Myocardial tissue remodeling in adolescent obesity

Abstract

Background: Childhood obesity is a significant risk factor for cardiovascular disease in adulthood. Although ventricular remodeling has been reported in obese youth, early tissue-level markers within the myocardium that precede organ-level alterations have not been described.

Methods and results: We studied 21 obese adolescents (mean age, 17.7±2.6 years; mean body mass index [BMI], 41.9±9.5 kg/m(2), including 11 patients with type 2 diabetes [T2D]) and 12 healthy volunteers (age, 15.1±4.5 years; BMI, 20.1±3.5 kg/m(2)) using biomarkers of cardiometabolic risk and cardiac magnetic resonance imaging (CMR) to phenotype cardiac structure, function, and interstitial matrix remodeling by standard techniques. Although left ventricular ejection fraction and left atrial volumes were similar in healthy volunteers and obese patients (and within normal body size-adjusted limits), interstitial matrix expansion by CMR extracellular volume fraction (ECV) was significantly different between healthy volunteers (median, 0.264; interquartile range [IQR], 0.253 to 0.271), obese adolescents without T2D (median, 0.328; IQR, 0.278 to 0.345), and obese adolescents with T2D (median, 0.376; IQR, 0.336 to 0.407; P=0.0001). ECV was associated with BMI for the entire population (r=0.58, P<0.001) and with high-sensitivity C-reactive protein (r=0.47, P<0.05), serum triglycerides (r=0.51, P<0.05), and hemoglobin A1c (r=0.76, P<0.0001) in the obese stratum.

Conclusions: Obese adolescents (particularly those with T2D) have subclinical alterations in myocardial tissue architecture associated with inflammation and insulin resistance. These alterations precede significant left ventricular hypertrophy or decreased cardiac function.

Keywords: CT or MRI; obesity; type 2 diabetes.

Figure 1.

Healthy volunteer versus obese diabetic individual. Four chamber cine‐SSFP image in end‐diastole and representative left‐ventricular measurements. This obese diabetic adolescent has left ventricular measures of function and volume similar to the healthy volunteer; however, the myocardial extracellular volume fraction is significantly higher in the obese diabetic adolescent. SSFP indicates steady‐state free precession; LVEF, left ventricular ejection fraction; LV mass, left ventricular mass; LVEDV, left ventricular end‐diastolic volume; ECV, extracellular volume fraction.

Figure 2.

A, Myocardial extracellular volume fraction assessment by CMR stratified by obesity and diabetic status. The central line represents the median, and the whiskers represent 1.5 times the interquartile range. Healthy volunteers had the lowest ECV by CMR, followed by obese adolescents without T2D. Obese adolescents with T2D had the highest ECV by CMR. P values for Kruskal–Wallis comparisons between groups are adjusted for multiple comparisons. B, Relationship of ECV to body mass index across healthy volunteers and obese individuals (fitted using a Loess spline), demonstrating a significant association of ECV with BMI. CMR indicates cardiac magnetic resonance imaging; ECV, extracellular volume fraction; BMI, body mass index; T2D, type 2 diabetes.

Figure 3.

Inflammation and dysglycemia are associated with myocardial tissue remodeling in obese adolescents. Myocardial ECV is associated with high‐sensitivity C‐reactive protein and triglycerides (markers of systemic inflammation and visceral adiposity), as well as hemoglobin A1c (marker of dysglycemia). A linear fit using a least‐squares (Spearman) correlation was used, utilizing a log‐transformed dependent variable (biomarker). A Loess spline was added to the figure to illustrate the nonuniform increase of ECV with BMI. The symbol ρ refers to Spearman's rank correlation. ECV indicates extracellular volume fraction; BMI, body mass index.