Exercise Capacity and the Obesity Paradox in Heart Failure: The FIT (Henry Ford Exercise Testing) Project

doi:10.1016/j.mayocp.2018.01.026

Mayo Clinic Proceedings

Volume 93, Issue 6, June 2018, Pages 701-708

https://doi.org/10.1016/j.mayocp.2018.01.026 Get rights and content

Abstract

Objectives

To assess the influence of exercise capacity and body mass index (BMI) on 10-year mortality in patients with heart failure (HF) and to synthesize these results with those of previous studies.

Patients and Methods

This large biracial sample included 774 men and women (mean age, 60±13 years; 372 [48%] black) with a baseline diagnosis of HF from the Henry Ford Exercise Testing (FIT) Project. All patients completed a symptom-limited maximal treadmill stress test from January 1, 1991, through May 31, 2009. Patients were grouped by World Health Organization BMI categories for Kaplan-Meier survival analyses and stratified by exercise capacity (<4 and ≥4 metabolic equivalents [METs] of task). Associations of BMI and exercise capacity with all-cause mortality were assessed using multivariable-adjusted Cox proportional hazards models.

Results

During a mean follow-up of 10.1±4.6 years, 380 patients (49%) died. Kaplan-Meier survival plots revealed a significant positive association between BMI category and survival for exercise capacity less than 4 METs (log-rank, P=.05), but not greater than or equal to 4 METs (P=.76). In the multivariable-adjusted models, exercise capacity (per 1 MET) was inversely associated, but BMI was not associated, with all-cause mortality (hazard ratio, 0.89; 95% CI, 0.85-0.94; P<.001 and hazard ratio, 0.99; 95% CI, 0.97-1.01; P=.16, respectively).

Conclusion

Maximal exercise capacity modified the relationship between BMI and long-term survival in patients with HF, upholding the presence of an exercise capacity-obesity paradox dichotomy as observed over the short-term in previous studies.

Section snippets

Patients and Methods

The FIT Project includes 69,885 patients who completed a physician-referred treadmill exercise test at Henry Ford Hospital and affiliated medical centers in metropolitan Detroit, Michigan, from January 1, 1991, through May 31, 2009. Additional information on participant characteristics and methods has been published elsewhere.¹⁵ Patients in the present study were drawn from a sample of 42,854 FIT Project participants who had complete information on BMI and METs achieved on a treadmill exercise

Results

During a mean follow-up of 10.1±4.6 years, 380 patients (49%) died. The baseline characteristics of the study cohort both overall and by EC category are summarized in Table 1. (Descriptive statistics for the full cohort of 1212 patients with HF are provided in Supplemental Table 1, available online at http://www.mayoclinicproceedings.org.) Overall, 326 (42%) patients were obese (BMI≥30.0 kg/m²). Patients with lower EC were older (P<.001) and were more likely to be female (P<.001) and black (P

Discussion

In this biracial sample of patients with HF, an obesity paradox was observed only in those with lower EC, as previously reported in studies with shorter follow-up periods of 2 to 3 years.11, 12, 13 The present study was the first to report this in a large sample with longer follow-up (>10 years), upholding the presence of an obesity paradox in patients with HF and low EC. Although we did not observe a significant interaction between BMI and EC in the overall study population (P=.97), EC

Conclusion

We found that higher BMI was associated with lower 10-year mortality in patients with HF and lower EC, but not higher EC. Our findings underscore the importance of stratifying patients with HF by EC. Future studies should investigate whether maintaining or gaining weight is advantageous to nonobese patients with HF who have a lower EC.

