Regional Adipose Distribution and its Relationship to Exercise Intolerance in Older Obese Patients Who Have Heart Failure With Preserved Ejection Fraction

Abstract

Objectives: This study sought to test the hypothesis that older obese patients with heart failure with preserved ejection fraction (HFpEF) have significantly greater abdominal, cardiac, and intermuscular fat than healthy, age-matched controls, out of proportion to total body fat, and that these abnormalities are associated with objective measurements of physical function.

Background: Recent studies indicate that excess total body adipose tissue contributes to exercise intolerance in patients with HFpEF. However, the impact of the pattern of regional (abdominal, cardiac, intermuscular) adipose deposition on exercise intolerance in patients with HFpEF is unknown.

Methods: We measured total body adiposity (using dual-energy x-ray absorptiometry) and regional adiposity (using cardiac magnetic resonance), peak oxygen uptake (Vo₂), 6-min walk distance (6MWD), short physical performance battery (SPPB), and leg press power in 100 older obese patients with HFpEF and 61 healthy controls (HCs) and adjusted for age, sex, race, and body surface area.

Results: Peak Vo₂ (15.7 ± 0.4 ml/kg/min vs. 23.0 ± 0.6 ml/kg/min, respectively; p < 0.001), 6MWD (427 ± 7 m vs. 538 ± 10 m, respectively; p < 0.001), SPPB (10.3 ± 0.2 vs. 10.9 ± 0.2, respectively; p < 0.05), and leg power (117 ± 5 W vs. 152 ± 9 W, respectively; p = 0.004) were significantly lower in patients with HFpEF than HCs. Total fat mass, total percent fat, abdominal subcutaneous fat, intra-abdominal fat, and thigh intermuscular fat were significantly higher, whereas epicardial fat was significantly lower in patients with HFpEF than in HC. After we adjusted for total body fat, intra-abdominal fat remained significantly higher, while epicardial fat remained significantly lower in patients with HFpEF. Abdominal subcutaneous fat, thigh subcutaneous fat, and thigh intermuscular fat:skeletal muscle ratio were inversely associated, whereas epicardial fat was directly associated with peak Vo₂, 6MWD, SPPB, and leg power. Using multiple stepwise regression, we found intra-abdominal fat was the strongest independent predictor of peak Vo₂ and 6MWD.

Conclusions: In metabolic obese HFpEF, the pattern of regional adipose deposition may have important adverse consequences beyond total body adiposity. Interventions targeting intra-abdominal and intermuscular fat could potentially improve exercise intolerance. (Exercise Intolerance in Elderly Patients With Diastolic Heart Failure [SECRET]; NCT00959660).

Keywords: adipose; aging; exercise; heart failure with preserved ejection fraction; obesity; physical function.

Figure 1. Peak VO₂ (ml/kg/min) versus Regional Fat Measures

Regression plots for baseline measures of Peak VO₂ (ml/kg/min) versus (A) Intra-Abdominal Fat, (B) Abdominal SCF, (C) Thigh IMF, (D) Thigh IMF as Percent of Thigh Compartment (TC), (E) Paracardial Fat, (F) Epicardial Fat. Similar results were found for non-indexed Peak VO₂ (ml/min) as well. Regional fat measures obtained using MRI. Thigh compartment calculated as Intermuscular Fat+Skeletal Muscle+Bone. Spearman r and p values additionally included for reference.