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Introduction: Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as an important marker of cardiovascular risk and a new target for therapeutic interventions. We aimed to study the influence of metformin on the level of circulating PCSK9 in patients with stable coronary artery disease (SCAD) and type 2 diabetes (T2DM) or metabolic syndrome (MetS), receiving moderate doses of statins used in routine clinical practice. Material and methods: The study included 80 patients with T2DM or MetS receiving rosuvastatin for at least three months prior the study. MetS was diagnosed based on the Global Consensus Definition of the International Diabetes Federation (IDF). Serum level of PCSK9 was measured with an ELISA kit. Results: Patients with T2DM or MetS, who took part in the research, were divided into 2 groups - those who received metformin prior the main study (21 patients - 1st group) and patients who did not (59 patients - 2nd group). Addition of metformin to the 3-month statin therapy of the 2nd group patients, divided into subgroup A (n = 27) with the addition of metformin and subgroup B (n = 29) without one, did not significantly affect the level of lipids. However, the level of circulating PCSK9 in subgroup A patients decreased, compared to subgroup B (p < 0.01). At the same time, ongoing metformin and rosuvastatin therapy in the 1st group patients was not accompanied by a further decrease of the PCSK9 level. Conclusions: The addition of metformin to ongoing rosuvastatin therapy did not significantly affect serum lipid levels, but stabilized the level of circulating PCSK9, compared with the group without metformin treatment. [ABSTRACT FROM AUTHOR]

Abstract Background and aims We aimed to assess the disease burden and to study the molecular genetic characteristics of heterozygous familial hypercholesterolemia (HeFH) patients within the Uzbek population to develop a program of early disease detection and effective treatment measures. Methods 201 patients were included in the study, of whom 57 with chronic stable coronary artery disease (SCAD) and HeFH, and 144 with SCAD without HeFH belonging to the control group, and divided into two subgroups: A, statin free before the study (n = 63) and B (n = 81), who took statin outpatiently. We applied the Dutch Lipid Clinic Network Criteria (DLCN) to diagnose HeFH. Serum level of PCSK-9 was measured with the ELISA Kit. The genetic typing at PCSK9 E670G (rs505151) polymorphism was performed with the PCR-RFLP method. Results Underestimation of early lipid studies and inadequate treatment in HeHF patients within the Uzbek population are accompanied by a 1.8-time increase of more frequent history of myocardial infarction (p < 0.05), a 3-time stroke (p < 0.05) and 2-time percutaneous coronary intervention (p < 0.05). The study of genotypes and alleles of PCSK9 E670G (rs505151) polymorphism allowed to state that сarriage of the «damaging » allele G in SCAD and HeHF patients was 2 times higher (11.4%), than in non HeHF (6.0%) and 3 times (3.0%) than in healthy ones, but the differences were not significant. Herewith, G-carriership is accompanied by a higher incidence of myocardial infarction (p < 0.05) and stroke (p < 0.05), coronary artery bypass grafting in anamnesis (p < 0.001), and number of plaques in carotids (p < 0.05). In group I of SCAD patients with HeFH, 18 (31.6%) cases of diabetes mellitus were observed, which did not exceed their number in group II (48, 33.3%). However, most of them were carriers of the G allele (82.0%, p < 0.001). Despite treatment with rosuvastatin 20–40 mg/day, in HeHF patients after 3 months, the level of total cholesterol (p < 0.001) and LDL-C (p < 0.001) was significantly higher than in the control group. Conclusions Improvement of early diagnosis of FH, including genetic confirmation, and preventional high-intensity statin therapy or a combination of statins with ezetimibe to achieve the target level of LDL-C, is the closest tactical objective for prevention of MACE within the Uzbek population. Highlights • FH patients were on 12 years younger, but they had a 1.8-fold increase in MI, 3-fold - Stroke and 2-fold - PCI, than non FH. PCSK9 level in FH group was higher than in healthy and in non FH patients free of statins (P < 0.05). • The number of G alleles of PCSK9 E670G polymorphism was 2 times higher in FH, than non FH and 3 times, than in healthy. Herewith, G-carriership, accompanied by a higher incidence of MI (P < 0.05), Stroke (P < 0.05), CABG (P < 0.001) and DM (P < 0.001). • Early diagnosis and intensive statin or a combination lipid-lowering therapy of FH is the closest aim of MACE prevention. [ABSTRACT FROM AUTHOR]