Triglyceride levels and remnant cholesterol triglyceride-rich lipoproteins in metabolic syndrome and diabetes

In recent years, new epidemiological and genetic data have been obtained on the role of triglycerides (TG) and remnant cholesterol (RC) triglyceride-rich lipoproteins in increasing the residual risk of atherosclerosis-associated cardiovascular diseases (ACCD) in metabolic disorders. The aim of the study was to study the associations of different levels of triglycerides and RC triglyceriderich lipoproteins with metabolic syndrome (MS) and type 2 diabetes mellitus (TDM2) in the Siberian population.

Material and methods. The research was carried out on the materials of the international epidemiological project HAPIEE (n = 9360 people) in people aged 45–69 years. In accordance with the protocol, a questionnaire, anthropometry, and biochemical research were conducted. Abdominal obesity (AO) was found with a waist circumference of ≥ 94 cm in men and ≥ 80 cm in women. MS was diagnosed according to the criteria of the IDF (2005), TDM2 – at fasting glucose levels ≥ 7.0 mmol/l (WHO, 1999, ADA, 2013), hypertriglyceridemia (hyperTG) – according to the definitions of NCEP ATP III, 2002 and the Russian Clinical Guidelines on lipid metabolism disorders, 2023. RC levels are calculated using the formula: total cholesterol (TC) – HDL cholesterol – LDL cholesterol mmol/L. The triglyceride-glucose index (TyG) was determined by the formula: TyG = ln [Fasting triglycerides (mg/dl) x Fasting glucose (mg/dl)/2].

Results. Median values and prevalence of various levels of TG have been determined (<1.7; ≥ 1.7 < 2.3; ≥ 2.3 < 5.6; ≥ 5.6 mmol/l). An increase in the prevalence of MS and TDM2 has been shown depending on the levels of hyperTG. High values of RC in AO, MS, and TDM2 were revealed in men and women: 0.68; 0.76; 0.90 and 0.68; 0.79 and 0.93, respectively. In 60 % of men and 80 % of women, RC was ≥ 0.5 mmol/l. An increase in RC was shown from values of 0.51–0.54 mmol/l at TG < 1.7 mmol/l to higher values of 1.26–1.29 at TG ≥ 2.3 < 5.6 mmol/l. The frequency of AO, MS, TDM2 in quintiles (Q) of RC increases linearly from Q1 to Q5. It is shown that from Q1 to Q5 TyG, the levels of RC increase in each subsequent quintile: from 0.36–0.38 in Q1 to 1.1–1.12 mmol/l in Q5.

Conclusions. The medians and prevalence of various levels of TG and RC in MS and TDM2 and without metabolic disorders were determined. RC values increase from mild to moderate and high hypertriglyceridemia.

1. Ezhov M.V., Kukharchuk V.V., Sergienko I.V., Alieva A.S., Antsiferov M.B., Ansheles A.A., Arabidze G.G., Aronov D.M., Arutyunov G.P., Akhmedzhanov N.M., Balakhonova T.V., Barbarash O.L., Boytsov S.A., Bubnova M.G., Voevoda M.I., Galstyan G.R., Galyavich A.S., Gornyakova N.B., Gurevich V.S., Dedov I.I., Drapkina O.M., Duplyakov D.V., Eregin S.Ya., Ershova A.I., Irtyuga O.B., Karpov R.S., Karpov Yu.A., Kachkovsky M.A., Kobalava Zh.D., Koziolova N.A., Konovalov G.A., Konstantinov V.O., Kosmacheva E.D., Kotovskaya Yu.V., Martynov A.I., Meshkov A.N., Nebieridze D.V., Nedogoda S.V., Obrezan A.G., Oleinikov V.E., Pokrovsky S.N., Ragino Yu.I., Rotar O.P., Skibitsky V.V., Smolenskaya O.G., Sokolov A.A., Sumarokov A.B., Filippov A.E., Halimov Yu.Sh., Chazova I.E., Shaposhnik I.I., Shestakova M.V., Yakushin S.S., Shlyakhto E.V. Disorders of lipid metabolism. Clinical Guidelines 2023. Russian Journal of Cardiology, 2023; 28 (5): 5471. (In Russ.)]. doi: 10.15829/1560-40712023-5471

