Relationship of dyslipoproteinemia features with arterial stiffness in young and middle-aged patients with ulcerative colitis

AIM: to study the features of dyslipoproteinemia and vascular wall elasticity in young and middle-aged patients with ulcerative colitis (UC).

PATIENTS AND METHODS: the work was carried in the period from January 2021 to January 2025. The first stage included a retrospective and prospective analysis of 495 medical records of patients with UC, of which: 48 patients (group I) in the debut of UC with a UC activity index (Mayo index) of 6–9 points; 401 patients (Group II) from the regional registry of patients with IBD with a history of UC up to 10 years inclusive, with a moderate to severe course of the disease and who did not receive targeted immunosuppressants and genetically engineered biological drugs (GIBPS) until the time of retrospective analysis; 46 patients with UC (group III) with a disease duration of up to 5 years inclusive and who used in the anamnesis of GIBP (vedolizumab, infliximab, ustekinumab). As part of the second stage of the study, 3 study groups (I-1, I-2, and I-3) and a control group (K) were formed. The I-1 group included 40 patients from group I, the I-2 group included 80 patients from group II, and the I-3 group included 31 patients from group III, with a duration of UC of 5 years, in whom the appointment of biological therapy occurred in the first year after the manifestation of UC. The I-2 and I-3 groups included patients in clinical remission for at least 3 months before being included in the study. The I-2 group included 39 patients with a duration of UC up to 5 years inclusive (I-2.1) and 41 patients with a duration of UC 6–10 years inclusive (I-2.2). 160 people from practically healthy individuals who had no clinical or endoscopic signs of UC were selected for the control group K. The study included people under the age of 60. All study participants underwent a lipid profile study, volumetric sphygmography with determination of the cardiovascular vascular index CAVI (Cardio-Ankle Vascular Index).

RESULTS: аs a result of the study, specific quantitative features of the components of the lipid profile in patients with UC were revealed, consisting in a lower level of atherogenic components: total cholesterol, low-density lipoprotein cholesterol (p < 0.001), against a background of a relatively higher amount of triglycerides ((p < 0.01), and low levels of high-density lipoprotein cholesterol (p < 0.001), as well as a higher atherogenicity index (p < 0.01), especially when the inflammatory process in the intestine is activated. When measuring the CAVI index, higher values of this indicator were recorded in the study groups than in the participants of the control group (p < 0.001). The maximum deviation of the CAVI index was found in the I-2.2 group (Me — 1.32, Q1–Q3: 1.06–1.58, rI-2.2 — K < 0.001), which included patients with UC experience from 6 to 10 years.

CONCLUSION: the quantitative features of the lipid profile revealed during the study suggest the presence of special changes in the biochemistry of all lipid fractions in UC and possibly a higher need for them during the development of IBD. Further study of the biochemistry of lipoproteins and their genetic determination in patients with IBD is necessary.

1. Liu JZ, van Sommeren S, Huang H, et al. Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations. Nat Genet. 2015;47:979–986. doi: 10.1038/ng.3359

2. Agrawal M, Jess T. Implications of the changing epidemiology of inflammatory bowel disease in a changing world. United European Gastroenterol J. 2022;10(10):1113–1120. doi: 10.1002/ueg2.12317

3. Kaplan GG, Windsor JW. The four epidemiological stages in the global evolution of inflammatory bowel disease. Nat Rev Gastroenterol Hepatol. 2021;18(1):56–66. doi: 10.1038/s41575-020-00360-x

4. Veselov A.V., Belousova E.A., Bakulin I.G., et al. Economic burden and current status of the drug supply management for immune inflammatory diseases (by example of ulcerative colitis and crohn's disease). Problemi socialnoi gigieni, zdravookhranenia i istorii meditsini. 2020;28(Special Issue):1137–1145. (In Russ.). doi: 10.32687/0869-866X-2020-28-s2-1137-1145

5. Peery AF, Crockett SD, Murphy CC, et al. Burden and Cost of Gastrointestinal, Liver, and Pancreatic Diseases in the United States: Update 2018. Gastroenterology. 2019;156(1):254–272. doi: 10.1053/j.gastro.2018.08.063

6. Czubkowski P, Osiecki M, Szymańska E, et al. The risk of cardiovascular complications in inflammatory bowel disease. Clin Exp Med. 2020;20(4):481–491. doi: 10.1007/s10238-020-00639-y

