Nitric oxide and fibrinogen in patients with subclinical hypothyroidism and their possible relation to cardiovascular damage
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Abstract
Endothelial dysfunction as well as hypercoagulability have been described as the initial triggers of atherosclerosis and cardiovascular damage and have been associated with subclinical hypothyroidism (SHC). The aim of this research was to determine the concentration of nitric oxide (NO), fibrinogen and circulating lipids in patients with subclinical hypothyroidism and to correlate these variables with thyrotropin (TSH) concentration to establish their possible association with the development of cardiovascular damage. A descriptive, cross-sectional, correlational study was conducted at the IESS Hospital in Riobamba, Ecuador, in the period from January 2019 to September 2021. Ninety-five subjects were studied (65 patients with CAH and 30 controls). The concentration of total cholesterol, triglycerides, HDL cholesterol and LDL cholesterol, TSH, free thyroxine, ON and fibrinogen were determined. Results: We found a decrease in the concentration of ON (p<0.001), accompanied by an increase in the concentration of total cholesterol (p<0.0001), LDL cholesterol (p<0.01) and fibrinogen (p<0.0001) in patients with CAH vs. controls. A negative correlation (p<0.0001; r= -0.5020) was observed between TSH and ON and a positive correlation (p<0.0001; r= 5412) between TSH and plasma fibrinogen in patients with CAH. Conclusion: patients with CAH showed a decrease in serum ON levels and an elevation in plasma fibrinogen concentration. Both measurements correlated significantly with TSH concentration. These parameters associated with an increase in total cholesterol and LDL cholesterol could favor vascular dysfunction, the development of atherosclerosis and consequent cardiovascular damage.
References
Bertrand, M.J., Tardif, J.C. (2017). Inflammation and beyond: new directions and emerging drugs for treating atherosclerosis. Expert opinion on emerging drugs., 22(1), 1–26. https://doi.org/10.1080/14728214.2017.1269743.
Biondi, B., Cappola, AR., Cooper, DS. (2019). Subclinical Hypothyroidism: A Review. JAMA., 322(2), 153–160. https://doi.org/10.1001/jama.2019.9052
Cantürk, Z., Cetinarslan, B., Tarkun, I., Cantürk, NZ., Ozden, M., Duman, C. (2003). Hemostatic system as a risk factor for cardiovascular disease in women with subclinical hypothyroidism. Thyroid : official journal of the American Thyroid Association., 13(10), 971–977. https://doi.org/10.1089/105072503322511382
Chaker, L., Bianco, AC., Jonklaas, J., Peeters, RP. (2017). Hypothyroidism. Lancet (London, England)., 390(10101), 1550–1562. https://doi.org/10.1016/S0140-6736(17)30703-1
Chen, J., Shi, M., Wang, N., Yi, P., Sun, L., Meng, Q. (2019). TSH inhibits eNOS expression in HMEC-1 cells through the TSHR/PI3K/AKT signaling pathway. Annales d'endocrinologie., 80(5-6), 273–279. https://doi.org/10.1016/j.ando.2019.06.007.
Clauss, A. (1957). Gerinnungsphysiologische Schnellmethode zur Bestimmung des Fibrinogens [Rapid physiological coagulation method in determination of fibrinogen]. Acta Haematol., 17(4):237-46. German. https://doi: 10.1159/000205234.
Dagre, AG., Lekakis, JP., Papaioannou, TG., Papamichael, CM., Koutras, DA., Stamatelopoulos, SF., Alevizaki, M. (2005). Arterial stiffness is increased in subjects with hypothyroidism. Int J Cardiol., 103(1):1-6. https://doi: 10.1016/j.ijcard.2004.05.068.
Dagre, AG., Lekakis, JP., Protogerou, AD., Douridas, GN., Papaioannou, TG., Tryfonopoulos, DJ., Papamichael, CM., Alevizaki, M. (2007). Abnormal endothelial function in female patients with hypothyroidism and borderline thyroid function. Int J Cardiol., 114(3):332-8. https://doi: 10.1016/j.ijcard.2005.12.013.
Drouet, L., Bal Dit Sollier, C. (2002). Fibrinogène et risque d'accident cardio-vasculaire [Fibrinogen: factor and marker of cardiovascular risk]. J Mal Vasc., 27(3):143-56. French.
Erem, C. (2006). Blood coagulation, fibrinolytic activity and lipid profile in subclinical thyroid disease: subclinical hyperthyroidism increases plasma factor X activity. Clin Endocrinol (Oxf)., 64(3):323-9. https://doi: 10.1111/j.1365-2265.2006.02464.x.
