Novel concept of cardiovascular-renal-hepatic-metabolic syndrome: what did the experts think about
E. V. Shlyakhto,
S. V. Nedogoda,
A. Yu. Babenko,
G. P. Arutyunov,
O. M. Drapkina,
Zh. D. Kobalava,
A. O. Konradi,
Yu. M. Lopatin,
S. V. Villevalde,
N. E. Zvartau,
O. P. Rotar https://doi.org/10.15829/1560-4071-2025-6534
Abstract
Cardiovascular-renal-hepatic-metabolic (CRHM) syndrome is a pressing healthcare problem. This interdisciplinary document outlines the key aspects and controversial points within the novel concept of CRHM syndrome — definition, diagnostic criteria, identification of its phenotypes and stages. The paper presents current ideas about the pathogenesis, course and management of CRHM syndrome, as well as the advantages of introducing a unified algorithm for managing such patients.
About the Authors
E. V. Shlyakhto
Almazov National Medical Research Center
Russian Federation
Competing Interests:
Russian Federation
St. Petersburg
Competing Interests:
None
S. V. Nedogoda
Volgograd State Medical University
Russian Federation
Competing Interests:
Russian Federation
Volgograd
Competing Interests:
None
A. Yu. Babenko
Almazov National Medical Research Center
Russian Federation
Competing Interests:
Russian Federation
St. Petersburg
Competing Interests:
None
G. P. Arutyunov
Pirogov Russian National Research Medical University
Russian Federation
Competing Interests:
Russian Federation
Moscow
Competing Interests:
None
O. M. Drapkina
National Medical Research Center for Therapy and Preventive Medicine
Russian Federation
Competing Interests:
Russian Federation
Moscow
Competing Interests:
None
Zh. D. Kobalava
Peoples’ Friendship University of Russia
Russian Federation
Competing Interests:
Russian Federation
Moscow
Competing Interests:
None
A. O. Konradi
Almazov National Medical Research Center
Russian Federation
Competing Interests:
Russian Federation
St. Petersburg
Competing Interests:
None
Yu. M. Lopatin
Volgograd State Medical University; Volgograd Regional Clinical Cardiology Center
Russian Federation
Competing Interests:
Russian Federation
Volgograd
Competing Interests:
None
S. V. Villevalde
Almazov National Medical Research Center
Russian Federation
Competing Interests:
Russian Federation
St. Petersburg
Competing Interests:
None
N. E. Zvartau
Almazov National Medical Research Center
Russian Federation
Competing Interests:
Russian Federation
St. Petersburg
Competing Interests:
None
O. P. Rotar
Almazov National Medical Research Center
Russian Federation
Competing Interests:
Russian Federation
St. Petersburg
Competing Interests:
None
References
1. Koziolova NV, Konradi AO. Optimization of criteria of metabolic syndrome. The Russian Institute of Metabolic Syndrome is a consistent position. Arterial hypertension. 2007;13(3): 195-6. (In Russ.) doi:10.18705/1607-419X-2007-13-3-195-196.
2. Alberti KG, Eckel RH, Grundy SM, et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 2009;120(16):1640-5. doi:10.1161/CIRCULATIONAHA.109.192644.
3. Kahn R, Buse J, Ferrannini E, Stern M; American Diabetes Association; European Association for the Study of Diabetes. The metabolic syndrome: time for a critical appraisal: joint statement from the American Diabetes Association," and the European Association for the Study of Diabetes. Diabetes Care. 2005;28(9):2289-304. doi:10.2337/diacare.28.9.228.
4. Polak-Iwaniuk A, Harasim-Symbor E, Gołaszewska K, Chabowski A. How Hypertension Affects Heart Metabolism. Front. Physiol. 2019;10:435. doi:10.3389/fphys.2019.00435.
5. Franklin SS. Hypertension in the metabolic syndrome. Metab Syndr Relat Disord. 2006;4(4):287-98. doi:10.1089/met.2006.4.287.
6. Andreadis EA, Tsourous GI, Tzavara CK, et al. Metabolic Syndrome and Incident Cardiovascular Morbidity and Mortality in a Mediterranean Hypertensive Population. Am J Hypertens. 2007;20(5):558-64. doi:10.1016/j.amjhyper.2006.12.001.
7. Catena C, Colussi G, Martinis F, et al. Plasma glucose levels and left ventricular diastolic function in nondiabetic hypertensive patients. Am J Hypertens. 2013;26:1353-61.
