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

Abstract

Objective: 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.

Research design and methods: 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).

Results: 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.

Conclusions: 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.

Figure 1

CAC score across tertiles of BMI (n = 90) (A), BMI SD scores (n = 90) (B), WC (n = 85) (panel C), TAT (n = 65) (D), SAT (n = 65) (E), and VAT (n = 66) (F). P values for ANOVA, unadjusted and adjusted for sex, race, IS_FFM, and glucose tolerance status. White bars represent unadjusted means, and dark bars represent adjusted means. Pairs of similar letters indicate two groups’ post hoc significant differences (a and b for unadjusted and c and d for adjusted model). In the adjusted model for SAT and TAT, glucose tolerance status (NGT vs. IGR) contributed to the variance of the model (P < 0.05) in addition to the main effect of SAT and TAT.

Figure 2

Relationship of Log (CAC score +1) to BMI (n = 90) (A), SAT (n = 65) (B), and IS_FFM (n = 67) (C). Relationship of PWV to IS_FFM (n = 52) (D) and of IMT to HbA_1c (n = 85) (E) in subjects with NGT (open circles) and IGR (filled circles).