Farah, C., Michel, LYM., Balligand, JL. (2018). Nitric oxide signalling in cardiovascular health and disease. Nat Rev Cardiol., 15(5):292-316. https://doi: 10.1038/nrcardio.2017.224.
Förstermann, U., Sessa, WC. (2012). Nitric oxide synthases: regulation and function. Eur Heart J., 33(7):829-37, 837a-837d. https://doi: 10.1093/eurheartj/ehr304.
Ghimire, K., Altmann, HM., Straub, AC., Isenberg, JS. (2017). Nitric oxide: what's new to NO? Am J Physiol Cell Physiol., 312(3):C254-C262. https://doi: 10.1152/ajpcell.00315.2016. Epub 2016 Dec 14.
Gluvic, ZM., Sudar-Milovanovic, EM., Samardzic, VS., Obradovic, MM., Jevremovic, DP., Radenkovic, SP., Isenovic, ER. (2019). Serum nitric oxide levels correlate with quality of life questionnaires scores of hypothyroid females. Med Hypotheses., 131:109299. https://doi: 10.1016/j.mehy.2019.109299.
Golia, E., Limongelli, G., Natale, F., Fimiani, F., Maddaloni, V., Pariggiano, I., Bianchi, R., Crisci, M., D'Acierno, L., Giordano, R., Di Palma, G., Conte, M., Golino, P., Russo, MG., Calabrò, R., Calabrò, P. (2014). Inflammation and cardiovascular disease: from pathogenesis to therapeutic target. Curr Atheroscler Rep., 16(9):435. https://doi: 10.1007/s11883-014-0435-z.
Hak, AE., Pols, HA., Visser, TJ., Drexhage, HA., Hofman, A., Witteman, JC. (2000). Subclinical hypothyroidism is an independent risk factor for atherosclerosis and myocardial infarction in elderly women: the Rotterdam Study. Ann Intern Med., 132(4):270-8. https://doi: 10.7326/0003-4819-132-4-200002150-00004.
Hevel, JM., Marletta, MA. (1994). Nitric-oxide synthase assays. Methods Enzymol., 233:250–8.
Infante, T., Costa, D., Napoli, C. (2021). Novel Insights Regarding Nitric Oxide and Cardiovascular Diseases. Angiology., 72(5):411-425. https://doi: 10.1177/0003319720979243.
Itakura, H., Sobel, BE., Boothroyd, D., Leung, LL., Iribarren, C., Go, AS., Fortmann, SP., Quertermous, T., Hlatky, MA. (2007). Atherosclerotic Disease, Vascular Function and Genetic Epidemiology Advance (ADVANCE) Study. Do plasma biomarkers of coagulation and fibrinolysis differ between patients who have experienced an acute myocardial infarction versus stable exertional angina? Am Heart J., 154(6):1059-64. https://doi: 10.1016/j.ahj.2007.09.015.
Kvetny, J., Heldgaard, PE., Bladbjerg, EM., Gram, J. (2004). Subclinical hypothyroidism is associated with a low-grade inflammation, increased triglyceride levels and predicts cardiovascular disease in males below 50 years. Clin Endocrinol (Oxf)., 61(2):232-8. https://doi: 10.1111/j.1365-2265.2004.02088.x.
Lindeman, RD., Romero, LJ., Schade, DS., Wayne, S., Baumgartner, RN., Garry, PJ. (2003). Impact of subclinical hypothyroidism on serum total homocysteine concentrations, the prevalence of coronary heart disease (CHD), and CHD risk factors in the New Mexico Elder Health Survey. Thyroid., 13(6):595-600. https://doi: 10.1089/105072503322238863.
Lowe, GD., Wood, DA., Douglas, JT., Riemersma, RA., Macintyre, CC., Takase, T., Tuddenham, EG., Forbes, CD., Elton, RA., Oliver, MF. (1991). Relationships of plasma viscosity, coagulation and fibrinolysis to coronary risk factors and angina. Thromb Haemost., 8;65(4):339-43.
