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• Factors Affecting Quality of Anticoagulation Control Among Patients With Atrial Fibrillation on Warfarin: The SAMe-TT2R2 Score(Chest. 2013;144(5):1555-1563.)

Biomarker Can Predict Events in Afib Patients

Published: Nov 6, 2013 | Updated: Nov 7, 2013

By Todd Neale, Senior Staff Writer, MedPage Today

Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner

Beta-trace protein (BTP), a biomarker that has been associated with both kidney damage and an increased cardiovascular risk, may help identify high-risk atrial fibrillation patients, researchers found.

Among patients with atrial fibrillation who were on stable oral anticoagulant therapy, high plasma levels of the protein were associated with significantly elevated risks of embolic events, adverse cardiovascular events, death, and major bleeding, according to Gregory Lip, MD, of the University of Birmingham in England, and colleagues.

Also, adding information about BTP levels modestly improved the predictive ability of models that included two established risk scores — CHAD2DS2-VASc and HAS-BLED — as indicated by higher C-statistics, they reported in the Nov. 5 issue of CHEST.

“This raises the possibility that BTP may help refine the clinical risk stratification for thrombotic or hemorrhagic events and mortality in these patients,” they wrote.

BTP has been proposed has a marker of renal damage, and it has also been associated with inflammation, atherogenesis, angina, vasomotor reactivity, and hypertension. Previous studies have also identified a relationship between BTP and the progression of cardiovascular disease.

In the current study, Lip and colleagues explored whether BTP levels were related to outcomes in 1,279 patients with nonvalvular atrial fibrillation who were on stable oral anticoagulant therapy with an international normalized ratio (INR) of 2.0 to 3.0. Their average age was 76.

The median estimated glomerular filtration rate at baseline was 71.28 mL/min/1.73 m²; BTP levels and renal function were inversely related (P<0.001).

The BTP cut-offs with the best sensitivity and specificity for predicting each of the endpoints varied — 0.561 mg/L for adverse cardiovascular events, 0.556 mg/L for embolic events, 0.670 mg/L for mortality, and 0.573 mg/L for major bleeds.

During a median follow-up of 2.7 years, cardiovascular events occurred at a rate of 3.99% per year, embolisms at 1.54% per year, deaths at 4.32% per year, and major bleeds at 3.04% per year.

After adjustment for renal function and the CHAD2DS2-VASc risk score — which incorporates congestive heart failure, hypertension, age, diabetes, stroke, vascular disease, and sex — a BTP level above the cutoff was associated with increased risks of cardiovascular events (HR 1.93, 95% CI 1.31-2.85), embolic events (HR 4.64, 95% CI 1.98-10.86), and mortality (HR 2.08, 95% CI 1.49-2.90).

Also, after adjustment for the HAS-BLED risk score — which takes into account hypertension, abnormal renal and liver function, stroke, bleeding history or predisposition, labile INR, age over 65, and concomitant use of drugs and alcohol — a high BTP level was associated with a greater risk of major bleeding (HR 1.88, 95% CI 1.18-3.00).

“We suggest that BTP, a proposed renal damage biomarker, may be a novel predictor of adverse cardiovascular events, major bleeding, and mortality in patients with atrial fibrillation,” the authors wrote.

They acknowledged some limitations of the analysis, however, including possible selection bias because all of the patients were on stable oral anticoagulant therapy, the measurement of renal function and BTP levels at a single time point only, and the exclusion of patients with end-stage renal disease.

SOURCE

http://www.medpagetoday.com/Cardiology/Arrhythmias/42751

These are promising early results, but the data include plenty of limitations. As the article notes, the researchers themselves acknowledge that their work only looked at patients on a regular oral anticlotting drug at a certain point in time. Further research must include a broader class of patients to determine if BTP can be a reliable biomarker to help identify atrial fibrillation patients with an added risk of other health problems.

As hard as it might be to spot atrial fibrillation patients at risk of more problems, doctors struggle to definitively identify the condition in the first place and apply targeted treatments. The med tech industry, meanwhile, is trying to fill the gap. Topera, a 2013 Fierce 15 winner, recently won U.S. and EU approval for a 3-D device and mapping tool designed to better detect cardiac rhythm problems such as atrial fibrillation in order to enable more targeted and accurate treatment. In late August, St. Jude Medical ($STJ) snatched up Endosense, which makes a cutting-edge irrigated ablation catheter designed to treat atrial fibrillation, and rival companies are developing or promoting electrophysiology treatments and other devices for the condition.

 SOURCE

From: FierceBiomarkers <editors@fiercebiomarkers.com>
Reply-To: <editors@fiercebiomarkers.com>
Date: Wednesday, November 13, 2013 10:31 AM
To: AvivaLev-Ari@alum.berkeley.edu
Subject: | 11.13.13 | Investigators flag new biomarkers for atrial fib

Articles related to Diagnosis of Atrial Fibrilation published on this Open Access Online Scientific Journal include the following:

Genetic Analysis of Atrial Fibrillation, Larry H Bernstein, MD, FCAP  and Aviva-Lev Ari, PhD, RN

http://pharmaceuticalintelligence.com/2013/10/27/genetic-analysis-of-atrial-fibrillation/

Cardiac Contractility & Myocardium Performance: Ventricular Arrhythmiasand Non-ischemic Heart Failure – Therapeutic Implications for Cardiomyocyte Ryanopathy (Calcium Release-related Contractile Dysfunction) and Catecholamine Responses
Justin Pearlman, MD, PhD, FACC, Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN
http://pharmaceuticalintelligence.com/2013/08/28/cardiac-contractility-myocardium-performance-ventricular-arrhythmias-and-non-ischemic-heart-failure-therapeutic-implications-for-cardiomyocyte-ryanopathy-calcium-release-related-contractile/

Oxidized Calcium Calmodulin Kinase and Atrial Fibrillation, Larry H. Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN
http://pharmaceuticalintelligence.com/2013/10/26/oxidized-calcium-calmodulin-kinase-and-atrial-fibrillation/

http://pharmaceuticalintelligence.com/2013/04/28/genetics-of-conduction-disease-atrioventricular-av-conduction-disease-block-gene-mutations-transcription-excitability-and-energy-homeostasis/

On Devices and On Algorithms: Prediction of Arrhythmia after Cardiac Surgery and ECG Prediction of an Onset of Paroxysmal Atrial Fibrillation, Justin D. Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN