Impact of overweight on myocardial infarct size in patients undergoing primary percutaneous coronary intervention: A magnetic resonance imaging study

Atherosclerosis 235 (2014) 570e575

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Impact of overweight on myocardial infarct size in patients undergoing primary percutaneous coronary intervention: A magnetic resonance imaging study Gwan Hyeop Sohn a, 1, Eun Kyoung Kim a, 1, Joo-Yong Hahn a, *, Young Bin Song a, Jeong Hoon Yang b, Sung-A Chang a, c, Sang-Chol Lee a, c, Yeon Hyeon Choe c, d, Seung-Hyuk Choi a, Jin-Ho Choi a, e, Sang Hoon Lee a, Jae K. Oh a, Hyeon-Cheol Gwon a a

Division of Cardiology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea Department of Critical Care Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea c Cardiovascular Imaging Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea d Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea e Department of Emergency Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea b

a r t i c l e i n f o

a b s t r a c t

Article history: Received 13 December 2013 Received in revised form 13 May 2014 Accepted 29 May 2014 Available online 11 June 2014

Objective: Although obesity is a risk factor for cardiovascular disease and mortality, several studies have reported that patients with obesity who have suffered acute myocardial infarction or have undergone percutaneous coronary intervention (PCI) have better clinical outcomes than their normal weight counterparts. We evaluated the impact of overweight on myocardial infarct size in patients undergoing primary PCI for ST-segment elevation myocardial infarction (STEMI). Methods: We performed contrast-enhanced magnetic resonance imaging on 193 patients undergoing primary PCI for STEMI. Infarct size was measured with delayed-enhancement imaging and the area at risk was quantified on T2-weighted images. Results: Baseline characteristics and angiographic findings were not significantly different between the normal weight group (body mass index [BMI] < 25 kg/m2, n ¼ 110) and the overweight group (BMI  25 kg/m2, n ¼ 83). The median percent infarct volume and area at risk were significantly smaller in the overweight group than the normal weight group (17.9% [9.0e24.9%] vs. 20.8% [11.4e33.1%], p ¼ 0.04 and 29.4% [20.5e37.6%] vs. 36.0% [25.7e49.6%], p < 0.01, respectively). However, the myocardial salvage index was not different between the 2 groups (overweight group vs. normal weight group, 43.2% vs. 39.2%, p ¼ 0.69). BMI  25 kg/m2 was an independent predictor of smaller infarct size in multivariate analysis (Odds ratio 0.51, 95% Confidence interval 0.27e0.97, p ¼ 0.039). Conclusion: Overweight (BMI  25 kg/m2) is independently associated with smaller infarct size in patients undergoing primary PCI for STEMI. © 2014 Elsevier Ireland Ltd. All rights reserved.

Keywords: Myocardial infarction Obesity Magnetic resonance imaging

1. Introduction Obesity defined using body mass index (BMI) or waist-to-hip ratio is known as an independent risk factor for death or cardiovascular disease, including acute myocardial infarction [1e3]. Early

* Corresponding author. Division of Cardiology, Department of Medicine, Cardiac and Vascular Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50, Irwon-dong, Gangnam-gu, Seoul, 135-710, Republic of Korea. Tel.: þ82 2 3410 6653; fax: þ82 2 3410 6278. E-mail addresses: [email protected], [email protected] (J.-Y. Hahn). 1 Drs GH Sohn and EK Kim contributed equally to this work. http://dx.doi.org/10.1016/j.atherosclerosis.2014.05.961 0021-9150/© 2014 Elsevier Ireland Ltd. All rights reserved.

studies suggest that obesity is related with adverse outcomes after acute myocardial infarction [4e6]. However, many studies have reported an “obesity paradox”: obese patients who have suffered acute myocardial infarction or who have undergone percutaneous coronary intervention (PCI) have better clinical outcomes [7e9]. Recently, a large registry of data on acute coronary syndrome revealed that the relationship between BMI and mortality was Ushaped, with the nadir located among overweight or obese patients [10]. The relationship between obesity and myocardial infarct size has not been demonstrated, although the relationship between obesity and clinical outcome has. Contrast-enhanced cardiac