References (42)

T.B. Horwich et al.
The relationship between obesity and mortality in patients with heart failure
J Am Coll Cardiol
(2001)
R. Shah et al.
Body mass index and mortality in acutely decompensated heart failure across the world: a global obesity paradox
J Am Coll Cardiol
(2014)
A. Sharma et al.
Meta-analysis of the relation of body mass index to all-cause and cardiovascular mortality and hospitalization in patients with chronic heart failure
Am J Cardiol
(2015)
G.M. Lin et al.
The obesity-mortality paradox in patients with heart failure in Taiwan and a collaborative meta-analysis for East Asian patients
Am J Cardiol
(2016)
S.J. Keteyian et al.
Peak aerobic capacity predicts prognosis in patients with coronary heart disease
Am Heart J
(2008)
G.E. Shaya et al.
High exercise capacity attenuates the risk of early mortality after a first myocardial infarction: the Henry Ford Exercise Testing (FIT) Project
Mayo Clin Proc
(2016)
P.A. McAuley et al.
Contribution of cardiorespiratory fitness to the obesity paradox
Prog Cardiovasc Dis
(2014)
C.J. Lavie et al.
Impact of cardiorespiratory fitness on the obesity paradox in patients with heart failure
Mayo Clin Proc
(2013)
A.L. Clark et al.
Impact of cardiorespiratory fitness on the obesity paradox in patients with systolic heart failure
Am J Cardiol
(2015)
A. Nigam et al.
Excess weight at time of presentation of myocardial infarction is associated with lower initial mortality risks but higher long-term risks including recurrent re-infarction and cardiac death
Int J Cardiol
(2006)

D.I. Feldman et al.

No evidence of an upper threshold for mortality benefit at high levels of cardiorespiratory fitness

J Am Coll Cardiol

(2015)

C.A. Brawner et al.

Comprehensive analysis of cardiopulmonary exercise testing and mortality in patients with systolic heart failure: the Henry Ford Hospital cardiopulmonary exercise testing (FIT-CPX) project

J Card Fail

(2015)

C.J. Lavie et al.

Does fitness completely explain the obesity paradox?

Am Heart J

(2013)

C. Kragelund et al.

A farewell to body-mass index?

Lancet

(2005)

S. Gielen et al.

The obesity paradox—a scientific artifact?

Int J Cardiol

(2013)

C.J. Lavie et al.

Body composition and prognosis in chronic systolic heart failure: the obesity paradox

Am J Cardiol

(2003)

A.L. Clark et al.

Waist circumference, body mass index, and survival in systolic heart failure: the obesity paradox revisited

J Card Fail

(2011)

K. Goel et al.

Combined effect of cardiorespiratory fitness and adiposity on mortality in patients with coronary artery disease

Am Heart J

(2011)

P. Srikanthan et al.

Relation of muscle mass and fat mass to cardiovascular disease mortality

Am J Cardiol

(2016)

A.R. Vest et al.

The heart failure overweight/obesity survival paradox: the missing sex link

JACC Heart Fail

(2015)

A.L. Clark et al.

The obesity paradox in men versus women with systolic heart failure

Am J Cardiol

(2012)

