Early Ventricular Remodeling and Dysfunction in Obese Children and Adolescents

Abstract

Obesity is an independent predictor of heart failure in adults. Obese individuals have increased hemodynamic load and neuro-hormonal activation that contribute, but cannot entirely explain the reported changes in ventricular structure and function leading to heart failure. There are intrinsic alterations in the myocardium that are independent of load. Insulin resistance promotes alterations in myocardial substrate metabolism that may play a role in the pathogenesis of decreased myocardial efficiency and cardiac dysfunction in obese individuals. The prevalence of obesity in childhood and adolescence has increased significantly over the last decade. Obese children and adolescents have left ventricular remodeling that transpires into adulthood, and subclinical systolic and diastolic dysfunction despite normal conventional parameters of ventricular function. These findings suggest that obesity has an early impact in the cardiovascular health of obese adolescents. Life-style modifications causing weight loss can reverse the ventricular dysfunction observed in this young population and must be strongly encouraged.

Cardiospecific CD36 suppression by lentivirus-mediated RNA interference prevents cardiac hypertrophy and systolic dysfunction in high-fat-diet induced obese mice

“…Obesity cardiomyopathy is characterized by cardiac hypertrophy, a phenotype that is commonly observed in both obese humans and animals [4, 29]. To investigate the effects of CD36 deficiency on cardiac hypertrophy, the hearts were excised and weighted.…”

“…Nevertheless, approximately half of the studies showed no significant difference in LV systolic function between obese and lean patients [4, 47, 48], whereas the remainder showed significantly lower mean LVEF or LVFS values in obese than in lean subjects [3, 5, 6]. We speculate that the strength of association between severity of obesity and cardiac damage is stronger in animal models, in which myocardial metabolism can be operate in a more extreme (though unphysiological) pattern.…”

Involvement of peroxisome proliferator-activated receptors in cardiac and vascular remodeling in a novel minipig model of insulin resistance and atherosclerosis induced by consumption of a high-fat/cholesterol diet

“…FFAs are regarded as potential biochemical markers of post-infarct myocardial remodeling [ 37 ]. Further, IR is also associated with left ventricular remodeling [ 38 ] and often is accompanied by hemodynamic stress, such as systemic hypertension, which could cause left ventricular pressure overload and result in heart failure [ 11 ]. Therefore, a long term HFC diet increases plasma FFA and aggravates IR, which leads to severe cardiac autonomic nervous dysfunction.…”

Anthropometric and Biochemical Markers as Possible Indicators of Left Ventricular Abnormal Geometric Pattern and Function Impairment in Obese Normotensive Children

“…The mechanisms implicated in the pathophysiology of altered LV structure and function in obesity have not been completely clarified. Increased metabolic activity caused by excess of adipose tissue leads obese individuals to volume overload and a subsequent alteration of LVM and geometric pattern of LV in response to hemodynamic changes [19]. Elevated blood pressure, present in up to 23% of obese youth [20], is also a well-studied risk factor for LVH due to increased afterload.…”

“…Progressive obesity leads adipocytes to loss of storage ability, eventually resulting in increased levels of circulating free fatty acids, lipid deposition on ectopic tissue (pancreas, liver, heart), and lipotoxicity [23]. Abundant visceral fat in obese subjects is also dysfunctional leading to increased synthesis of pro-inflammatory cytokines, such as leptin and resistin, and decreased secretion of protective insulin-sensitizing adiponectins [19]. This "adiposopathy" results in insulin resistance and hyperinsulinemia, glucotoxicity, increased angiotensin synthesis, and activation of the sympathetic nervous system, contributing further to myocardial dysfunction [24].…”