Body Composition, Natriuretic Peptides, and Adverse Outcomes in Heart Failure With Preserved and Reduced Ejection Fraction

Abstract

Objectives: The purpose of this study was to determine the relationship between body composition, N-terminal B-type natriuretic peptide (NT-proBNP) levels, and heart failure (HF) phenotypes and outcomes.

Background: Abnormalities in body composition can influence metabolic dysfunction and HF severity; however, data assessing fat distribution and skeletal muscle (SM) size in HF with reduced (HFrEF) and preserved EF (HFpEF) are limited. Further, whether NPs relate more closely to axial muscle mass than measures of adiposity is not well studied.

Methods: We studied 572 adults without HF (n = 367), with HFrEF (n = 113), or with HFpEF (n = 92). Cardiac magnetic resonance was used to assess subcutaneous and visceral abdominal fat, paracardial fat, and axial SM size. We measured NT-proBNP in 334 participants. We used Cox regression to analyze the relationship between body composition and mortality.

Results: Compared with controls, pericardial and subcutaneous fat thickness were significantly increased in HFpEF, whereas patients with HFrEF had reduced axial SM size after adjusting for age, sex, race, and body height (p < 0.05 for comparisons). Lower axial SM size, but not fat, was significantly predictive of death in unadjusted (standardized hazard ratio: 0.63; p < 0.0001) and multivariable-adjusted analyses (standardized hazard ratio = 0.72; p = 0.0007). NT-proBNP levels more closely related to lower axial SM rather than fat distribution or body mass index (BMI) in network analysis, and when simultaneously assessed, only SM (p = 0.0002) but not BMI (p = 0.18) was associated with NT-proBNP. However, both NT-proBNP and axial SM mass were independently predictive of death (p < 0.05).

Conclusions: HFpEF and HFrEF have distinct abnormalities in body composition. Reduced axial SM, but not fat, independently predicts mortality. Greater axial SM more closely associates with lower NT-proBNP rather than adiposity. Lower NT-proBNP levels in HFpEF compared with HFrEF relate more closely to muscle mass rather than obesity.

Keywords: heart failure; muscle mass; natriuretic peptides; obesity; sarcopenia.

FIGURE 1. Methods for Axial Muscle, Pericardial, Subcutaneous, and Visceral Fat Measurements

(A) Segmentation of axial muscle groups; (B) measurement of abdominal visceral and subcutaneous fat thickness; (C) segmentation of pericardial fat.

FIGURE 2. Differences in Body Composition in Patients With HF Compared With Controls

Comparisons are adjusted for sex, age, race, and body height. Compared with patients without heart failure (HF), patients with HF with preserved ejection fraction (HFpEF) had greater pericardial, subcutaneous, and visceral fat, whereas patients with HR with reduced ejection fraction (HFrEF) had reduced axial muscle mass (p values shown in Table 2). CSA = cross-sectional area.

FIGURE 3. Heatmap and Network Analysis of Fat Depots, Axial Muscle Mass, and Natriuretic Peptides

Correlation matrix heatmap (A) and network connectivity backbone (B) of fat depots, measures of axial muscle mass, and NT-proBNP. In B, node size represents eigenvector centrality (which depends both on the number of neighbors and the strength of its connections). Eigenvector centrality measures a node’s importance while giving consideration to the importance (number of connections) of its neighbors. The node color represents betweenness centrality (which quantifies the number of times a node acts as a bridge along the shortest path between 2 other nodes). BMI = body mass index; CSA = cross-sectional area; NT-proBNP = N-terminal pro-B-type natriuretic peptide.

FIGURE 4. Adjusted Relationship Between Fat Depots, Muscle Mass, and Heart Failure With NT-proBNP

Standardized effect sizes shown for axial muscle mass, various fat depots, HF status, and body mass index (BMI) are shown in relationship to N-terminal pro-brain natriuretic peptide (NT-proBNP). All effect sizes are simultaneously adjusted for the presence of other variables presented in the figure. HF = heart failure; HFpEF = heart failure with preserved ejection fraction; HFrEF = heart failure with reduced ejection fraction.

FIGURE 5. Statistical Mediation Analyses to Quantify Direct and Indirect (Axial SM–mediated) Effects of BMI on NT-proBNP

Regression coefficients, SE, and p values are shown in the path graph as well as in the mediation table. BMI = body mass index; NT-proBNP = N-terminal pro-B-type natriuretic peptide; SM = skeletal muscle.

CENTRAL ILLUSTRATION. Relative Differences in Body Composition in Heart Failure Patients Compared With Controls

A radar plot (top) and heatmap (bottom) demonstrating key differences in z-scores in various parameters of body composition between the groups is shown. In the radar plot, variables are compared in a normalize scale (z-score) between the groups, and the mean z-score of each group is plotted from low (center) to high (periphery) of the plot. The thickness of the dashed radial lines are proportional to the magnitude of the maximum standardized difference between the groups (maximum minus minimum z-score value) and the shade of the dashed radial lines is proportional to the statistical significance of the differences between the groups (i.e., the −log10 of the analysis of variance p value).