Genetic risk score in patients with the APOE2/E2 genotype as a predictor of familial dysbetalipoproteinemia.

BACKGROUND: Familial dysbetalipoproteinemia (FD) is an autosomal recessive (rarely dominant) inherited disorder that is almost exclusively associated with the apolipoprotein E gene (APOE) variability. Nonetheless, only a small proportion of APOE2/E2 subjects develop the phenotype for mixed dyslipidemia; the context of other trigger metabolic or genetic factors remains unknown. METHODS: One hundred and one patients with FD and eighty controls (all APOE2/E2 homozygotes; rs429358) were screened for 18 single-nucleotide polymorphisms (SNPs) within the genes involved in triglyceride metabolism. RESULTS: Two SNPs were significantly associated with the FD phenotype (rs439401 within APOE; P < 0.0005 and rs964184 within ZPR1/APOA5/A4/C3/A1 gene cluster; P < 0.0001). Unweighted genetic risk scores - from these two SNPs (GRS2), and, also, additional 13 SNPs with P-value below 0.9 (GRS15) - were created as an additional tool to improve the risk estimation of FD development in subjects with the APOE2/E2 genotype. Both GRS2 and GRS15 were significantly (P < 0.0001) increased in patients and both GRSs discriminated almost identically between the groups (P = 0.86). Subjects with an unweighted GRS2 of three or more had an almost four-fold higher risk of FD development than other individuals (OR 3.58, CI: 1.78-7.18, P < 0.0005). CONCLUSIONS: We identified several SNPs that are individual additive factors influencing FD development. The use of unweighted GRS2 is a simple and clinically relevant tool that further improves the prediction of FD in APOE2/E2 homozygotes with corresponding biochemical characteristics.

Don't we forget about biological therapy of hypercholesterolemia with PCSK9-inhibitors?

In many patients it is difficult to achieve the current very low target LDL-cholesterol levels, recommended for the prevention of atherosclerotic cardiovascular events. If statin therapy or statins in combination with ezetimibe are not sufficient, addition of PCSK9 inhibitors should be considered. PCSK9 inhibitors reduce LDL-CH by an average of 50-60 % and reduce the risk of atherosclerotic cardiovascular events. They are currently reserved for patients with atherosclerotic cardiovascular disease and for patients with familial hypercholesterolaemia, in whom despite intensive hypolipidemic therapy statins with ezetimibe the target LDL-cholesterol value is not reached. In these patients, PCSK9 inhibitors may also be indicated in case of statin intolerance.

A case of homozygous familial hypercholesterolemia with an atypical phenotype and delayed clinical symptoms.

We describe the casuistry of a homozygous familial hypercholesterolemia female patient with a biallelic missense variant (NM_000527.4:c.1775G>A, p.Gly592Glu) in the LDLR gene, severe hypertriglyceridemia and late manifestation of coronary heart disease not earlier than at the age of 45 years. An atypical phenotype led to a delayed diagnosis.

Some causes of poor adherence to long-term statin therapy and their solution.

Statins are among the most important drugs in preventive cardiology because they greatly improve the prognosis of risk patients in both primary and secondary prevention of atherosclerotic cardiovascular disease. Adherence to long-term statin therapy is poor and decreases with the duration of statin use. A number of fake news about adverse effects of statins disseminated on the internet, such as damage of the brain, liver or kidney, contribute to worsening adherence. Statins therapy is sometimes unnecessary discontinued before planned surgery. The worse adherence to statin therapy may be also due to the fact that the patient does not know the connection between cholesterol lowering and improving his cardiovascular prognosis. Key words: adherence - brain - cholesterol - liver function - renal function - statins - surgery.

Real-life LDL-C treatment goals achievement in patients with heterozygous familial hypercholesterolemia in the Czech Republic and Slovakia: Results of the PLANET registry.

BACKGROUND AND AIMS: Despite the high prevalence of familial hypercholesterolemia (FH) and available effective lipid-lowering therapy, most of the individuals with this disorder remain undiagnosed and undertreated. The aim of the PLANET registry was to assess the real-life attainment of low-density lipoprotein cholesterol (LDL-C) therapeutic target level in patients with heterozygous FH, to characterize prescribed lipid-lowering therapy with assessment of its efficiency according to the attainment of the target LDL-C level, and to characterize cardiovascular events observed in this patient population again in relation to LDL-C target level attainment. METHODS: PLANET registry was designed as a non-interventional, retrospective, cross-sectional, multicentre disease registry for adult patients with heterozygous FH in the Czech Republic and Slovakia. RESULTS: Overall, 1755 patients were enrolled at 32 sites specialized in FH treatment. 15.4% of patients attained the target LDL-C value. The proportion of patients with LDL-C goal achievement increased to 17.3% in the subgroup of patients receiving high-intensity statin therapy (54.6% of study population). Out of 55 patients receiving inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9), 61.8% reached the LDL-C treatment goal. Of all cardiovascular events reported, 14.0% occurred in patients attaining the LDL-C goal, while it was 86.0% in the not-at-target group. It was documented (p=0.004) that the longer is the patient in care at the specialized FH centre, the higher is the probability that he/she will attain the target LDL-C level. CONCLUSIONS: Although target LDL-C level attainment remains relatively low, the likelihood of LDL-C goal attainment increases with duration of specialized care.

[Is it possible to improve long-term compliance of patients to statin therapy?] / Lze zlepsit komplianci pacientu k dlouhodobé terapii statiny?

Statins are key drugs for patients in secondary prevention of cardiovascular disease, as well as for primary prevention patients at high or very high risk of fatal cardiovascular events. However, long-term compliance of patients to statin therapy is relatively low, decreasing with the time of statin use; moreover a significant proportion of patients stop statins medication over the course of several years. To the early termination of statin treatment often contributes apprehension of the occurence of statin´s side effects (i.g. increased creatine kinase in the blood and muscle problems), although these symptoms are usually not causally related to statin therapy. To the low compliance may also contribute administration of statins in the evening hours, as well as the fear of developing diabetes or drug interactions. The above issues are discussed in the text of this article.Key words: compliance - creatinkinase - diabetes mellitus -LDL-cholesterol - statins.