+While obesity itself is a major risk factor for developing heart failure, overweight and obese patients have been reported to have paradoxically better prognoses in heart failure compared to normal and underweight patients. N-terminal pro-B-type NP (NT-proBNP), one of the gold standard biomarkers for risk stratification, diagnosis, and prognostication in heart failure, is also lower in obese individuals. This post-hoc analysis examined patients with heart failure with reduced ejection fraction (HFrEF) from the GUIDE-IT trial (Guiding Evidence-Based Therapy Using Biomarker-Intensified Treatment in HF). Multi-variable adjusted Cox proportional hazard models were used to compare the risks for adverse cardiovascular events between obese aad nonobese patients and a likelihood ratio test was used to evaluate whether this risk could be predicted by NT-proBNP levels or improved by lowering NT-proBNP. 873 participants with HFrEF were stratified by baseline BMI into obese (BMI >30 kg/m2) and nonobese (BMI <30 kg/m2) groups. In GUIDE-IT, patients in the treatment arm had their medical therapy titrated to reach an NT-proBNP target of <1000 pg/mL. Medical therapy, computed as a GDMT (guideline-directed medical therapy) score, having NT-proBNP levels <1000 pg/mL, and change in NYHA class from baseline were treated as time-varying covariates, calculated per visit. In patients with HF who had NT-proBNP levels <1000 pg/mL, both obese and non-obese patients had lower risks for the primary outcome, a composite of HF hospitalization and cardiovascular-associated mortality (HR 0.48, 95% CI 0.29-0.59 and HR 0.32, 95% CI 0.19-0.57 respectively). While NT-proBNP levels were 59% lower in obese patients, obesity and having NT-proBNP <1000pg/mL were not associated with adverse cardiovascular event risk. Nonetheless, obese patients were at a greater risk of experiencing adverse cardiovascular events compared to non-obese patients (HR 1.39, 95% CI 1.01-1.90). Although this study was underpowered to detect a significant interaction between obesity and NT-proBNP <1000pg/mL with the primary outcome, this analysis highlighted NT-proBNP as the strongest predictor examined of adverse cardiovascular event risk, irrespective of obesity status.
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