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Obesity Status and Physical Rehabilitation in Older Patients Hospitalized With Acute HF: Insights From REHAB-HF
2022, JACC: Heart Failure
In the REHAB-HF (Rehabilitation Therapy in Older Acute Heart Failure Patients) trial, a novel, early, transitional, multidomain rehabilitation intervention improved physical function, frailty, quality of life (QOL), and depression in older patients hospitalized for acute decompensated heart failure (ADHF), but the potential impact of baseline obesity on this intervention has not been studied.
This study assessed for treatment interactions by body mass index (BMI) subgroups for a novel rehabilitation intervention in ADHF.
Three-month outcomes including Short Physical Performance Battery (SPPB) (primary outcome), 6-minute walk distance (6MWD), and Kansas City Cardiomyopathy Questionnaire (KCCQ) were assessed by baseline BMI (≥30 kg/m² vs <30 kg/m²). Six-month end points included all-cause rehospitalization and death. All analyses were adjusted for age, sex, clinical site, and ejection fraction category, and 3-month outcomes were also adjusted for baseline measure. The prespecified significance level for treatment interaction by BMI category was P ≤ 0.10.
Of 349 trial participants, 204 (58%) had BMI ≥30 kg/m² and 145 (42%) <30 kg/m². Compared with patients with BMI <30 kg/m², participants with BMI ≥30 kg/m² were younger (age 71 ± 7 years vs 75 ± 9 years), more frequently women (57% vs 46%), and had significantly worse baseline physical function and QOL. Although interaction P values for 3-month outcomes by BMI were not significant (interaction P > 0.15 for overall measures), adjusted SPPB effect sizes were nominally larger for participants with BMI ≥30 kg/m² compared with those with BMI <30 kg/m²: +1.7 (95% CI: 0.8-2.7) vs +1.1 (95% CI: −0.1 to 2.2). This difference in SPPB effect size was due largely to improvements in the balance component of the SPPB for participants with BMI ≥30 kg/m²: +0.6 (95% CI: 0.2-1.0) vs 0.0 (−0.6 to 0.5) for those with BMI <30 kg/m² (interaction P = 0.02). In contrast, adjusted 6MWD and KCCQ effect sizes were smaller for participants with BMI ≥30 kg/m² compared with those with BMI <30 kg/m²: +21 meters (−17 to 59) vs +53 meters (6-100), and +5.0 (−4 to 14) vs +11 (−0.5 to 22), respectively. There was no significant interaction by BMI for 6-month clinical outcomes (all interaction P > 0.30).
Older patients with ADHF benefit from the rehabilitation therapy regardless of BMI. Benefits for patients with obesity may be more evident in the multidomain measure of physical function (SPPB), compared with the 6MWD or KCCQ, which may be driven, in part, by the unique aspects of the novel rehabilitation intervention. (A Trial of Rehabilitation Therapy in Older Acute Heart Failure Patients [REHAB-HF]; NCT02196038)
The Impact of Obesity in Heart Failure
2022, Cardiology Clinics
Citation Excerpt :
Similarly, in a recent analysis of 774 patients with HFrEF and HFpEF followed for up to 12 years, those with preserved CRF, defined as having an estimated METs of 4 or more, presented with a similar prognosis independent of BMI. In contrast, in those with a lower CRF (<4 METs), an obesity paradox was reported.29 Taken together, these results suggest that the obesity paradox is highly relevant in those individuals with reduced CRF, proposing the addition of measured or estimated CRF for a more accurate risk stratification in patients with HF.
Frailty Measures of Patient-reported Activity and Fatigue May Predict 1-year Outcomes in Ambulatory Advanced Heart Failure: A Report From the REVIVAL Registry
2022, Journal of Cardiac Failure
Citation Excerpt :
We also identified a low prevalence of weight loss (approximately 1% of patients) similar to that reported by Reeves et al, but disparate from the 38% reported by Vidan et al,29 likely owing to the advanced age of their cohort compared with the current analysis. In fact, in the REVIVAL population body-mass index was actually higher with increasing degree of frailty.27,28 Assessment of weight changes in HF is challenging owing to fluctuations in volume status, where loss of muscle mass may be masked by hypervolemia, again suggesting that weight loss may not be a critical component of the frailty assessment in patients living with HF. 12,24,25
The Fried Frailty Phenotype predicts adverse outcomes in geriatric populations, but has not been well-studied in advanced heart failure (HF). The Registry Evaluation of Vital Information for Ventricular Assist Devices (VADs) in Ambulatory Life (REVIVAL) study prospectively collected frailty measures in patients with advanced HF to determine relevant assessments and their impact on clinical outcomes.
