IDENTIFICATION OF PATIENTS WITH FAMILIAL HYPERCHOLESTEROLEMIA IN THE RUSSIAN POPULATION USING THE EXAMPLE OF MOSCOW CITY AND MOSCOW REGION

Aim. To estimate the prevalence of familial hypercholesterolemia (FH) in a sample of Moscow city and Moscow region patients with hypercholesterolemia (HCh) based on lipid spectrum and instrumental methods.

Material and methods. The study included two samples of patients (age >18 years), with total cholesterol (TCh) level ≥7.5 mmol/l and/or low-density lipoprotein (LDL) cholesterol level ≥4.9 mmol/l. First sample (n=60) was included to determine secondary hyperlipidemia frequency in newly diagnosed HCh, with measurement of thyroid hormone, glucose and glycated hemoglobin (HbA1c) levels. Patients of the second sample (n=432) from Russian registry of FH (RuFH) were studied by drug therapy assessment, lipid profile measurements, calculation of FH probability according to Dutch and British criteria, carotids duplex scanning (CDS), cardiac perfusion single-photon emission computed tomography (SPECT/CT) using rest/stress protocol.

Results. The incidence of secondary dyslipidemia due to diabetes or hypothyroidism in patients with severe HCh was 18.3%. Monotherapy with atorvastatin (34.2%) or rosuvastatin (31.8%), combined therapy with statins and other lipid-lowering drugs (24.4%) prevails in the structure of lipidlowering therapy in patients with severe HCh. The frequency of "definite" FH according to Dutch criteria in HCh patients was 15.3%, "probable" – 18.1%. Patients with definite FH diagnosis showed higher level of TCh (p<0.001), LDL cholesterol (p<0.001), proprotein convertase subtilisin/kexin type 9 (p<0.001), lower high-density lipoprotein (HDL; p=0.02), and triglycerides (p<0.001). At that HDL cholesterol levels differed only in patients treated with lipid-lowering drugs. Patients with lipid-lowering therapy had significantly higher values of total stenosis percent, the number of plaques, intima-media complex thickness (p<0.001). Patients with lipid-lowering therapy with a definite and probable FH diagnosis had significantly worse values of CDS parameters. CDS parameters correlated with age in both therapeutic groups, and with maximal TCh levels in history in lipid-lowering therapy group (p<0.01). Patients with HCh and established ischemic heart disease showed higher frequency of positive exercise test result, higher values of left ventricle myocardial perfusion heterogeneity and defect severity parameters according to SPECT.

Conclusion. Patients with severe HCh and suspected FH in Moscow city and region demonstrate satisfactory awareness, but low adherence to therapy, which is also extremely rarely sufficient to achieve target LDL levels and reduce coronary risks. This leads to early manifestations of atherosclerosis, including characteristic progressive impairments of myocardial perfusion. Despite the ongoing work on primary prevention, it is advisable to recommend sending such patients to specialized clinics for more qualified consultations and selection of optimal lipid-lowering therapy with mandatory further monitoring of its effectiveness.

1. Benn M., Watts G.F., Tybjaerg-Hansen A., Nordestgaard B.G. Familial Hypercholesterolemia in the Danish General Population: Prevalence, Coronary Artery Disease, and Cholesterol-Lowering Medication. The Journal of Clinical Endocrinology & Metabolism. 2012;97(11):3956-3964. doi: 10.1210/jc.2012-1563.

2. Nordestgaard B.G., Chapman M.J., Humphries S.E., et al. Familial hypercholesterolaemia is under diagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: Consensus Statement of the European Atherosclerosis Society. Eur Heart J. 2013;34(45):3478-3490. doi: 10.1093/eurheartj/eht273.

3. Sergienko V.B., Sayutina E.V., Samoilenko L.E., et al. The role of endothelial dysfunction in the development of myocardial ischemia in patients with ischemic heart disease with unchanged and initially impaired coronary arteries. Kardiologiia. 1999;39(1):25-30. (In Russ.) [Сергиенко В.Б., Саютина Е.В., Самойленко Л.Е., и др. Роль дисфункции эндотелия в развитии ишемии миокарда у больных ишемической болезнью сердца с неизмененными и малоизмененными коронарными артериями. Кардиология. 1999;39(1):25-30].

