The Obesity Paradox in Heart Failure: Why Does It Clinically Matter?

In the U.S., the prevalence of obesity in adults exceeds 30%.1 Obesity is linked to the development of cardiovascular diseases, including atherosclerosis and hypertension, and to an increased risk for heart failure (HF).2 Obesity has been shown to adversely affect left ventricular structure, as well as systolic and diastolic function.3,4 The rising obesity epidemic is, therefore, an obvious challenge faced by the health care system. In this regard, patient counseling on weight reduction and exercise is important. However, it has been shown in several studies that despite being an independent risk factor for the development of HF, obesity is associated with lower mortality in patients with established HF, giving rise to the phrase "obesity paradox."5,6,7 Although initially hypothesized that weight loss associated with severe HF, or cardiac cachexia, was the likely explanation for better survival in the overweight and obese HF patients, several other reasons have been postulated. These include attenuation of certain neurohumoral pathways, higher metabolic reserve, lead-time bias due to earlier diagnosis of HF in obese patients, a lower specificity of diagnosis of HF in obese individuals, and greater uptitration of HF therapies due to higher blood pressure present in obese patients.5 A recent study has shown that compared to normal weight, presence of overweight and obesity even prior to incident HF development (i.e., pre-HF higher body mass index [BMI]) was associated with improved survival after the onset of HF, further supporting the fact that weight loss due to advanced HF may not completely explain the protective effect of higher BMI in HF patients.8 Keeping the obesity paradox in mind, should physicians discourage obese HF patients from intentional weight loss? Or should physicians still recommend weight reduction in HF patients in an attempt to prevent obesity-related complications?

There are several theoretical reasons to believe why obese patients with HF may benefit from intentional weight loss. These include the following: improved control of obesity-related comorbidities, such as diabetes or insulin resistance, hypertension, and obstructive sleep apnea; better quality of life; better mental health; and improved candidacy for advanced HF therapies, such as ventricular assist device placement or cardiac transplantation. In addition, various favorable cardiovascular effects of weight reduction have been seen in obese non-HF individuals, including decreased left ventricular mass, decreased ventricular filling pressures and mean arterial pressure, and improvement in several systolic and diastolic parameters.9-15 Therefore, it is intuitive to think that weight loss via diet, exercise, pharmacotherapy or bariatric surgery may result in improved cardiovascular outcomes in obese patients with HF. Although intentional weight loss in obese individuals without HF has been a subject of several studies in preventive cardiology,12 there have not been any large long-term trials to specifically address effects of intentional weight loss in obese patients with HF.

Few short-term studies have investigated the role of intentional weight loss in HF. Two such studies assessed the impact of dietary intervention in obese patients with HF. In a pilot study, 14 HF patients with BMI ≥27 kg/m2 were randomized to a high protein diet, standard protein diet, or control (conventional diet). The only difference between the standard protein diet and the conventional diet was that the former was hypoenergetic while the conventional diet had no energy restrictions. Both of the intervention groups were associated with weight reduction with a significant improvement in quality of life but without any change in left ventricular structure or function compared with the control group.16 In another pilot trial to assess the safety and effectiveness of lifestyle modification, 20 patients with HF were randomized to standard medical therapy versus medical therapy and lifestyle modification. Lifestyle modification involved a walking program and a reduced calorie diet with two meal replacement products. There was no significant difference between the two groups in terms of weight reduction or cardiac structural and functional parameters at three months of follow-up.17 Both studies had patients with mean BMI >35 kg/m2, and neither study reported any adverse events related to the interventions. In terms of pharmacotherapy, orlistat, a lipase inhibitor, has been studied in another pilot study of obese patients with HF.18 Twenty-one patients with HF were randomized to orlistat plus dietary counseling versus dietary counseling alone for 12 weeks. Compared to the control group, the orlistat group had an average weight loss of 8.55 kg. The orlistat group also had better results on the six-minute walk test and did not have any major safety issues. Thus, there exists a need for a large randomized clinical trial assessing the safety and efficacy of intentional weight loss in obese HF patients with cardiovascular outcomes; however, preliminary feasibility studies suggest that monitored weight loss may be safe.