2. Vallejo-Vaz A.J., Fayyad R., Boekholdt S.M., Hovingh G.K., Kastelein J.J., Melamed S., Barter P., Waters D.D., Ray K.K. Triglyceride-rich lipoprotein cholesterol and risk of cardiovascular events among patients receiving statin therapy in the TNT trial. Circulation, 2018; 138 (8): 770–781. doi: 10.1161/CIRCULATIONAHA.117.032318

3. Carey V.J., Bishop L., Laranjo N., Harshfield B.J., Kwiat C., Sacks F.M. Contribution of high plasma triglycerides and low high-density lipoprotein cholesterol to residual risk of coronary heart disease after establishment of low-density lipoprotein cholesterol control. Am. J. Cardiol., 2010; 106 (6): 757–763. doi: 10.1016/j.amjcard.2010.05.002

4. Filtz A., Parihar S., Greenberg G.S., Park C.M., Scotti A., Lorenzatti D., Badimon J.J., Soffer D.E., Toth P.P., Lavie C.J., Bittner V., Virani S.S., Slipczuk L. New approaches to triglyceride reduction: Is there any hope left? Am. J. Prev. Cardiol., 2024; 18: 100648. doi: 10.1016/j.ajpc.2024.100648

5. Borén J., Taskinen M.R., Björnson E., Packard C.J. Metabolism of triglyceride-rich lipoproteins in health and dyslipidaemia. Nat. Rev. Cardiol., 2022; 19 (9): 577–592. doi: 10.1038/s41569-022-00676-y.

6. Nordestgaard B.G. Triglyceride-rich lipoproteins and atherosclerotic cardiovascular disease: new insights from epidemiology, genetics, and biology. Circ. Res., 2016; 118 (4): 547–563. doi: 10.1161/CIRCRESAHA.115.306249

7. Navarese E.P., Vine D., Proctor S., Grzelakowska K., Berti S., Kubica J., Raggi P. Independent causal effect of remnant cholesterol on atherosclerotic cardiovascular outcomes: a mendelian randomization study. Arterioscler. Thromb. Vasc. Biol., 2023; 43 (9): e373– e380. doi: 10.1161/ATVBAHA.123.319297

8. Zhao Y., Zhuang Z., Li Y., Xiao W., Song Z., Huang N., Wang W., Dong X., Jia J., Clarke R., Huang T. Elevated blood remnant cholesterol and triglycerides are causally related to the risks of cardiometabolic multimorbidity. Nat. Commun., 2024; 15 (1): 2451. doi: 10.1038/s41467-024-46686-x

9. Vaduganathan M., Mensah G.A., Turco J.V., Fuster V., Roth G.A. The Global burden of cardiovascular diseases and risk: a compass for future health. J. Am. Coll. Cardiol., 2022 80 (25): 2361–2371. doi: 10.1016/j.jacc.2022.11.005

10. Magnussen C., Ojeda F.M., Leong D.P., AlegreDiaz J., Amouyel P., Aviles-Santa L., de Bacquer D., Ballantyne C.M., Bernabé-Ortiz A., Bobak M., Brenner H., Carrillo-Larco R.M., de Lemos J., Dobson A., Dörr M., Donfrancesco C., Drygas W., Dullaart R.P., Engström G., Ferrario M.M., Ferrières J., de Gaetano G., Goldbourt U., Gonzalez C., Grassi G., Hodge A.M., Hveem K., Iacoviello L., Ikram M.K., Irazola V., … Global Cardiovascular Risk Consortium. Global effect of modifiable risk factors on cardiovascular disease and mortality. N. Engl. J. Med., 2023; 389 (14): 1273–1285. doi: 10.1056/NEJMoa2206916

11. WHO Regional Office for Europe. WHO European regional obesity report 2022. 226 p. Available at: https://www.who.int/europe/publications/i/item/9789289057738

12. Balanova Yu.A., Shalnova S.A., Deev A.D., Imaeva A.E., Kontsevaya A.V., Muromtseva G.A., Kapustina А.V., Evstifeeva S.E., Drapkina О.M. Obesity in russian population — prevalence and association with the non-communicable diseases risk factors. Russian Journal of Cardiology, 2018; (6): 123–130. (In Russ.)]. doi: 10.15829/1560-4071-2018-6-123-130

13. Simonova G.I., Mustafina S.V., Shcherbakova L.V. Prevalence of abdominal obesity in the Siberian population. Siberian Scientific Medical Journal, 2015; 35 (1): 60–64. (In Russ.)].

