FAMILIAL HYPERCHOLESTEROLAEMIA - A DIAGNOSIS THAT EVERY PLASTIC SURGEON CAN EXPERIENCE.

Familial hypercholesterolaemia (FH) is the most common autosomal dominant inheritable disease caused by a defective catabolism of LDL particles. Their subsequent accumulation in circulation accelerates atherosclerotic vascular disease. Untreated FH increases the risk of premature manifestation of atherosclerosis (myocardial infarction - MI- or stroke); it is known that homozygous patients, if not adequately treated, are usually affected by atherothrombotic complications of the underlying disease before 20 years of age and often do not live longer than 30 years. Patients with FH are asymptomatic for a long period of time; their elevated blood lipid levels are often a random laboratory finding. The cardiovascular complications (MI or stroke) may be the primary manifestation of this disease. Clinical signs (xanthomas, xanthelasma or arcus corneae lipoides) occur rarely in these patients but are pathognomic, so at least basal awareness of these findings is necessary. Upon detection of such findings, a diagnostic procedure of FH including blood lipid measuring, careful personal and family history of cardiovascular disease (CVD) and subsequent referral to GPs or to MEDPED specialist is crucial. MEDPED (Make Early Diagnosis to Prevent Early Deaths in MEDical PEDigrees) project associates physicians specializing in patients with severe lipid metabolism disorders including FH. Treatment is based on statins, often in combination with ezetimibe. A great benefit in the treatment of these patients was the discovery of PCSK9 inhibitors, which are very effective and represent a therapeutic option especially for patients with very severe dyslipidaemia or with intolerance of statin therapy. The FH awareness of a plastic surgeon as a first-contact physician, who may be confronted with typical skin or eye manifestations of FH, is essential for the early detection of FH patients, who can then be internally examined and followed-up.

Strong Association between APOA5 Gene Polymorphisms and Hypertriglyceridaemic Episodes.

Plasma triglyceride (TG) levels represent a significant risk factor of cardiovascular and total mortality. Concentrations of TG in the plasma depend, to a large extent, on the genetic background, and the apolipoprotein A5 (APOA5) gene seems to be one of the most powerful players in the plasma TG metabolism regulation. In total, we analysed three tagging APOA5 (rs964184 rs662799, rs3135506) SNPs in 209 patients with plasma TG levels over 10 mmol/l (HTG) on at least one occasion and in 379 treatment-naïve controls (NTG) with plasma TG values within the normal range. Minor alleles of all three analysed APOA5 polymorphisms significantly (all P < 0.0001) increased the risk of hypertriglyceridaemia. The most significant association (P < 0.0000001) was observed for the rs964184 polymorphism, where the minor GG homozygotes had the odds ratio (OR, 95% CI) for hypertriglyceridaemia development 21.30 (8.09-56.07, P < 0.000001) in comparison with the major CC allele homozygotes. Carriers of at least one minor allele at rs3135506 had OR (95% CI) 4.19 (2.75-6.40); (P < 0.000005) for HTG development and similarly, carriers of a minor allele at rs662799 had OR (95% CI) 3.07 (2.00-4.72) (P < 0.0001). The cumulative presence of risk alleles (unweighted gene score) significantly differed between patients with episodes of high TG and controls at P < 0.0000001. There were 73 % of subjects without any of the risk alleles among the controls and 46 % in the patients. In contrast, the controls just included 3 % of subjects with score 3 and more in comparison with 18 % in HTG patients. We conclude that common APOA5 variants are very important genetic determinants of episodic hypertriglyceridaemia in the Czech population with a high potential to be applied in personalized medicine.

Familial hypercholesterolemia in the Czech Republic: more than 17 years of systematic screening within the MedPed project.

Familial hypercholesterolemia (FH) is the most common autosomal dominant disorder. It is characterized by a decrease in LDL cholesterol catabolism and an early clinical manifestation of atherosclerotic vessel damage. The aim of the MedPed (Make early diagnosis to Prevent early deaths) project is an early diagnosis of FH patients in order to profit from early treatment and prevent cardiovascular events. Till November 30, 2016 The Czech National MedPed Database has registered 7,001 FH patients from 5,223 different families that is 17.4 % of expected patients in the Czech Republic considering 1:250 FH prevalence. The improvement in diagnostic accuracy, patient cooperation and above all familial cascade screening is enabled by FH mutation detection using the modern technology of next-generation sequencing. FH still remain undiagnosed even though the Czech Republic is one of the most successful countries with respect to FH detection. The opportunities of international collaboration and experience sharing within international programs (e.g. EAS FHSC, ScreenPro FH etc.) will improve the detection of FH patients in the future and enable even more accessible and accurate genetic diagnostics.