Burden of familial heterozygous hypercholesterolemia in Uzbekistan: Time is muscle

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.

Keywords: Heterozygous hypercholesterolemia; PCSK-9.