14. Voevoda M.I., Kovalkova N.A., Ragino Yu.I., Travnikova N.Yu., Denisova D.V. Prevalence of metabolic syndrome in 25–45-yearold Novosibirsk dwellers. Therapeutic Archive, 2016; 88 (10): 51–56. (In Russ.)]. doi: 10.17116/terarkh2016881051-56

15. Balanova Yu.A., Drapkina O.M., Kutsenko V.A., Imaeva A.E., Kontsevaya A.V., Maksimov S.A., Muromtseva G.A., Kotova M.B., Karamnova N.S., Evstifeeva S.E., Kapustina A.V., Litinskaya O.A., Pokrovskaya M.S., Kuzyakina S.O., Ivlev O.E., Gomanova L.I., Doludin Yu.V., Efimova I.A., Borisova A.L., Nazarov B.M., Yarovaya E.B., Repkina T.V., Gonoshilova T.O., Kudryavtsev A.V., Belova N.I., Shagrov L.L., Samotrueva M.A., Yasenyavskaya A.L., Chernysheva E.N., Glukhovskaya S.V., Levina I.F., Shirshova T.F., Dorzhieva E.B., Urbanova E.Z., Borovkova N.Yu., Kurashin V.K., Tokareva A.S., Ragino Yu.I., Simonova G.I., Khudyakova A.D., Nikulin V.N., Aslyamov O.R., Khokhlova G.V., Solovyova A.V., Rodionov A.A., Kryachkova O.V., Shamurova Yu.Yu., Tantsyreva I.V., Baryshnikova I.N., Ataev M.G., Radjabov M.O., Isakhanova M.M., Umetov M.A., Elgarova L.V., Khakuasheva E.A., Yamashkina E.I., Esina M.V., Kunyaeva T.A., Nikitina A.M., Savvina N.V., Spiridonova Yu.E., Naumova E.A., Keskinov A.A., Yudin V.S., Yudin S.M., Shalnova S.A. Obesity in the Russian population during the COVID-19 pandemic and associated factors. Data from the ESSE-RF3 study. Cardiovascular Therapy and Prevention, 2023; 22 (8S): 3793. (In Russ.)]. doi: 10.15829/1728-8800-2023-3793

16. Drapkina O.M., Imaeva A.E., Kutsenko V.A., Kapustina A.V., Balanova Yu.A., Maksimov S.A., Muromtseva G.A., Kotova M.B., Karamnova N.S., Evstifeeva S.E., Litinskaya O.A., Pokrovskaya M.S., Imaeva N.A., Filichkina E.M., Ivlev O.E., Svinin G.E., Gomanova L.I., Doludin Yu.V., Efimova I.A., Borisova A.L., Nazarov B.M., Yarovaya E.B., Repkina T.V., Gonoshilova T.O., Kudryavtsev A.V., Belova N.I., Shagrov L.L., Samotrueva M.A., Yasenyavskaya A.L., Chernysheva E.N., Glukhovskaya S.V., Levina I.A., Shirshova E.A., Dorzhieva E.B., Urbanova E.Z., Borovkova N.Yu., Kurashin V.K., Tokareva A.S., Ragino Yu.I., Simonova G.I., Shramko V.S., Nikulin V.N., Aslyamov O.R., Khokhlova G.V., Solovyova A.V., Rodionov A.A., Kryachkova O.V., Shamurova Yu.Yu., Tantsyreva I.V., Baryshnikova I.N., Ataev M.G., Radjabov M.O., Isakhanova M.M., Umetov M.A., Elgarova L.V., Khakuasheva I.A., Yamashkina E.I., Esina M.V., Kunyaeva T.A., Nikitina A.M., Savvina N.V., Spiridonova Yu.E., Naumova E.A., Keskinov A.A., Yudin V.S., Yudin S.M., Kontsevaya A.V., Shalnova S.A. Dyslipidemia in the Russian Federation: population data, associations with risk factors. Cardiovascular Therapy and Prevention, 2023; 22 (8S): 3791. (In Russ.)]. doi: 10.15829/1728-8800-2023-3791

17. Ginsberg H.N., Packard C.J., Chapman M.J., Borén J., Aguilar-Salinas C.A., Averna M., Ference B.A., Gaudet D., Hegele R.A., Kersten S., Lewis G.F., Lichtenstein A.H., Moulin P., Nordestgaard B.G., Remaley A.T., Staels B., Stroes E.S.G., Taskinen M.R., TokgÖzoğlu L.S., Tybjaerg-Hansen A., Stock J.K., Catapano A.L. Triglyceride-rich lipoproteins and their remnants: metabolic insights, role in atherosclerotic cardiovascular disease, and emerging therapeutic strategies-a consensus statement from the European Atherosclerosis Society. Eur. Heart J., 2021; 42 (47): 4791–4806. doi: 10.1093/eurheartj/ehab551

