independence from left ventricular function.
It is somewhat surprising that CRP did not fare better in this project. Individually, values over 6 mg/L had a HR of 1.26 (P = .04), whereas Nt-proBNP > 18 pmol/L had a HR of 1.83 (P < .0001) and CRP did not add to the predictive power of clinical risk factors. Perhaps CRP would perform better in a primary prevention population. However, recent studies in community populations have not shown an incremental value of CRP beyond traditional risk factors, whereas BNP has performed well in such populations. Thus, perhaps we should shuck CRP and start measuring BNP. Unfortunately, many things effect BNP levels, and I believe only low values (< 100) would be valuable to reassure patients. Higher values may or may not indicate a risk of a cardiovascular event in an individual patient, even though they seem to be quite predictive in groups of patients.
Although levels of various inflammatory biomarkers are significantly related to future cardiovascular risk, their incremental predictive value is modest.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content