Clinical, laboratory, and molecular genetic peculiarities of lipid metabolism in high- and very high-risk patients among residents of Saint Petersburg and the Northwestern region of the Russian Federation
Abstract. The highest risk of cardiovascular diseases development is associated with certain types of hereditary hyperlipidemias, the most common of which are familial heterozygous hypercholesterolemia (FH) and high lipoprotein a (Lp(a)) level.K.V. Legostaeva, A.K. Musonova, D.V. Sidorenko, V.D. Nazarov, E.A. Surkova, T.V. Blinova, A.V. Mazing, S.V. Lapin, A.N. Kulikov
The aim: to assess the incidence of FH and hyperlipoproteinemia(a) in high- and very-high-risk patients in the Northwestern region of Russia, as well as to determine the clinical manifestations of atherosclerosis depending on the genetic variant of these hereditary dyslipidemias.
Material and methods. The study included 51 patient aged 18 to 60 years at high and very high risk, with a score of ≥ 3 points according to the Dutch criteria for FH. All subjects underwent a thorough medical history, determination of the concentration of Lp(a), apolipoprotein B-100 (apoB), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very-low-density lipoprotein (VLDL) cholesterol, triglycerides (TG), and total cholesterol levels, as well as serum lipid electrophoresis. To verify FH, the presence of pathogenic variants in LDLR, APOB, and PCSK9 genes was analyzed.
Results. FH-associated variants were detected in 19.6% (n = 10) of patients, but only 7 (13.7%) of these could be classified as pathogenic. Thus, pathogenic variants were detected in every 7th to 8th patient, which is approximately 24 times more frequent than the expected incidence of FH in Russian population. Pathogenic variants of LDLR gene were predominant (5 patients), and pathogenic variants of APOB gene were detected in additional 2 patients. Elevated Lp(a) levels (> 50 mg/dL) were present in 27.4% of the study participants, which is also significantly higher than in the general population. A comparison of clinical data revealed no significant phenotypic differences between patients with FH or high Lp(a) levels and patients without signs of hereditary dyslipidemias. The sensitivity of the Dutch criteria for FH based on genetic verification was 42.9% with 100% specificity. A more sensitive marker was a serum apoB level ≥ 1.68 g/L (sensitivity 100%, specificity 72%).
Conclusion. The incidence of FH in high- and very high-risk patients in the population of Saint Petersburg and the Northwestern area of the Russian Federation was 1 case per 7–8 patients. The Dutch criteria for FH demonstrated low sensitivity in the context of widespread use of lipid-lowering agents, inferior to that for serum apoB concentration. No significant phenotypic differences were identified between patients with FH and other examined individuals.
Keywords
familial heterozygous hypercholesterolemia
LDLR
APOB
and PCSK9 genes
lipoprotein (a)
phenotypic peculiatrities
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About the Authors
Kristina V. Legostaeva, MD, assistant at the Department of propaedeutics of internal medicine with clinic named after academician M.D. Tushinsky, Academician I.P. Pavlov First Saint Petersburg State Medical University, Saint Petersburg, Russian Federation.E-mail: marmazetka71@yandex.ru
ORCID: https://orcid.org/0000-0002-7006-0215
Anastasia K. Musonova, MD, clinical laboratory diagnostics physician of the Department of autoimmune disease diagnostics of the Scientific and Methodological Center for Molecular Medicine, Academician I.P. Pavlov First Saint Petersburg State Medical University, Saint Petersburg, Russian Federation.
E-mail: amusonova@mail.ru
ORCID: https://orcid.org/0000-0003-0986-5150
Darya V. Sidorenko, MD, laboratory geneticist of the Department of autoimmune disease diagnostics of the Scientific and Methodological Center for Molecular Medicine, Academician I.P. Pavlov First Saint Petersburg State Medical University, Saint Petersburg, Russian Federation.
E-mail: si-do-renko@mail.ru
ORCID: https://orcid.org/0000-0001-8503-0759
Vladimir D. Nazarov, MD, PhD (Medicine), junior researcher at the Department of autoimmune disease diagnostics of the Scientific and Methodological Center for Molecular Medicine, Academician I.P. Pavlov First Saint Petersburg State Medical University, Saint Petersburg, Russian Federation.
E-mail: nazarov19932@mail.ru
ORCID: https://orcid.org/0000-0002-9354-8790
Elena A. Surkova, PhD (Biology), senior researcher at the Department of autoimmune disease diagnostics of the Scientific and Methodological Center for Molecular Medicine of the Ministry of Healthcare of Russia, Academician I.P. Pavlov First Saint Petersburg State Medical University of the Ministry of Healthcare of Russia. Address: 197022, 6–8/28 Lva Tolstogo St.
E-mail: easurkova@mail.ru
ORCID: https://orcid.org/0000-0001-5191-0221
Tatiana V. Blinova, PhD (Biology), senior researcher at the Department of autoimmune disease diagnostics of the Scientific and Methodological Center for Molecular Medicine, Academician I.P. Pavlov First Saint Petersburg State Medical University, Saint Petersburg, Russian Federation.
E-mail: tvblinova@list.ru
ORCID: https://orcid.org/0000-0003-4896-3319
Alexandra V. Mazing, MD, PhD (Medicine), leading researcher at the Department of autoimmune disease diagnostics of the Scientific and Methodological Center for Molecular Medicine, Academician I.P. Pavlov First Saint Petersburg State Medical University, Saint Petersburg, Russian Federation.
E-mail: alex_mazing@mail.ru
ORCID: https://orcid.org/0000-0002-3055-6507
Sergey V. Lapin, MD, PhD (Medicine), head of the Department of autoimmune disease diagnostics of the Scientific and Methodological Center for Molecular Medicine, Academician I.P. Pavlov First Saint Petersburg State Medical University, Saint Petersburg, Russian Federation.
E-mail: svlapin@mail.ru
ORCID: https://orcid.org/0000-0002-4998-3699
Alexander N. Kulikov, MD, Dr. Sci. (Medicine), professor, head of the Department of propaedeutics of internal medicine with clinic named after academician M.D. Tushinsky, Academician I.P. Pavlov First Saint Petersburg State Medical University, Saint Petersburg, Russian Federation.
E-mail: ankulikov2005@yandex.ru
ORCID: https://orcid.org/0000-0002-4544-2967
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