Adiposity facilitates increased strength capacity in heart failure patients with reduced ejection fraction

Abstract

Background

Obesity is associated with relatively improved prognosis among heart failure (HF) patients. Mechanisms explaining this so-called “obesity paradox” have been unclear. We hypothesized that increased adiposity may contribute to increased strength capacity, and may thereby facilitate clinical benefits.

Methods and results

In a controlled, cross-sectional study, adults aged ≥50 years with HF with reduced ejection fraction (HFREF) (LVEF ≤40%) were compared to age matched controls. Body composition was determined by dual-energy X-ray absorptiometry (DXA). Aerobic (cardiopulmonary exercise testing), maximum strength (one repetition maximum [1RM]), and power (submaximal resistance/time) were assessed. 70 adults (31 HFREF, 39 controls; mean age 66.2 ± 9.6 years) were studied. Peak oxygen consumption (VO₂) (15.4 ± 4.2 vs. 23.4 ± 6.6 ml O₂·kg⁻¹·min⁻¹, p<0.0001), 1RM (154.8 ± 52.0 vs. 195.3 ± 56.8 kg, p<0.01) and power (226.4 ± 99.2 vs. 313.3 ± 130.6, p<0.01) were lower in HFREF vs. controls. 1RM correlated with total fat (r=0.56, p<0.01), leg fat (r=0.45, p<0.05) and arm fat (r=0.39, p<0.05) in HFREF. Moreover, among HFREF patients with a high (≥30 kg/m²) body mass index (BMI), 1RM and fat mass were significantly greater than those with lower (<30 kg/m²) BMIs. Correlations between 1RM and total fat (r=0.65, p<0.05) and leg fat (r=0.64, p<0.05) were particularly notable in the high BMI subgroup.

Conclusion

Increased adiposity correlates with relatively greater strength in HFREF patients which may explain some of the clinical benefits that result from obesity.

1. Introduction

While obesity is generally considered detrimental to those who are healthy [1,2], increased adiposity is associated with a relatively better prognosis among older adults with heart failure with reduced ejection fraction (HFREF) [3]. This so-called obesity paradox is often attributed to the “cardio-protective benefits” [4–7], of adipose tissue wherein adipose tissue is thought to impart neuroendocrine and metabolic benefits [8–10]. While a multitude of studies corroborate the favorable implications of obesity in heart failure (HF) patients, mechanisms of cardiac benefit remain controversial [11]. We hypothesized that the benefits of adiposity may relate to functional implications of body composition. Adults with surplus body fat carry extra weight throughout the course of daily living. Differences in prognosis may result from what is a defacto resistance training stimulus and relates to differences in body composition and strength.

Although elevated body mass index (BMI) of ≥30 kg/m² is usually used to demarcate excess adiposity, simple quantification of body habitus does not discriminate between lean muscle and fat tissue [12]. Using dual energy X-ray absorptiometry (DXA) to more accurately quantify adiposity and fat distribution in HF patients and age-matched controls, we studied the impact of aerobic and strength performance relative to fat and lean body tissue.

Functional decline is typical among HFREF patients, with poor prognostic implications as well as diminished quality of life, increased frailty, and reduced independence [13,14]. Diminished muscular strength is also typical [15,16]. The relationship of lean body mass, fat mass, and the relative implications on aerobic and strength abilities have not been delineated. High fat mass may impart paradoxical health benefits by its favorable functional ramifications.

2. Materials and methods

Non-cachectic (BMI≥18.5), clinically stable, male HFREF patients aged 50 years and older were compared to age-matched controls. All patients were on a standard regimen of evidence-based HF therapy with medications and doses determined by their primary cardiologists. All HFREF patients were euvolemic during a physical exam immediately prior to the functional assessments. Additionally, each HFREF patient completed an echocardiogram within 6 months of enrollment to confirm a left ventricular ejection fraction (LVEF) ≤40%. Both HF patients and control subjects were excluded if they had neurological dysfunction, musculoskeletal problems, or severe pulmonary disease, which might have confounded functional assessments. Control subjects had no history of cardiovascular disease. Control candidates or HFREF patients who exercised ≥150 min/week for the three months prior to enrollment were also excluded to avoid confounding effects of exercise training. The study was approved by the VA Institutional Review Board and informed consent was obtained from each subject.

