Early echocardiographic signs of cardiovascular affection in pediatric familial hypercholesterolemia

Familial hypercholesterolemia (FH) is a rare autosomal dominant genetic disorder caused by defective low-density lipoprotein (LDL) receptors or abnormal apolipoprotein B. FH raises the risk of premature atherosclerotic disease and cardiovascular death in young adults. However, cardiovascular affection in children needs to be more adequately studied. Our study aimed to evaluate the effect of hypercholesterolemia on the cardiovascular system of pediatric patients with homozygous FH using conventional and advanced echocardiographic parameters such as tissue Doppler imaging (TDI) and 2-dimensional speckle-tracking echocardiography (2D-STE). This case-control study matched 25 healthy children with 21 patients with homozygous FH. Both groups had conventional echocardiography, TDI, and 2D-STE. Myocardial velocities of the left and right ventricles, left ventricular strain, and aortic stiffness parameters were measured. The FH group had greater systolic blood pressure, dilated coronary arteries, and hypertrophied left ventricle (LV) compared to the control (P = 0.0001, P = 0.001, P = 0.01, respectively). The mitral E/E' ratio was higher in the patient group than in the control group (P = 0.007), indicating LV diastolic dysfunction in patients. At the same time, LV systolic function evaluated by 2D-STE was comparable to that in the control group. The abdominal aorta circumferential strain and ascending aorta M-mode-derived strain were significantly lower in patients compared to those in the control (P = 0.024, P = 0.0001, respectively), indicating increased aortic stiffness in the patients' group; moreover, 85.7% of patients had mild aortic insufficiency.  Conclusion: Mild aortic insufficiency, coronary artery dilatation, left ventricular (LV) diastolic dysfunction, and increased aortic stiffness are among early cardiovascular markers in pediatric patients with homozygous FH before impaired LV systolic function. What is Known: • Familial hypercholesterolemia (FH) in adults is associated with accelerated atherosclerosis, aortic valvopathy, dilated coronary arteries, ischemic heart disease, and premature cardiovascular death. • The cardiovascular effects of FH in children require additional research. What is New: • Pediatric patients with familial hypercholesterolemia tend to have an early affection for left ventricular diastolic function before the affection for the systolic function. • The diastolic dysfunction associated with pediatric FH is correlated to the aortic stiffness and low-density lipoprotein levels.