Overweight or obese BMI is associated with earlier, but not later survival after common acute illnesses

The impact of obesity on survival from acute medical illness remains a source of debate. While obesity is associated with worse health-related outcomes overall [1], it is often associated with a short-term (e.g. in-hospital or 30-day) survival advantage after acute decompensated congestive heart failure (CHF) [2], pneumonia [3‐5], acute myocardial infarction (AMI) [6], and hospitalizations for critical illness in general—the so-called “obesity paradox”. Far less is known, however, about the association of obesity with longer-term survival. While a limited number of studies have included an extended follow-up period, they have not considered the risk of mortality conditional on surviving the shorter-term [7‐9]. We hypothesized that obesity may offer short-term protection but, after surviving an initial window, may still be hazardous in the longer term given the strong association of obesity with negative health outcomes [1, 10, 11].

Recent meta-analyses and large observations studies have suggested that a body mass index of 25 to 35 appears to be protective in older patients [12, 13], leading some to argue that current weight control guidelines targeting a normal body mass index (18.5 to 25) may be harmful to older patients [14]. However, the obesity paradox may simply be the result of confounding and bias in epidemiological studies [15], explained by unmeasured differences in patients across BMI categories. Indeed, after careful control for potential confounders, a recent study found the risk of mortality increases steeply with BMIs of 27 and higher [16]. Understanding the long-term association of obesity on survival after acute hospitalization is important to guiding weight control recommendations.

Furthermore, most prior work examining the association of obesity with survival after acute hospitalization is of variable quality and limited generalizability [17]. Much of the existing data is single-center studies, often post hoc analyses of clinical databases or randomized clinical trials with limited ability to adjust for potential confounders and exclusion of large numbers of patients with missing weight [17]. Patients’ weights are generally obtained after hospital admission [17, 18], when they may be biased by acute fluid shifts. Indeed, this practice may misclassify body mass index (BMI) category in as many as 20% of patients [19]. Furthermore, many studies examine in-hospital mortality, which may be biased by discharge to nursing and long-term acute care facilities [20]. Discharge practices could plausibly be different for obese patients, who typically require more intensive nursing care for a given level of illness.

Given the high prevalence of obesity (34.6% of US adults aged 65 years and older [21]) and limited data on longer term survival after acute hospitalization, we sought to examine the association of overweight or obese BMI on longer-term survival following three common acute illnesses—congestive heart failure, acute myocardial infarction, and pneumonia—in a national sample with long-term mortality data and height and weight measurements collected prior to hospitalization. These hospitalization diagnoses accounts for 6% of US hospitalizations and 8.4% of US hospitals costs [22].

In this national sample of older Americans, we have shown that overweight or obese BMI is common among patients hospitalized with CHF, pneumonia, and AMI. Over half of all patients in this study had a BMI greater than 25. We found that overweight or obese BMIs were independently associated with decreased short-term mortality up to one year following hospitalization for CHF, pneumonia, and AMI, relative to normal BMI (18.5 to < 25.0 kg/m²). Adjusted rates of 1-year mortality were about 10% lower in overweight and obese patients, relative to normal weight patients, across each of the three cohorts. Our findings were robust to several sensitivity analyses, including analyses that accounted for BMI trajectory prior to hospitalization and severity of illness during hospitalization. They were also robust to direct standardization for age and sex in a matched analysis. The protective association of overweight and obese BMI was slightly attenuated when using a referent group of BMI 22.0 to < 25.0 kg/m², suggesting that some – but not all – of the protective association may be due to increased risk of mortality for patients with low-normal BMI.

Importantly, we find that the protective effect of overweight or obese BMI does not extend into the longer term. Among patients hospitalized with CHF, pneumonia, and AMI who survived to one year, the association between overweight or obese BMI and 5-year mortality was not statistically significant in any of our analyses.

While our findings are consistent with several prior studies showing that obesity is associated with decreased in-hospital and short-term mortality following acute medical illnesses [2, 6, 18], less is known about whether such a potential advantage would extend into longer-term mortality. While there are some studies that examined longer-term survival after admission, they did not model the risk of mortality conditional on surviving the shorter-term [7‐9]. Data on longer-term mortality is of central importance to the evaluation of clinical guidelines for weight management. For example, obesity may be protective against in-hospital mortality but, conditional on surviving the short term, still be hazardous for longer-term mortality. To our knowledge, this study is among the first to examine conditional, longer-term survival.

