In this population-based study of residents of central Massachusetts, underweight patients had 50% higher odds of mortality by 5 years after hospital admission for decompensated heart failure than normal weight patients, and Class I and II obesity were associated with 20% and 40% lower odds of mortality. These results support previous studies that found an inverse or U-shaped relationship between weight and mortality in patients with heart failure.10-12,20
To our knowledge, this study is the first to examine the impact of weight status on survival following hospitalization for decompensated heart failure among patients with diabetes.
Several mechanisms have been proposed to explain the paradoxical association between increased body mass and reduced mortality in heart failure. Obese patients with heart failure tend to be considerably younger than patients who are normal weight or underweight,12,13
which may confer a survival advantage. In the current study, age was inversely associated with weight status, and adjustment for weight status attenuated the estimated association between weight and all-cause mortality, especially among patients with Class III obesity, lending support to this hypothesis. The observed association may not reflect a benefit of increased adiposity, but rather the adverse influence of cardiac cachexia on mortality in patients with heart failure.21
Cardiac cachexia is characterized by loss of fat, muscle, and bone.22
BMI may not accurately differentiate adults with elevated body fat among the general population23
and specifically in patients with heart failure.24
We did not have data available on body fat or waist circumference to further refine our classification of obesity, which is a common limitation of clinical research studies. Since BMI is correlated with both body fat and lean mass,23,24
the survival advantage of overweight and Class I or II obesity may reflect higher lean mass. This potential misclassification of obesity in terms of body composition may partially explain the observed association between weight status and mortality following hospitalization for decompensated heart failure.
Increased adiposity might also reflect enhanced metabolic reserve which might partially protect patients with heart failure from the negative effects of cachexia. Adipose tissue has important endocrine and paracrine effects that not only regulate metabolism, but also influence cardiac structure and function, natriuretic responsiveness, and metabolism of circulating inflammatory cytokines.25-27
Several inflammatory and adipocytokines are known to be associated with the development of, and poorer prognosis after, heart failure.28,29
Differential expression of these cytokines at different body mass indices may also explain our findings.
Underweight among patients with comorbid diabetes and heart failure is uncommon.6
While only 3% of our sample were underweight, all 47 underweight patients died within five years of hospitalization for heart failure. Underweight may be a sign of occult non-cardiac disease, poorly-controlled diabetes, or may indicate the presence of cardiac cachexia.22
Given the strong link between increased body mass and incident diabetes,7,8
underweight in a patient with diabetes and heart failure may indicate the presence of more severe cardiac cachexia.
In addition to the 100% 5-year mortality among underweight patients, 87% of normal weight patients, 83% of overweight patients, and 70 to 80% of obese patients died within 5 years of hospitalization for acute heart failure. These 5-year mortality rates are similar to rates of 63 – 88% observed in two population-based studies of heart failure among adults with diabetes.3,30
Current major guidelines have not reached a consensus regarding recommendations for weight management in obese patients with heart failure. The American Heart Association recommends weight loss for patients with Class III obesity with the goal of reducing their BMI t less than 40 kg/m2
the Heart Failure Society of America recommends weight loss in patients with Class II or III obesity,32
and the European Society of Cardiology recommends weight loss for all obese patients.33
Therefore, it is difficult for clinicians to incorporate evidence-based weight loss recommendations into heart failure self-care. A dearth of evidence regarding intentional weight changes among patients with heart failure likely contributes to this lack of consistency in guidelines. Weight loss is common among patients with heart failure; one study found that more than 40% of patients lost at least 5% of their baseline weight and such weight loss during follow-up was associated with higher subsequent mortality.34
Another study found a gradient of elevated mortality with increasing degree of weight loss.35
Among adults with diabetes, intentional weight loss has been linked to lower mortality but unintentional weight loss was associated with higher mortality.36
It is possible that categorization as underweight and normal weight at hospital admission in many patients with diabetes and heart failure is a result of recent unintentional weight loss. Unintentional weight loss could offer an alternative explanation for the higher mortality observed in normal weight patients compared to overweight and obese patients with heart failure. Additional research is needed to better understand the impact of weight changes and weight history on mortality in patients with diabetes and heart failure.
Study strengths and limitations
The strengths of the present study include the population-based sample of patients hospitalized with acute heart failure at all medical centers in Central Massachusetts and the detailed, high-quality clinical data collected using standardized procedures. Our study also has limitations. Since the vast majority (94%) of our sample was non-Hispanic white, we cannot extrapolate our findings to other racial/ethnic groups. Ejection fraction findings during hospitalization were available for only 35% of participants; thus, we could not further classify the study population into those with systolic versus diastolic heart failure. While reduced ejection fraction findings were less often observed among overweight and obese patients with acute heart failure 13
and patients with preserved ejection fraction have lower mortality,12
the relationship between weight status and subsequent mortality was similar in patients with preserved and reduced left ventricular dysfunction.12,13
We considered a plasma glucose level of at least 200 mg/dL (11.1 mmol/L) indicative of Type 2 diabetes mellitus in the absence of a recorded medical history of Type 2 diabetes. It is likely that many of these glucose measurements were obtained while the patient was not fasting and our definition of diabetes may be less sensitive than criteria recommended by the American Diabetes Association37
and may be more likely to identify more severe cases of diabetes. However, the vast majority of our sample had previously-diagnosed diabetes (88%), and the proportion of these patients whose admission glucose levels > 200 mg/dl did not differ by weight status. Additional information on indices of diabetes control, such as HbA1c, was not available. The Worcester Heart Failure Study only collected information about cardiac medications and thus information about medication used to manage diabetes, such as insulin or oral agents, was not available. Therefore, confounding by different diabetes treatment across weight status is possible.
Patients’ BMI was calculated from weights and heights abstracted from their medical records. We did not collect information on recent changes in patients’ weight prior to hospitalization, nor did we have information on patients’ discharge weight following diuresis, which may have resulted in partial misclassification of their weight status. Among patients who did not report symptoms suggestive of recent weight changes and thus potentially misclassified dry weight (reported symptoms of weight gain, weight loss, and/or edema; n = 418), crude and age-adjusted HRs for 1-year and 5-year mortality in relation to weight status were similar to our main results (data not shown). A previous study observed a similar association between weight and mortality in their overall sample and subset of patients without edema,20
suggesting that the use of admission weight status is unlikely to explain our results.
The results of this population-based investigation provide insights into the role of the weight on 1- and 5-year mortality following hospitalization for decompensated heart failure among patients with diabetes. Underweight patients had 50% higher odds of mortality by 5 years than normal weight patients, and Class I and II obesity were associated with 20% and 40% lower odds of dying. The mechanisms underlying the observed association between weight and all-cause mortality are not fully understood and additional research is needed to explore the relationship between body composition, recent weight changes, and prognosis following hospitalization for heart failure among patients with diabetes.