Cardiac Biomarkers and Left Ventricular Hypertrophy in Relation to Outcomes in Patients With Atrial Fibrillation: Experiences From the RE - LY Trial

Ziad Hijazi, Paolo Verdecchia, Jonas Oldgren, Ulrika Andersson, Gianpaolo Reboldi, Giuseppe Di Pasquale, Giovanni Mazzotta, Fabio Angeli, John W Eikelboom, Michael D Ezekowitz, Stuart J Connolly, Salim Yusuf, Lars Wallentin, Ziad Hijazi, Paolo Verdecchia, Jonas Oldgren, Ulrika Andersson, Gianpaolo Reboldi, Giuseppe Di Pasquale, Giovanni Mazzotta, Fabio Angeli, John W Eikelboom, Michael D Ezekowitz, Stuart J Connolly, Salim Yusuf, Lars Wallentin

Abstract

Background Cardiac biomarkers and left ventricular hypertrophy ( LVH ) are related to the risk of stroke and death in patients with atrial fibrillation. We investigated the interrelationship between LVH and cardiac biomarkers and their independent associations with outcomes. Methods and Results Plasma samples were obtained at baseline in 5275 patients with atrial fibrillation in the RE - LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial. NT -proBNP (N-terminal pro-B-type natriuretic peptide), cardiac troponin I and T, and growth differentiation factor-15 were determined using high-sensitivity (hs) assays. LVH was defined by ECG . Cox models were adjusted for baseline characteristics, LVH , and biomarkers. LVH was present in 1257 patients. During a median follow-up of 2.0 years, 165 patients developed a stroke and 370 died. LVH was significantly ( P<0.0001) associated with higher levels of all biomarkers in linear regression analyses adjusting for baseline characteristics. Geometric mean ratios (95% CIs) were as follows: NT -pro BNP , 1.32 (1.25-1.38); hs cardiac troponin I, 1.67 (1.57-1.78); hs troponin T, 1.38 (1.32-1.44); and growth differentiation factor-15, 1.09 (1.05-1.12). For stroke, the hazard ratios (95% CIs) per 50% increase were as follows: NT -pro BNP, 1.09 (1.00-1.19); hs cardiac troponin I, 1.09 (1.03-1.15); hs troponin T, 1.14 (1.06-1.24); and growth differentiation factor-15, 1.22 (1.08-1.38) (all P<0.05). For death, hazard ratios (95% CIs) were as follows: NT -pro BNP , 1.24 (1.17-1.31); hs cardiac troponin I, 1.13 (1.10-1.17); hs troponin T, 1.28 (1.23-1.34); and growth differentiation factor-15, 1.31 (1.22-1.42) (all P<0.0001). LVH was not significantly associated with stroke or death after adjustment for biomarkers. Conclusions Cardiac biomarkers are significantly associated with LVH . The prognostic value of biomarkers for stroke and death is not affected by LVH . The prognostic information of LVH is attenuated in the presence of cardiac biomarkers. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 00262600.

Trial registration: ClinicalTrials.gov NCT00262600.

Keywords: atrial fibrillation; biomarker; left ventricular hypertrophy; risk prediction.

Figures

Figure 1
Figure 1
Impact of left ventricular hypertrophy (LVH) on the association between baseline biomarkers and stroke or systemic embolism (SEE), all‐cause mortality, and major bleeding outcomes. GDF‐15 indicates growth differentiation factor‐15; HR, hazard ratio; NT‐proBNP, N‐terminal pro‐B‐type natriuretic peptide.
Figure 2
Figure 2
One‐year risk for all‐cause mortality by left ventricular hypertrophy (LVH) category according to levels of NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide; A), troponin I (B), troponin T (C), and growth differentiation factor‐15 (GDF‐15; D). The biomarkers were included as continuous, log transformed, and fitted using restricted cubic splines with 4 knots, located at the 5th, 35th, 65th, and 95th percentiles.

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