Original Article

Obesity

EPIDEMIOLOGY/GENETICS

Association of Metabolically Healthy Obesity with Subclinical Coronary Atherosclerosis in a Korean Population Chang Hee Jung1*, Min Jung Lee1*, Jenie Yoonoo Hwang1, Jung Eun Jang1, Jaechan Leem1, Dong Hyun Yang2, Joon-Won Kang2, Eun Hee Kim3, Joong-Yeol Park1, Hong-Kyu Kim3, and Woo Je Lee1

Objective: The degree of subclinical coronary atherosclerosis detected by coronary multidetector computed tomography (MDCT) in four groups defined by the state of metabolic health and obesity in an asymptomatic Korean population was compared. Methods: The data of 4009 asymptomatic subjects who participated in a routine health screening examination were collected. Significant coronary artery stenosis defined as >50% stenosis, plaque, and coronary artery calcium scores (CACS) were assessed by MDCT. Participants were stratified by BMI (cut-off value, 25 kg/m2) and metabolically healthy state, which was defined by Wildman criteria. Results: Metabolically healthy obese (MHO) subjects had a significantly higher prevalence of significant subclinical coronary atherosclerotic burden compared with metabolically healthy nonobese (MHNO) subjects. The adjusted odds ratios of the MHO group for various coronary MDCT findings (MHNO group as the reference), such as coronary artery stenosis, any plaque, calcified plaque, mixed plaque, CACS > 0, and CACS > 100, were 1.87 (95% CI 1.15-3.03), 1.31 (1.01-1.71), 1.40 (1.05-1.86), 1.57 (1.01-2.48), 1.38 (1.04-1.82), and 1.69 (1.03-2.78), respectively. Conclusions: Our data illustrate that MHO subjects have substantial subclinical coronary atherosclerotic burden. Thus, it is important to consider the metabolic health state and obesity in evaluating cardiovascular risk. Obesity (2014) 22, 2613–2620. doi:10.1002/oby.20883

Introduction Obesity associates with increased risk of metabolic syndrome (MetS), type 2 diabetes, and cardiovascular disease (CVD), which can result in a higher mortality risk (1). However, not all obese subjects have a higher mortality risk, which suggests the existence of a subset of obese individuals, the so-called metabolically healthy obese (MHO) (2-4). In addition, a subgroup of normalweight individuals with abnormal metabolic parameters has also been described (5). The long-term effects of subjects with MHO have been investigated in numerous studies. However, results are conflicting (6-8). In a population study conducted in Italy, there was no increase in mortality from CVD or any other cause during the 15-year follow-

up period (8). Similarly, an observational study that followed community-dwelling adults from Scotland and England for 7 years demonstrated that MHO participants were not at increased risk for CVD and mortality (7). On the contrary, a recent cohort study from the United Kingdom showed that both metabolically healthy and unhealthy obese subjects carried an elevated risk of mortality, regardless of the definition of metabolic health (6). In the background of these inconsistence among studies, a meta-analysis was recently performed to determine the effect of metabolic status on all-cause mortality and cardiovascular (CV) events in normalweight, overweight, and obese persons (9). In this analysis, obese persons were at increased risk for adverse long-term outcomes, even in the absence of metabolic abnormalities, compared with metabolically healthy normal-weight individuals, suggesting that there is no healthy pattern of increased weight (9). Despite this

1 Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. Correspondence: Woo Je Lee ([email protected]) 2 Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea 3 Department of Health Screening and Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. Correspondence: Hong-Kyu Kim ([email protected])

*These two authors contributed equally to this work. Disclosure: The authors declared no conflict of interest. Author contributions: C.H.J. and M.J.L researched data and wrote the manuscript. M.J.L. contributed to the data analysis and edited the manuscript. J.Y.H., J.E.J., J.L., D.H.Y, J.-W.K, and E.H.K researched data and contributed to discussion. J.-Y.P. contributed to discussion and reviewed the manuscript. H.-K.K and W.J.L. researched data and edited the manuscript. H.-K.K and W.J.L are guarantors of this article. Additional Supporting Information may be found in the online version of this article. Received: 5 April 2014; Accepted: 10 August 2014; Published online 24 August 2014. doi:10.1002/oby.20883

www.obesityjournal.org

Obesity | VOLUME 22 | NUMBER 12 | DECEMBER 2014

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Obesity

MHO and Coronary Atherosclerosis Jung et al.

Figure 1 Study population. CVD, cardiovascular disease; hsCRP, high-sensitive C-reactive protein; MHNO, metabolically healthy, nonobese; MUNO, metabolically unhealthy, nonobese; MHO, metabolically healthy, obese; MUO, metabolically unhealthy, obese.

increased risk for CVD and mortality in subjects with MHO, there remains controversy on the degree of atherosclerosis in subjects with MHO (10-13). In this study, we compared the degree of subclinical coronary atherosclerosis detected by coronary multidetector computed tomography (MDCT), an established quantitative and objective method for the noninvasive evaluation of coronary atherosclerosis (14), in four groups defined by the state of metabolic health and obesity in an asymptomatic Korean population. Through this comparison, we determined whether MHO is a benign condition. We also provide insights to help us understand the aforementioned controversy regarding MHO and increased mortality.

Methods Study population The study population consisted of 7300 subjects who had underwent coronary computed tomography (CT) angiography using the 64-slice MDCT scanner during routine health evaluations at the Asan Medical Center (AMC, Seoul, Republic of Korea) between January 2007 and June 2011. Each subject completed a questionnaire that listed a history of previous medical and/or surgical diseases, medications, and drinking and smoking habits. Drinking habits were categorized as frequency per week (i.e., 1 times/week and 2 times/week, moderate drinker); smoking habits as noncurrent or current, and exercise habits as frequency per week (i.e., 2 times/week and 3 times/week, physically active) (15). The history of CVD was based on each subject’s history of angina, myocardial infarction, and/or cerebrovascular accidents. Subjects with diabetes were defined as those with fasting plasma glucose (FPG) levels of 7.0 mmol/L or HbA1c levels 6.5% (16). In addition, subjects who reported the use of antidiabetic medications on a self-report questionnaire were considered to have diabetes (17). We excluded subjects with a history of CVD or percutaneous coronary intervention, or prior coronary arterial bypass surgery (n 5 415), as well as those who had taken drugs for more than 6 months or within the previous 12 months that could potentially affect lipid metabolism (n 5 929). In addition, subjects with abnormal thyroid function [thyroid stimulating hormone (TSH) 5.0 mU/L

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Obesity | VOLUME 22 | NUMBER 12 | DECEMBER 2014

and/or free T4 24.5 pmol/L, n 5 685], leukocytosis (blood leukocyte count >10.0 3 103/mm3; n 5 83), leukopenia (blood leukocyte count

Association of metabolically healthy obesity with subclinical coronary atherosclerosis in a Korean population.

The degree of subclinical coronary atherosclerosis detected by coronary multidetector computed tomography (MDCT) in four groups defined by the state o...
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