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'Obesity Paradox' Apparent in Heart Failure

— Normal-weight heart failure patients did not fare as well as their heavier counterparts.

Last Updated December 23, 2014
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Overweight and obese heart failure patients outlived their normal-weight patients even after adjustment for various factors, researchers found.

Among patients with incident heart failure, overweight and obese patients had lower mortality rates compared to normal-weight patients, (hazard ratio [HR] 0.72, and 0.70, respectively), , of Baylor College of Medicine in Houston, Texas, and colleagues reported in the .

"The nicely-designed study by Khalid et al. in this issue of the Journal provides perhaps the best evidence that the obesity paradox is not simply due to cachexia in late-stage [heart failure] or reverse causality," , of Vanderbilt University Medical Center, in Nashville, Tenn., wrote in an accompanying editorial.

The Atherosclerosis Risk In Communities (ARCI) study was an ongoing study involving 15,792 men and women who were ages 45 to 64 when they were recruited from 1987 to 1989. Participants came from one of four communities spread across the U.S..

Khalid and colleagues looked at 1,487 patients from the ARCI study who had heart failure. The group was 54% male, 66% white, and had an average age of 67. The researchers measured body mass index (BMI) at least 6 months prior to incident heart failure and again at the time of death.

Among the patients, 35% were overweight and 47% were obese. The pre-morbid BMI was measured an average of 4.3 years (±3.1) before the diagnosis of heart failure. Throughout the 10-year follow-up period, 43% of the heart failure patients died.

Adjustments were made for hypertension, history of myocardial infarction, coronary heart disease, diabetes, stroke, and demographics.

Compared with the normal-weight group, and after adjustments, overweight patients had a lower risk of dying (HR 0.72, 95% CI 0.58-0.90, P=0.004), and obese patients had an even lower risk of dying (HR 0.70, 95% CI 0.56-0.87, P=0.001).

The phenomenon of excess weight appearing to protect patients is known as the "obesity paradox," and in the case of this cohort, the protection did not change significantly based on smoking status, history of cancer, or diabetes status.

The authors noted that the "obesity paradox" is not uncommon in heart failure development, and that although several studies have investigated this link, the longitudinal nature of this study allows for an independent association between higher pre-morbid BMI and long-term survival advantage.

Several factors could explain the study results. The investigators suggested that obese patients could have a higher metabolic reserve compared with normal-weight patients and thus have a survival advantage when cardiac cachexia follows the development of heart failure.

Wang agreed that cardiac cachexia and muscle wasting in late-stage heart failure could explain the protective function of excess body weight.

Another possible theory the authors posed was that obesity alters the natural history of heart failure through neurohumoral pathways. Also, these results could be a survivor effect, as frailer older adults die sooner.

The researchers listed the observational design of the study and its reliance on ICD-9 codes as potential study limitations. Other study limitations, according to Wang, included selection bias, information bias, misclassification bias, and lead-time bias.

The effects of being overweight or obese might have led many of the patients to seek medical care for things like edema, dyspnea, or easy fatigue, leading to an earlier diagnosis of heart failure and therefore earlier treatment, Wang wrote.

Wang suggested incorporating more detailed metabolic phenotyping in heart failure studies, such as metabolomics, novel imaging techniques, and dietary interventions, to unravel the mysterious "obesity paradox."

Disclosures

The ARIC study was supported by the National Heart, Lung and Blood Institute.

Co-authors disclosed relevant relationships with Sanofi, Roche, Abbott Diagnostic, Amarin, Amgen, Eli Lilly, Esperion, GlaxoSmithKline, Genetech, Merck and Co., Novartis, Pfizer, Regeneron, Roche, Sanofi-Sythelabo, Genzyme, Resverlogix, and Kowa.

Primary Source

Journal of the American College of Cardiology

Source Reference: Khalid U, et al "Pre-morbid body mass index and mortality after incident heart failure: the ARIC study" J Am Coll Cardiol 2014; DOI: 10.1016/j.jacc.2014.09.067.

Secondary Source

Journal of the American College of Cardiology

Source Reference: Wang TJ, et al "The obesity paradox in heart failure: weighing the evidence" J Am Coll Cardiol 2014; DOI: 10.1016/j.jacc.2014.09.068.