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Title: Coronary artery calcification in obese youth: What are the phenotypic and metabolic determinants?

item BACHA, FIDA - Children'S Nutrition Research Center (CNRC)
item EDMUNDOWICZ, DANIEL - Temple University
item SUTTON-TYRELL, KIM - University Of Pittsburgh
item LEE, SOJUNG - University Of Pittsburgh Medical Center
item TFAYLI, HALA - American University Of Beirut
item ARSLANIAN, SILVA - University Of Pittsburgh Medical Center

Submitted to: Diabetes Care
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/23/2014
Publication Date: 9/1/2014
Citation: Bacha, F., Edmundowicz, D., Sutton-Tyrell, K., Lee, S., Tfayli, H., Arslanian, S.A. 2014. Coronary artery calcification in obese youth: What are the phenotypic and metabolic determinants? Diabetes Care. 37(9):2632-2639.

Interpretive Summary: Childhood obesity has been linked to cardiovascular disease in adulthood. Also, atherosclerosis (changes in the heart vessels with plaque formation and narrowing) has been found to start in the adolescent years. The determining factors for the risk of early vessel disease in youth with obesity are not clear. Also, the best tools to measure early atherosclerosis are not well identified. In this study, we evaluated early atherosclerosis (before clinical signs appear) in youth and the underlying risk factors. We measured calcium deposits in the heart (part of early plaque formation), the stiffness of the vessels and thickness of the vessel wall in relation to body fat and insulin resistance Insulin resistance refers to the body requiring higher levels of insulin to regulate sugar levels and other functions. We found that the degree of obesity, total body fat and abdominal fat determine the risk of having early small amounts of calcium deposits in the vessels of the heart. In addition, insulin resistance that occurs with increased body weight was the significant determinant of vessel stiffness, whereas exposure to higher sugar levels plays a role in the thickening of the wall of the blood vessels. Identification of these different mechanisms by which obesity affects cardiovascular disease risk in childhood is important to focus the intervention efforts in the childhood years in high risk individuals.

Technical Abstract: Obesity in adolescence has been associated with increased risk for coronary heart disease in adulthood. This study evaluated subclinical atherosclerosis in obese youth and the underlying risk factors. Ninety obese adolescents (37 normal glucose tolerant, 27 prediabetes, and 26 type 2 diabetes) underwent evaluation of coronary artery calcifications (CACs) by electron beam computed tomography, aortic pulse wave velocity (PWV), carotid intima-media thickness (IMT), lipids, leptin, inflammatory markers, and body composition (DEXA). A total of 68 underwent evaluation of insulin sensitivity (IS) (hyperinsulinemic-euglycemic clamp) and abdominal adiposity (computed tomography). A total of 50% had CACs (CAC+: Agatston CAC score >/= 1). CAC+ youth had higher BMI, fat mass, and abdominal fat, with no difference in sex, race, IS per fat-free mass (ISFFM), glucose tolerance, PWV, or IMT compared with the CAC- group. PWV was inversely related to IS. In multiple regression analyses with age, race, sex, HbA1c, BMI (or waist circumference), ISFFM, diastolic blood pressure, non-HDL cholesterol, and leptin as independent variables, BMI (or waist) (R(2) = 0.41; P = 0.001) was the significant determinant of CAC; leptin (R(2) = 0.37; P = 0.034) for PWV; and HbA1c, race, and age (R(2) = 0.34; P = 0.02) for IMT. Early in the course of obesity, there is evidence of CAC independent of glycemia. The different biomarkers of subclinical atherosclerosis appear to be differentially modulated, adiposity being the major determinant of CAC, hyperglycemia, age, and race for IMT, and leptin and IS for arterial stiffness. These findings highlight the increased cardiovascular disease risk in obese youth and the need for early interventions to reverse obesity and atherosclerosis.