8. Wise J. High blood pressure is linked to increased risk of diabetes BMJ. 2015;351:h5167. doi:10.1136/bmj.h5167.
9. Colussi G, Da Porto A, Cavarape A. Hypertension and type 2 diabetes: lights and shadows about causality. J Hum Hypertens. 2020;34:91-3. doi:10.1038/s41371-019-0268-x.
10. Petrie JR, Guzik TJ, Touyz RM. Diabetes, Hypertension, and Cardiovascular Disease: Clinical Insights and Vascular Mechanisms. Can J Cardiol. 2018;34(5):575-84. doi:10.1016/j.cjca.2017.12.005.
11. Kim MJ, Lim NK, Choi SJ, Park HY. Hypertension is an independent risk factor for type 2 diabetes: the Korean genome and epidemiology study. Hypertens Res. 2015;38(11):783-9. doi:10.1038/hr.2015.72.
12. Chen Y, Ma J, Lu D, Fang Y. The risk factors of type 2 diabetes in hypertensive subjects. Front. Endocrinol. 2022;13:901614. doi:10.3389/fendo.2022.901614.
13. Rus M, Crisan S, Andronie-Cioara FL, et al. Prevalence and Risk Factors of Metabolic Syndrome: A Prospective Study on Cardiovascular Health. Medicina. 2023;59:1711. doi:10.3390/medicina59101711.
14. Lin L, Pan X, Feng Y, et al. DCRM 2.0: Multispecialty practice recommendations for the management of diabetes, cardiorenal, and metabolic diseases. Metabolism. 2024;159:155931. doi:10.1016/j.metabol.2024.155931.
15. Ndumele CE, Rangaswami J, Chow SL, et al.; American Heart Association. Cardiovascular-Kidney-Metabolic Health: A Presidential Advisory From the American Heart Association. Circulation. 2023;148(20):1606-35. doi:10.1161/CIR.0000000000001184. Erratum in: Circulation. 2024;149(13):e1023. doi:10.1161/CIR.0000000000001241.
16. Lin L, Pan X, Feng Y, et al. Chronic kidney disease combined with metabolic syndrome is a non-negligible risk factor. Therapeutic Advances in Endocrinology and Metabolism. 2024;15. doi:10.1177/20420188241252309.
17. Kanbay M, Guldan M, Ozbek L, et al. Exploring the nexus: The place of kidney diseases within the cardiovascular-kidney-metabolic syndrome spectrum. Eur J Intern Med. 2024;127:1-14. doi:10.1016/j.ejim.2024.07.014.
18. Zhu D, Judge PK, Wanner C, et al. The prevention and management of chronic kidney disease among patients with metabolic syndrome. Kidney International. 2025;107:816-24. doi:10.1016/j.kint.2024.12.021.
19. Zheng H, Sechi LA, Navarese EP, et al. Metabolic dysfunction-associated steatotic liver disease and cardiovascular risk: a comprehensive review. Cardiovasc Diabetol. 2024;23(1):346. doi:10.1186/s12933-024-02434-5.
20. Platek AE, Szymanska A. Metabolic dysfunction-associated steatotic liver disease as a cardiovascular risk factor. Clin Exp Hepatol. 2023;9(3):187-92. doi:10.5114/ceh.2023.130744.
21. Mellemkjær A, Kjær MB, Haldrup D, et al. Management of cardiovascular risk in patients with metabolic dysfunction-associated steatotic liver disease. Eur J Intern Med. 2024; 122:28-34. doi:10.1016/j.ejim.2023.11.012.
22. Michalopoulou E, Thymis J, Lampsas S, et al. The Triad of Risk: Linking MASLD, Cardiovascular Disease and Type 2 Diabetes; From Pathophysiology to Treatment. J. Clin. Med. 2025;14:428. doi:10.3390/jcm14020428.
23. Chung GE, Yu SJ, Yoo JJ, et al. Metabolic dysfunction-associated steatotic liver disease increases cardiovascular disease risk in young adults. Sci Rep. 2025;15(1):5777. doi:10.1038/s41598-025-89293-6.
24. Rector RS, Thyfault JP, Wei Y, Ibdah JA. Non-alcoholic fatty liver disease and the metabolic syndrome: an update. World J Gastroenterol. 2008;14(2):185-92. doi:10.3748/wjg.14.185.
25. Radu F, Potcovaru CG, Salmen T, et al. The Link between NAFLD and Metabolic Syndrome. Diagnostics (Basel). 2023;13(4):614. doi:10.3390/diagnostics13040614.
26. Almeda-Valdés P, Cuevas-Ramos D, Aguilar-Salinas CA. Metabolic syndrome and non-alcoholic fatty liver disease. Ann Hepatol. 2009;8 Suppl 1:S18-24.