7. Chen B, Collen LV, Mowat C, et al. Inflammatory Bowel Disease and Cardiovascular Diseases. Am J Med. 2022;135(12):1453–1460. doi: 10.1016/j.amjmed.2022.08.012

8. Weissman S, Sinh P, Mehta TI, et al. Atherosclerotic cardiovascular disease in inflammatory bowel disease: The role of chronic inflammation. World J Gastrointest Pathophysiol. 2020;11(5):104–113. doi: 10.4291/wjgp.v11.i5.104

9. Ferrari GM, Bugianesi E, Armandi A, et al. Patients with inflammatory bowel disease are at increased risk of atherothrombotic disease: A systematic review with meta-analysis. Int J Cardiol. 2023;5(1):378:96–104. doi: 10.1016/j.ijcard.2023.02.042

10. Luo J, Yang H, Song BL. Mechanisms and regulation of cholesterol homeostasis. Nat Rev Mol Cell Biol. 2020;21:225–245. doi: 10.1038/s41580-019-0190-7

11. Leuti A, Fazio D, Fava M, et al. Bioactive lipids, inflammation and chronic diseases. Adv Drug Deliv Rev. 2020;159:133–169. doi: 10.1016/j.addr.2020.06.028

12. Rizzello F, Gionchetti P, Spisni E, et al. Dietary Habits and Nutrient Deficiencies in a Cohort of European Crohn's Disease Adult Patients. Int J Mol Sci. 2023;24:1494. doi: 10.3390/ijms24021494

13. Liu Z, Tang H, Liang H, et al. Dyslipidaemia Is Associated with Severe Disease Activity and Poor Prognosis in Ulcerative Colitis: A Retrospective Cohort Study in China. Nutrients. 2022;14:3040. doi: 10.3390/nu14153040

14. Wang D, Zhao XJ, Cui XF, et al. Correlation of serum lipid profile and disease activity in patients with inflammatory bowel disease. Zhonghua Nei Ke Za Zhi. 2021;60:834–836. doi: 10.3760/cma.j.cn112138-20200930-00847

15. Agrawal M, Kim ES, Colombel JF. JAK Inhibitors Safety in Ulcerative Colitis: Practical Implications. J Crohns Colitis. 2020;14:755–760. doi: 10.1093/ecco-jcc/jjaa017

16. Cuspidi C, Facchetti R, Quarti-Trevano F, et al. Cardio-Ankle Vascular Index as a Marker of Left Ventricular Hypertrophy in Treated Hypertensives: Findings From the Pamela Study. Am J Hypertens. 2024;37(6):399–406. doi: 10.1093/ajh/hpae022

17. Sotoda Y, Hirooka S, Orita H, et al. Difference in right and left cardio-ankle vascular index as a useful marker for evaluation of leg ischemia in patients with lower extremity arterial disease. Vascular. 2024;21:134–137. doi: 10.1177/17085381241263905

18. Sinh P, Tabibian JH, Biyani PS, et al. Inflammatory Bowel Disease Does Not Impact Mortality but Increases Length of Hospitalization in Patients with Acute Myocardial Infarction. Dig Dis Sci. 2021;66(12):4169–4177. doi: 10.1007/s10620-020-06818-x

19. Kaplan GG, Goddard Q, Gorospe J, et al. The 2023 Impact of Inflammatory Bowel Disease in Canada: Special Populations-IBD in Seniors. J Can Assoc Gastroenterol. 2023;6(suppl 2):45–54. doi: 10.1093/jcag/gwad013

20. Mironova O.I., Isaikina M.A, Khasieva S.A. Аtherosclerosis and cardiovascular risk in patients with inflammatory bowel disease. Terapevticheskii Arkhiv. 2021;93(12):1533–1538. (In Russ.). doi: 10.26442/00403660.2021.12.201225

21. Choi YJ, Lee DH, Shin DW, et al. Patients with inflammatory bowel disease have an increased risk of myocardial infarction: a nationwide study. Aliment Pharmacol Ther. 2019;50(7):769–779. doi: 10.1111/apt.15446

22. Bikbavova G.R., Livzan M.A., Morova N.A., et al. Relationship between endothelial dysfunction and systemic inflammation in ulcerative colitis patients. Russian Journal of Preventive Medicine. 2024;27(7):85–93. (In Russ.). doi: 10.17116/profmed20242707185

