Normal-weight obesity is associated with increased risk of subclinical atherosclerosis

BACKGROUND: Subjects with normal body mass index (BMI) but elevated amounts of body fat (normal-weight obesity; NWO) show cardiometabolic dysregulation compared to subjects with normal BMI and normal amounts of body fat (normal-weight lean; NWL). In this study, we aimed to evaluate whether NWO individuals have higher rates of subclinical atherosclerosis compared to NWL subjects. METHODS: From a large-scale health checkup system, we identified 2078 normal weight (18.5 ≤ BMI < 25 kg/m(2)) subjects with no previous history of coronary artery disease who underwent analysis of atherosclerosis using coronary computed tomography angiography (CCTA) and pulse wave velocity (PWV). NWO was defined as normal BMI and highest tertile of body fat percentage by sex (men ≥25. 4 % and women ≥31.4 %). CCTA was performed using a 64-detector row CT. A plaque was defined as a structure >1 mm(2) within and/or adjacent to the vessel lumen and classified according to the presence/proportion of intraplaque calcification. RESULTS: NWO subjects (n = 283) demonstrated metabolic dysregulation compared to NWL individuals (n = 1795). After adjusting for age, sex, and smoking, NWO individuals showed higher PWV values than NWL individuals (1474.0 ± 275.4 vs. 1380.7 ± 234.3 cm/s, p = 0.006 by ANCOVA). Compared with NWL subjects, NWO subjects had a higher prevalence of soft plaques even after age, sex, and smoking adjustment (21.6 % vs. 14.5 %, p = 0.039 by ANCOVA). The PWV value and the log{(number of segments with plaque) + 1} showed a positive correlation with numerous parameters such as age, systolic blood pressure, visceral fat, fasting glucose level, serum triglyceride level, and C-reactive protein (CRP) in contrast to the negative correlation with high-density lipoprotein-cholesterol level. The visceral fat was an independent determinant of log{(number of segments with plaque) + 1} (ß = 0.027, SE = 0.011, p = 0.016) even after adjustment for other significant factors. Most importantly, NWO was an independent risk factor for the presence of soft plaques (odds ratio 1.460, 95 % confidence interval 1.027–2.074, p = 0.035) even after further adjustment for multiple factors associated with atherosclerosis (blood pressure, blood glucose, lipid level, CRP, medication, smoking status, physical activity). CONCLUSIONS: NWO individuals carry a higher incidence of subclinical atherosclerosis compared with NWL individuals, regardless of other clinical risk factors for atherosclerosis.