Exercise testing was completed on a motorized treadmill using a modified Balke protocol [17] in conjunction with ventilatory expired gas analysis through a snorkel device [18]. The ventilatory expired gas analysis system (MedGraphics BreezeSuite St. Paul, MN) was calibrated prior to each test. ECG waveforms, blood pressure, oxygen saturation, and subjective symptoms were assessed before, during, and after exercise, in routine clinical fashion.

Peak oxygen consumption (VO₂) was defined as the 30-second averaged value during the last stage of exercise. Ventilatory anaerobic threshold (VAT) was determined by the V-slope method [19]. Ventilatory efficiency represented as the ventilation to carbon dioxide production (VE/VCO₂) slope was evaluated during exercise. VE and VCO₂ values, acquired from the initiation of exercise to maximal exertion, were input into a spreadsheet software (Microsoft Excel, Microsoft Corp., Bellevue, WA) to calculate the VE/VCO₂ slope via least squares linear regression (y=mx + b, m=slope). All of the subjects achieved a minimum peak respiratory exchange ratio (RER) of 1.0, ensuring a standard of high physical exertion [20] among patients who had predominantly sedentary lifestyles.

Muscle strength and power were measured using a pneumatic leg press (Keiser A420, Fresno, CA). To assess maximal strength capacity, participants performed a leg press (i.e. knee extension and flexion) initially using a minimal weight. Subjects rated the leg press according to the rating of perceived exertion (RPE) using the Borg scale [21] The physiologist then increased the weight and the participant completed another leg press with the heavier weight and rated the difficulty of the leg press. The weight was progressively increased until the participant was unable to complete a full repetition. The last weight that was used to complete a full repetition was recorded as the one repetition maximum (1RM). Thereafter, the resistance was reduced to 60% of the 1RM, and subjects completed up to 30 repetitions continuously to assess submaximal power. A desktop computer was connected to the leg press machine, which generated power curves (watts) for each leg press. Upon completion of the 30 repetitions, the peak for each curve was determined and averaged with one another.

Total and anthropometric lean and fat mass were measured with iDXA (GE Lunar, Madison, WI) and analyses were performed using Encore 13.60 software. The DXA scanner (Lunar iDXA, Madison, WI 53718,) was calibrated with a phantom provided by GE Healthcare, prior to each scan, according to manufacturer’s specifications [22]. iDXA is a fan beam system which uses a staggered array of sixty-four detectors (CZT-HD digital detectors) to enhance precision and eliminate dead space between detectors, thus creating a high resolution image [23]. DXA measurements were normalized to height.

SAS statistical software version 9.0 (SAS, Cary, NC) was used to analyze the data and values are reported as mean ± SD (unless otherwise indicated). Comparison of HF and controls was determined using non-paired t-tests and Pearson correlations were used to evaluate the correlation coefficients. A p-value of <0.05 was used to define statistical significance for all tests.

3. Results

Seventy subjects (31 HF patients [mean age 67.4 ± 8.9 years] and 39 controls [mean age 65.3 ± 10.1 years]) were assessed. All subjects were male. Table 1 lists the demographics and medications among the study population.

Table 1.

Participant demographics.

	HF	Controls	Significance
Age (years)	67.4±8.9	65.3±10.1	0.37
Weight (kg)	86.0±27.4	86.6±14.9	0.91
Height (meters)	1.7±0.07	1.7±0.09	0.98
Medications
Beta-blocker	23	2	<0.0001
ACE-inhibitor	25	6	<0.0001
ARB	2	2	0.80
Statin	24	16	<0.001
Diuretics	20	5	<0.0001

HF indicates heart failure; ACE, angiotensin converting enzyme; ARB, angiotensin II receptor blocker.

Table 2 demonstrates impaired aerobic ability in HF patients evidenced by a significantly decreased peak VO₂ and VAT and an increased VE/VCO₂ slope. Strength and power were also decreased in HF patients, suggesting further abnormalities in peripheral skeletal muscle function. Leg lean muscle mass was diminished in HF patients but since “lean tissue” measures incorporate both bone and muscle tissues, isolated skeletal muscle implications are uncertain. Total adiposity was similar between HF patients and controls.