18. Nordestgaard L.T., Christoffersen M., Afzal S., Nordestgaard B.G., Tybjærg-Hansen A., Frikke-Schmidt R. Triglycerides as a shared risk factor between dementia and atherosclerotic cardiovascular disease: a study of 125 727 individuals. Clin. Chem., 2021; 67 (1): 245– 255. doi: 10.1093/clinchem/hvaa269

19. Zhang B.H., Yin F., Qiao Y.N., Guo S.D. Triglyceride and triglyceride-rich lipoproteins in atherosclerosis. Front. Mol. Biosci., 2022; 9: 909151. doi: 10.3389/fmolb.2022.909151

20. Farnier M., Zeller M., Masson D., Cottin Y. Triglycerides and risk of atherosclerotic cardiovascular disease: An update. Arch Cardiovasc Dis., 2021; 114 (2): 132–139. doi: 10.1016/j.acvd.2020.11.006

21. Jørgensen A.B., Frikke-Schmidt R., West A.S., Grande P., Nordestgaard B.G., Tybjærg-Hansen A. Genetically elevated non-fasting triglycerides and calculated remnant cholesterol as causal risk factors for myocardial infarction. Eur. Heart J., 2013; 34 (24): 1826–1833. doi: 10.1093/eurheartj/ehs431

22. Thomsen M., Varbo A., Tybjærg-Hansen A., Nordestgaard B.G. Low nonfasting triglycerides and reduced all-cause mortality: a mendelian randomization study. Clin. Chem., 2014; 60 (5): 737–746. doi: 10.1373/clinchem.2013.219881

23. Matsunaga A., Nagashima M., Yamagishi H., Saku K. variants of lipid-related genes in adult Japanese patients with severe hypertriglyceridemia. J. Atheroscler. Thromb., 2020; 27 (12): 1264–1277. doi: 10.5551/jat.51540

24. Generoso G., Janovsky C.C.P.S., Bittencourt M.S. Triglycerides and triglyceride-rich lipoproteins in the development and progression of atherosclerosis. Curr. Opin Endocrinol. Diabetes Obes., 2019; 26 (2): 109–116. doi: 10.1097/MED.0000000000000468

25. Laufs U., Parhofer K.G., Ginsberg H.N., Hegele R.A. Clinical review on triglycerides. Eur. Heart J., 2020; 41 (1): 99–109. doi: 10.1093/eurheartj/ehz785

26. Peasey A., Bobak M., Kubinova R., Malyutina S., Pajak A., Tamosiunas A., Pikhart H., Nicholson A., Marmot M. Determinants of cardiovascular disease and other non-communicable diseases in Central and Eastern Europe: rationale and design of the HAPIEE study. BMC Public Health, 2006; 6: 255. doi: 10.1186/1471-2458-6-255

27. Metelskaya V.A., Shalnova S.A., Deev A.D., Perova N.V., Gomyranova N.V., Litinskaya O.A., Evstifeeva S.E., Artamonova G.V., Gatagonova T.M., Grinshtein Yu.I., Dupliakov D.V., Efanov A.Iu., Zhernakova Yu.V., Il’in V.A., Libis R.A., Minakov A.V., Nevzorova V.A., Nedogoda S.V., Romanchuk S.A., Rotar O.P., Trubacheva I.A., Shliakhto E.V., Boytsov S.A. Analysis of atherogenic dyslipidemias prevalence among population of Russian Federation (results of the ESSERF Study). Russian Journal of Preventive Medicine, 2016; 19 (1): 15–23. (In Russ.)]. doi: 10.17116/profmed201619115-23

28. Yezhov M.V., Sergienko I.V., Aronov D.M., Arabidze G.G., Akhmedzhanov N.M., Bazhan S.S., Balakhonova T.V., Barbarash O.L., Boitsov S.A., Bubnova M.G., Voevoda M.I., Galyavich A.S., Gornyakova N.B., Gurevich V.S., Drapkina O.M., Duplyakov D.V., Eregin S.Ya., Zubareva M.Yu., Karpov R.S., Karpov Yu.A., Koziolova N.A., Konovalov G.A., Konstantinov V.O., Kosmacheva E.D., Martynov A.I., Nebieridze D.V., Pokrovsky S.N., Ragino Yu.I., Skibitsky V.V., Smolenskaya O.G., Chazova I.E., Shalnova S.A., Shaposhnik I.I., Kukharchuk V.V. Diagnosis and correction of lipid metabolism disorders for the prevention and treatment of atherosclerosis. Russian recommendations, VI revision. Atherosclerosis and Dyslipidemia, 2017; 3 (28): 5–22. (In Russ.)].

29. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation, 2002; 106 (25): 3143–3421.

30. Liu X., Tan Z., Huang Y., Zhao H., Liu M., Yu P., Ma J., Zhao Y., Zhu W., Wang J. Relationship between the triglyceride-glucose index and risk of cardiovascular diseases and mortality in the general population: a systematic review and meta-analysis. Cardiovasc. Diabetol., 2022; 21 (1): 124. doi: 10.1186/s12933-022-01546-0

31. Varbo A., Nordestgaard B.G. Remnant lipoproteins. Curr. Opin Lipidol., 2017; 28 (4): 300–307. doi: 10.1097/MOL.0000000000000429

32. Salinas C.A., Chapman M.J. Remnant lipoproteins: are they equal to or more atherogenic than LDL? Curr. Opin Lipidol., 2020; 31 (3): 132–139. doi: 10.1097/MOL.0000000000000682

33. Packard C.J. Remnants, LDL, and the quantification of lipoprotein-associated risk in atherosclerotic cardiovascular disease. Curr. Atheroscler. Rep., 2022; 24 (3): 133–142. doi: 10.1007/s11883-022-00994-z

34. Lopez-Jaramillo P., Gomez-Arbelaez D., MartinezBello D., Abat M.E.M, Alhabib K.F., Avezum Á., Barbarash O., Chifamba J., Diaz M.L., Gulec S., Ismail N., Iqbal R., Kelishadi R., Khatib R., Lanas F., Levitt N.S., Li Y., Mohan V., Mony P.K., Poirier P., Rosengren A., Soman B., Wang C., Wang Y., Yeates K., Yusuf R., Yusufali A., Zatonska K., Rangarajan S., Yusuf S. Association of the triglyceride glucose index as a measure of insulin resistance with mortality and cardiovascular disease in populations from five continents (PURE study): a prospective co- hort study. Lancet Healthy Longev., 2023; 4 (1): e23– e33. doi: 10.1016/S2666-7568(22)00247-1

35. Salazar J., Bermúdez V., Calvo M., Olivar L.C., Luzardo E., Navarro C., Mencia H., Martinez M., RivasRios J., Wilches-Durán S., Cerda M., Graterol M., Graterol R., Garicano C., Hernández J., Rojas J. Optimal cutoff for the evaluation of insulin resistance through triglyceride-glucose index: A cross-sectional study in a Venezuelan population. F1000Res., 2017; 6: 1337. doi: 10.12688/f1000research.12170.3

36. Chait A., Ginsberg H.N., Vaisar T., Heinecke J.W., Goldberg I.J., Bornfeldt K.E. Remnants of the triglyceride-rich lipoproteins, diabetes, and cardiovascular disease. Diabetes, 2020; 69 (4): 508–516. doi: 10.2337/dbi19-0007

37. Meshkov A.N., Ershova A.I., Deev A.D., Metelskaya V.A., Zhernakova Yu.V., Rotar O.P., Shalnova S.A., Boytsov S.A. Distribution of lipid profile values in economically active men and women in Russian Federation: results of the ESSE-RF study for the years 2012–2014. Cardiovascular Therapy and Prevention, 2017; 16 (4): 62–67. (In Russ.)]. doi: 10.15829/1728-8800-2017-4-62-67

38. Metelskaya V.A., Shalnova S.A., Yarovaya E.B., Kutsenko V.A., Boytsov S.A., Shlyakhto E.V., Drapkina O.M. Lipoprotein profile in populations from regions of the Russian Federation: ESSE-RF study. Int. J. Environ. Res. Public Health, 2022; 19 (2): 931. doi: 10.3390/ijerph19020931

39. Bhatt D.L., Steg P.G., Miller M., Brinton E.A., Jacobson T.A., Ketchum S.B., Doyle R.T. Jr., Juliano R.A., Jiao L., Granowitz C., Tardif J.C., Ballantyne C.M; REDUCE-IT Investigators. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N. Engl. J. Med., 2019; 380 (1): 11–22. doi: 10.1056/NEJMoa1812792

