The LDLR, APOB, and PCSK9 Variants of Index Patients with Familial Hypercholesterolemia in Russia.

Familial hypercholesterolemia (FH) is a common autosomal codominant disorder, characterized by elevated low-density lipoprotein cholesterol levels causing premature atherosclerotic cardiovascular disease. About 2900 variants of LDLR, APOB, and PCSK9 genes potentially associated with FH have been described earlier. Nevertheless, the genetics of FH in a Russian population is poorly understood. The aim of this study is to present data on the spectrum of LDLR, APOB, and PCSK9 gene variants in a cohort of 595 index Russian patients with FH, as well as an additional systematic analysis of the literature for the period of 1995-2020 on LDLR, APOB and PCSK9 gene variants described in Russian patients with FH. We used targeted and whole genome sequencing to search for variants. Accordingly, when combining our novel data and the data of a systematic literature review, we described 224 variants: 187 variants in LDLR, 14 variants in APOB, and 23 variants in PCSK9. A significant proportion of variants, 81 of 224 (36.1%), were not described earlier in FH patients in other populations and may be specific for Russia. Thus, this study significantly supplements knowledge about the spectrum of variants causing FH in Russia and may contribute to a wider implementation of genetic diagnostics in FH patients in Russia.

Subclinical arterial wall damage in patients at low to moderate cardiovascular risk.

AIM: The aim of this paper is to study the degree of subclinical arterial wall damage in subjects at low and moderate risk of cardiovascular death by the SCORE scale using instrumental research methods. METHODS: We enrolled 600 patients (mean age 49.0 +/- 7.1 years, 74% women) with a calculated SCORE 5%, who passed a carotid duplex ultrasonography with a measurement of the intima-media thickness (IMT) and carotid plaque (CP) severity. In the study a computer sphygmography was also performed on the subjects to determine ankle-brachial pulse wave velocity (abPWV) and an ankle-brachial index (ABI). RESULTS: We found 389 (64%) patients with subclinical signs of atherosclerosis. CPs were found in 359 patients (60%), thickened IMT in 28 patients (5%), increased abPWV in 227 patients (38%), and ABI of <0.9 in 29 patients (5%). In the patients with a thickened IMT only two had no CPs. In contrast, 92% of the patients with CPs had normal IMT. Increased abPWV was determined in 87% participants with CPs, and only in 30 subjects no CPs were found. All 29 patients with an ABI of less than 0.9 had CPs. The "presence of CP"was the most sensitive parameter in the patients included in the study, in terms of atherosclerosis determination (92%). The identification of individuals with CPs significantly increased in men over 45 years of age (in 68.4% of cases, P = 0.009), and in women over 50 (in 61.8% of cases, P = 0.001). CONCLUSION: Our data reinforces the importance of non-invasive imaging of atherosclerosis in subjects at low and moderate cardiovascular risk. The study demonstrated a high prevalence of subclinical atherosclerosis signs in patients at low to moderate risk by the SCORE scale and a high detection frequency of carotid plaques. This suggests that wider implementation of carotid ultrasound in primary care algorithms may improve risk stratification with timely initiation of preventive strategies.