Lipid-lowering therapy opportunities in young men with metabolic syndrome

Metabolic syndrome (MS) is a combination of risk factors such as abdominal obesity, arterial hypertension, dyslipidemia, and insulin resistance, significantly increasing the risk of cardiovascular disease and type 2 diabetes mellitus. Despite traditionally being associated with older populations, the prevalence of MS is rising among young men, making the issue particularly relevant.

Objective. To evaluate the potential of lipid-lowering therapy in young men with metabolic syndrome.

Materials and methods. A prospective observational cohort study included 46 men aged 25–45 years diagnosed with metabolic syndrome, divided into two comparable groups. The 6-month observation period focused on patients with controlled hypertension and elevated atherogenic cholesterol levels. Group 1 received pitavastatin at a dose of 2 mg/day; Group 2 received omega‑3 polyunsaturated fatty acid ethyl esters (1000 mg capsules containing 46% EPA and 38% DHA), 2000 mg/day. Clinical and laboratory parameters, adherence to lipid-lowering therapy, and psychosomatic status were assessed.

Results. Lipid profile analysis under controlled blood pressure revealed a statistically significant difference in total cholesterol levels between Group 2 (5.31 mmol/L) and Group 1 (4.79 mmol/L). Group 1 also showed lower LDL–C levels (2.37 mmol/L vs. 2.71 mmol/L), though the difference was not statistically significant. High-sensitivity C-reactive protein (hs-CRP) was elevated in both groups (mean ±5.60 mg/L), but was significantly lower in Group 1 after pitavastatin therapy (2.21 mg/L). Glucose levels were significantly lower in Group 1 (4.1 mmol/L vs. 5.5 mmol/L). Adherence was notably higher in Group 1: 66.32% [42%; 82%] vs. 32.18% [45%; 71%]. Subclinical anxiety was prevalent (n = 32), though no statistically significant difference was found between groups.

Conclusion. The efficacy and safety of pitavastatin contribute to improved patient adherence, which is crucial for long-term management of metabolic syndrome and the prevention of complications. Integrating therapy that addresses both metabolic and psychosomatic factors leads to substantial health benefits for young men with MS, reducing atherosclerosis risk and enhancing quality of life.

1. Yezhov M.V., Kukharchuk V.V., Sergienko I.V. et al. Disorders of lipid metabolism. Clinical guidelines 2023. Russian Journal of Cardiology. 2023; 28 (5): 5471. (In Russ.). https://doi. org:10.15829/1560 4071 2023 5471. EDN YVZOWJ

2. Kukharchuk V.V., Malyshev P.P., Meshkov A.N. Familial hypercholesterolemia: current aspects of diagnosis, prevention and therapy. Cardiology. 2009; 49 (1): 76–83. (In Russ.).

3. Yuan G, Wang J, Hegele RA. Heterozygous familial hypercholesterolemia: an under recognized cause of early cardiovascular disease. CMAJ. 2006; 174 (8): 1124–9. DOI: 10.1503/cmaj.051313.202

4. Yezhov M.V., Sergienko I.V., Alekseeva I.A. Pitavastatin (Livazo) in the treatment of dyslipidemia in routine clinical practice. Atherosclerosis and dyslipidemia. 2020; 3 (40): 5–14. (In Russ.). https://doi.org/10.34687/2219-8202.JAD.2020.03.0001

5. Hopkins PN, Toth PP, Ballantyne CM, Rader DJ. Familial hypercholesterolemias: prevalence, genetics, diagnosis and screening recommendations from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. J Clin Lipidol. 2011; 5 (3 Suppl): S9–17. https://doi.org:10.1016/j.jacl.2011.03.452

6. Sedykh D. Yu., Khryachkova O.N., Kashtalap V.V. et al. Treatment of comorbid patients with dyslipidemia in real clinical practice: the possibilities of pitavastatin. Breast cancer. Medical review. 2021; 5 (4): 218–224. (In Russ.). https://doi.org/10.32364/2587 6821 2021 5 4 218 224

7. Burns S.A., Kashtalap V.V. Endothelioprotective effect of pitavastatin. Cardiovascular therapy and prevention. 2023; 22 (8): 3671. (In Russ.). https://doi.org/10.15829/1728 8800 2023 3671. EDN: PBVGNY

8. Ohbayashi H, Miyazawa C, Miyamoto K. Pitavastatin improves plasma pentraxin 3 and arterial stiffness in atherosclerotic patients with hypercholesterolemia. J Atheroscler Thromb. 2009; 16 (4): 490–500. https://doi.org/10.5551/jat.no613

9. Sedykh D. Yu., Khryachkova O.N., Kashtalap V.V. Treatment of comorbid patients with dyslipidemia in real clinical practice: the possibilities of pitavastatin. breast cancer. Medical review. 2021; 5 (4): 218–24. (In Russ.). https://doi.org/10.32364/2587 6821 2021 5 4 218 224

10. Srichatrapimuk S, Wongsa A, Sungkanuparph S. et al. Effects of pitavastatin on atherosclerotic-associated inflammatory biomarkers in people living with HIV with dyslipidemia and receiving ritonavir-boosted atazanavir: a randomized, doubleblind, crossover study. AIDS Res Ther. 2023; 20 (1): 13. https://doi.org/10.1186/s12981 023 00506 2

11. Endo I., Sasaki K., Ikewaki K. Residual cardiovascular risk, determined by post-factum analysis of the REAL–CAD study. J Arterioscler Thromb. 2024 January 1; 31 (1): 21–22. DOI: 10.5551/JAT.ED245. Epub 2023 October 17th. PMID: 37853635; PMCID: PMC10776336.