HF-Fried Frailty was defined by 5 baseline components (1 point each): (1) weakness: hand grip strength less than 25% of body weight; (2) slowness based on time to walk 15 feet; (3) weight loss of more than 10 lbs in the past year; (4) inactivity; and (5) exhaustion, both assessed by the Kansas City Cardiomyopathy Questionnaire. A score of 0 or 1 was deemed nonfrail, 2 prefrail, and 3 or greater was considered frail. The primary composite outcome was durable mechanical circulatory support implantation, cardiac transplant or death at 1 year. Event-free survival for each group was determined by the Kaplan–Meier method and the hazard of prefrailty and frailty were compared with nonfrailty with proportional hazards modeling. Among 345 patients with all 5 frailty domains assessed, frailty was present in 17%, prefrailty in 40%, and 43% were nonfrail, with 67% (n = 232) meeting the criteria based on inactivity and 54% (n = 186) for exhaustion. Frail patients had an increased risk of the primary composite outcome (unadjusted hazard ratio [HR] 2.82, 95% confidence interval [CI] 1.52–5.24; adjusted HR 3.41, 95% CI 1.79–6.52), as did prefrail patients (unadjusted HR 1.97, 95% CI 1.14–3.41; adjusted HR 2.11, 95% CI 1.21–3.66) compared with nonfrail patients, however, the predictive value of HF-Fried Frailty criteria was modest (Harrel's C-statistic of 0.603, P = .004).
The HF-Fried Frailty criteria had only modest predictive power in identifying ambulatory patients with advanced HF at high risk for durable mechanical circulatory support, transplant, or death within 1 year, driven primarily by assessments of inactivity and exhaustion. Focus on these patient-reported measures may better inform clinical trajectories in this population.
Pooled Cohort Equations and the competing risk of cardiovascular disease versus cancer: Multi-Ethnic study of atherosclerosis
2021, American Journal of Preventive Cardiology
many of the modifiable variables in the Pooled Cohort Equations (PCE) are shared risk factors for cardiovascular disease (CVD) and cancer, which are the two leading causes of death in the United States. We sought to determine the utility of the PCE risk for the synergistic risk prediction of CVD and cancer.
we identified 5,773 participants (61.5 years and 53% women) without baseline CVD or cancer from the Multi-Ethnic study of atherosclerosis. The primary outcome was time to first event of either incident CVD or incident cancer. We calculated competing risk and cause-specific hazard models to examine the association of the PCE groups (<7.5%, 7.5–<20%, ≥20%) with the competing risk of CVD and cancer.
the rate of incident CVD and cancer was higher with higher PCE risk, but the absolute event rate was low for both CVD and cancer when the PCE risk was <7.5%. Participants with a PCE <7.5% had a higher rate of cancer (4.8) compared to CVD (3.3) per 1000 person-years, while the rate of CVD (11.5) was higher than cancer (8.6) for PCE between 7.5 and <20%. The ratio of CVD to cancer increased in a logarithmic manner and at a PCE risk of approximately 7.2% the risk for CVD and cancer was equal. In adjusted competing risk modeling, a PCE risk of ≥20% compared to <7.5% was associated with a greater risk of both CVD [7.18 (95% CI 5.77–8.94)] and cancer [3.59 (95% CI 2.91–4.43)].
these findings highlight the importance of age and modifiable risk factors for CVD and cancer prevention. In addition, it suggests that the PCE can provide important information for both CVD and cancer risk stratification, which may guide a synergistic approach to screening and preventive therapies for the two leading causes of death in the United States.
Body Mass Index and 90-Day Mortality Among 35,406 Danish Patients Hospitalized for Infection
2021, Mayo Clinic Proceedings
Citation Excerpt :
This pattern was robust after controlling for potential confounding factors, and the greater impact of underweight compared with obesity on mortality was consistent for major subtypes of infections. Our findings corroborate and extend the few previous findings and support the hypothesis of a protective effect of overweight/obesity against death from severe infections.12-16 The mechanisms are not clear, but evolutionarily, a possible survival benefit among individuals with obesity may be related to proinflammatory defenses and large energy reserves, protecting against death from infections such as sepsis when starvation and infection were common and life span was short.34,35