Table 2.

Differences in function and body composition between HF patients and control subjects.

	HF	Controls	Significance
Aerobic capacity
Peak VO2 (ml‧kg−1‧min−1)	15.4±4.2	23.4±6.6	<0.0001
VAT (ml‧kg−1‧min−1)	10.9±2.1	14.4±4.0	<0.0001
VE/VCO2 slope	35.7±10.6	29.1±4.6	<0.01
Strength capacity
1RM (kg)	154.8±52.0	195.3±56.8	<0.01
Power (watts)	226.4±99.2	313.3±130.6	<0.01
DXA fat and lean body mass distributions (normalized to height)
Total lean (kg)	31.2±4.8	32.5±3.8	0.20
Legs lean (kg)	10.3±2.0	11.1±1.4	<0.05
Arms lean (kg)	3.8±0.7	4.0±0.9	0.24
Total fat (kg)	16.7±9.4	16.3±5.0	0.82
Leg fat (kg)	4.6±2.8	4.3±1.4	0.62
Arm fat (kg)	1.6±.9	1.6±0.6	0.80

Peak VO₂ indicatesmaximal oxygen consumption; VAT oxygen consumption at anaerobic threshold; VE/VCO₂ slope ventilatory efficiency; 1RM the one repetition maximum.

Table 3 demonstrates the lack of correlation between lean mass and aerobic indices in HF patients. However, Table 4 shows that lean mass is significantly associated with strength capacity in HF patients, suggesting that lean mass has a greater influence on strength than aerobic ability. Table 4 also shows that fat mass correlates with strength; correlations were stronger in the HF group than in the controls.

Table 3.

Correlations between aerobic capacity and body anthropometrics in HF patients and controls.

	Peak VO2		VAT		VE/VCO2 slope
	HF	Controls	HF	Controls	HF	Controls
Lean body tissue distribution
Total lean	−0.18	0.17	−0.06	0.05	−0.08	−0.09
Legs lean	−0.13	0.26	−0.09	0.19	−0.11	−0.02
Arms lean	−0.04	0.44†	0.05	0.21	−0.18	−0.22
Adipose tissue distribution
Total fat	−0.17	−0.23	−0.17	−0.17	−0.10	0.04
Leg fat	−0.21	−0.22	−0.19	−0.14	−0.06	−0.10
Arm fat	−0.27	−0.22	−0.28	−0.17	−0.06	−0.03

Peak VO₂ indicates maximal oxygen consumption; VAT oxygen consumption at anaerobic threshold; VE/VCO₂ slope ventilatory efficiency.

^†p<0.01.

Table 4.

Correlations between strength capacity and body composition in HF patients and controls.

	1RM		Power
	HF	Controls	HF	Controls
Lean body tissue distribution
Total lean	0.54†	0.63‡	0.19	0.16
Legs lean	0.53†	0.54‡	0.13	0.11
Arms lean	0.48†	0.38*	0.34	0.12
Body fat distribution
Total fat	0.56†	0.40*	0.24	0.17
Leg fat	0.45*	0.37*	0.06	0.11
Arm fat	0.39*	0.41*	0.23	0.14

1RM is the one repetition maximum.

^*p<0.05.

^†p<0.01.

^‡p<0.001.

To further compare the effects of fat and lean body mass on strength capacity, HF patients were stratified into groups according to a <30 kg/m² (n=21) and ≥30 kg/m² (n=10) BMI threshold; mean BMI 25.0 ± 3.1 vs. 37.0 ± 7.5 kg/m², p<0.001, respectively. Although aerobic indices were similar between the two groups [peak VO₂ (14.9 ± 4.3 vs. 15.6 ± 4.2 mlO₂·kg⁻¹·min⁻¹, p=0.66), VAT (11.0 ± 2.7 vs. 10.9 ± 1.7 mlO₂·kg⁻¹·min⁻¹, p=0.84), and VE/VCO₂ slope (36.9 ± 13.2 vs. 35.1 ± 9.4, p=0.67)], those in the high BMI group had a significantly higher 1RM (181.0 ± 55.6 vs. 141.6 ± 46.0 kg, p<0.05).