The Heart Failure and A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) study examined the influence of exercise intervention in 2,331 patients with systolic HF, and showed an overall non-significant trend towards decrease in all-cause mortality (hazard ration [HR] 0.96, 95% confidence interval [CI] 0.79-1.17) and cardiovascular mortality or HF hospitalizations (HR 0.87, 95% CI 0.75-1.00) in the exercise training group compared to the usual care group over a median follow up of 30.1 months.19 At baseline, quality of life, including both physical and emotional dimensions, was worse in obese HF patients compared to their normal-weight HF counterparts.20 The impairment in quality of life in obese HF patients has been seen more in the emotional compared to the physical aspect, and more in females compared to males.21,22 In HF-ACTION, the exercise intervention was associated with improved quality of life in all BMI sub-groups, with greater benefit in higher BMI categories.20,23 Another study has demonstrated the importance of cardiorespiratory fitness in patients with HF. Patients with a high level of fitness did not demonstrate the obesity paradox, although the paradox was observed in HF patients with low levels of fitness.24 Taken together, these findings suggest that obese HF patients may benefit from maintaining a higher level of fitness by exercising on a routine basis. The association of obesity with incident HF is even stronger in HF with preserved ejection fraction (HFpEF) compared to HF with reduced ejection fraction (HFrEF). A meta-analysis of 228 patients with HFpEF showed that exercise training was associated with improved exercise capacity as well as improved quality of life.25 While adherence to exercise therapy can be difficult to maintain, home-based exercise programs may be easier and cheaper to implement. Exercise diaries and pedometers could further assist in improving compliance.26

Advanced HF is generally considered a contraindication to bariatric surgery;27 albeit few studies have examined the safety and efficacy of weight-reduction surgeries in obese patients with HF.28-30 In smaller studies, bariatric surgery was found to result in significant reduction in BMI, with improved left ventricular ejection fraction and New York Heart Association (NYHA) functional class.31.32 Large, randomized controlled trials will be needed to definitively confirm the safety and efficacy of bariatric surgery in obese HF patients.

Based on current evidence, the American College of Cardiology/American Heart Association HF guidelines do not specifically recommend weight reduction in obese patients with HF. They do, however, provide a Class I recommendation for exercise training (or regular physical activity) as safe and effective for patients with HF who are able to participate to improve functional status.33 It should be noted that this recommendation applies to all patients with HF, without stratification by obesity status. Moreover, from a prevention standpoint, intentional weight loss in obese individuals without HF can help to reduce the risk of development of HF. Large randomized controlled trials with long-term follow-up will be needed to definitively evaluate the effectiveness of various intentional weight loss interventions in obese patients with HF on clinical outcomes, morbidity related to obesity and obesity-related comorbidities.

References

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Clinical Topics: Cardiac Surgery, Diabetes and Cardiometabolic Disease, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Prevention, Sleep Apnea, Cardiac Surgery and Heart Failure, Acute Heart Failure, Heart Transplant, Mechanical Circulatory Support , Diet, Exercise, Hypertension

Keywords: Actigraphy, Adult, American Heart Association, Arterial Pressure, Atherosclerosis, Bariatric Surgery, Blood Pressure, Body Mass Index, Cachexia, Cardiovascular Diseases, Comorbidity, Confidence Intervals, Control Groups, Counseling, Diabetes Mellitus, Diet, Exercise, Exercise Therapy, Feasibility Studies, Female, Follow-Up Studies, Heart Failure, Heart Transplantation, Heart-Assist Devices, Hospitalization, Humans, Hypertension, Insulin Resistance, Lactones, Life Style, Lipase, Male, Mental Health, New York, Obesity, Overweight, Pilot Projects, Prevalence, Quality of Life, Risk Factors, Sleep Apnea, Obstructive, Stroke Volume, United States, Walking, Weight Loss


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