To examine the association between body mass index (BMI) and mortality after hospitalization for infection because obesity is associated with increased energy reserves that may protect against death from severe infections.
Of 76,044 patients admitted with a primary infection diagnosis from January 1, 2011, to September 30, 2015, in Central Denmark, we examined a subgroup of 35,406 patients with a known BMI. We compared the 90-day death risk among patients with underweight, overweight, or obesity with a reference cohort of normal-weight patients. We also examined the impact of comorbid conditions, including cancer, tobacco smoking, and recent weight changes, on the associations and adjusted for other potential confounding factors.
The 90-day mortality after hospital admission was 9.8% (3479 of 35,406) for any infection, 10.5% (466 of 4425) for urinary tract infection, 17.3% (1536 of 8855) for pneumonia, 24.9% (986 of 3964) for sepsis, and 6.2% (114 of 1831) for skin infection. The 90-day adjusted hazard ratio (aHR) for death was substantially increased in patients with underweight (aHR, 1.75; 95% CI, 1.58 to 1.94) compared with normal-weight patients. In contrast, mortality aHRs were decreased in patients with overweight (aHR, 0.64; 95% CI; 0.58 to 0.69) and obesity (aHR, 0.55; 95% CI; 0.49 to 0.62). Mortality reductions with overweight and obesity were consistent for all major infection types and remained robust independent of recent weight changes, smoking status, or comorbid conditions. Mortality was highest in patients without an apparent reason for their underweight (smoking/known disease), suggesting a role of undiagnosed comorbid conditions.
We found evidence that higher BMI (overweight and obesity) is associated with improved survival following acute hospitalization for infection, whereas underweight increases the risk for death.
Implications of obesity across the heart failure continuum
2020, Progress in Cardiovascular Diseases
Citation Excerpt :
For example, Lavie et al.51 evaluated 2066 patients with systolic HF and found that BMI was a significant predictor of improved survival in the low fitness group defined as peak Vo2 < 14, but not in the high CRF group. More recently, a study from the Henry Ford Exercise Training Project found no relationship between BMI and mortality in the subgroup with exercise tolerance at or above 4 METs, while the obesity paradox was observed in the low exercise capacity group.52 These studies suggest that in the unfit population, obese HF patients have better outcomes, whereas this benefit is lost when compared to groups with preserved fitness.
The obesity paradox, which suggests a survival advantage for the obese in heart failure (HF) has sparked debate in the medical community. Studies demonstrate a survival advantage in obese patients with HF, including those with advanced HF requiring continuous inotropic support for palliation or disease modifying therapy with a left ventricular assist device (LVAD) or heart transplantation (HT). Importantly, the obesity paradox is affected by the level of cardiorespiratory fitness (CRF). It is now recommended that HF patients with body mass index ≥35 kg/m² achieve at least 5–10% weight loss, in order to improve symptoms and cardiac function, though more robust data are urgently needed. CRF may be the single best predictor of overall health and small improvements in fitness levels may lead to improved outcomes in HF. In addition to implications of obesity in chronic HF, we also discuss management of obese patients with advanced HF and their implications for therapies such as LVAD implantation and HT.

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: For editorial comment, see page 676; for a related article, see page 709

: Potential Competing Interests: The authors report no competing interests.

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Original articleExercise Capacity and the Obesity Paradox in Heart Failure: The FIT (Henry Ford Exercise Testing) Project

Abstract

Objectives

Patients and Methods

Results

Conclusion

Section snippets

Patients and Methods

Results

Discussion

Conclusion

J Am Coll Cardiol

J Am Coll Cardiol

Am J Cardiol

Am J Cardiol

Am Heart J

Mayo Clin Proc

Prog Cardiovasc Dis

Mayo Clin Proc

Am J Cardiol

Int J Cardiol

J Am Coll Cardiol

J Card Fail

Am Heart J

Lancet

Int J Cardiol

Am J Cardiol

J Card Fail

Am Heart J

Am J Cardiol

JACC Heart Fail

Am J Cardiol

Original article
Exercise Capacity and the Obesity Paradox in Heart Failure: The FIT (Henry Ford Exercise Testing) Project