A body mass index (BMI) in the overweight range (25.0 to 29.9 kg/m2) may be associated with significant survival benefits for women with advanced systolic heart failure, according to research published in the Journal of the American College of Cardiology.

Leslie Cho, MD, of the Cleveland Clinic, and colleagues sought to investigate how gender may play a role in the paradoxical relationship between BMI and mortality in heart failure (HF).

“Given the female survival advantage in HF, and the recognition that female myocardium shows greater fatty acid metabolism and lower glucose utilization, we hypothesized that females with HF may derive a great degree of protection from excess adiposity than males,” the authors wrote.


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The study included 3811 patients with left ventricular ejection fraction (≤40%) who underwent cardiopulmonary exercise testing at the Cleveland Clinic between January 1995 and November 2011. Patients were excluded if they had a baseline left ventricular ejection fraction (LVEF) between 41% and 51%, received a heart transplant or left ventricular assist device (LVAD), had primary valvular cardiomyopathy etiology or severe congenital heart disease, or had BMIs below the normal weight range (<18.5 kg/m2).

To accurately test their hypothesis, the researchers used an adjusted hazard ratio (HR) for all-cause mortality, plotted according to a set of references, including age, race, medication regimen, smoking status, and diagnoses of other diseases.

Women had a slight but significantly lower BMI (27.2 vs 28.0 kg/m2, P<0.0015), were younger (52.5 vs 54.6 years, P<.0001), had a lower coronary artery disease burden (30% vs 57%, P<.0001), and less ischemic etiology (26% vs 54%, P<.0001) compared with men.

During a 6-year follow-up period, women were found to have a lower crude mortality rate than men (32.9% vs 42.9%). In both genders, the obese groups had a significantly lower unadjusted all-cause mortality rate (HR 0.88, 95% CI 0.85-0.92, P<.0001), which supported the notion of an overall unadjusted “obesity survival paradox.”

Interestingly, the unadjusted survival paradox was seen in both women and men, but distributed differently: in women, both the obese and overweight groups were associated with lower mortality, but in men, only the obese group benefited. After adjusting for relevant confounders, men in the overweight and obese groups actually showed an increased adjusted mortality rate compared with those in the normal weight group.

“A nadir in mortality hazard was seen just below 30 kg/m2 in females with both ischemic and non-ischemic etiologies. This relationship also persisted regardless of diabetes status,” the authors wrote. “Conversely males demonstrated the highest mortality hazard around a BMI of 30 kg/m2.”

In previous studies, women have been identified as having greater myocardial fatty acid uptake and lower myocardial glucose utilization. One study in particular compared the mortality risks between men and women via increased BMI, but there was no risk adjustment for cardiorespiratory fitness and the relationship between BMI mortality was found to be log-linear.1

“It is notable that the unadjusted HRs in this analysis suggested an obesity survival paradox in both males and females, but that this disappeared with risk adjustment,” the authors observed. “A more favorable response to modest excess adiposity may partially explain the female HF survival advantage.”

References

  1. Shah R, Gayat E, Januzzi JL, et al. Body Mass Index and Mortality In Acutely Decompensated Heart Failure Across The World: A Global Obesity Paradox. J Am Coll Cardiol. 2014;63(8):778-785. doi:10.1016/j.jacc.2013.09.072
  2. Vest A, Wu Y, Hackamovitch R, Young JB, Cho LS.  The Heart Failure Overweight/Obesity Survival Paradox: The Missing Sex Link. J Am Coll Cardiol. 2015; doi:10.1016/j.jchf.2015.06.009.