27. Godoy-Matos AF, Silva Júnior WS, Valerio CM. NAFLD as a continuum: from obesity to metabolic syndrome and diabetes. Diabetol Metab Syndr. 2020;12:60. doi:10.1186/s13098-020-00570-y.
28. Prasoppokakorn T. Applicability of Statins in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). Livers. 2025;5:4. doi:10.3390/livers5010004.
29. Feng X, Yang Y, Xie H, et al. The Association Between Hyperuricemia and Obesity Metabolic Phenotypes in Chinese General Population: A Retrospective Analysis. Front. Nutr. 2022;9:773220. doi:10.3389/fnut.2022.773220.
30. Lee MJ, Khang AR, Kang YH, et al. Synergistic Interaction between Hyperuricemia and Abdominal Obesity as a Risk Factor for Metabolic Syndrome Components in Korean Population. Diabetes Metab J. 2022;46(5):756-66. doi:10.4093/dmj.2021.0166.
31. Maloberti A, Tognola C, Garofani I, et al. Uric acid and metabolic syndrome: Importance of hyperuricemia cut-off. Int J Cardiol. 2024;417:132527. doi:10.1016/j.ijcard.2024.132527.
32. King C, Lanaspa MA, Jensen T, et al. Uric Acid as a Cause of the Metabolic Syndrome. Contrib Nephrol. 2018;192:88-102. doi:10.1159/000484283.
33. Raya-Cano E, Vaquero-Abellán M, Molina-Luque R, et al. Association between metabolic syndrome and uric acid: a systematic review and meta-analysis. Sci Rep. 2022;12:18412. doi:10.1038/s41598-022-22025-2.
34. Kanbay M, Jensen T, Solak Y, et al. Uric acid in metabolic syndrome: From an innocent bystander to a central player. Eur J Intern Med. 2016;29:3-8. doi:10.1016/j.ejim.2015.11.026.
35. Copur S, Demiray A, Kanbay M. Uric acid in metabolic syndrome: Does uric acid have a definitive role? Eur J Intern Med. 2022;103:4-12. doi:10.1016/j.ejim.2022.04.022.
36. Bowden RG, Richardson KA, Richardson LT. Uric Acid as a Novel Component of Metabolic Syndrome. Int J Clin Cardiol. 2023;10:278. doi:10.23937/2378-2951/1410278.
37. Hao H, Su Y, Feng M. Association Between Metabolic and Obesity Phenotypes and Diabetes Risk in Children and Adolescents. Diabetes Metab Syndr Obes. 2024;17:4479-87. doi:10.2147/DMSO.S484639.
38. Pujia R, Tarsitano MG, Arturi F, et al. Advances in Phenotyping Obesity and in Its Dietary and Pharmacological Treatment: A Narrative Review. Front. Nutr. 2022;9:804719. doi:10.3389/fnut.2022.804719.
39. Patti AM, Giglio RV, Ciaccio M, et al. New Frontiers in Nutritional and Therapeutic Interventions for Obesity Phenotypes. Medicina. 2025;61:664. doi:10.3390/medicina61040664.
40. Preda A, Carbone F, Tirandi A, et al. Obesity phenotypes and cardiovascular risk: From pathophysiology to clinical management. Rev Endocr Metab Disord. 2023;24(5):901-19. doi:10.1007/s11154-023-09813-5.
41. Jiang J, Wang P, Jiang J, et al. Association between metabolic phenotype and diabetic kidney disease in adult-onset type 1 diabetes patients from China: A multicenter cross-sectional study. Diabetes Res Clin Pract. 2025;226:112347. doi:10.1016/j.diabres.2025.112347.
42. Zhao L, Zou Y, Wu Y, et al. Metabolic phenotypes and risk of end-stage kidney disease in patients with type 2 diabetes. Front. Endocrinol. 2023;14:1103251.
43. Tanabe H, Masuzaki H, Shimabukuro M. Novel strategies for glycaemic control and preventing diabetic complications applying the clustering-based classification of adult-onset diabetes mellitus: A perspective. Diabetes Res Clin Pract. 2021;180:109067. doi:10.1016/j.diabres.2021.109067.
44. Murray EC, Delles C, Orzechowski P, et al. Vascular phenotypes in early hypertension.J Hum Hypertens. 2023;37:898-906. doi:10.1038/s41371-022-00794-7.
45. Mensah GA. Commentary: Hypertension Phenotypes: The Many Faces of a Silent Killer. Ethn Dis. 2019;29(4):545-8. doi:10.18865/ed.29.4.545.
