N-Terminal Pro-Brain Natriuretic Peptide and Heart Failure Risk Among Individuals With and Without Obesity: The Atherosclerosis Risk in Communities (ARIC) Study

Abstract

Background: Obesity is a risk factor for heart failure (HF) but is associated with lower N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. It is unclear whether the prognostic value and implications of NT-proBNP levels for HF risk differ across body mass index (BMI) categories.

Methods and results: We followed up 12 230 ARIC participants free of prior HF at baseline (visit 2, 1990-1992) with BMI ≥18.5 kg/m(2). We quantified and compared the relative and absolute risk associations of NT-proBNP with incident HF across BMI categories. There were 1861 HF events during a median 20.6 years of follow-up. Despite increased HF risk in obesity, a weak inverse association was seen between baseline BMI and NT-proBNP levels (r=-0.10). Nevertheless, higher baseline NT-proBNP was associated with increased HF risk in all BMI categories. NT-proBNP improved HF risk prediction overall, even among those with severe obesity (BMI ≥35 kg/m(2); improvement in C statistic, 0.032; 95% confidence interval, 0.011-0.053). However, given the higher HF rates among those with obesity, at each NT-proBNP level, higher BMI was associated with greater absolute HF risk. Indeed, among those with NT-proBNP of 100 to <200 pg/mL, the average 10-year HF risk was <5% among normal-weight individuals but >10% among the severely obese.

Conclusions: Despite its inverse relationship with BMI, NT-proBNP provides significant prognostic information on the risk of developing HF even among individuals with obesity. Given the higher baseline HF risk among persons with obesity, even slight elevations in NT-proBNP may have implications for increased absolute HF risk in this population.

Keywords: epidemiology; heart failure; natriuretic peptides; obesity; risk assessment.

Figure 1

Median NT-proBNP levels within BMI Categories, Stratified by Race/Gender Subgroups. The median NT-proBNP levels and associated interquartile ranges within each BMI category are displayed for white men, white women, black men and black women.

Figure 2

Relative and Absolute Risks of HF Associated with Higher NT-proBNP Within BMI Categories. Linear spline models demonstrating the relative (Figure 2a) and absolute (Figure 2b) risk associations of NT-proBNP with incident HF within each BMI category, using a common reference of 25 pg/ml and knots at NT-proBNP levels of 50, 100, 200 and 400 pg/ml. The color-coded triangles and plus signs at the bottom of each panel indicate significantly negative (smaller effect size) and positive (greater effective size) pointwise interactions, respectively, for a given BMI category compared with normal weight. All regression models are adjusted for the variables in the ARIC HF Risk score: age, race, sex, smoking status, prior CHD, DM, mean systolic blood pressure, use of anti-hypertensive medications, and heart rate.

Figure 3

Predicted 10-year HF Risk (and Associated 95% Confidence Intervals) within NT-proBNP Ranges for Each BMI Category. The predicted risk of incident HF events over 10 years was calculated at mean levels of each of the covariates in the ARIC HF Risk Score (age, race, sex, smoking status, prior CHD, DM, mean systolic blood pressure, use of anti-hypertensive medications, and heart rate) using Cox regression. The average predicted 10-year HF risk for the NT-proBNP ranges of <50, 50 to <100, 100 to <200, 200 to <400 and ≥400 pg/ml are displayed for each BMI category. 95% confidence intervals were calculated using bootstrapping techniques.