Features of comorbidity in the presence of clusters of associated risk factors

The problem of comorbidity is of great importance due to its severe medical and social consequences. In the etiopathogenesis of comorbid pathology in patients with somatic disease, a significant role is played by risk factors that tend to appear in the form of clusters. Aim of the study was to investigate the features of the severity and structure of comorbidity in patients with a therapeutic profile in the presence of each of the three clusters of risk factors for chronic non-communicable diseases (cluster 1: age over 52 years, obesity, hyperglycemia; cluster 2: arterial hypertension, hypertriglyceridemia, elevated serum concentration of C-reactive protein (CRP), hyperuricemia; cluster 3: low(LDL) and high-density lipoprotein (HDL) hypocholesterolemia).

Material and methods. The study included data from case histories of 4908 people, 2026 men (41.3 %) and 2882 women (58.7 %), aged 57.9 ± 0.2 years (arithmetic mean ± standard error of the mean). Three groups of patients were formed depending on the presence of a particular cluster of risk factors: Group 1 – age over 52 years, obesity, hyperglycemia (n = 434); Group 2 – arterial hypertension, hypertriglyceridemia, elevated serum concentration of CRP, hyperuricemia (n = 108); Group 3 – LDL hypercholesterolemia, HDL hypocholesterolemia (n = 363). The frequency of all available nosological forms was analyzed in accordance with ICD-10. Transnosological comorbidity was assessed by the number of nosological forms, transsystemic comorbidity – by the number of ICD-10 classes in one patient.

Results and discussion. A high level of transsystemic and transnosological comorbidity was revealed in patients with any of the considered clusters, which emphasizes their importance in the development of comorbidity. The highest comorbidity rates were found in patients with a cluster of factors: age over 52 years, obesity and hyperglycemia (transnosological comorbidity – 8.86 ± 0.19; transsystemic comorbidity – 4.60 ± 0.06). The most common nosologies in patients in all 3 groups were hypertension, deforming dorsopathy and non-alcoholic fatty liver disease, which may be due to the common pathogenetic mechanisms of these diseases (dysregulatory, vascular and metabolic disorders), which can be initiated by the considered risk factors.

Conclusions. Among the clusters of factors associated with comorbidity, the most significant are the following: age over 52 years, obesity, hyperglycemia; arterial hypertension, hypertriglyceridemia, hyperuricemia, increased serum concentration of CRP.

1. Efremov L.I., Komissarenko I.A. Metabolic continuum and polymorbidity in geriatrics. Eksperimental’naya i klinicheskaya gastroenterologiya = Experimental and Clinical Gastroenterology. 2014;(6):4–7. [In Russian].

2. Sao R., Aronow W.S. Association of non-alcoholic fatty liver disease with cardiovascular disease and subclinical atherosclerosis. Arch. Med. Sci. 2018;14(6):1233–1244. doi: 10.5114/aoms.2017.68821

3. Sevost’yanova E.V., Nikolaev Yu.A., Mitrofanov I.M., Polyakov V.Ya., Seljatitskaja V.G. Clusters of risk factors for the development of comorbidity in patients with somatic pathology. Sibirskij nauchnyj medicinskij zhurnal = Siberian Scientific Medical Journal. 2024;44(6):218–225. [In Russian]. doi: 10.18699/SSMJ20240623

4. Mitrofanov I.M., Nikolaev Yu.A., Dolgova N.A., Pospelova T.I. Regional features of present-day polymorbidity of internal diseases. Klinicheskaya meditsina = Clinical Medicine. 2013;91(6):26–29. [In Russian].

5. Kivimäki M., Kuosma E., Ferrie J.E., Luukkonen R., Nyberg S.T., Alfredsson L., Batty G.D., Brunner E.J., Fransson E., Goldberg M., … Jokela M. Overweight, obesity, and risk of cardiometabolic multimorbidity: pooled analysis of individual-level data for 120 813 adults from 16 cohort studies from the USA and Europe. Lancet Public Health. 2017;19;2(6):277– 285. doi: 10.1016/S2468-2667(17)30074-9

6. Pollack L.M., Wang M., Leung M., Yee M., Colditz G., Herrick C., Chang S.H. Obesity-related multimorbidity and risk of cardiovascular disease in the middle-aged population in the United States. Prev. Med. 2020;139:106225. doi: 10.1016/j.ypmed.2020.106225

7. Vasilevskiy D.I., Balandov S.G., Anisimova K.A., Zavgorodnyaya M.V. Pathogenesis of arterial hypertension (Lecture). Rossiyskiye biomeditsinskiye issledovaniya =Russian Biomedical Research. 2020;5(3):59–62. [In Russian].

