Effect of rosuvastatin and ezetimibe therapy on LDL- cholesterol reduction and non- invasive arterial injury markers in children with heterozygous familial hypercholesterolemia: a prospective, open-label, randomized study
Description
Description We analysed the effect of rosuvastatin and ezetimibe therapy on LDL- cholesterol reduction and non- invasive arterial injury markers in children with heterozygous familial hypercholesterolemia. In this dataset, we provide the raw data we used to analyse 45 children with FH [median age 10.5 years (IQR 8.7–14.5)] received rosuvastatin 5 mg OD or ezetimibe 10 mg OD for 6.2 months. Carotid intima-media thickness (cIMT), reactive hyperemia index (RHI), pulse wave velocity (PWV), and beta stiffness were evaluated in relation to anthropometric and lipid-related variables. Our conclusion were: - Greater short-term LDL-C reduction with rosuvastatin compared with ezetimibe (37% vs. 18%), with 45% of children achieving LDL-C <3.5 mmol/L in the rosuvastatin group and 13% in the ezetimibe group. Importantly, no differences in safety or tolerability were observed, as no adverse events occurred in either group. Taken together, these findings support the short-term efficacy and tolerability of rosuvastatin in pediatric patients. - All analysed arterial injury markers (cIMT,PWV, RHI and beta stiffness) were predominantly correlated by age or anthropometry and only RHI showed relevant correlations with lipids. During the short-term LTT, changes in arterial injury markers were unrelated to treatment allocation or LDL-C reduction, although our analyses were underpowered to detect such small effects and larger cohorts or longer follow-up would be needed to evaluate these associations with greater sensitivity.
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Body height, weight and BMI Z scores/percentiles were calculated from the UK-WHO growth charts. Morning blood samples were used for laboratory measurements. Cumulative TC (TC Exp), ApoB (ApoB Exp), and LDL-C (LDL-C Exp) exposures were calculated by multiplying serum TC, ApoB, or LDL-C (in mmol/L) at V1 by the patient’s age (in years) at V1. Elevated Lp(a) concentrations above 50 mg/dL were considered a risk modifier for atherosclerotic cardiovascular disease (ASCVD) (13). Treatment response was classified as sufficient if LDL-C at V2 was <3.5 mmol/L (14). Safety assessments included elevations in transaminases (ALT and AST) and creatine kinase (CK), defined as ≥2× the upper limit of normal for transaminases and ≥3.5× for CK. Endothelial function was assessed using the RHI, measured with the EndoPAT 2000 device (Itamar Medical Ltd., Caesarea, Israel). RHI was calculated according to the manufacturer’s algorithm, based on the ratio of pulse wave amplitudes during the reactive hyperaemia and baseline phases. RHI values of ≤1.67 indicate endothelial dysfunction, values between 1.67 and 2.00 represent a borderline ("grey zone"), and values of ≥2.00 are considered normal. In this study, the RHI cut-off for endothelial dysfunction was set at 1.67. Ultrasound measurements were performed by a single investigator who was blinded to the patients' treatment status and did not have access to previous scans during follow-up assessments. Examinations were conducted using the Aloka 5500 SSD Pro-sound ultrasound system (Aloka Co., Ltd., Tokyo, Japan) with a UST-5539 (7.5 MHz) linear probe, in accordance with the manufacturer's guidelines. The Auto-cIMT modality was used, and the cIMT value, reported in millimetres, was calculated as the average of six bilateral measurements. Additionally, a high-definition echo-tracking system (Aloka E-tracking software) was used to generate the artery’s pressure–diameter curve. Beta stiffness was calculated using the following equation: beta stiffness = ln (Ps/Pd)/[(Ds−Dd)/Dd], where Ps is systolic BP, Pd is diastolic BP, Ds is arterial systolic diameter, and Dd is arterial diastolic diameter. Pulse wave velocity (PWV) was calculated from the time delay between the two adjacent distension waveforms of the water hammer equation for forward travelling waves using the beta stiffness.
Institutions
- Ljubljana University Medical CentreLjubljana, Ljubljana