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Background Familial hypercholesterolemia (FH) increases the risk of atherosclerosis in children and adults. Atherosclerotic cardiovascular disease in young patients FH is usually subclinical but recognition of children with more pronounced changes is crucial for adjusting effective management. Aim of this research was to use ultrasonography with two-dimensional speckle tracking (2DST) and tonometry to evaluate atherosclerotic changes in patients with FH (parents and their offspring). Methods Applanation tonometry and carotid arteries sonography with evaluation of the intima-media complex thickness (IMCT) and application of the 2DST were performed in 20 families with FH (20 parents and 29 children). The same size control group (age and sex matched) was included. Results were compared between peers and between generations together with the correlation analysis. Results Adults with FH, in comparison with healthy peers, presented significantly more atherosclerotic plaques (9 vs. 2, p = 0.0230), had significantly thicker IMC (0.84 ± 0.19 vs. 0.56 ± 0.06 mm, p < 0.0001) and had stiffer arterial wall (for stain: 6.25 ± 2.3 vs. 8.15 ± 2.46, p = 0.0103). In children from both groups there were no atherosclerotic plaques and IMCT did not differ significantly (0.42 ± 0.07 vs. 0.39 ± 0.04, p = 0.1722). However, children with FH had significantly stiffer arterial wall according to 2DST (for strain: 9.22 ± 3.4 vs. 11.93 ± 3.11, p = 0.0057) and tonometry (for the pulse wave velocity: 4.5 ± 0.64 vs.3.96 ± 0.62, p = 0.0047). These parameters correlated with atherosclerosis surrogates in their parents ( p < 0.001) but were not significantly affected by presence of presumed pathogenic gene variant. Conclusions Children with FH presented subclinical atherosclerosis manifested as decreased arterial wall elasticity. Degree of stiffening was associated with advancement of atherosclerosis in their parents but did not present significant association with gene variants. Sonography with application of 2DST seems to be a good candidate for comprehensive evaluation of atherosclerosis in families with FH.

Background: Familial hypercholesterolemia (FH) is a genetic autosomal co-dominant metabolic disorder leading to elevated circulating concentrations of low-density lipoprotein cholesterol (LDL-C). Early development of atherosclerotic cardiovascular disease (ASCVD) is common in affected patients. We aimed to evaluate the characteristics and differences in the diagnosis and therapy of FH children and adults. Methods: All consecutive patients who were diagnosed with FH, both phenotypically and with genetic tests, were included in this analysis. All patients are a part of the European Atherosclerosis Society FH-Study Collaboration (FHSC) regional center for rare diseases at the Polish Mother’s Memorial Hospital Research Institute (PMMHRI) in Lodz, Poland. Results: Of 103 patients with FH, there were 16 children (15.5%) at mean age of 9 ± 3 years and 87 adults aged 41 ± 16; 59% were female. Children presented higher mean levels of total cholesterol, LDL-C, and high-density lipoprotein cholesterol (HDL-C) measured at the baseline visit (TC 313 vs. 259 mg/dL (8.0 vs. 6.6 mmol/L), p = 0.04; LDL 247 vs. 192 mg/dL (6.3 vs. 4.9 mmol/L), p = 0.02, HDL 53 vs. 48 mg/dL (1.3 vs. 1.2 mmol/L), p = 0.009). Overall, 70% of adult patients and 56% of children were prescribed statins (rosuvastatin or atorvastatin) on admission. Combination therapy (dual or triple) was administered for 24% of adult patients. Furthermore, 13.6% of adult patients and 19% of children reported side effects of statin therapy; most of them complained of muscle pain. Only 50% of adult patients on combination therapy achieved their treatment goals. None of children achieved the treatment goal. Conclusions: Despite a younger age of FH diagnosis, children presented with higher mean levels of LDL-C than adults. There are still urgent unmet needs concerning effective lipid-lowering therapy in FH patients, especially the need for greater use of combination therapy, which may allow LDL-C targets to be met in most of the patients.

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Background Familial hypercholesterolaemia (FH) affects approximately 150,000 people in Poland. However, there are many patients still unaware of this diagnosis. On the other hand, it might lead to early cardiovascular mortality and morbidity due to the lifetime exposure to high levels of LDL-C. Therefore, increased awareness of FH is very important. Purpose We aimed to evaluate the clinical features of FH in children and adults based on the preliminary data from the Polish Mother's Memorial Hospital Research Institute (PMMHRI) Registry. Methods The registry of children and adults with FH conducted in PMMHRI (2nd largest, supra-regional hospital in Poland) was established to investigate the clinical characteristics, management and clinical outcomes data of FH patients. All consecutive patients with diagnosed (genetically and/or phenotypically) FH were included in the study. Results Of 103 patients with FH, there were 16 children aged 9±3 and 87 adults aged 41±16; 59% were female. The diagnosis of FH in adults was late – at the mean age of 41 years. Among children with FH, as compared with adults, the levels of highest TC and LDL-C ever were similar. However, children presented higher mean levels of total cholesterol, LDL-C and HDL-C measured at baseline visit (Table). Interestingly there was no difference in BMI between children and adults (Table). Among adults, chronic coronary syndrome was diagnosed in 11.5% patients, from which 5.7% patients had a history of myocardial infarction and 7% patients required revascularization. The prevalence of chronic coronary disease, peripheral artery disease as well as stroke in family history was definitely higher (in 44 patients – 50%, 17 patients – 20% and 22 patients – 25%, respectively). Most of adult patients at baseline visit were prescribed statins (rosuvastatin or atorvastatin). 14 patients (13.6%) declared statin intolerance, most of them complained of muscle pain, 4.6% patients reported hepatic disturbances. The frequency of statin use in children was lower – 56% children were prescribed statin, 19% declared statin intolerance with muscle pain as the side-effect of treatment. Ezetimibe, as a part of combination therapy, was taken by 29% adult patients. PCSK9 inhibitors were prescribed (within drug program) for 11.5% adult patients. Fibrates were prescribed for 13.7% adult patients, the same was for n-3 fatty acids. Conclusions Despite definitely younger age of FH diagnosis children present higher mean levels of LDL cholesterol than adults. Therefore, the lifetime exposure to LDL cholesterol starts at a very young age. As a result, there is a need to the earlier initiation of therapy and strict monitoring of the atherosclerosis progression. On the other hand, late diagnosis of FH in adults is an unmet need, that might be associated with poorer prognosis. FUNDunding Acknowledgement Type of funding sources: None.