Cardiovascular-kidney-metabolic syndrome: from a new clinical concept to practical lipid-lowering treatment | Ukrainian Medical Journal

Cardiovascular-kidney-metabolic (CKM) syndrome is a systemic health disorder driven by interactions among metabolic risk factors, cardiovascular and kidney disease, diabetes, and obesity, resulting in adverse health outcomes. CKM syndrome contributes to accelerated atherogenesis and increases the risk of atherosclerotic cardiovascular disease (ASCVD) events. Its key value for clinical practice lies in shifting from the isolated management of individual diagnoses to the early identification of patients with a shared trajectory of multiorgan risk. In patients with CKM syndrome, lowering low-density lipoprotein cholesterol (LDL-C) through lifestyle modification and pharmacotherapy is a central component of primary and secondary ASCVD prevention. In the presence of hypertriglyceridaemia, non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein B should be considered more reliable markers of atherogenic lipoprotein burden. This article presents a practical approach to CKM syndrome staging, lipid assessment, determination of LDL-C targets, and intensification of lipid-lowering therapy. The role of rosuvastatin is considered separately, including the selection of treatment intensity, considerations in patients with impaired kidney function, and safety monitoring. The choice between monotherapy and fixed-dose combinations should be based on the clinical goal, the additional LDL-C reduction required, concomitant therapy, and approved indications.

References

1. Ndumele C.E., Rangaswami J., Chow S.L. et al. (2023) Cardiovascular-Kidney-Metabolic Health: A Presidential Advisory From the American Heart Association. Circulation, 148(20): 1606–1635. doi: 10.1161/CIR.0000000000001184.
2. Romeo S., Vidal-Puig A., Husain M. et al. (2025) Clinical staging to guide management of metabolic disorders and their sequelae: a European Atherosclerosis Society consensus statement. Eur. Heart J., Oct 7; 46(38): 3685–3713. doi: 10.1093/eurheartj/ehaf314.
3. Ndumele C.E. Rodriguez F., Dixon D.L. et al. (2026) 2026 AHA/ACC/ADA/ASN Guideline for the Prevention, Detection, Evaluation, and Management of Cardiovascular-Kidney-Metabolic Syndrome: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation, Jul 28; 154(4): e50–e158. doi: 10.1161/CIR.0000000000001453.
4. Braunwald E. (2025) From cardiorenal to cardiovascular-kidney-metabolic syndromes. Eur. Heart J., 21; 46(8): 682–684. doi: 10.1093/eurheartj/ehae775.
5. Lassen M.C.H., Ostrominski J.W., Claggett B.L. et al. (2026) Cardiovascular-Kidney-Metabolic Syndrome Stages, Echocardiographic Characteristics, and Heart Failure Risk: The Atherosclerosis Risk in Communities Study. Circulation, Apr 28; 153(17): 1268–1280. doi: 10.1161/CIRCULATIONAHA.125.077894.
6. Kosiborod M.N., Deanfield J., Pratley R. et al. (2024) SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM Trial Committees and Investigators. Semaglutide versus placebo in patients with heart failure and mildly reduced or preserved ejection fraction: a pooled analysis of the SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM randomised trials. Lancet, Sep 7; 404(10456): 949–961. doi: 10.1016/S0140-6736(24)01643-X.
7. Perkovic V., Tuttle K.R., Rossing P. et al. (2024) Effects of semaglutide on chronic kidney disease in patients with type 2 diabetes. N. Engl. J. Med., 391: 109–121. doi: 10.1056/NEJMoa2403347.
8. Solomon S.D., McMurray J.J.V., Vaduganathan M. et al. (2024) Finerenone in heart failure with mildly reduced or preserved ejection fraction. N. Engl. J. Med., 391: 1475–1485. doi: 10.1056/NEJMoa2407107.
9. Agarwal R., Fouque D. (2023) The foundation and the four pillars of treatment for cardiorenal protection in people with chronic kidney disease and type 2 diabetes. Nephrol. Dial. Transplant., 38: 253–257. doi: 10.1093/ndt/gfac331.
10. Mach F., Koskinas K.C., Casula M. et al. (2025) 2025 Focused Update of the 2019 ESC/EAS Guidelines for the management of dyslipidaemias. Eur. Heart J., 46(42): 4359–4378. doi: 10.1093/eurheartj/ehaf190.
11. Blumenthal R.S. Morris P.B., Gaudino M. et al. (2026) 2026 ACC/AHA/AACVPR/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Dyslipidemia: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J. Am. Coll. Cardiol., May 19; 87(19): 2624–2757. doi: 10.1016/j.jacc.2025.11.016.
12. Ridker P.M., Danielson E., Fonseca F.A.H. et al. (2008) JUPITER Study Group. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N. Engl. J. Med., Nov 20; 359(21): 2195–207. doi: 10.1056/NEJMoa0807646.
13. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group (2024) KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int., 105(4S): S117–S314. doi: 10.1016/j.kint.2023.10.018.
14. Pedicino D., Volpe M. (2026) Weekly Journal Scan: An individual participant data meta-analysis of large randomized trials shows that any adverse events associated with statins are greatly outweighed by their cardiovascular benefits. Eur. Heart J., Jul 7; 47(26): 3437–3439. doi: 10.1093/eurheartj/ehag230.
15. Cholesterol Treatment Trialists’ (CTT) Collaboration (2024) Effects of statin therapy on diagnoses of new-onset diabetes and worsening glycaemia in large-scale randomised blinded statin trials: an individual participant data meta-analysis. Lancet Diabetes Endocrinol., 12: 306–319. doi: 10.1016/S2213-8587(24)00040-8.
16. Khan S.S., Matsushita K., Sang Y. et al. (2024) Development and validation of the American Heart Association’s PREVENT equations. Circulation, 149: 430–449. doi: 10.1161/CIRCULATIONAHA.123.067626.
17. Jones P.H., Davidson M.H., Stein E.A. et al. (2003) Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR Trial). Am. J. Cardiol., 92: 152–160. doi: 10.1016/S0002-9149(03)00530-7.
18. Lee Y.J., Lee S.H., You S.C. et al. (2024) Moderate-intensity statin with ezetimibe combination therapy versus high-intensity statin monotherapy in patients with metabolic syndrome and atherosclerotic cardiovascular disease: A post-hoc analysis of the RACING trial. Diabetes Obes. Metab., 26(3): 829–839. doi: 10.1111/dom.15374.
19. Cho Y., Rhee H., Kim Y.E. et al. (2022) Ezetimibe combination therapy with statin for non-alcoholic fatty liver disease: an open-label randomized controlled trial (ESSENTIAL study). BMC Med., 21; 20(1): 93. doi: 10.1186/s12916-022-02288-2.
20. Поліщук О.В., Гук І.А., Асмолова Н.М. (2026) Фармацевтичні аспекти розробки препарату Клівас, таблетки: якість, стабільність та безпека. Укр. мед. часопис, 2(176). DOI 10.32471/umj.1680-3051.275270
21. Інструкція для медичного застосування лікарського засобу Клівас^®. Державний реєстр лікарських засобів України. www.drlz.com.ua.
22. Інструкція для медичного застосування лікарського засобу Клівас^® Плюс. Державний реєстр лікарських засобів України. www.drlz.com.ua.
23. Інструкція для медичного застосування лікарського засобу Клівас^® Дуо. Державний реєстр лікарських засобів України. www.drlz.com.ua.