Fat mass, as assessed by DXA, was increased in the high BMI subgroup: total fat mass (26.5 ± 10.1 vs. 12.1 ± 3.9 kg, p<0.01) as well as leg fat mass (7.2 ± 3.4 vs. 3.3 ± 1.2 kg, p<0.01), and arm fat mass (2.4 ± 1.0 vs. 1.2 ± 0.5 kg, p<0.01). 1RM correlated positively with total fat (r=0.65, p<0.05) and leg fat (r=0.64, p<0.05) only in the HF group with high BMI.

Patients in the high BMI group also had increased total lean mass (36.4 ± 4.3 vs. 29.7 ± 2.6 kg, p<0.0001) as well as leg lean mass (12.3 ± 2.1 vs. 9.4 ± 1.2 kg, p<0.01) and arm lean mass (4.3 ± 0.7 vs. 3.5 ± 0.5 kg, p<0.01). However, there were no significant correlations between lean mass and function in this group.

4. Discussion

The obesity paradox insinuates that increased body fat imparts protective benefits in a HF population. The current investigation shows that adiposity correlates with strength capacity in HFREF patients. Paradoxical benefits of obesity might relate to increased strength and/or the metabolic, biological, and/or physiological derivatives of increased strength capacity.

HFREF patients were subdivided into groups with high and low BMI; in the subgroup with BMI ≥30 kg/m², both fat mass and lean body mass were greater than in the subgroup with BMI <30 kg/m², but only fat mass correlated to strength capacity. This suggests that fat itself may underlie a fundamental functional benefit rather than it serving primarily as a stimulus for increased lean body mass as its only mechanism of benefit. Nonetheless, the coexistence of higher fat and lean body mass among those with high BMI highlights the complex interrelationship between fat and lean body mass in relation to high BMI.

Our findings are consistent with those of Anker et al. [24] who showed that the ability to perform work in HF reflects measures of both distance and mass. HF patients who carry more mass (i.e. those who are overweight or obese) over a longer distance are inevitably doing more work. This study indicates that overweight and obese adults inevitably incorporate strength training into everyday activities, since their muscles must support excess adipose tissue as compared to normal or under-weight patients. We extend these findings by applying DXA to show that HFREF patients with increased body fat achieve greater strength capacities. While lean muscle and fat mass were both elevated in the patients with BMI ≥30 kg/m², only fat mass correlated with strength, possibly indicating a unique health benefit from adiposity.

Lavie et al. [4] demonstrated that HF patients who suffered cardiovascular events had lower BMIs and body surface areas than those who did not experience an event over two-years. This study suggests that a greater fat mass in HF patients protects them from clinical events. Those with less fat mass, including those who had similar amounts of lean tissue, were more likely to develop an event.

Despite Lavie’s study and others indicating lower mortality rates among obese HF patients [3,6,25,26], clarification regarding the cardio-protective aspects of fat is needed. It remains unclear if fat provides direct benefits or if it primarily stimulates muscle mass and strength. These differences have bearing on HF management priorities as well as other chronic disease for which body composition affects clinical course and prognosis (e.g., kidney disease [27,28], and chronic obstructive pulmonary disease [29]).

4.1. Limitations

While our study population was small, our data distinguished functional ramifications in HF vs. controls that were consistent with larger studies, corroborating the implications of body composition data. Furthermore, our protocol was rigorous, with comprehensive physical function assessments as well as DXA scans, providing an important and relatively exceptional opportunity for novel assessments of body composition and exercise attributes.

While a cardiologist examined each patient prior to enrollment to ensure that they were euvolemic and stable, some patients may have had water retention which could potentially have confounded DXA assessments. Additionally, diet and serology (including adipocytokines) were not measured and these would have helped refine/enhance our conclusions. Our study also only enrolled male subjects and therefore further evaluation is needed to determine the effects of adipose tissue on function in the female population. This is not a longitudinal study and further research is therefore needed to determine prognostic implications. Finally, this study relied on a cross-sectional design; further research is needed to clarify causal benefits of adipose tissue.

4.2. Conclusion

Fat mass is related to increased muscle strength in obese HF patients, probably as a natural source of chronic resistance exercise, with paradoxical beneficial implications on health.