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Heterozygous familial hypercholesterolemia (heFH) is an autosomal dominant lipid metabolism disorder. Its prevalence is 1:250-1:300 people in the population. Patients with heFH have an up to 13-fold increased risk of premature coronary artery disease (CAD). If left untreated, men and women with heFH typically develop early CAD before the ages of 55 and 60, respectively. There is evidence that coronary artery calcification (CAC) and aortic valve calcification (AoVC) are more prevalent in FH patients than in the general population. It is documented that CAC and AoVC are predictors of increased risk of cardiovascular morbidity and mortality in heFH patients, like in the general population. However, the etiology and pathogenesis of vascular calcification in FH patients is not well understood. Risk factors for vascular calcification include age, increased levels of atherogenic lipoproteins, Lp(a), increased blood pressure, and inflammation. There are convincing data from clinical studies and animal atherosclerotic mouse models using low-density lipoprotein receptor (LDL-R) knockout mice that the vascular calcification processes in FH are associated with LDL-R mutations, probably partly due to a higher total cholesterol burden of FH subjects. Data from animal models as well as clinical studies indicate that the Wnt/beta-catenin pathway components and LDL receptor-related proteins 5 and 6 (LRP-5/6) might be involved in calcification processes in FH patients. The purpose of the review is to describe the prevalence of coronary and aortic calcification and its risk factors in FH patients. The review covers data about the role of the Wnt/beta-catenin pathway and factors modulating calcification processes.

Background: In Poland, treatment with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors has become available free of charge in a therapeutic program. Assessed herein, is the efficacy and safety of alirocumab and evolocumab in patients with heterozygous familial hypercholesterolemia (FH)., Methods: Data of 55 adult FH patients who participated in the program were analyzed upon meeting the criteria established by the Ministry of Health (low density lipoprotein cholesterol [LDL-C] above 160 mg/dL on max. tolerated statin dose and ezetimib). The efficacy of PCSK9 inhibitors in reducing LDL-C with drug administration every 2 weeks was assessed after 3 months and 1 year of therapy. A safety profile evaluation was performed at each visit. 48 patients completed the 3-month and 21 for the 1-year observation periods (34 patients treated with alirokumab and 14 with evolocumab)., Results: The mean concentration of direct-measured LDL-C decreased from the initial level of 215.1 ± 74.5 mg/dL to 75.3 ± 64.1 mg/dL, i.e., by 65 ± 14% following 3 months of treatment. This effect was stable in 1-year observation (77.7 ± 72.8 mg/dL). Adverse effects were flu-like symptoms (13.0%), injection site reactions (11.1%), fatigue (5.6%) and musculoskeletal symptoms (5.6%). Seven patients failed to complete the 3-month treatment period due to side effects or non-compliance, and 1 patient failed to complete the 1-year treatment due to myalgia., Conclusions: This study confirmed high effectiveness of PCSK9 inhibitors in reducing LDL-C levels in patients with FH. Due to restrictive inclusion criteria with LDL-C threshold level > 160 mg/dL (> 4.1 mmol/L) required for participation in the therapeutic program, a relatively small number of FH patients were eligible for treatment.

Background: Familial hypercholesterolaemia (FH) is a monogenic lipid metabolism disorder characterised by markedly elevated serum low-density lipoprotein (LDL) cholesterol level due to a mutation in the LDL receptor gene. Clinical features of FH include premature atherosclerosis and coronary artery disease., Aim: To explore associations between noninvasive markers of atherosclerosis including intima-media thickness (IMT) and pulse wave velocity (PWV) and blood lipids, blood pressure (BP) and obesity in a group of young patients with FH., Methods: Study population included 36 patients aged < 35 years with the diagnosis of FH based on the Simon Broome Register criteria, and their 49 relatives who comprised the control group free of FH., Results: Mean IMT values were higher in FH patients than controls (0.60 ± 0.19 vs. 0.53 ± 0.07 mm, respectively, p < 0.05).Mean body mass index (BMI) and waist circumference were similar in patients and controls. The prevalence of carotid atherosclerotic plaques was significantly higher among FH patients (n = 6) than in controls (n = 1) (21.4% vs. 2.6%, p = 0.012). Arterial hypertension was present in 27.8% of patients with FH and 16.3% of subjects in the control group. Systolic blood pressure (SBP) in FH patients correlated significantly with age (r = 0.35), BMI (r = 0.48) and waist circumference (r = 0.47), and diastolic blood pressure (DBP) correlated with BMI (r = 0.42) and waist circumference (r = 0.41). PWV correlated significantly with age (r = 0.44), SBP (r = 0.63) and DBP (r = 0.52). We did not find any correlations between IMT and serum lipids, BP or obesity indices in FH patients., Conclusions: Our findings show a higher rate of arterial hypertension in young FH patients compared to their relatives free of FH, with significant associations between BP and indices of obesity and arterial stiffness. Intensive lipid lowering and antihypertensive therapy along with a reduction in central fat may be considered a mandatory treatment strategy in young FH patients to prevent atherosclerosis and increased arterial stiffness.