‘Obesity Paradox’ Is Alive and Well Across Racial/Ethnic Spectrum of Heart Failure Patients

Among heart failure patients both with and without reduced ejection fraction, neither race nor ethnicity seem to alter the lower 30-day mortality risk seen in those with higher body mass index (BMI), a large-scale study has found. While the prevalence of obesity varies—black and Hispanic patients in the study were more likely to be obese than white and Asian patients—the findings suggest that the so-called obesity paradox exists across the board.

The findings are surprising “given particularly how common heart failure is among African-Americans,” lead study author Tiffany Powell-Wiley, MD, MPH (National Institutes of Health, Bethesda, MD), told TCTMD. “We still need to better understand the pathophysiology behind heart failure and what pathophysiologic mechanisms explain the paradoxical relationship between obesity and heart failure.”

For the study, published in the February 2018 issue of JACC: Heart Failure, Powell-Wiley and colleagues looked at almost 40,000 patients with heart failure from the Get With The Guidelines–Heart Failure (GWTG–HF) database between 2005 and 2011, of which 81.8% were white, 9.6% were black, 4.9% were Hispanic, 1.4% were Asian, and 2.3% were classified as “other.” Among them, 59.7% had heart failure with preserved ejection fraction (≥ 40%) and the rest had reduced ejection fraction (≤ 40%).

Six in 10 individuals were considered to be at normal weight (BMI 18.5-24.9 kg/m2) or overweight (BMI 25-29.9 kg/m2), while 35.5% were obese (BMI ≥ 30 kg/m2) and 4.6% were underweight (≤ 18.5 kg/m2).

In patients with preserved ejection fraction, higher BMI from 18.5 up to 30 kg/m2 was linked to lower 30-day all-cause mortality (HR 0.63; 95% CI 0.54-0.73) compared with a BMI of 18.5 kg/m2 or less, with “little change in risk” above 30 kg/m2, the researchers report. One-year mortality was 4% lower for each increasing unit of BMI up to 30 kg/m2 (HR 0.96; 95% CI 0.95-0.96).

A smaller but significant relationship was observed between mortality and BMI up to 30 kg/m2 in heart failure patients with reduced ejection fraction at 30 days (HR 0.73; 95% CI 0.60-0.89). At 1 year among patients with a BMI of above 30 kg/m2, each unit of BMI increase was associated with a 1% increase in all-cause mortality risk.

Notably, there were no significant relationships between BMI and race/ethnicity in terms of 30-day mortality for all patients (P > 0.05 for all) and Powell-Wiley et al found no evidence of the J-shaped curve for obesity and mortality that has been noted for coronary artery disease.

Black and Hispanic patients were more likely to be classified as obese compared with white, Asian, and other patients (P < 0.0001). Most patients overall with preserved ejection fraction were women, and white patients were more likely to have heart failure due to ischemia compared with all other subsets.

“Our work extends the findings from [prior] GWTG–HF studies to demonstrate that BMI differences do not appear to explain differences in 30-day all-cause mortality across racial and ethnic groups,” the researchers write. “Second, our findings enhance the body of knowledge about perplexing repercussions of increasing BMI on HF outcomes. . . . Our study is one of the first to suggest that the BMI paradox for 30-day mortality exists at all BMI levels.”

Unanswered Questions

In an accompanying editorial, Michael Hall, MD, MSc (University of Mississippi Medical Center, Jackson), said the study “adds to the growing body of literature suggesting a ‘protective’ effect of increased BMI against mortality after patients develop major chronic debilitating diseases, such as HF, cancer, or end-stage renal disease.”

But Jennifer Ho, MD (Massachusetts General Hospital, Boston), who was not involved in the study, told TCTMD it is important that clinicians properly interpret the data because “we certainly don't want to misinform patients or the public that being obese improves their health.”

A limitation to these results, Hall writes, is that it only uses BMI as a measure of obesity. “Simple measures, such as waist circumference, waist-to-hip ratio, or sagittal abdominal diameter can be easily obtained in the clinical setting and are more reflective of central adiposity than BMI,” he says.

Powell-Wiley acknowledged the shortcomings of using BMI to estimate adiposity, especially when dealing with diverse patient populations. “We know that even at a higher BMI levels, particularly for African-Americans, you have lower levels of body fat,” she said. Conversely, “for Asian-Americans or Asian populations at lower body mass index, you are more likely to have higher levels of body fat.”

Another quandary Hall raises relates to the relationship age plays on body weight and how that can affect heart failure outcomes, given that many of these patients are older. “As people age, weight (and BMI) may remain relatively stable while muscle mass decreases and body fat increases,” he explains. “Perhaps excess body weight in older individuals helps counteract the catabolic effects of HF and provides a ‘metabolic cushion’ to attenuate cachexia. A more plausible explanation is that age-related reductions in skeletal muscle mass and redistribution of body fat to visceral organs may contribute to elevated mortality risk in aged subjects.”

Ho added that there are two additional biases that may affect the results of this study. First, “lead-time bias” relates to the fact that heart failure patients with higher BMI may present earlier in their disease course and would hence have better outcomes. Also, reverse causation could be a possible issue. “In this case, we know that advanced heart failure can actually lead to cardiac cachexia and low BMI, and so we have to obviously be mindful of that as well,” said Ho.

Regardless, Hall, Powell-Wiley, and Ho all agree that clinicians should continue to focus on lifestyle modifications including physical activity, diet, and weight control with all patients, especially those with high BMI, irrespective of race, ethnicity, or age.

Future research should focus on both alternate measures of adiposity as well as the effect of long-term obesity (or “obesity-years”) on heart failure mortality outcomes, Hall writes.