23. Grinevich V.B., Radchenko V.G. Gut microbiota and metabolic syndrome. Experimental and Clinical Gastroenterology. 2020;183(11):11–19. (In Russ.). doi: 10.31146/1682-8658-ecg-183-11-11-19

24. Qu S, Fan L, Qi Y, et al. Akkermansia muciniphila Alleviates Dextran Sulfate Sodium (DSS)-Induced Acute Colitis by NLRP3 Activation. Microbiol Spectr. 2021;9(2):e0073021. doi: 10.1128/Spectrum.00730-21

25. Wang L, Tang L, Feng Y, et al. A purified membrane protein from Akkermansia muciniphila or the pasteurised bacterium blunts colitis associated tumourigenesis by modulation of CD8 + T cells in mice. Gut. 2020;69(11):1988–1997. doi: 10.1136/gutjnl-2019-320105

26. Rodrigues VF, Elias-Oliveira J, Pereira ÍS, et al. Akkermansia muciniphila and Gut Immune System: A Good Friendship That Attenuates Inflammatory Bowel Disease, Obesity, and Diabetes. Front Immunol. 2022;13:934695. doi: 10.3389/fimmu.2022.934695

27. Babayeva G.H., Babayev Z.M. Frequency of detection of some markers of endothelial dysfunction in patientswith inflammatory bowel diseases. Terapevticheskii Arkhiv. 2018;90(4):12–16. (In Russ.). doi: 10.26442/terarkh201890412-16

28. Kudinov V.A., Alekseeva O.Y., Torkhovskaya T.I., et al. High-Density Lipoproteins as Homeostatic Nanoparticles of Blood Plasma. Int J Mol Sci. 2020;21(22):8737. doi: 10.3390/ijms21228737

29. Jozefczuk E, Guzik TJ, Siedlinski M. Significance of sphingosine-1-phosphate in cardiovascular physiology and pathology. Pharmacol Res. 2020;156:104793. doi: 10.1016/j.phrs.2020.104793

30. Meilhac O, Tanaka S, Couret D. High-density lipoproteins are bug scavengers. Biomolecules. 2020;10:598. doi: 10.3390/biom10040598

31. Nguyen NH, Ohno-Machado L, Sandborn WJ, et al. Infections and Cardiovascular Complications are Common Causes for Hospitalization in Older Patients with Inflammatory Bowel Diseases. Inflamm Bowel Dis. 2018;24(4):916–923. doi: 10.1093/ibd/izx089

32. Xepapadaki E, Zvintzou E, Kalogeropoulou C, et al. The anti-oxidant function of HDL in atherosclerosis. Angiology. 2020;71:112–121. doi: 10.1177/0003319719854609

33. Qin S. LDL and HDL oxidative modification and atherosclerosis. Adv Exp Med Biol. 2020;1276:157–169. doi: 10.1007/978-981-15-6082-8_10

34. Xu D, Ma R, Ju Y, et al. Cholesterol sulfate alleviates ulcerative colitis by promoting cholesterol biosynthesis in colonic epithelial cells. Nat Commun. 2022;13:4428. doi: 10.1038/s41467-022-32158-7

35. Schade DS, Shey L, Eaton RP. Cholesterol Review: A Metabolically Important Molecule. Endocr Pract. 2020;26:1514–1523. doi: 10.4158/EP-2020-0347

36. Bruscoli S, Febo M, Riccardi C, et al. Glucocorticoid Therapy in Inflammatory Bowel Disease: Mechanisms and Clinical Practice. Front Immunol. 2021;12:691480. doi: 10.3389/fimmu.2021.691480

37. Thomas JP, Modos D, Rushbrook SM, et al. The Emerging Role of Bile Acids in the Pathogenesis of Inflammatory Bowel Disease. Front Immunol. 2022;13:829525. doi: 10.3389/fimmu.2022.829525

38. Lavelle A, Sokol H. Gut microbiota-derived metabolites as key actors in inflammatory bowel disease. Nat Rev Gastroenterol Hepatol. 2020;17:223–237. doi: 10.1038/s41575-019-0258-z

39. Biagioli M, Marchiano S, Carino A, et al. Bile Acids Activated Receptors in Inflammatory Bowel Disease. Cells. 2021;10:1281. doi: 10.3390/cells10061281

40. Li Y, Tang R, Leung PSC, et al. Bile acids and intestinal microbiota in autoimmune cholestatic liver diseases. Autoimmun Rev. 2017;16:885–896. doi: 10.1016/j.autrev.2017.07.002