Changes in carotid stiffness in patients with familial hypercholesterolemia treated with Evolocumab®: A prospective cohort study

Background and aim: Protein convertase subtilisin kexin type 9 (PCSK-9) inhibitors demonstrated efficacy in cholesterol reduction and in the prevention of cardiovascular events. We evaluated changes in lipid profile and carotid stiffness in patients with familial hypercholesterolemia during 12 weeks of treatment with a PCSK-9 inhibitor, Evolocumab®. Methods and results: Patients with familial hypercholesterolemia starting a treatment with Evolocumab® were included. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), small dense LDL (assessed by LDL score) and carotid stiffness were evaluated before starting treatment with Evolocumab® and during 12 weeks of treatment. Twenty-five subjects were enrolled (52% males, mean age 51.5 years). TC and LDL-C were reduced of 38% and 52%, respectively during treatment, with LDL score reduced of 46.1%. In parallel, carotid stiffness changed from 8.8 (IQR: 7.0–10.4) m/sec to 6.6 (IQR: 5.4–7.5) m/sec, corresponding to a median change of 21.4% (p < 0.001), with a significant increase in carotid distensibility (from 12.1, IQR: 8.73–19.3 kPA−1 × 10−3 at T0 to 21.8, IQR: 16.6–31.8 kPA−1 × 10−3 at T12w) corresponding to a median change of 62.8% (p < 0.001). A multivariate analysis showed that changes in LDL score were independently associated with changes in carotid stiffness (β = 0.429, p = 0.041). Conclusion: Small dense LDL reduction, as assessed by LDL score, is associated with changes in carotid stiffness in patients with familial hypercholesterolemia treated with Evolocumab®.