46. Cuspidi C, Facchetti R, Gherbesi E, et al. Ambulatory Blood Pressure Phenotypes, Arterial Stiffness, and Cardiac Remodeling. Am J Hypertens. 2024;37(12):978-86. doi:10.1093/ajh/hpae106.
47. Soares-Jr JM, Hayashida SAY, Marcondes JAM, et al. Influence of Phenotypes on the Metabolic Syndrome of Women with Polycystic Ovary Syndrome over a Six-Year Follow-Up in Brazil. Biomedicines. 2023;11(12):3262. doi:10.3390/biomedicines11123262.
48. Fakhry TK, Mhaskar R, Schwitalla T, et al. Bariatric surgery improves nonalcoholic fatty liver disease: a contemporary systematic review and meta-analysis. Surg Obes Relat Dis. 2019;15(3):502-11. doi:10.1016/j.soard.2018.12.002.
49. Eslam M, Ahmed A, Despres JP, et al. Incorporating fatty liver disease in multidisciplinary care and novel clinical trial designs for patients with metabolic diseases. Lancet Gastroenterol Hepatol. 2021;6(9):743-53. doi:10.1016/S2468-1253(21)00132-1.
50. Liu Q, Zhao G, Li Q, et al. A comparison of NAFLD and MAFLD diagnostic criteria in contemporary urban healthy adults in China: a cross-sectional study. BMC Gastroenterol. 2022;22(1):471. doi:10.1186/s12876-022-02576-4.
51. Grabherr F, Grander C, Effenberger M, et al. MAFLD: what 2 years of the redefinition of fatty liver disease has taught us. Ther Adv Endocrinol Metab. 2022;13:20420188221139101. doi:10.1177/20420188221139101.
52. Koskinas KC, Van Craenenbroeck EM, Antoniades C, et al.; ESC Scientific Document Group. Obesity and cardiovascular disease: an ESC clinical consensus statement. Eur Heart J. 2024;45(38):4063-98. doi:10.1093/eurheartj/ehae508.
53. Tutor AW, Lavie CJ, Kachur S, et al. Updates on obesity and the obesity paradox in cardiovascular diseases. Prog Cardiovasc Dis. 2023;78:2-10. doi:10.1016/j.pcad.2022.11.013.
54. Liu M, Zhang Z, Zhou C, et al. Predicted fat mass and lean mass in relation to all-cause and cause-specific mortality. J Cachexia Sarcopenia Muscle. 2022;13(2):1064-75. doi:10.1002/jcsm.12921.
55. Bril F, Portillo Sanchez P, Lomonaco R, et al. Liver Safety of Statins in Prediabetes or T2DM and Nonalcoholic Steatohepatitis: Post Hoc Analysis of a Randomized Trial. J Clin Endocrinol Metab. 2017;102(8):2950-61. doi:10.1210/jc.2017-00867.
56. Pastori D, Pani A, Di Rocco A, et al. Statin liver safety in non-alcoholic fatty liver disease: A systematic review and metanalysis. Br J Clin Pharmacol. 2022;88(2):441-51. doi:10.1111/bcp.14943.
57. Fatima K, Moeed A, Waqar E, et al. Efficacy of statins in treatment and development of non-alcoholic fatty liver disease and steatohepatitis: A systematic review and meta-analysis. Clin Res Hepatol Gastroenterol. 2022;46(4):101816. doi:10.1016/j.clinre.2021.101816.
58. Khoo S, Wong VW, Goh GB, et al. Suboptimal treatment of dyslipidemia in patients with non-alcoholic fatty liver disease. J Gastroenterol Hepatol. 2020;35(2):320-5. doi:10.1111/jgh.14794.
59. Speliotes EK, Balakrishnan M, Friedman LS, Corey KE. Treatment of Dyslipidemia in Common Liver Diseases. Clin Gastroenterol Hepatol. 2018;16(8):1189-96. doi:10.1016/j.cgh.2018.04.023.
60. Thapar M, Russo MW, Bonkovsky HL. Statins and liver injury. Gastroenterol Hepatol (N Y). 2013;9(9):605-6.
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For citations:
Shlyakhto E.V., Nedogoda S.V., Babenko A.Yu., Arutyunov G.P., Drapkina O.M., Kobalava Zh.D., Konradi A.O., Lopatin Yu.M., Villevalde S.V., Zvartau N.E., Rotar O.P. Novel concept of cardiovascular-renal-hepatic-metabolic syndrome: what did the experts think about. Russian Journal of Cardiology. 2025;30(1S):6534. (In Russ.) https://doi.org/10.15829/1560-4071-2025-6534
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