8. Mordovin V.F., Zyubanova I.V., Manukyan M.A., Dorzhieva I.K., Vtorushina A.A., Khunkhinova S.A., Fal’kovskaya A.Yu. The role of immune-inflammatory mechanisms in the pathogenesis of hypertension. Sibirskiy zhurnal klinicheskoy i eksperimental’noy meditsiny = Siberian Journal of Clinical and Experimental Medicine. 2023;38(1):21–27. [In Russian]. doi: 10.29001/2073-8552-2023-38-1-21-27

9. Mikhaylov A.N., Malevich E.E., Kopytok E.S. Topical issues of clinical and radiological diagnosis of cervical degenerative-dystrophic dorsopathies. Meditsinskie novosti = Medical News. 2023;(4):11–20. [In Russian].

10. Sall T.S., Shcherbakova E.S., Sitkin S.I., Vakhitov T.Ya., Bakulin I.G., Demyanova E.V. Molecular mechanisms of non-alcoholic fatty liver disease development. Profilakticheskaya meditsina = The Russian Journal of Preventive Medicine and Public Health. 2021;24(4):120–131. [In Russian]. doi: 10.17116/profmed202124041120

11. Shariq O., McKenzie T. Obesity-related hypertension: a review of pathophysiology, management, and the role of metabolic surgery. Gland. Surg. 2020;9(1):80–93. doi: 10.21037/gs.2019.12.03

12. Kawai T., Autieri M.V., Scalia R. Adipose tissue inflammation and metabolic dysfunction in obesity. Am. J. Physiol. Cell. Physiol. 2021;320(3):375–391. doi: 10.1152/ajpcell.00379.2020

13. Pokrovskaya E.V., Shestakova E.A., Shestakova M.V. Endothelial dysfunction in patients with obesity and type 2 diabetes mellitus or normoglycemia: assessment of specific markers. Sakharnyy diabet = Diabetes Mellitus. 2023;26(5):439–445. [In Russian]. doi: 10.14341/DM13088

14. Meza C.A., La Favor J.D., Kim D.H., Hickner R.C. Endothelial dysfunction: is there a hyperglycemia-induced imbalance of NOX and NOS? Int. J. Mol. Sci. 2019;20(15):3775. doi: 10.3390/ijms20153775

15. An Y., Xu B.T., Wan S.R., Ma X.M., Long Y., Xu Y., Jiang Z.Z. The role of oxidative stress in diabetes mellitus-induced vascular endothelial dysfunction. Cardiovasc. Diabetol. 2023;22(1):237. doi: 10.1186/s12933-023-01965-7

16. Pizov A.V., Pizov N.A., Skachkova O.A., Pizova N.V. Endothelial dysfunction as early predictor of atherosclerosis. Meditsinskiy alfavit = Medical Аlphabet. 2019;(4):28–33. [In Russian]. doi: 10.33667/2078-5631-2019-4-35(410)-28-33

17. Sergienko I.V., Ansheles A.A., Kuharchuk V.V. Dyslipidemia, atherosclerosis and ischemic heart disease. Genetics, pathogenesis, phenotypes, diagnostics, therapy, comorbidity. Moskow: PatiSS, 2020. 298 p. [In Russian].

18. Zaric B., Obradovic M., Trpkovic A., Banach M., Mikhailidis D.P., Isenovic E.R. Endothelial dysfunction in dyslipidaemia: molecular mechanisms and clinical implications. Curr. Med. Chem. 2020;27(7):1021–1040. doi: 10.2174/0929867326666190903112146

19. Shabalin V.V., Grinshteyn Yu.I., Ruf R.R., Samsonov N.S. Asymptomatic hyperuricemia: obvious, controversial, hypothetical. Profilakticheskaya meditsina = The Russian Journal of Preventive Medicine and Public Health. 2023;26(7):103–109. [In Russian]. doi: 10.17116/profmed202326071103