Value of Biomarkers in Atrial Fibrillation Patients
Abstract & Commentary
By John P. DiMarco, MD, PhD, Professor of Medicine, Division of Cardiology, University of Virginia, Charlottesville. Dr. DiMarco does research for Medtronic, is a consultant for Medtronic, Novartis, and St. Jude, and is a speaker for Boston Scientific.
Source: Hijazi Z, et al. Cardiac biomarkers are associated with an increased risk of stroke and death in patients with atrial fibrillation: A randomized evaluation of long-term anticoagulation therapy (RE-LY) substudy. Circulation 2012;125:1605-1616.
The Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) Study compared two doses of dabigatran, a direct thrombin inhibitor, with warfarin for the prevention of stroke and systemic emboli in patients with nonvalvular atrial fibrillation (AF). This report describes the results of a substudy that looked at the ability of cardiac biomarkers to enhance risk prediction in this population. Patients in RE-LY had documented nonvalvular AF and at least one additional stroke risk factor. In this substudy, which included 6189 patients, venous blood was drawn at the time of randomization before initiation of study treatment. Plasma samples were analyzed in a central laboratory for both troponin I and N-terminal pro-B-type natriuretic peptide (NT-proBNP). For troponin I, levels < 0.010 mcg/L were regarded as undetectable and levels ≥ 0.020 mcg/L were considered elevated. Patient NT-proBNP levels were separated into quartiles for this analysis. The ability of troponin I or NT-proBNP to predict vascular and nonvascular mortality, embolic events, or myocardial infarction was then examined.
Detectable troponin I levels were found in 57% of the patients and levels were elevated (≥ 0.020 mcg/L) in 24.6% of the patients. Elevated troponin levels were associated with higher age, previous myocardial infarction, congestive heart failure, atrial fibrillation rhythm at randomization, and lower creatinine clearance. The median NT-proBNP level of 801 ng/L was well above the 97.5 percentile for both men and women. NT-proBNP levels were related to older age, AF rhythm at randomization, a history of congestive heart failure, and lower creatinine clearance. Low CHADS2 risk scores (0 to 1) were also correlated with lower levels of both troponin I and NT-proBNP.
Median follow-up in this study was 2.2 years. There was a stepwise increase in the annual rate of stroke or systemic embolism based on the troponin I level increasing from 0.84% in the group with undetectable troponin I to 2.09% in the highest (≥ 0.020 mcg/L) troponin I group. Similarly, the annual rates of stroke or systemic embolism were low (0.92%) in the lowest NT-proBNP quartile and increased (2.30%) in the highest NT-proBNP quartile. Both tronopin I and NT-proBNP levels remained significant predictors of stroke and systemic embolism in multivariate analysis. Troponin I and NT-proBNP levels were significantly associated with increased vascular mortality. Troponin I levels were also associated with increased risk for myocardial infarction but there was no significant relationship between NT-proBNP levels and myocardial infarction. There was not a strong relationship between nonvascular mortality and either elevated troponin I or NT-proBNP levels. Troponin I levels were correlated with the risk for major bleeding, which was 1.72% in the group with undetectable troponin I levels and 4.38% in the highest troponin I group. There was no significant association between NT-proBNP levels and major bleeding. Troponin I levels and NT-proBNP levels were related to CHADS2 and CHA2DS2-VASc scores. When combined with these scores, the result was an improved predictive value. The effects of study treatment with either warfarin or dabigatran did not affect these observations.
The authors conclude that elevated levels of troponin I and NT-proBNP are associated with an increased risk for stroke or systemic embolism, and vascular events and mortality. Additional prognostic information can be gleaned from troponin I and NT-proBNP levels when added to other risk scoring systems currently used.
Commentary
There are several interesting observations in this report. Although elevated NT-proBNP levels are not unexpected in patients with AF, the large proportion of patients with elevated troponin I levels is surprising. Since the samples were drawn at the time of randomization into a clinical trial of anticoagulant therapy, we can assume that the patients were thought to be clinically stable. The elevated troponin I levels in many patients suggest that clinical evaluation may be misleading in AF patients and cell damage may be ongoing. The CHADS2 and CHA2DS2-VASc scores are widely used for risk stratification in patients with AF, but their predictive power as measured by a C-statistic is relatively poor. Adding biomarker data seems to be helpful and should be considered in patients with borderline indications.
The Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) Study compared two doses of dabigatran, a direct thrombin inhibitor, with warfarin for the prevention of stroke and systemic emboli in patients with nonvalvular atrial fibrillation (AF).You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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