Concept of an interdisciplinary consensus document on cardiovascular-renal-hepatic-metabolic syndrome

Cardiovascular-renal-hepatic-metabolic (CRHM) syndrome is a complex and interrelated variety of diseases with common pathophysiological mechanisms. This interdisciplinary consensus document on CRHM syndrome provides a definition, diagnostic criteria, and describes its phenotypes and stages. Despite the growing prevalence of CRHM syndrome, unified strategies for patient management remain understudied. A paradigm shift in favor of CRHM syndrome makes it possible to withdraw from fragmented, organ-oriented management in favor of a more unified approach, facilitating collaboration between specialists and marking an advance in precision cardiometabolic medicine.

1. Visseren FLJ, Mach F, Smulders YM, et al.; ESC Scientific Document Group. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. Eur J Prev Cardiol. 2022;29(1):5-115. doi:10.1093/eurjpc/zwab154.

2. Savina AA, Feiginova SI. The prevalence of obesity among the population of the Russian Federation: the period before the COVID-19 pandemic. Social aspects of public health [online edition]. 2022;68(5):4. (In Russ.) doi:10.21045/2071-5021-2022-68-5-4.

3. Balanova YuA, Imaeva AE, Kutsenko VA, et al. Metabolic syndrome and its associations with socio-demographic and behavioral risk factors in the Russian population aged 25-64 years. Cardiovascular Therapy and Prevention. 2020;19(4):2600. (In Russ.) doi:10.15829/1728-8800-2020-2600.

4. Boyarinova MA, Rotar OP, Erina AM, et al. Metabolically healthy obesity: predictors of transformation to unhealthy phenotype in St Petersburg population (according to the ESSE-RF study). "Arterial’naya Gipertenziya" ("Arterial Hypertension"). 2021;27(3):279-90. (In Russ.) doi:10.18705/1607-419X-2021-27-3-279-290.

5. Viktorova IA, Moiseeva MV, Shirlina NG, et al. Abdominal obesity is an independent risk factor for the development of fatal and non-fatal cardiovascular events according to the prospective observational, epidemiological study ESSE-RF2. Russian Journal of Preventive Medicine. 2022;25(6):40-6. (In Russ.) doi:10.17116/profmed20222506140.

6. Whitlock G, Lewington S, Sherliker P, et al.; Prospective Studies Collaboration. Body-mass index and cause-specific mortality in 900000 adults: collaborative analyses of 57 prospective studies. Lancet. 2009;373:1083-96. doi:10.1016/S0140-6736(09)60318-4.

7. Salehidoost R, Mansouri A, Amini M, et al. Diabetes and all-cause mortality, a 18-year follow-up study. Sci Rep. 2020;10:3183. doi:10.1038/s41598-020-60142-y.

8. Turin TC, Tonelli M, Manns BJ, et al. Chronic kidney disease and life expectancy. Nephrol Dial Transplant. 2012;27:3182-6. doi:10.1093/ndt/gfs052.

9. Afkarian M, Sachs MC, Kestenbaum B, et al. Kidney disease and increased mortality risk in type 2 diabetes. J Am Soc Nephrol. 2013;24:302-8. doi:10.1681/ASN.2012070718.

10. Sidney S, Quesenberry CP, Jaffe MG, et al. Recent trends in cardiovascular mortality in the United States and public health goals. JAMA Cardiol. 2016;1:594-9. doi:10.1001/jamacardio.2016.1326.

11. Grundy SM. Metabolic syndrome: a multiplex cardiovascular risk factor. J Clin Endocrinol Metab. 2007;92(2):399-404. doi:10.1210/jc.2006-0513.

12. Ndumele CE, Neeland IJ, Tuttle KR, et al.; American Heart Association. A Synopsis of the Evidence for the Science and Clinical Management of Cardiovascular-Kidney-Metabolic (CKM) Syndrome: A Scientific Statement From the American Heart Association. Circulation. 2023;148(20):1636-64. doi:10.1161/CIR.0000000000001186.

13. Wang W, Hu M, Liu H, et al. Global Burden of Disease Study 2019 suggests that metabolic risk factors are the leading drivers of the burden of ischemic heart disease. Cell Metabolism. 2021;33(10):1943-1956.e2. doi: 10.1016/j.cmet.2021.08.005.

14. Mendenhall E, Singer M. What constitutes a syndemic? Methods, contexts, and framing from 2019. Curr. Opin. 2020;15(4):213-7.