4. Matsunari I., Taki J., Nakajima K., et al. Myocardial viability assessment using nuclear imaging. Ann Nucl Med. 2003;17(3):169-79.

5. Primary P., Genest J., Hegele R.A., et al. Canadian Cardiovascular Society position statement on familial hypercholesterolemia. Can J Cardiol. 2014;30(12):1471-81. doi: 10.1016/j.cjca.2014.09.028.

6. Watts G.F., Gidding S., Wierzbicki A.S., et al. Integrated guidance on the care of familial hypercholesterolaemia from the International FH Foundation. Int J Cardiol. 2014;171(3):309-25. doi: 10.1016/j.ijcard.2013.11.025.

7. Diagnosis and correction of lipid metabolism disorders in order to prevent and treat atherosclerosis. Russian guidelilnes. VI revision. Ateroskleroz i Dislipidemii. 2017;3:4-52. (In Russ.) [Диагностика и коррекция нарушений липидного обмена с целью профилактики и лечения атеросклероза. Российские рекомендации. VI пересмотр. Атеросклероз и Дислипидемии. 2017;3:4-52].

8. Oosterveer D.M., Versmissen J., Schinkel A.F.L., etal. Clinical and genetic factors influencing cardiovascular risk in patients with familial hypercholesterolemia. Clinical Lipidology. 2010;5(2):189-97. doi: 10.2217/clp.10.9.

9. Catapano A.L., Graham I., De Backer G., et al. 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias. Eur Heart J. 2016;37(39):2999-3058. doi: 10.1093/eurheartj/ehw272.

10. Corrao G., Scotti L., Zambon A., et al. Cost-effectiveness of enhancing adherence to therapy with statins in the setting of primary cardiovascular prevention. Evidence from an empirical approach based on administrative databases. Atherosclerosis. 2011;217(2):479-85. doi: 10.1016/j.atherosclerosis. 2011.04.014.

11. Dragomir A., Cote R., Roy L., et al. Impact of adherence to antihypertensive agents on clinical outcomes and hospitalization costs. Med Care. 2010;48(5):418-25. doi: 10.1097/MLR.0b013e3181d567bd.

12. McConnachie A., Walker A., Robertson M., et al. Long-term impact on healthcare resource utilization of statin treatment, and its cost effectiveness in the primary prevention of cardiovascular disease: a record linkage study. Eur Heart J. 2014;35(5):290-8. doi: 10.1093/eurheartj/eht232.

13. Nordestgaard B.G., Chapman M.J., Humphries S.E., et al. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society. Eur Heart J. 2013;34(45):3478-90a. doi: 10.1093/eurheartj/eht273.

14. de Ferranti S.D., Rodday A.M., Mendelson M.M., et al. Prevalence of Familial Hypercholesterolemia in the 1999 to 2012 United States National Health and Nutrition Examination Surveys (NHANES). Circulation. 2016;133(11):1067-72. doi: 10.1161/CIRCULATIONAHA.115.018791.

15. Mann D.M., Woodward M., Muntner P., et al. Predictors of nonadherence to statins: a systematic review and meta-analysis. Ann Pharmacother. 2010;44(9):1410-21. doi: 10.1345/aph.1P150.

16. Latry P., Molimard M., Dedieu B., et al. Adherence with statins in a real-life setting is better when associated cardiovascular risk factors increase: a cohort study. BMC Cardiovasc Disord. 2011;11:46. doi: 10.1186/1471-2261-11-46.

17. Rubak S., Sandbaek A., Lauritzen T., Christensen B. Motivational interviewing: a systematic review and meta-analysis. Br J Gen Pract. 2005;55(513):305-12.

18. Weintraub W.S., Daniels S.R., Burke L.E., et al. Value of primordial and primary prevention for cardiovascular disease: a policy statement from the American Heart Association. Circulation. 2011;124(8):967-90. doi: 10.1161/CIR.0b013e3182285a81.