A CROSS-SECTIONAL STUDY OF INFLAMMATORY MARKERS AND HOMOCYSTEINE IN PREDICTING ATHEROSCLEROTIC CARDIOVASCULAR RISK IN PRE, PERI, AND POSTMENOPAUSAL WOMEN

Main Article Content

P. Samatha1,2, *V. Siva Prabodh2, E. Sukumar1, S. Xavier3.

Keywords

Inflammatory markers; Homocysteine; Atherosclerotic Cardiovascular diseases; Menopause.

Abstract

Background: Atherosclerotic cardiovascular diseases (ASCVD) and its consequences are heavily influenced by inflammatory markers and homocysteine. Some research has been done on CVD biomarkers in postmenopausal women, but none has yet focused on perimenopausal women. Methods: In this study, 210 women between the ages of 20 and 65 who visited the Gynecology Outpatient Department of a tertiary care hospital were enrolled and stratified according to the Stages of Reproductive Aging Workshop (STRAW) classification into premenopausal, perimenopausal, and postmenopausal groups. In addition to homocysteine (Hcy), lipid parameters, and estradiol, inflammatory markers such as high sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and fibrinogen were estimated from their blood samples. Results: In perimenopausal and postmenopausal women, researchers found that the levels of inflammatory markers and Hcy were higher, and a strong positive association was identified between them. Conclusions: The significant association between inflammatory markers and Hcy in perimenopausal women, could be considered as a potential biomarker for atherosclerotic cardiovascular disease (ASCVD) in postmenopausal women.