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magnetic resonance imaging (CMR) is an emerging technique that is gaining widespread acceptance and applicability in measuring jeopardized or irreversibly injured myocardium following STsegment elevation myocardial infarction (STEMI) [11,12]. We evaluated the impact of overweight on myocardial infarct size using contrast-enhanced CMR in patients undergoing primary PCI for STEMI. 2. Methods 2.1. Study population From January 2006 to November 2009, 349 STEMI patients visited the emergency room at Samsung Medical Center. Among them, 62 patients presented >12 h after symptom onset and 30 patients who did not receive primary PCI, but received coronary artery bypass surgery or thrombolysis, and were thus excluded from this study. Twenty-seven patients who refused to undergo CMR or did not undergo CMR because of hemodynamic instability were also excluded. All patients met the following criteria: presented <12 h after symptom onset and had ST-segment elevation >1 mm in 2 contiguous leads or presumably a new-onset left bundle-branch block on electrocardiogram. Exclusion criteria were history of myocardial infarction, prior coronary artery bypass grafting, requirement for multivessel intervention during the index procedure, evidence of previous myocardial infarction on contrastenhanced CMR, subacute stent thrombosis before CMR, and BMI < 18.5 kg/m2. Finally, 193 patients were enrolled in this study. Baseline characteristics, angiographic and procedural data, medication use, and outcome data were recorded prospectively by research coordinators of the dedicated registry. The local institutional review board approved this study, and all patients gave their informed consent to participate. 2.2. Percutaneous coronary intervention Dual oral antiplatelet therapy with 300 mg aspirin and either 300 mg or 600 mg clopidogrel were prescribed before PCI. Coronary angiography and stent implantation were performed using standard interventional techniques [13]. All baseline and procedural cine coronary angiograms were reviewed and analyzed quantitatively at the angiographic core laboratory at Samsung Medical Center (Seoul, Korea). Myocardial blush grade (MBG) was evaluated using the final angiogram, as described previously [14]. 2.3. Magnetic resonance imaging protocol and analysis A 1.5-T magnetic scanner (Achieva, Philips Medical Systems, Best, Netherlands) with a SENSE cardiac coil was used. The CMR protocol consisted of cine, T2-weighted imaging, first-pass perfusion, and delayed enhancement imaging. Specific sequences were described previously [15]. T2-weighted imaging was performed using a dark-blood inversion recovery fast spin echo sequence with 8e10 continuous short-axis slices to cover the entire LV. Delayed hyperenhancement and the extent of microvascular obstruction (MVO) were evaluated 5, 10, and 15 min after injection of 0.15 mmol/kg Gadovist (gadobutrol; Bayer Schering Pharma, Berlin, Germany) in continuous short-axis image acquisition of 10e12 slices 6 mm in thickness with a 4-mm inter-slice gap. The inversion delay time varied from 200 to 300 ms. To minimize an impact of obesity on MR quality, we used a 32-channel phased-array receiver coil in all patients and used smallest field of view for the area of interest. All measurements were performed at CMR core laboratory. Image analysis was performed using commercialized software

