Obesity paradox in ST-elevation myocardial infarction: is it all about infarct size?

Obesity is one of the major modifiable risk factors for cardiovascular diseases, including acute myocardial infarction. Paradoxically, once acute myocardial infarction has occurred, obesity may be associated with a survival benefit (‘obesity paradox’).1 The pathophysiological mechanisms behind this association are, however, controversial.2,3 Results from some studies suggested that patients with overweight might have a smaller infarct size as a possible explanation for better outcomes.4,5 However, these results were partially contradictory and derived from very small numbers of included patients.4,5 Another reason for these inconclusive findings may be the lack of a method to precisely quantify myocardial damage. Cardiac magnetic resonance (CMR) imaging allows the most comprehensive view on the myocardium at tissue level and thus evolved as ideal tool for the quantification of myocardial damage after myocardial infarction. Infarct size and microvascular obstruction as visualized by CMR imaging are also increasingly recognized as major outcome determinants. Therefore, this study sought to investigate the relationship of admission body mass index (BMI) with myocardial tissue injury in a large cohort of ST-elevation myocardial infarction (STEMI) patients treated by primary percutaneous coronary intervention (PPCI). Patients presenting with first STEMI defined in accordance with the redefined European Society of Cardiology (ESC)/American College of Cardiology (ACC) committee criteria were enrolled. The following exclusion criteria were applied: age <18 years, history of previous coronary intervention or myocardial infarction, an ischaemia time of >24 h, and any contraindication for performing a CMR exam. Patients were grouped into three categories (BMI <25 kg/m2, 25–30 kg/m2, and >30 kg/m2). Cardiac magnetic resonance examinations were conducted within 2 (interquartile range 2–4) days after infarction. Major adverse cardiovascular events (MACE) comprising all-cause mortality, non-fatal re-infarction, stroke and new congestive heart failure were recorded within 12 months after STEMI. Differences between groups were tested by means of the Kruskal–Wallis test. Proportions were compared by χ2 test. Spearman Rho correlation analysis was performed. All tests were two-tailed and a P < 0.05 was considered statistically significant. Statistical analysis was performed using SPSS Statistics 24.0.0 (IBM, Armonk, NY, USA). The study was approved by the local research ethics committee and conducted in accordance with the Declaration of Helsinki. Of the total 426 patients, 153 (36%) had a BMI of <25 kg/m2, 211 (49%) had a BMI between 25 and 30 kg/m2, and 62 (15%) had a BMI of >30 kg/m2. The baseline clinical characteristics as well as CMR findings of the entire study population and according to BMI groups are depicted in Table 1. CMR findings of myocardial function and infarct severity were well balanced between groups with no significant differences (Table 1 and Figure 1). In line, there was no correlation between BMI and infarct size (r = −0.01, P = 0.87) or extent of microvascular obstruction (r = −0.05, P = 0.30). In an exploratory analysis, we compared the incidence of MACE at 12 months (n = 14 events, 3.3%) between overweight (BMI >25 kg/m2, n = 273, 64%) and normal weight (<25 kg/m2, n = 153, 36%) patients. Comparison between both groups revealed a significantly lower MACE-free survival rate in patients with BMI <25 kg/m2 (P = 0.03). Patient characteristics BMI, body mass index; CMR, cardiac magnetic resonance; LAD, left anterior descending artery; LCX, left circumflex artery; LVEF, left ventricular ejection fraction; LVMM, left ventricular myocardial mass; RCA, right coronary artery; RI, ramus intermedius; TIMI, thrombolysis in myocardial infarction. Significance of bold values are P < 0.05. Patient characteristics BMI, body mass index; CMR, cardiac magnetic resonance; LAD, left anterior descending artery; LCX, left circumflex artery; LVEF, left ventricular ejection fraction; LVMM, left ventricular myocardial mass; RCA, right coronary artery; RI, ramus intermedius; TIMI, thrombolysis in myocardial infarction. Significance of bold values are P < 0.05. Myocardial damage and obesity. Box-and-whisker plots (box: 25th percentile, median, and 75th percentile; whisker: minimum and maximum within 1.5 interquartile range of the lower and upper quartile, respectively) of infarct size (A) and microvascular obstruction (B) according to body mass index groups. BMI, body mass index; LVMM, left ventricular myocardial mass. Although obesity is a well-established risk factor for the development of acute myocardial infarction, it may be related with better outcomes after the acute event.1 In line with this so called ‘obesity paradox’, we could also observe a lower likelihood of MACE in STEMI patients with higher BMI. However, the pathophysiological concepts behind the relationship between higher BMI and better outcome after infarction are highly uncertain with some experimental and clinical4,5 studies suggesting that patients with overweight might have smaller infarcts, less post-infarction remodelling and subsequently a more favourable prognosis. Cepeda-Valery et al.4 also used biomarkers to estimate infarct size instead of direct in vivo CMR measurement and concluded that obesity was associated with greater infarct size in non-STEMI patients (n = 73), while in STEMI patients (n = 29) it was related with smaller infarct size. Sohn et al.5 described that overweight (BMI >25 kg/m2) was independently associated with reduced CMR-determined infarct size in 193 STEMI patients undergoing PPCI. Surprisingly, this study could, however, not detect any difference in microvascular obstruction between groups, which is also known to be of major prognostic significance after STEMI. In the current study including >400 STEMI patients, about two-thirds of patients had a higher than normal BMI of 25 or greater which fits well with existing literature. Importantly, we could not confirm any difference in infarct size or microvascular injury as assessed by CMR imaging in the different BMI groups. Likewise, BMI was not associated with infarct size or microvascular obstruction in linear correlation analysis. As such, our large study complements and extends previous literature by showing that tissue reperfusion by PPCI is similar effective in obese and non-obese patients presenting with acute STEMI and that the lower risk of adverse events in obese patients is not explained by less infarct severity. These results should be taken into consideration for future ‘obesity paradox’ studies, particularly when evaluating optimized treatment strategies for this group of patients suffering acute STEMI. This study was supported by the ‘Austrian Society of Cardiology’ and by an intramural funding program of the Medical University Innsbruck for young scientists MUI-START, Project 2015-06-013. Conflict of interest: none declared.