15. Singer M, Bulled N, Ostrach B. Whither syndemics?: Trends in syndemics research, a review 2015-2019. Glob Public Health. 2020;15(7):943-55.

16. Singer M, Bulled N, Ostrach B, Mendenhall E. Syndemics and the biosocial conception of health. Lancet. 2017;389(10072):941-50.

17. Dobrowolski P, Prejbisz A, Kuryłowicz A, et al. Metabolic syndrome — a new definition and management guidelines: A joint position paper by the Polish Society of Hypertension, Polish Society for the Treatment of Obesity, Polish Lipid Association, Polish Association for Study of Liver, Polish Society of Family Medicine, Polish Society of Lifestyle Medicine, Division of Prevention and Epidemiology Polish Cardiac Society, "Club 30" Polish Cardiac Society, and Division of Metabolic and Bariatric Surgery Society of Polish Surgeons. Archives of Medical Science. 2022;18(5):1133-56. doi:10.5114/aoms/15292.

18. 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.

19. Mechanick JI, Farkouh ME, Newman JD, Garvey WT. Cardiometabolic-Based Chronic Disease, Addressing Knowledge and Clinical Practice Gaps: JACC State-of-the-Art Review. J Am Coll Cardiol. 2020;75(5):539-55. doi:10.1016/j.jacc.2019.11.046.

20. Shlyakhto EV. Classification of heart failure: focus on prevention. Russian Journal of Cardiology. 2023;28(1):5351. (In Russ.) Шляхто Е. В. Классификация сердечной недостаточности: фокус на профилактику. Российский кардиологический журнал. 2023;28(1):5351. doi:10.15829/1560-4071-2023-5351. EDN: RVHDCY.

21. Manla Y, Almahmeed W. Cardiometabolic Clinics: Is There a Need for a Multidisciplinary Clinic? Front. Clin. Diabetes Healthc. 2022;3:880468. doi:10.3389/fcdhc.2022.880468.

22. de Oliveira Almeida G, Nienkötter TF, Balieiro CCA, et al. Cardiovascular Benefits of GLP-1 Receptor Agonists in Patients Living with Obesity or Overweight: A Meta-analysis of Randomized Controlled Trials. Am J Cardiovasc Drugs. 2024;24(4):509-21. doi:10.1007/s40256-024-00647-3.

23. Theodorakis N, Nikolaou M. Integrated Management of Cardiovascular-Renal-Hepatic-Metabolic Syndrome: Expanding Roles of SGLT2is, GLP-1RAs, and GIP/GLP-1RAs. Biomedicines. 2025;13(1):135. doi:10.3390/biomedicines13010135.

24. Arutyunov GP, Drapkina OM, Kobalava ZhD, et al. The concept of fixed-dose combination drugs in primary and secondary prevention of cardiovascular disease. Position paper of the Russian Society of Cardiology, the Russian Society for the Prevention of Noncommunicable Diseases, the Russian Scientific Medical Society of Internal Medicine, the Russian Association of Endocrinologists, the Association of Clinical Pharmacologists, the Eurasian Association of Internal Medicine, the Russian Association of Gerontologists and Geriatricians. Russian Journal of Cardiology. 2024;29(9):6074. (In Russ.) doi:10.15829/1560-4071-2024-6074. EDN: RVMZQE.

25. Lloyd-Jones DM, Allen NB, Anderson CAM, et al.; on behalf of the American Heart Association. Life’s Essential 8: updating and enhancing the American Heart Association’s construct of cardiovascular health: a presidential advisory from the American Heart Association. Circulation. 2022;146: e18-e43. doi:10.1161/CIR.0000000000001078.

26. Mechanick JI, Christofides EA, Marchetti AE, et al. The syndromic triad of COVID-19, type 2 diabetes, and malnutrition. Front Nutr. 2023;10:1122203. doi:10.3389/fnut.2023.1122203.

27. 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.

28. Vera-Ponce VJ, Loayza-Castro JA, Zuzunaga-Montoya FE, et al. Associations between metabolic phenotypes and diabetes risk: A systematic review and meta-analysis. Endocrine and Metabolic Science. 2023;13:100142. doi:10.1016/j.endmts.2023.100142.

29. Baccarelli AA, Ordovas J. Epigenetics of early cardiometabolic disease: mechanisms and precision medicine. Circ Res. 2023;132:1648-62. doi:10.1161/CIRCRESAHA.123.322135.