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(CAAS MRV version 1.0, Pie Medical Imaging B.V., the Netherlands) by two experienced CMR imagers (training level III) who were blinded to the patient's data. After the short-axis images were acquired at end-diastole and end-systole and the endocardial borders were traced, the left ventricular end-diastolic volume, end-systolic volume, and ejection fraction were computed using Simpson's algorithm. The endocardial and epicardial borders were planimetered to calculate myocardial area and summated in the same manner to calculate left ventricular myocardial volume. Infarct size by delayed enhanced images and area at risk (AAR) on T2-weighted images were analyzed with visual assessment by consensus of 2 experienced radiologists who were blinded to the clinical information of the patient (Fig. 1). AAR on T2 image was compared with anatomical AAR measured by a modified version of the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) scores [16]. The infarct volume was calculated from the summation of the area with delayed hyperenhancement within each segment of the short-axis images, multiplied by the slice thickness to cover the entire left ventricle. The percentage infarct volume was expressed as a percentage of the left ventricular myocardial volume. The extent of MVO, which was defined as a late hypoenhanced region within the infarcted myocardium on the delayed enhancement image, was calculated in the same manner. T2-weighted images were used to determine the presence of myocardial hemorrhage [17]. The myocardial salvage index was computed as follows: myocardial salvage index ¼ (AAReinfarct size)  100/AAR [18]. The transmural extent of infarction was expressed as the sum of segments with >75% of infarct transmurality. 2.4. End points and definitions The primary objective was to compare myocardial infarct size as assessed by contrast-enhanced CMR between the overweight group and the normal weight group. The secondary objectives were the variables assessed by T2 weighted images and contrastenhanced CMR, including AAR, myocardial salvage index, the extent of MVO, the number of segments with >75% of infarct transmurality, and the presence of myocardial hemorrhage, and the composite of major adverse cardiovascular events (MACE) including cardiac death, nonfatal reinfarction, hospitalization for congestive heart failure, and target lesion revascularization at the 6-month follow-up. Participants were classified into a normal weight group (18.5 kg/ m2  BMI < 25 kg/m2) and an overweight group (BMI  25 kg/m2) [10,19]. All deaths were considered cardiac unless a definite noncardiac cause could be established. Reinfarction was defined as elevated cardiac enzyme levels (troponin or MB fraction of creatine kinase, CK-MB) greater than the upper limit of the normal value with ischemic symptoms or electrocardiography findings indicative of ischemia that were not related to the index procedure. Hospitalization for congestive heart failure was defined as hospitalization because of exacerbation of congestive heart failure occurring after discharge. 2.5. Statistical analysis Continuous variables were expressed as mean ± SD or median and interquartile range and were compared using the independent t-test or ManneWhitney test. Categorical variables were compared with Pearson c2 or Fisher exact tests. Multivariate logistic regression analysis was performed with a stepwise, backward selection process to determine the independent predictors of a large infarct (percent infarct volume > median infarct size in the present study). Covariates included age, sex, hypertension, diabetes mellitus,

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Fig. 1. Short-axis slices of T2-weighted image (A) and the corresponding delayed enhancement image (B) in patient with inferior ST-segment elevation myocardial infarction. In this case, the extent of area at risk (C) and that of infarct size (D) was 37.55% and 19.15%, respectively, yielding myocardial salvage index of 49.01%.

BMI  25 kg/m2, 600 mg clopidogrel loading dose, anterior infarction, initial Thrombolysis In Myocardial Infarction (TIMI) flow of 0 or 1, no reflow, stent diameter, collateral flow and proximity of culprit vessel. A value of p < 0.05 in the 2-tailed test was considered significant. All analyses were performed with PASW software version 18.0 (SPSS Inc., Chicago, IL, USA). 3. Results

The implanted stent diameter in patients who were overweight was larger than in patients who were normal weight (3.35 ± 0.48 mm vs. 3.21 ± 0.39 mm, p ¼ 0.03). Otherwise, there were no differences in the angiographic and procedural

Table 1 Baseline characteristics of the study patients.

3.1. Patients and baseline characteristics A total of 193 patients were enrolled in this study. Among them, 110 patients had a BMI < 25 kg/m2 and 83 patients had a BMI  25 kg/m2. Among patients in the overweight group, 5 had a BMI  30 kg/m2. The clinical and demographic characteristics of the patients according to BMI are shown in Table 1. Baseline characteristics including age, sex, and past medical history were not significantly different between the 2 groups. Heart rate and systolic blood pressure at admission, symptom to balloon time, and doorto-balloon time were similar in both groups. Prescribed medication after PCI, including aspirin, clopidogrel, beta-blocker, statins, and angiotensin converting enzyme inhibitors, were not different between the 2 groups. 3.2. Angiographic and procedural data Although we noted that the likelihood of the left anterior descending artery as the culprit vessel and the proximity of the culprit artery were lesser, but the presence of collateral vessels was greater in patients who were overweight compared to patients who were normal weight, those trends were not statistically significant.