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1. Kuznetsova T, Prange KHM, Glass CK, de Winther MPJ. Transcriptional and epigenetic regulation of macrophages in atherosclerosis. Nat Rev Cardiol 2020;17(4):216-228. http:/doi: 10.1038/s41569-019-0265-3. PMID: 31578516; PMCID: PMC7770754. 2. Howard Alpe GM, Sear JW, Foex P. Methods of detecting atherosclerosis in non-cardiac surgical patients; the role of biochemical markers. Br J Anaesth 2006;97(6):758-769. https://doi.org/10.1093/bja/ael303. PMID: 17074779. 3. Blake GJ, Ridker PM. C-reactive protein: a surrogate risk marker or mediator of atherothrombosis? Am J Physiol Regul Integr Comp Physiol 2003; 285(5): R1250-1252. https://doi.org/10.1152/ajpregu.00227.2003. PMID: 14557240. 4. Harlow SD, Gass M, Hall JE,Lobo R, Maki P, Rebar RW, et al. Executive summary of the Stages of Reproductive Aging Workshop + 10: addressing the unfinished agenda of staging reproductive aging. Menopause 2012;19(4):387-395. https://doi.org/10.1097/gme.0b013e31824d8f40. PMID: 22343510; PMCID: PMC3340903. 5. Allain CC, Poon LS, Chan CS, Richmond W, Fu PC. Enzymatic Determination of Total Cholesterol in Serum. Clin. Chem 1974; 20:470-475. PMID: 4818200. 6. Spayd R, Spayd RW, Bruschi B, Burdick BA, Dappen GM, Eikenberry JN, Esders TW,et al (1978). Multilayer Film Elements for Clinical Analysis:applications to representative chemical determinations. Clin. Chem 1978;24(8):1343–1350. 7. Burstein M, Scholnick HR, Morfin R. Rapid Method for the Isolation of Lipoproteins from Human Serum by Precipitation with Polyanions. J. Lipid Research 1970;11:583-595. PMID: 4100998. 8. Clauss A. Rapid physiological coagulation method in determination of fibrinogen. Acta Haematol. 1957; 17(4): 237-246.https://doi.org/10.1159/000205234. PMID: 13434757. 9. Varu, D. S., Vegad, D. M., Jani, D. H. A. Savalia CV, varsha S Joshi. A Comparative Study of Serum Lipid Profile between Premenopausal And Postmenopausal Women.: Study Of Lipid Profile In Pre And Post Menopausal Women. National Journal of Integrated Research in Medicine 2012; 3(1): 43–45. https://doi.org/nicpd.ac.in/ojs-/index.php/njirm/article/view/1964. 10. DL Cozlea, DM Farcas, A Nagy, Keresztesi AA, Tifrea R, Cozlea L, et al.The impact of C-reactive protein on global cardiovascular risk on patients with coronary artery disease. Curr Health Sci J 2013;39: 225-231. PMID: 24778862; PMCID: PMC3945266. 11. M. Abu-Taha, C. Rius C, Hermenegildo C, Noguera I, Cerda-Nicolas JM, Issekutz AC, et al. Menopause and ovariectomy cause a low grade of systemic inflammation that may be prevented by chronic treatment with low doses of estrogen or losartan. Journal of Immunology 2009;183(2):1393–1402. https://doi.org/10.4049/jimmunol.0803157. PMID: 19553526. 12. Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 2000;342(12):836–843. https://doi.org/10.1056/NEJM200003233421202. PMID: 10733371. 13. Suguna S, Mary PJ. Association of menopause with inflammation sensitive protein the c-reactive protein among the indian women. Journal of Evolution of Medical and Dental Sciences 2013;2(52):10144‒10153. 14. Devaraj S, Venugopal S, Jialal I. Native pentameric C-reactive protein displays more potent pro-atherogenic activities in human aortic endothelial cells than modified C-reactive protein. Atherosclerosis 2006;184:48–52. https://doi.org/10.1016/j.atherosclerosis.2005.03.031. PMID: 15894319. 15. Ridker PM, Rifai N, Stampfer MJ, Hennekens CH. Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation 2000; 101(15): 1767–1772.https://doi.org/10.1161/01.cir.101.15.1767. PMID: 10769275. 16. Han KH, Hong KH, Park JH, Ko J, Kang DH, Choi KJ, et al. C-reactive protein promotes monocyte chemoattractant protein-1-mediated chemotaxis through upregulating CC chemokine receptor 2 expression in human monocytes. Circulation 2004;109(21):2566–2571. https://doi.org/10.1161/01.CIR.0000131160.94926.6E. PMID: 15136507. 17. Dana Pop, Alexandra Dadarlat, D Zdrenghea. Novel cardiovascular risk markers in women with ischemic heart disease. Cardiovasc J Afr 2014;25(3): 137-141. https://doi.org/10.5830/CVJA-2014-014. PMID: 25000444; PMCID: PMC4120125. 18. Kim OY, Chae JS, Paik JK, Seo HS, Jang Y, Cavaillon JM, Lee JH. Effects of aging and menopause on serum interleukin-6 levels and peripheral blood mononuclear cell cytokine production in healthy nonobese women. Age (Dordr) 2012;34(2): 415-425. https://doi.org/10.1007/s11357-011-9244-2. PMID: 21487705; PMCID: PMC3312621. 19. Canonico M, Brailly-Tabard S, Gaussem P, Setiao J, Rouaud O, Ryan J, et al. Endogenous oestradiol as a positive correlate of plasma fibrinogen among older postmenopausal women: a population-based study (the Three-City cohort study). Clinical Endocrinology 2012; 77(6):905-910.https://doi.org/10.1111/j.1365-2265.2012.04448.x. PMID: 22642405. 20. Miyao Y, Yasue H, Ogawa H, Misumi I, Masuda T, Sakamoto T, et al. Elevated plasma interleukin-6 levels in patients with acute myocardial infarction. Am Heart J 1993;126(6):1299-1304.https://doi.org/10.1016/0002-8703(93)90526-f.PMID: 8249785. 21. Shenov V, Mehendale V, Prabhu K Shetty R, Rao P.Correlation of serum homocysteine levels with the severity of coronary artery disease. Ind J Clin Biochem 2014;29(3):339–344.https://doi.org/10.1007/s12291-013-0373-5. PMID: 24966483; PMCID: PMC4062675. 22. Ozkan Y, Ozkan E, Simsek B. Plasma total homocysteine and cysteine levels as cardiovascularrisk factors in coronary heart disease. Int J Cardiol 2002;82(3):269-277. https://doi.org/10.1016/s0167-5273(02)00010-4. PMID: 11911915. 23. Zhu Z, Jiang S, Li C Liu J, Tao M. Relationship between serum homocysteine and different menopausal stage. Climacteric 2020.23(1):59-64. https://doi.org/10.1080/13697137.2019.1634045. PMID: 31294633. 24. Antoniades C, Antonopoulos AS, Tousoulis D, Marinou K, Stefanadis C. Homocysteine and coronary atherosclerosis: from folate fortification to the recent clinical trials. Eur Heart J 2009;30(1):6–15.https://doi.org/10.1093/eurheartj/ehn515. PMID: 19029125. 25. Naruszewicz M, Mirkiewicz E, Olszewski AJ. Thiolation of low-density lipoprotein by homocysteine thiolactone causes increased aggregation and altered interaction with cultured macrophages. Nutr Metab Cardiovasc Dis 1994;4:70–77. 26. Stampfer MJ, Colditz GA, Willett WC. Menopause and heart disease. A review. Ann N Y Acad Sci 1990. 592:193–203.https://doi.org/10.1111/j.1749-6632.1990.tb30329.x. PMID: 2197944. 27. Jensen J, Nilas L, Christiansen C. Influence of menopause on serum lipids and lipoproteins. Maturitas 1990;12(4):321–331.https://doi.org/10.1016/0378-5122(90)90012-u. PMID: 2124647. 28. Riedel M, Rafflenbeul W, Lichtlen P. Ovarian sex steroids and atherosclerosis. Clin Investig 1993; 71(5):406-412. https://doi.org/10.1007/BF00186631. PMID: 8508011. 29. Arenas IA, Armstrong SJ, Xu Y Davidge ST. Chronic tumor necrosis factor-alpha inhibition enhances NO modulation of vascular function in estrogen-deficient rats. Hypertension 2005;46(1):76-81. https://doi.org/10.1161/01. PMID: 15911738. 30. Huang H, He J, Yuan Y, Eriko Aoyagi , Hidetaka Takenaka , Tatuzo Itagaki, et al. Opposing effects of estradiol and progesterone on the oxidative stress-induced production of chemokine and proinflammatory cytokines in murine peritoneal macrophages. J Med Invest 2008; 55:133–141. 31. Pang X, Liu J, Zhao J, Mao J, Zhang X, Feng L, et al. Homocysteine induces the expression of C - reactive protein via NMDAr-ROS-MAPK-NF-κB signal pathway in rat vascular smooth muscle cells. Atherosclerosis 2014;236(1):73–81.https://doi.org/10.1016/j.atherosclerosis.PMID: 25016361. 32. Baszczuk A, Kopczynski Z. Hyperhomocysteinemia in patients with cardiovascular disease. Postepy Hig Med Dosw 2014;68:579-589. https://doi.org/10.5604/17322693.102340. PMID: 24864108.