SCAAR Data Support Obesity Paradox: Overweight ACS Patients Show Lower Mortality

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In over 38,000 Swedish patients with acute coronary syndromes (ACS), those with a body-mass index (BMI) indicative of overweight or obesity had lower mortality rates than their normal-weight or underweight counterparts. According to the study, appearing online September 4, 2012, ahead of print in the European Heart Journal, the data add strong support for the “obesity paradox,” which posits that adiposity is cardioprotective.

Researchers led by Oskar Angerås, MD, of the University of Gothenburg (Gothenburg, Sweden), looked at 38,667 patients with a significant coronary stenosis who underwent angiography due to ACS from May 2005 to December 2008 and were enrolled in the Swedish Coronary Angiography and Angioplasty Registry (SCAAR). Patients were divided into 9 BMI categories ranging from underweight to normal weight to overweight to obese.

The mortality rate over a maximum 3-year follow-up was 4.7%, with a substantial difference in all-cause mortality between the different BMI categories. Patients who were underweight (BMI < 18.5 kg/m²) had the highest risk followed by normal-weight patients, whereas overweight patients had the lowest risk (P < 0.001 for trend). The unadjusted hazard ratio ranged from 2.94 (95% CI 2.25-3.83) to 0.52 (95% CI 0.44-0.61) compared with the normal weight reference group.

Paradox Strongest in PCI Patients

The same pattern was maintained in the 28,956 ACS patients who underwent PCI. In this group, mortality ranged from 12.4% in underweight patients (HR 2.31; 95% CI 1.67-3.21) to 3.9% in overweight and obese patients (HR 0.66; 95% CI 0.53-0.82). However, in patients treated with CABG (n = 5,420) or medical therapy alone (n = 4,291), the differences in mortality between BMI categories were minimal, and in patients with no CAD, there was no difference in mortality between the overweight groups compared with the normal weight group.

When studying BMI as a continuous variable in patients with significant CAD, adjusted risk for mortality decreased with increasing BMI up to about 35 kg/m² and then increased. These results were maintained on regression analysis that adjusted for multiple confounders (table 1).

Table 1. Cumulative Mortality According to BMI Group

There was no interaction between BMI category and age or sex, and there was no difference between BMI categories with regard to in-hospital mortality or 30-day mortality.

The authors conclude that “the relation between BMI and mortality was U-shaped, with the nadir among overweight or obese patients and underweight and normal-weight patients having the highest risk,” adding that, “These data strengthen the concept of the obesity paradox substantially.”

Still, Dr. Angerås and colleagues acknowledge that their study does little to provide any explanation or mechanism for such a paradox. They note 2 possibilities: (1) that the obesity paradox is a consequence of 1 or more confounding factors in overweight patients, or (2) there is something cardioprotective about the biology of obese individuals.

Arrhythmias to Blame?

The authors also suggest that obesity may protect against malignant ventricular arrhythmias during and after MI, thereby decreasing the risk of sudden death. They note that during follow-up of the current study, obese patients did not differ in the frequency of hospitalization for heart failure, MI, and stroke, common causes of death in this population.

Therefore, since obesity is not associated with lower risk for these clinical events, “By process of elimination,” they reason, “these observations strengthen the hypothesis that obesity may protect against malignant ventricular arrhythmias as it is another frequent cause of mortality in patients with CAD.”

In a telephone interview with TCTMD, Robert M. Minutello, MD, of Weill Cornell Medical College (New York, NY), called that theory “pretty far fetched. They’re trying to figure out why these people do better, and it seems it’s not because of MIs, heart failure, and stroke, so it may be ventricular arrhythmias but that’s a big stretch.”

Explanations Hard to Come By

Overall, though, “I do think [the study] does solidify previous theories of the obesity paradox, so I do agree with them,” Dr. Minutello said, adding that it is difficult to tell which of the 2 prevalent theories as described by the authors is the driving force behind the paradox. “They’re not mutually exclusive. It could be some of both, but I don’t have any other answers than I had 8 years ago when I published my own study [supporting the obesity paradox],” he noted. “You read about adiponectin, leptin, and all these hormones that are produced to different degrees in obese patients that may be cardioprotective, [but] it’s theoretical at this point.”

In an accompanying editorial, Stephan von Haehling, MD, PhD, Oliver Hartmann, MSc, and Stefan D. Anker, MD, PhD, of Charité Medical School, Campus Virchow-Klinikum (Berlin Germany), agree that “fat tissue has several beneficial effects, for example in its action as an endocrine organ. . . .” They note, however, that since the patients in the study were investigated after an ACS, “it may also well be that this event prompted some patients to follow a more healthy lifestyle, and such an effect may have influenced outcomes: surprisingly, the difference in survival between BMI groups was only observed after 3 years of follow-up, but not for in-hospital or 30-day outcomes.”

Regardless, the results should have no bearing on clinical decision making, Dr. Minutello stressed. “Are we going to be more likely to do PCI in an overweight patient because they have a better prognosis than a lighter patient? No. And we’re certainly not going to tell them to lose weight because of all the other comorbidities associated with being overweight,” he said. “I honestly don’t think there’s anything we do with this from a clinical point of view. If indeed obesity or adipose tissue is cardioprotective, from a bench research standpoint we may want to investigate these hormones in terms of new drug therapies in the setting of ACS in the future. That’s the only thing I see.”

Study Details

Obese patients were more likely to be younger and to have hyperlipidemia, hypertension, and diabetes, but were less likely to smoke and to have high-risk coronary anatomy. Underweight patients were more likely to be female and to present with STEMI as the indication for angiography.

Sources:

1. Angerås O, Albertsson P, Karason K, et al. Evidence for obesity paradox in patients with acute coronary syndromes: A report from the Swedish Coronary Angiography and Angioplasty Registry. Eur Heart J. 2012;Epub ahead of print.
2. Haehling SV, Hartmann O, Anker SD. Does obesity make it better or worse: Insights into cardiovascular illnesses. Eur Heart J. 2012;Epub ahead of print.

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