Age (y) Age>70y Male Body mass index (kg/m2) History of smoking Diabetes mellitus Hypertension Dyslipidemia Previous myocardial infarction Previous PCI Systolic blood pressure at admission Heart rate at admission Door-to-balloon time (min) Symptom-to-balloon time (min) Medication after PCI Aspirin Clopidogrel b-Blocker ARB or ACEi Statins Clopidogrel loading 600 mg

BMI < 25 kg/m2 (n ¼ 110)

BMI  25 kg/m2 (n ¼ 83)

P-value

58.3 ± 12.6 22 (20.0%) 93 (84.5%) 22.6 ± 1.6 78 (70.9%) 25 (22.7%) 29 (26.4%) 25 (22.7%) 8 (7.3%) 5 (4.5%) 129.8 ± 26.7

56.2 ± 11.0 11 (13.3%) 75 (90.4%) 27.0 ± 1.9 53 (63.9%) 21 (25.3%) 33 (39.8%) 21(25.3%) 3 (3.6%) 2 (2.4%) 136.5 ± 28.6

0.21 0.22 0.23 <0.01 0.30 0.68 0.06 0.68 0.36 0.70 0.10

75.1 ± 15.9 87 (67e120) 288 (168e445)

75.2 ± 13.4 81 (67e113) 260 (156e405)

0.96 0.62 0.60

109 (99.1%) 104 (94.5%) 96 (87.3%) 72 (65.5%) 102 (92.7%) 66 (60.0%)

83 82 71 53 78 48

1.00 0.24 0.73 0.82 0.73 0.76

(100%) (98.8%) (85.5%) (63.9%) (94.0%) (57.8%)

ACEi: angiotensin converting enzyme inhibitor; ARB: angiotensin II receptor blocker; BMI: body mass index; PCI: percutaneous coronary intervention.

G.H. Sohn et al. / Atherosclerosis 235 (2014) 570e575

characteristics between the normal weight and overweight groups (Table 2).

Table 3 Results of cine, T2-weighted and contrast-enhanced magnetic resonance imaging. BMI < 25 kg/m2 (n ¼ 110)

3.3. MRI findings Results of contrast-enhanced CMR were available for all patients. Contrast-enhanced CMR was performed a median of 7 days after the index event (interquartile range [IQR] 4e28 days) and the CMR findings are summarized in Table 3. There was no difference in the intervals from the index procedure to CMR between the normal weight group and overweight group (6 [IQR 4e20] days vs. 8 [IQR 4e29] days, p ¼ 0.24). The mean percentage infarct volume and AAR were significantly smaller in the overweight group than in the normal weight group. Comparing the absolute value of infarct size and AAR, the patients with overweight showed a trend to have relatively small infarct size and area at risk despite larger LV mass in patients with overweight, but these were not statistically significant (infarct size; 25.9 ± 18.2 vs. 28.0 ± 19.5, p ¼ 0.43 and AAR; 42.8 ± 21.6 vs. 45.2 ± 21.2, p ¼ 0.44). The anatomical extent of myocardium at risk by APPROACH score showed a weak, but significant correlation with AAR on the image of T2-weighted MRI (r ¼ 0.30, p < 0.001). However, there was no significant difference in the anatomic myocardium at risk between the 2 groups. The left ventricular end-diastolic volume, left ventricular mass, and left ventricular ejection fraction of the overweight group were greater than those of the normal weight group; however, the left ventricular end-systolic volume, myocardial salvage index, MVO area, and presence of hemorrhagic infarction were not different between the 2 groups. BMI 25 kg/m2 reduced the risk of a large infarct significantly (odds ratio [OR] 0.51, 95% confidence interval [CI] 0.27e0.97, p ¼ 0.039). Anterior infarction (OR 2.05, 95% CI 1.07e3.93, p ¼ 0.03), initial TIMI flow grade of 0 or 1 (OR 3.63, 95% CI 1.51e8.76, Table 2 Angiographic and procedural findings. BMI < 25 kg/m2 BMI  25 kg/m2 P-value (n ¼ 110) (n ¼ 83) Culprit vessel Left anterior descending artery Left circumflex artery Right coronary artery Proximity of culprit vessel Anterior infarction No. of diseased vessel 1 2 3 APPROACH score Presence of collateral vessels Baseline TIMI flow grade 0 1 2 3 Final TIMI flow grade 3 Angiographic no-reflow Final MBG 3 Thrombus aspiration Glycoprotein IIb/IIIa inhibitor Type of stents No stenting Bare-metal stents Drug-eluting stents Stent diameter (mm) Stent length (mm)