There are several biological hypotheses for why obesity may be protective during acute illness. First, while obesity is associated with greater inflammation during times of health, it also modulates the pro-inflammatory response to acute illness. In patients with acute lung injury, obesity is associated with lower levels of pro-inflammatory cytokines [32]. Obese patients have a decreased catecholamine response to stress [33]. Furthermore, adipose tissue serves as a storage reservoir for M2 macrophages, which have a protective anti-inflammatory phenotype during critical illness [34]. A recent prospective study of pneumonia patients by Singanayagam, et al., however, found that obese patients had better 30-day survival despite higher rates of sepsis and higher levels of c-reactive protein (markers of greater systemic inflammation) [5]. Moreover, Braun,et al. have recently reported improved survival in obese patients with community-acquired pneumonia, despite similar levels of c-reactive protein, white blood cell count, and procalcitonin [7]. Together, these studies suggest that alternative or additional mechanisms are likely to be involved in the protective effect.

Second, obesity may be associated with improved host response to bacterial infection. Leptin is produced by adipose tissue, modulates the immune response, and tightly correlates with BMI [35]. Leptin-deficient mice die when exposed to bacterial challenge [35].

Third, obese patients may be better poised to tolerate the catabolic stress associated with critical illness. Herridge, et al. found that patients surviving acute respiratory distress syndrome lost an average 18% of their body weight during hospitalization, and many did not return to their baseline weight by one year of follow-up [36]. This degree of acute weight loss is likely to be better tolerated by patients with a higher BMI.

Lastly, it is possible that the association it not due to a protective effect of overweight or obesity, but rather, is due to differences in the clinical presentation and/or treatment in overweight and obese patients. For example, obesity is associated with lower pulmonary reserve [37], so obese patients may become symptomatic and present earlier in their course or heart failure or pneumonia. In acute myocardial infarction, obese patients are less likely to have extensive coronary disease and left ventricular dysfunction [38]. Obese patients may also get more aggressive acute treatment, especially in cardiovascular disease, where obesity itself is viewed as a major risk factor. In two studies of patients admitted for ischemic heart disease, obese patients were more likely to receive guideline recommended therapy and undergo revascularization procedures, after adjusting for clinical risk [39, 40].

Again, we find that the protective association of excess weight is short-term and diminishes beyond one year, which is consistent with the potential biological mechanisms of benefit. Obesity may help blunt an acute inflammatory response, mediate host response to infection, and provide resilience during catabolic stress, but once these threats have resolved, obesity may cease to be protective. Thus, our findings suggest that weight control guidelines should not be reversed, as any survival benefit associated with obesity is short-term. Moreover, despite our sensitivity analyses, any residual confounding due to weight loss from severe illness is more likely to manifest in short-term mortality.

There are several limitations to our study. First, we used self-reported height and weight, which may contribute to underestimation of BMI. However, a prior analysis of the HRS cohort suggests that the magnitude of reporting errors is small [27]. Additional measures of adiposity (e.g. bioelectrical impedance, waist circumference)—which may better reflect fat mass and distribution—were not available. Secondly, CHF, pneumonia, and AMI hospitalizations were identified by ICD-9-CM codes in Medicare claims. While we used commonly employed and validated definitions, there still may be misspecification in both directions. Third, while we were able to adjust for many potential confounders not typically available in clinical or administrative data sources (e.g. household wealth and education), we could not adjust for differences in illness severity on hospital presentation beyond the crude measures of acute organ dysfunction and intensive care use. We were also unable to adjust for differences in treatment. Fourth, because HRS surveys pre-dated hospitalization by an average of one year, dynamic variables such as weight and number of functional limitations may not precisely reflect the patient’s status at the time of hospital admission. Weight at the time of admission, however, is more likely to reflect an acute fluid imbalance for some of our conditions. Fifth, because our data are from 1996 to 2012, they may not accurately represent current Medicare beneficiaries.

In older Americans, overweight or obese BMI was associated with improved survival to 1 year following hospitalization for congestive heart failure, pneumonia, and acute myocardial infarction. Conditional on surviving to one year after admission, however, there is no survival advantage to 5 years associated with overweight or obese BMI.