40. Christian J.B., Bourgeois N., Snipes R., Lowe K.A. Prevalence of severe (500 to 2,000 mg/dl) hypertriglyceridemia in United States adults. Am. J. Cardiol., 2011; 107 (6): 891–897. doi: 10.1016/j.amjcard.2010.11.008

41. Nordestgaard B.G., Varbo A. Triglycerides and cardiovascular disease. Lancet, 2014; 384 (9943): 626– 635. doi: 10.1016/S0140-6736(14)61177-6

42. Nordestgaard B.G., Benn M., Schnohr P., TybjaergHansen A. Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women. JAMA, 2007; 298 (3): 299–308. doi: 10.1001/jama.298.3.299

43. Bansal S., Buring J.E., Rifai N., Mora S., Sacks F.M., Ridker P.M. Fasting compared with nonfasting triglycerides and risk of cardiovascular events in wom- en. JAMA, 2007; 298 (3): 309–316. doi: 10.1001/jama.298.3.309

44. Freiberg J.J., Tybjaerg-Hansen A., Jensen J.S., Nordestgaard B.G. Nonfasting triglycerides and risk of ischemic stroke in the general population. JAMA, 2008; 300 (18): 2142–2152. doi: 10.1001/jama.2008.621

45. Karpov Y., Khomitskaya Y. PROMETHEUS: an observational, cross-sectional, retrospective study of hypertriglyceridemia in Russia. Cardiovasc. Diabetol., 2015; 14: 115. doi: 10.1186/s12933-015-0268-2

46. Yezhov M.V., Batluk T.I., Tokmin D.S., Tsyplukhina E.F., Arutyunov A.G. The prevalence of dyslipidemia before and against the background of the COVID-19 pandemic. Analysis of a large laboratory database. Atherosclerosis and Dyslipidemia, 2023; 2 (51): 31–42. (In Russ.)]. doi: 10.34687/2219-8202.JAD.2023.02.0004

47. Quispe R., Martin S.S., Michos E.D., Lamba I., Blumenthal R.S., Saeed A., Lima J., Puri R., Nomura S., Tsai M., Wilkins J., Ballantyne C.M., Nicholls S., Jones S.R., Elshazly M.B. Remnant cholesterol predicts cardiovascular disease beyond LDL and ApoB: a primary prevention study. Eur. Heart J., 2021; 42 (42): 4324–4332. doi: 10.1093/eurheartj/ehab432

48. Varbo A., Freiberg J.J., Nordestgaard B.G. Extreme nonfasting remnant cholesterol vs extreme LDL cholesterol as contributors to cardiovascular disease and all-cause mortality in 90000 individuals from the general population. Clin. Chem., 2015; 61 (3): 533–543. doi: 10.1373/clinchem.2014.234146

49. Jin J., Hu X., Francois M., Zeng P., Wang W., Yu B., Zhou Y., Dong H. Association between remnant cholesterol, metabolic syndrome, and cardiovascular disease: post hoc analysis of a prospective national cohort study. Eur. J. Med. Res., 2023; 28 (1): 420. doi: 10.1186/s40001-023-01369-z

50. Duran E.K., Pradhan A.D. Triglyceride-rich lipoprotein remnants and cardiovascular disease. Clin. Chem., 2021; 67 (1): 183–196. doi: 10.1093/clinchem/hvaa296

51. Doi T., Nordestgaard B.G., Langsted A. Can remnant cholesterol (triglyceride-rich lipoproteins) reclassify estimated risk of atherosclerotic cardiovascular disease? Curr. Opin Endocrinol. Diabetes Obes., 2023; 30 (2): 128–135. doi: 10.1097/MED.0000000000000799

52. Varbo A., Nordestgaard B.G. Directly measured vs. calculated remnant cholesterol identifies additional overlooked individuals in the general population at higher risk of myocardial infarction. Eur. Heart J., 2021; 42 (47): 4833–4843. doi: 10.1093/eurheartj/ ehab293

53. Zhao M., Xiao M., Tan Q., Ji J., Lu F. Cumulative residual cholesterol predicts the risk of cardiovascular disease in the general population aged 45 years and older. Lipids Health Dis., 2024; 23 (1): 19. doi: 10.1186/s12944-023-02000-0