This is the first study to assess the effects of a comprehensive lifestyle modification program with diet and exercise in obese patients with systolic HF. Achieving significant intentional weight loss proved difficult in this population.
There is great debate over the optimal BMI for HF patients. Data suggest that obesity, classified as a BMI from 30–34 kg/m2
, portends an improved survival [22
]. Recent HF care guidelines suggest that intentional weight loss is not recommended in HF patients unless the BMI exceeds 40 kg/m2
(based on expert opinion, level of evidence C) [23
]. This is in part due to several studies that have demonstrated similar energy intake between HF patients and healthy adults, but an increased energy expenditure in HF patients leading to a negative energy balance [24
]. The negative energy balance is driven by the activation of catecholamines and proinflammatory cytokines that not only increase the metabolic rate of tissue, but induce an anorectic response [25
]. Yet, the fact remains that ~65% of heart failure patients are overweight or obese [26
]. This substantial prevalence brings with it concomitant comorbidities such as diabetes, hyperlipidemia, and sleep apnea, aggravates symptoms of heart failure, and limits or excludes patients from transplant candidacy. Thus, there may be a role for instituting a moderate amount of weight loss in this population. We chose to implement a lifestyle modification program as it is a non-invasive, non-pharmacologic approach to intentional weight loss.
Institution of lifestyle modification to achieve significant and sustainable weight loss is challenging in the general population, and plausibly more so in a HF population that is unable to achieve increased levels of exercise. In the general population, weight loss of >7% of baseline body weight is accepted as metabolically meaningful weight loss. This degree of weight loss has been associated with improved lipid profile and glucose control, lower blood pressure, as well as reduced inflammatory and prothrombotic factors [31
]. Successful weight loss has been achieved with lifestyle modification programs that have utilized the following components: frequent interactive sessions with a registered dietitian that assisted participants with goal-setting, self-monitoring, stimulus control, and problem solving as well as provision of meal replacement products. Recent studies of such lifestyle programs in the general population have achieved ~10.7 kg weight loss with ~21% attrition [32
]. Specifically, trials utilizing meal replacement products generally produce 6.19 – 6.5 kg weight loss with a 16% drop-out rate at 3 months [33
]. Comparatively, the lifestyle group in this study lost only 0.50 ± 3.64 kg (after exclusion of 1 patient with increased diuretic dose) despite similar adherence to the intervention program. One possible explanation for the failure to achieve significant weight loss may be an inability to achieve adequate negative caloric balance secondary to failure to achieve a substantial increase in caloric expenditure (i.e. limited exercise tolerance) or actual non-compliance with diet despite apparent adherence with the lifestyle program. Yet, if HF is truly a negative energy state, any further tipping of the balance should result in weight loss. Another possibility is that there is a biochemical resistance to weight loss.
There is limited data regarding intentional weight loss in heart failure patients using other modalities, such as bariatric surgery or orlistat therapy. Ramani et al. [34
] performed a retrospective analysis of 12 morbidly obese, HF patients who underwent bariatric surgery compared to 10 matched controls At 12 months, the bariatric surgical group had decreased BMI (from 53 to 38 kg/m2
), improved NYHA classification and increased left ventricular ejection fraction (from 21.7 to 35.0%) compared to baseline. The control group exhibited no significant change in BMI or ejection fraction and had a worsening NYHA class. The surgical group also had reduced heart failure hospitalizations compared to the controls (0.42 vs. 2.4 admissions). Twenty one obese, systolic heart HF patients were randomized to orlistat (n=11), a gastrointestinal lipase inhibitor, versus standard care. At 12 weeks, the orlistat group attained a 4.65 kg weight loss with accompanied improved lipid profile, a trend toward increased 6 minute walk distance, but no significant change in glucose, brain natriuretic peptide, or C-reactive protein levels [12
]. There was one death in each group. Further research is necessary to assess various weight loss modalities and their impact on metabolic and cardiovascular outcomes in those with HF.
