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

Figures

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  Figure 1. Study flowchart. N, number of patients; V, visit; LLT, lipid-lowering therapy; VUS, variant of uncertain significance.

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  Figure 2. Correlation heatmap showing Spearman partial correlation coefficients between arterial injury markers and age and sex adjusted lipid characteristics at baseline (V0). Red colour indicates positive, while blue indicates negative correlation coefficient between listed variables; significant correlations are bolded (p < 0.05). cIMT, carotid intima-media thickness; PWV, pulse wave velocity; RHI, reactive hyperemia index; TC, total cholesterol; ApoB, apolipoprotein B; LDL-C, low-density lipoprotein cholesterol; Lp(a), lipoprotein(a); TG, triglycerides.

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  Figure 3. Changes in LDL-C during short-term lipid-lowering therapy (LLT). Adjusted LS mean percentage change in LDL cholesterol from baseline over study visits (V0, V1, and V2) for the rosuvastatin and ezetimibe groups. Error bars indicate 95% confidence intervals. LDL-C, low-density lipoprotein cholesterol; V, study visit.

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  Figure 4. Adjusted mean changes in carotid intima–media thickness (cIMT), pulse wave velocity (PWV), reactive hyperaemia index (RHI), and beta stiffness following short-term lipid-lowering therapy with rosuvastatin or ezetimibe. Values represent estimated marginal means (EMM). Adjusted mean changes with 95% confidence intervals were derived from ANCOVA models including only baseline marker value and LDL-C reduction. Treatment-group EMMs (rosuvastatin and ezetimibe) were obtained from extended models that additionally included treatment allocation as a fixed factor. All values shown are EMMs with 95% confidence intervals. If the 95% CI included 0, the EMM change was regarded as non-detectable in our cohort. Across all vascular markers, baseline marker values consistently showed the largest effect sizes and were the only predictors with sufficient power for detection in our sample (partial η2 ≈ 0.12–0.36). By contrast, LDL-C reduction (partial η2 ≤ 0.05) and treatment-group contrasts (rosuvastatin vs. ezetimibe) (partial η2 0.04–0.07) exhibited small effect sizes and were therefore underpowered. The magnitude of observed EMM for beta stiffness (0.1–0.3 units) is not clinically meaningful.…