12. Katapano A., Kukharchuk V.V., Sergienko I.V. and others. Pitavastatin is a modern statin for the correction of dyslipidemia and the risk of cardiovascular complications. Resolution of the Expert Council. Atherosclerosis and dyslipidemia. 2017; 2: 104–6. (In Russ.).

13. Vlasov T.D., Nesterovich I.I., Szymanski D.A. Endothelial dysfunction: from particular to general. A return to the «old paradigm»? Regional blood circulation and microcirculation. 2019; 18 (2): 19–27. (In Russ.). https://doi.org/10.24884/1682 6655 2019 18 2 19 27

14. Barrios V., Escobar K. Clinical benefits of pitavastatin: focus on patients with diabetes mellitus or at risk of developing diabetes. The future cardinal. 2016; 12 (4): 449–66. https://doi.org/10.2217/FCA 2016–0018. Epub 2016 April 14th. PMID: 27076402.

15. Torimoto K, Okada Y, Tanaka Y. Type 2 Diabetes and Vascular Endothelial Dysfunction. J UOEH. 2018; 40 (1): 65–75. https://doi.org/10.7888/juoeh.40.65

16. Podzolkov V.I., Bragina A.E., Rodionova Yu.N., Osadchy K.K., Vasilchenko M.K., Sizova Zh.M., Mospanova E.V., Litvinenko N.S., Muradova I.D., Akvitskaya D.V. Ectopic adipose tissue: association of obesity phenotypes with integral metabolic parameters of obesity. Rational pharmacotherapy in cardiology. 2024; 20 (3): 285–293. (In Russ.). https://doi.org/10.20996/1819 6446 2024 3035. EDN: DYLRKZ

17. Novikova A. I., Pavlova M.G., Potemkina N.A., Fadeev L.B., Poltavskaya M.G. The development of dyslipidemia in patients after complex treatment of tumors of the central nervous system in childhood. Rational pharmacotherapy in cardiology. 2024; 20 (6): 605–609. (In Russ.). https://doi.org/10.20996/1819 6446 2024 3118. EDN: TJMKNJ

18. Bocheran K., Dupre E. Validation study of the hospital Anxiety and Depression Scale (HADS) on a large sample of French employees. BMC Psychiatry. 2014; 14: 354. https://doi.org/10.1186/s12888 014 0354 0

19. Lukina Yu.V., Martsevich S. Yu., Kutishenko N.Р. The Morisky-Green scale: the pros and cons of the universal test, error correction. Rational pharmacotherapy in cardiology. 2016; 12 (1): 63–65. (In Russ.). https://doi.org/10.20996/1819 6446 2016 12 1 63 65

20. Clearfield M.B., Amerena J., Bassani J.P. et al. Comparison of the efficacy and safety of rosuvastatin 10 mg and atorvastatin 20 mg in high-risk patients with hypercholesterolemia is a prospective study to evaluate the use of low-dose statins Atorvastatin and Rosuvastatin (PULSAR). 2006; 7: 35. https://doi.org/10.1186/1745 6215 7 35

21. Zhou Y, Wang Y, Wang G. et al. Association Between Statin Use and Progression of Arterial Stiffness Among Adults With High Atherosclerotic Risk. JAMA Netw Open. 2022; 5 (6): e2218323. https://doi.org/10.1001/jamanetworkopen.2022.18323

22. Hugeven R.K., Gaubats J.V., Sun V., Dodge R.K., Krosby J.R., Jiang J., Cooper D., Virani S.S., Kathiresan S., Burwinkle E., Ballantine S.M. Small dense concentrations of lipoproteins and low-density cholesterol predict the risk of coronary heart disease: a study the risk of atherosclerosis in communities (ARIC). Arterioscler Thromb Vasc Biol. 2014; 34: 1069–1077.

23. Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980; 288: 373–6. https://doi.org/10.1038/288373a0

24. Bleakley C, Hamilton PK, Pumb R. et al. Endothelial Function in Hypertension: Victim or Culprit? The Journal of Clinical Hypertension. 2015; 17 (8): 651–4. https://doi.org/10.1111/jch.12546

25. Khidirova L.D., Gordeev A. I. Statin-induced diabetes mellitus. The Russian Journal of Preventive Medicine. 2023; 26 (5): 84–87. (In Russ.). https://doi.org/10.17116/profmed20232605184

26. Duggan S.T. Pitavastatin: a review of its use in the treatment of hypercholesterolemia or mixed dyslipidemia. Drugs. March 5, 2012; 72 (4): 565–84. https://doi: 10.2165/11207180 0000000000 00000 00000. PMID: 22356292.

27. Masana L. Pitavastatin – from clinical trials to clinical practice. Atheroscler Suppl. 2010; 11 (3): 15–22. https://doi: 10.1016/S1567–5688(10)71065 5. PMID: 21193154.

28. Lee Hye-sung, Chang Hee-jung, Song of the River m, PROFIT Research Group. The effect of pitavastatin treatment on ApoB48 and Lp-PLA2 in patients with metabolic syndrome: a sub-study of a promising comparative clinical trial to evaluate the efficacy and safety of pitavastatin in patients with metabolic syndrome. Endocrinology and metabolism. 2016; 31 (1):120–126. doi.org/10.3803/EnM.2016.31.1.120

29. Namitokov A.M., Chubykina U.V., Zafiraki V.K., Ezhov M.V. Impact of hyperlipoproteinemia(a) on the diagnosis of familial hypercholesterolemia and cardiovascular risk assessment. Rational Pharmacotherapy in Cardiology. 2025; 21 (1): 47–53. (In Russ.). DOI: 10.20996/1819 6446 2025 3106. EDN GUFWHD.