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0.77 65 13 32 64 65

(59.1%) (11.8%) (29.1%) (58.2%) (59.1%)

45 10 28 38 45

(54.2%) (12.0%) (33.7%) (45.8%) (54.2%)

62 (56.4%) 32 (29.1%) 16 (14.5%) 32.3 ± 15.6 17 (15.5%)

46 (55.4%) 26 (31.3%) 11 (13.3%) 36.0 ± 16.4 21 (25.3%)

76 (69.1%) 11 (10.0%) 8 (7.3%) 15 (13.6%) 105 (95.5%) 8 (7.3%) 48 (43.6%) 36 (32.7%) 23 (20.9%)

67 (80.7%) 3 (3.6%) 6 (7.2%) 7 (8.4%) 77 (92.8%) 13 (15.7%) 30 (36.1%) 26 (31.3%) 15 (18.1%)

9 (8.2%) 9 (8.2%) 92 (83.6%) 3.21 ± 0.39 23.8 ± 6.0

4 (4.8%) 13 (15.7%) 66 (79.5%) 3.35 ± 0.48 24.6 ± 6.1

0.09 0.50 0.93

BMI  25 kg/m2 (n ¼ 83)

P-value

LVEDV (ml) 123.1 (100.6e146.8) 134.7 (112.9e164.7) 0.01 LVESV (ml) 63.1 (46.0e80.6) 63.0 (45.4e83.9) 0.96 LV mass (g) 115.0 (97.5e133.8) 138.0 (122.2e158.7) <0.01 LV ejection fraction (%) 50.0 (37.9e56.5) 51.0 (43.8e62.3) 0.02 Infarct size (% of LV) 20.8 (11.4e33.1) 17.9 (9.0e24.9) 0.04 Area at risk (% of LV) 36.0 (25.7e49.6) 29.4 (20.5e37.6) <0.01 Myocardial salvage index 39.2 (24.6e59.6) 43.2 (27.7e54.4) 0.69 Hemorrhagic infarction, 61 (55.5) 46 (55.4) 1.00 n (%) MVO area (% of LV) 0.9 (0e2.9) 1.2 (0e3.1) 0.76 4 (2e6) 4 (2e6) 0.18 No. of segments with >75% of infarct transmurality BMI: body mass index; LV: left ventricle; LVEDV: left ventricular end-diastolic volume; LVESV: left ventricular end-systolic volume; MVO: microvascular obstruction.

p ¼ 0.004) and angiographic no reflow (OR 3.09, 95% CI 1.05e9.08, p ¼ 0.04) were also independent predictors of larger infarct size (percentage infarct volume >18.7% of median infarct size) in multivariate binary logistic regression analysis.