Other than restricting sodium to <2 g daily, there are no specific dietary HF guidelines. The U.S. Department of Health and Human Services and World Health Organization recommend sedentary adults over the age of 51 should have an estimated caloric intake of 1600 kcal for females and 2000 kcal for males with a recommended fat intake of <65 g (or 20–37% of total calories), and fiber intake of >25 g [35
]. The reported dietary intake in the lifestyle group suggests a wide variation in caloric intake (baseline range 640–7998 kcal/day). The sodium intake, 4018 mg (1252, 9398) and total fat intake, 98 g, (20,198) exceed the recommended amounts, but compare similarly to other studies reporting nutritional intake in HF populations [37
]. Given the small study size and known variability in reporting dietary intake [41
], it is difficult to ascertain an accurate difference in intake at 3 months. The degree of caloric reduction with lifestyle modification was not significantly different between those who lost weight versus those who did not. In general, institution of dietary changes in systolic HF patients, including use of meal replacement beverages, did not cause rapid or drastic weight loss or worsened heart failure. Despite the limitations of this data, the wide caloric intake would suggest that some participants would be in a negative energy balance, yet failed to lose weight, and were in fact obese. As well, the study by Lichtman et al. [41
] demonstrated that the inaccuracies of dietary reporting are an under-reporting of dietary intake by 47%, if this is the case and then some participants’ consumption greatly exceeds the recommended intake.
The safety of exercise in HF is supported by Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION), a large randomized controlled clinical trial, as well as meta-analysis data [42
]. Benefits of regular exercise in HF include reduced hospitalization/death, improved functional capacity and quality of life, as well as attenuation of LV remodeling and improved ejection fraction [45
]. Our study documents the extreme limitation in activity in this population with only 1259 steps/day (1028, 4519). This is far below the recommended goal of 10,000 steps/day in the general population, but consistent with published data of pedometer-determined physical activity in populations with chronic illnesses [47
]. The lifestyle modification program was successful in increasing participants’ activity with those losing weight increasing to a greater degree than those who did not (Δ1434 vs.862 steps/day). No adverse events occurred while exercising.
The study was not adequately powered to detect significant differences in biomarkers. However, the baseline levels of biomarkers in our study are consistent with those reported in the literature for heart failure populations [49
], except BNP levels fell within normal limits despite a mean EF of 26% and leptin levels were markedly elevated (median 52.3 ng/mL (30.6, 109.4)) consistent with levels reported for obese populations [55
]. The TNFα receptor and leptin levels were highly correlated at baseline (rs
= 0.82) and there was a trend for reduction in both biomarkers in those who lost weight versus those who did not. Yet, it remains unclear what the overall effects of such elevated levels of leptin are as well as its subsequent reduction with weight loss. Leptin, a hormonal product of adipose tissue and cardiomyocytes [57
], has been shown to be elevated in HF, with increasing levels correlating with worsening disease (lower VO2
]. Leptin has been reported to decrease fatty acid oxidation leading to intracellular lipid accumulation [59
], suppress myocyte peak shortening rate [60
], alter extracellular matrix turnover [61
], stimulate sympathetic activation [62
], and is associated with increased proinflammatory cytokines (such as TNFα) [64
] each of which may be detrimental in heart failure. Yet, leptin appears to exert cardioprotective effects such as attenuation of cardiomyocyte apoptosis [65
], stimulation of cardiomyocyte hypertrophy [66
], and nitric oxide mediated vasodilation [67
]. In the general population, leptin levels are correlated with BMI and decline with intentional weight loss. There is some data that suggest that elevated leptin concentrations are associated with lower resting energy expenditure and may predict failure to maintain weight loss [55
]. As leptin plays a role in appetite regulation, it has been proposed that obese individuals (obesity being a hyperleptinemic state) are resistant to the effects of leptin. Complicating the situation is evidence suggesting that this resistance may be to selective functions of leptin [66
]. Given the paradoxical cardiovascular effects of leptin and the leptin resistant state of obesity, it is difficult to interpret whether the trend toward a decreased leptin level with weight loss is beneficial or not [69
This was a small pilot study to assess the feasibility and safety of a lifestyle modification intervention in systolic HF patients. While the intervention was well tolerated, it did not result in significant intentional weight loss. Given the small amount of weight lost, participants remained obese so it is expected that this would not result in a change in functional status, metabolic or hemodynamic parameters. A larger magnitude of weight loss is likely necessary to detect these changes. Further investigation is needed to define the metabolic and nutritional requirements of HF as well as the ideal body composition and weight in this population. A better understanding of the interaction of obesity and HF on the underlying cytokine milieu is critical to understanding this process. Following this, larger scale trials of lifestyle modification or pilot studies of other novel weight management modalities should be considered.