Impact of Body Mass Index on the Accuracy of N-Terminal Pro-Brain Natriuretic Peptide and Brain Natriuretic Peptide for Predicting Outcomes in Patients With Chronic Heart Failure and Reduced Ejection Fraction
Authors: Wilson Nadruz, Brian L. Claggett, John J. McMurray, Milton Packer, Michael R. Zile, Jean L. Rouleau, Akshay S. Desai, Karl Swedberg, Martin Lefkowitz, Victor C. Shi, Margaret F. Prescott, Scott D. Solomon
Journal: Circulation (2016)

Circulating levels of natriuretic peptides (NP) are inversely related to body mass index (BMI), and obese patients with heart failure (HF) have lower brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) concentrations than nonobese patients. 1,2These observations have raised concerns about the prognostic value of NP in patients with HF with an elevated BMI.Prior observational studies suggested that NP may retain their capacity to predict mortality across all BMI categories in HF with individuals with reduced ejection fraction. 3,4evertheless, these studies included a relatively small number of events and did not evaluate additional cardiovascular end points.Because it remains uncertain whether BMI may influence the prognostic utility of NP in patients with HF, we examined the influence of BMI on the predictive value of NT-proBNP and BNP in patients with reduced ejection fraction from the PARADIGM-HF trial (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure; URL: http://www.clinicaltrials.gov.Unique identifier: NCT01035255).The design and primary results of the PARADIGM-HF trial have been previously described. 5The patients randomized in the trial (n=8399) were required to have a plasma BNP ≥150 pg/mL or an NT-proBNP ≥600 pg/mL or, if they were hospitalized for HF within the previous 12 months, a BNP ≥100 pg/mL or an NT-proBNP ≥400 pg/ mL.The present study included patients with available BMI data and who had BNP and NT-proBNP locally measured at the time of screening (n=8217).It considered the primary outcome of the PARADIGM-HF trial, the composite of death from cardiovascular causes or a first hospitalization for HF, as the study outcome.The patients were categorized into 4 groups according to BMI: <25.0 (nonoverweight/obese; n=2536); 25.0 to 29.9 (overweight; n=3116); 30.0 to 34.9 (obese; n=1694); and ≥35.0 kg/m 2 (moderately/severely obese; n=871).BNP and NT-proBNP were divided into quartiles within the whole studied population.The trial was approved by the ethics committee at each participating institution, and all the patients provided written informed consent.Multivariable Cox proportional hazards models were used to evaluate the relationship between NP quartiles and primary outcome within each BMI category and to assess the potential interaction between NP quartiles and BMI categories for the studied outcome.The incremental value of NP quartiles when added to clinical covariates for the primary outcome was evaluated with Harrell's C-statistic considering the whole follow-up period, and continuous net reclassification improvement and integrated diagnostic improvement 2 years after randomization.The covariates included in the analyses were age, sex, and variables that were selected by forward stepwise selection, including all baseline variables reported in the primary manuscript as candidate covariates. 5he patients had a mean age of 64±11 years, 78% men, and a mean BMI of 28.0±5.6 kg/m 2 .NP levels were inversely related to BMI (P for trend <0.