3.4. Laboratory and clinical outcome Peak CK-MB was not different between the overweight and normal weight groups (163.6 [IQR 83.7e276.4] ng/ml vs. 190.9 [IQR 87.4e302.4] ng/ml, p ¼ 0.53). There was a trend that the levels of Nterminal pro B-type natriuretic peptide (NT-proBNP) in the normal weight group were higher than those of the overweight group for 1 year; however, the difference was not significant statistically because of the small number of patients who were followed up completely. There had been no cardiac deaths in the overweight group and 3 (2.7%) in the normal weight group at 6 months follow-up (p ¼ 0.26). There was no difference in MACE between the two groups (p ¼ 0.59). Nonfatal reinfarction (1.2% vs. 3.6%, p ¼ 0.39), hospitalization for congestive heart failure (3.6% vs. 3.6%, p ¼ 1.00), and target lesion revascularization (2.4% vs. 3.6%, p ¼ 0.70) were not different in the overweight group vs. the normal weight group at 6 months follow-up.

4. Discussion 0.12 0.09 0.20

0.54 0.06 0.29 0.84 0.62 0.39

0.03 0.37

BMI: body mass index; MBG: myocardial blush grade; TIMI: Thrombolysis in myocardial infarction; APPROACH score: a modified version of the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease scores.

This was the first study to explain the obesity paradox with myocardial infarct size measured by contrast-enhanced CMR in patients who undergoing primary PCI for STEMI. Overweight patients with a BMI  25 kg/m2 who suffered STEMI showed a smaller infarct size and AAR than patients with normal weight. BMI  25 kg/m2 was found to be independently associated with a smaller infarct size than normal BMI; however, no clinical differences were demonstrated in this study. Early studies reported that obesity was significantly associated with the risk of myocardial infarction and a higher risk of long-term mortality than normal body weight after acute myocardial infarction [3,4,6]. Recent registry studies showed an inverse or U-shaped relationship between BMI and mortality after PCI and acute coronary syndrome, even in STEMI [10,20]. Taken together, the nadir of mortality was among overweight or obese patients. However, there is no study on myocardial infarct size which could contribute to short- and long-term mortality in patients with acute STEMI. Myocardial infarct size measured by CMR may explain the

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mechanism of the obesity paradox. Our study results support the obesity paradox, especially in patient with STEMI undergoing primary PCI. Myocardial infarct size was directly related to left ventricular remodeling and future events, more so than measures of left ventricular systolic performance [21]. There was only one report to evaluate obesity paradox using CMR. Pingitore et al. analyzed contrast-enhanced CMR in 89 patients with old myocardial infarction and reported that obesity defined by BMI  30 kg/m2 was an independent predictor of infarct size [22]. Our study included only 5 patients with BMI  30 kg/m2 and 3 of them had a smaller infarct size than the median infarct size (18.7%) for the total study population. Although overweight was defined as BMI  25 kg/m2 in our study, both studies had similar results in that overweight, and not only obesity, was associated with smaller myocardial infarct size. Predominant differences between their study and ours were different patient characteristics and the number of participants. Participants in their study were stabilized patients with old myocardial infarction, while participant in our study were patients undergoing primary PCI for acute STEMI. Moreover, less than half of patients received reperfusion therapy including fibrinolysis in Pingitore et al.'s study, while our patients exclusively underwent primary PCI. Most of all, the number of participants in our study was more than two times than that of their study. Although an inverse relationship between obesity and infarct size after myocardial infarction could explain the obesity paradox, other questions about why smaller infarct sizes are observed in obesity still exist. There have been several possible explanations for this phenomenon. First, Kosuge et al. proposed that the obesity paradox may be explained by the fact that obese patients were younger at presentation [23]. However, the mean ages of subjects in two groups were not different and overweight was still an independent risk factor after multivariate analysis including age in our study. Therefore, the differences in baseline characteristics do not appear to be sufficient to explain the mechanism of the obesity paradox. Second, many authors suggested clinical or neurohormonal aspects [10,24]. Several animal studies reported that infusion of leptin or adiponectin reduced ischemia-reperfusion injury and infarct size [25,26]. Production of adiponectin and anti-inflammatory cytokines such as tumor necrosis factor (TNF)-a receptor, and the ability to store glucose in obese patients are increased in medical or surgical critical illness [22,27]. We infer that in STEMI, a severely stressful situation, similar responses by adipose tissue or pericardial fat may function as cardio-protectors that decrease myocardial infarct size. It is possible that patients with overweight, but not with morbidly obesity, have relatively lower levels of harmful adipokines compared to lean patients because most participants had a BMI < 30 kg/m2 in this study (only 5 subjects had a BMI > 30 kg/m2). A study on blood levels of TNF-a receptor, adiponectin, and leptin in patients with STEMI might help clarify this presumption. Third explanation is a strong association between pericardial fat volume measured by computed tomography and ischemia by single photon emission computed tomography was demonstrated by Tamarappoo et al. [28]. So, we expect that larger patients with larger hearts would have larger arteries, explaining the difference in the average diameter size of implanted stents. Furthermore, epicardial adipose tissue might contribute beneficially to coronary artery disease by fulfilling anti-inflammatory, anti-oxidant, vasodilatory, and neuroprotective functions and may serve as a reservoir of free fatty acids for the energy needs of myocardium during fasting. This study has several limitations. First, we used a nonrandomized, observational study design, which might have unrecognized confounding factors. Although we performed