Lundberg, JO., Gladwin, MT., Ahluwalia, A., Benjamin, N., Bryan, NS., Butler, A., Cabrales, P., Fago, A., Feelisch, M., Ford, PC., Freeman, BA., Frenneaux, M., Friedman, J., Kelm, M., Kevil, C G., Kim-Shapiro, DB., Kozlov, AV., Lancaster, JR., Jr, Lefer, DJ., McColl, K., Weitzberg, E. (2009). Nitrate and nitrite in biology, nutrition and therapeutics. Nature chemical biology., 5(12), 865–869. https://doi.org/10.1038/nchembio.260
Luyendyk, JP., Schoenecker, JG., Flick, MJ. (2019). The multifaceted role of fibrinogen in tissue injury and inflammation. Blood., 133(6), 511–520. https://doi.org/10.1182/blood-2018-07-818211
McQuade, C., Skugor, M., Brennan, DM., Hoar, B., Stevenson, C., Hoogwerf, BJ. (2011). Hypothyroidism and moderate subclinical hypothyroidism are associated with increased all-cause mortality independent of coronary heart disease risk factors: a PreCIS database study. Thyroid., 21(8):837-43. https://doi: 10.1089/thy.2010.0298.
Müller, B., Tsakiris, DA., Roth, CB., Guglielmetti, M., Staub, JJ., Marbet, GA. (2001). Haemostatic profile in hypothyroidism as potential risk factor for vascular or thrombotic disease. Eur J Clin Invest., 31(2):131-7. https://doi: 10.1046/j.1365-2362.2001.00777.x.
Obradovic, M., Gluvic, Z., Sudar-Milovanovic, E., Panic, A., Trebaljevac, J., Bajic, V., Zarkovic, M., Isenovic, ER. (2016). Nitric Oxide as a Marker for Levo-Thyroxine Therapy in Subclinical Hypothyroid Patients. Curr Vasc Pharmacol., 14(3):266-70. https://doi: 10.2174/1570161114666160208143537.
Peeters, RP. (2017). Subclinical Hypothyroidism. N Engl J Med., 5;377(14):1404. https://doi: 10.1056/NEJMc1709853.
Sue, LY., Leung, AM. (2020). Levothyroxine for the Treatment of Subclinical Hypothyroidism and Cardiovascular Disease. Front Endocrinol (Lausanne)., 21;11:591588. https://doi: 10.3389/fendo.2020.591588.
Tesauro, M., Mauriello, A., Rovella, V., Annicchiarico-Petruzzelli, M., Cardillo, C., Melino, G., Di Daniele, N. (2017). Arterial ageing: from endothelial dysfunction to vascular calcification. J Intern Med., 281(5):471-482. https://doi: 10.1111/joim.12605.
Thompson, WD., Smith, EB. (1989). Atherosclerosis and the coagulation system. J Pathol., 159(2):97-106. https://doi: 10.1002/path.1711590203.
Tousoulis, D., Kampoli, AM., Tentolouris, C., Papageorgiou, N., Stefanadis, C. (2012). The role of nitric oxide on endothelial function. Curr Vasc Pharmacol., 10(1):4-18. https://doi: 10.2174/157016112798829760.
Tousoulis, D., Papageorgiou, N., Androulakis, E., Briasoulis, A., Antoniades, C., Stefanadis, C. (2011). Fibrinogen and cardiovascular disease: genetics and biomarkers. Blood Rev., 25(6):239-45. https://doi: 10.1016/j.blre.2011.05.001.
Yang, C., Lu, M., Chen, W., He, Z., Hou, X., Feng, M., Zhang, H., Bo, T., Zhou, X., Yu, Y., Zhang, H., Zhao, M., Wang, L., Yu, C., Gao, L., Jiang, W., Zhang, Q., & Zhao, J. (2019). Thyrotropin aggravates atherosclerosis by promoting macrophage inflammation in plaques. The Journal of experimental medicine., 216(5), 1182–1198. https://doi.org/10.1084/jem.20181473
Yasar, H Y., Demirpence, M., Colak, A., Yurdakul, L., Zeytinli, M., Turkon, H., Ekinci, F., Günaslan, A., Yasar, E. (2019). Serum irisin and apelin levels and markers of atherosclerosis in patients with subclinical hypothyroidism. Archives of endocrinology and metabolism., 63(1), 16–21. https://doi.org/10.20945/2359-3997000000106.
Zhang, X., Shao, S., Geng, H., Yu, Y., Wang, C., Liu, Z., Yu, C., Jiang, X., Deng, Y., Gao, L., Zhao, J. (2014). Expression profiles of six circulating microRNAs critical to atherosclerosis in patients with subclinical hypothyroidism: a clinical study. J Clin Endocrinol Metab., 99(5): E766-74. https://doi: 10.1210/jc.2013-1629.