Obesity and Serial NT-proBNP Levels in Guided Medical Therapy for Heart Failure With Reduced Ejection Fraction: Insights From the GUIDE-IT Trial

Vibhu Parcha, Nirav Patel, Rajat Kalra, Sarabjeet S Suri, Garima Arora, Thomas J Wang, Pankaj Arora, Vibhu Parcha, Nirav Patel, Rajat Kalra, Sarabjeet S Suri, Garima Arora, Thomas J Wang, Pankaj Arora

Abstract

Background Obese patients have lower NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels. The prognostic implications of achieving NT-proBNP levels ≤1000 pg/mL in obese patients with heart failure (HF) receiving biomarker-guided therapy are not completely known. We evaluated the prognostic implications of obesity and having NT-proBNP levels (≤1000 pg/mL) in the GUIDE-IT (Guiding Evidence-Based Therapy Using Biomarker-Intensified Treatment in HF) trial participants. Methods and Results The risk of adverse cardiovascular events (HF hospitalization or cardiovascular mortality) was assessed using multivariable-adjusted Cox proportional hazard models based on having NT-proBNP ≤1000 pg/mL (taken as a time-varying covariate), stratified by obesity status. The study outcome was also assessed on the basis of the body mass index at baseline. The predictive ability of NT-proBNP for adverse cardiovascular events was assessed using the likelihood ratio test. Compared with nonobese patients, obese patients were mostly younger, Black race, and more likely to be women. NT-proBNP levels were 59.0% (95% CI, 39.5%-83.5%) lower among obese individuals. The risk of adverse cardiovascular events was lower in obese (hazard ratio [HR], 0.48; 95% CI, 0.29-0.59) and nonobese (HR, 0.32; 95% CI, 0.19-0.57) patients with HF who had NT-proBNP levels ≤1000 pg/mL, compared with those who did not. There was no interaction between obesity and having NT-proBNP ≤1000 pg/mL on the study outcome (P>0.10). Obese patients had a greater risk of developing adverse cardiovascular events (HR, 1.39; 95% CI, 1.01-1.90) compared with nonobese patients. NT-proBNP was the strongest predictor of adverse cardiovascular event risk in both obese and nonobese patients. Conclusions On-treatment NT-proBNP level ≤1000 pg/mL has favorable prognostic implications, irrespective of obesity status. NT-proBNP levels were the strongest predictor of cardiovascular events in both obese and nonobese individuals in this trial. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01685840.

Keywords: cardiovascular outcomes; heart failure; mortality; natriuretic peptides; obesity.

Conflict of interest statement

Dr Wang has taken personal fees from Novartis outside of submitted work. The remaining authors have no disclosures to report.

Figures

Figure 1. NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide)…
Figure 1. NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) levels during study period: stratified by obesity.
The data are represented as median (point) and interquartile range (error bars). Red represents obese, and blue represents nonobese. Adjusted for age, sex, race, blood urea nitrogen, left ventricular ejection fraction, diabetes mellitus, guideline‐directed medical therapy score, systolic and diastolic blood pressure, New York Heart Association class, ischemic heart disease history, history of cancer in past 5 years, sleep apnea, and treatment arm. IQR indicates interquartile range.
Figure 2. Obesity and risk of adverse…
Figure 2. Obesity and risk of adverse cardiovascular events.
The figure shows the risk of adverse cardiovascular events based on baseline body mass index (BMI), stratified on obesity status (A) and quartiles (B). C, The relationship of the risk of adverse cardiovascular events with baseline BMI. Adjusted for age, sex, race, blood urea nitrogen, left ventricular ejection fraction, diabetes mellitus, guideline‐directed medical therapy score, systolic and diastolic blood pressure, log‐transformed NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) (time varying), New York Heart Association class, ischemic heart disease history, history of cancer in past 5 years, sleep apnea, and treatment arm. HF indicates heart failure; HR, hazard ratio; and Ref., reference.
Figure 3. Ranking of strength of association…
Figure 3. Ranking of strength of association of risk factors with adverse cardiovascular events: stratified by obesity.
The figure depicts the relative contribution of each variable to the risk of adverse cardiovascular events in terms of χ2 values in obese (A) and nonobese (B) individuals. To ensure comparison on the same scale, the covariates were corrected for the degree of freedom. BUN indicates blood urea nitrogen; GDMT, guideline‐directed medical therapy; LV, left ventricular; NYHA, New York Heart Association; NT‐proBNP, N‐terminal pro‐B‐type natriuretic peptide; and S., serum.
Figure 4. NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide)…
Figure 4. NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) ≤1000 mg/dL and risk of adverse cardiovascular events.
A, The risk of adverse cardiovascular events stratified by achieved NT‐proBNP levels. B, The risk of adverse cardiovascular events stratified by obesity and having NT‐proBNP ≤1000 mg/dL. Adjusted for age, sex, race, blood urea nitrogen, left ventricular ejection fraction, diabetes mellitus, guideline‐directed medical therapy score, systolic and diastolic blood pressure, body mass index, log‐transformed baseline NT‐proBNP, New York Heart Association class, ischemic heart disease history, history of cancer in past 5 years, sleep apnea, and treatment arm. HR indicates hazard ratio; and Ref., reference.

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