multivariate analysis to adjust for potential confounding factors, we were not able to correct for unmeasured variables. Second, the anatomical AAR by APPROACH score did not differ between two groups in our study. However, for calculation of the APPROACH score, jeopardized territories are defined as those supplied by vessels with 70% stenosis not by vessels with total occlusion. The myocardium at risk by the APPROACH score is indicative of the myocardium at risk of “ischemia” rather than “myocardial infarct.” Moreover, the APPROACH score have limitations to reflect accurate myocardial volume at risk because of the heterogeneity of diameter and distribution of coronary arteries. Third, a possible selection bias exists because patients with hemodynamic instability were excluded. These patients might be obese and have large infarct sizes. However, there was no significant difference of weight and BMI between the included and excluded patients. Fourth, we used the volume of LV mass to normalize an absolute infarct volume and AAR instead of body habitus or distant structure such as diameter of the descending thoracic aorta. However, it is well known that BMI is strongly correlated with LV ventricular mass, which the increase in LV mass associated with increasing adiposity [29,30]. As also shown out results, LV mass was significantly different between two groups. Therefore, by adjusting the value of infarct volume and area at risk with the volume of the LV mass, we tried to reduce the influence of LV mass. Fifth, we did not consider the effect of obesity on CMR image quality. An increased body habitus can introduces noise and the large field of view decreases the in-plane resolution of the images. However, in the present study, because the maximal weight of enrolled patients is less than 110 kg enough to use phased-array body coils in obese patients, the degree of attenuation of radiofrequency could be minimized. And we used the smallest field of view for the area of interest to reduce wrap-around artifact. Lastly, we presented no data about visceral obesity, which could be a more potent marker of obesity than BMI. And, the U-shaped relationship between BMI and mortality in acute coronary syndrome indicates that too much excess fat is no longer protective. Further study is needed to prove the obesity paradox, to understand the exact impact of obesity on myocardial infarct size, and to determine the long-term prognosis in lean vs. obese subjects with STEMI. 5. Conclusions Overweight, defined as a BMI of 25 kg/m2 or more, is independently associated with a smaller myocardial infarct size measured by MRI in patients undergoing primary PCI for STEMI. Our study supports the so-called ‘obesity paradox’, although the exact mechanism of association between BMI and infarct size needs to be elucidated in future study. Relationship with industry policy None of the authors have any disclosure to show. Financial disclaimer None. References [1] Calle EE, Thun MJ, Petrelli JM, Rodriguez C, Heath Jr CW. Body-mass index and mortality in a prospective cohort of U.S. adults. N Engl J Med 1999;341(15): 1097e105. [2] Hubert HB, Feinleib M, McNamara PM, Castelli WP. Obesity as an independent risk factor for cardiovascular disease: a 26-year follow-up of participants in the Framingham heart study. Circulation 1983;67(5):968e77.

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