Óxido nítrico y fibrinógeno en pacientes con hipotiroidismo subclínico y su posible relación con el daño cardiovascular
Barra lateral del artículo
Detalles del artículo
Esta obra está bajo una licencia internacional Creative Commons Atribución-NoComercial-SinDerivadas 4.0.
La publicación se distribuye bajo la Licencia Creative Commons Atribución- 4.0 Internacional (CC BY 4.0). Los derechos de los trabajos publicados en esta revista son propiedad del autor, los cuales son libres de distribuir y difundir las mismas, siempre que cite correctamente la fuente.
Contenido principal del artículo
Resumen
La disfunción endotelial así como la hipercoagulabilidad han sido descritas como los factores iniciales desencadenantes de la aterosclerosis y del daño cardiovascular y se han asociado con el Hipotiroidismo subclínico (HSC). El objetivo de esta investigación fue determinar la concentración de óxido nítrico (ON), fibrinógeno y lípidos circulantes en pacientes con Hipotiroidismo subclínico y correlacionar dichas variables con la concentración de tirotropina (TSH) para establecer su posible asociación con el desarrollo de daño cardiovascular. Se realizó un estudio descriptivo, correlacional de corte transversal en el Hospital IESS de Riobamba, Ecuador, en el periodo comprendido desde enero de 2019 hasta septiembre de 2021. Se estudiaron 95 sujetos (65 pacientes con HSC y 30 controles).Se determinó la concentración de colesterol total, triglicéridos, HDL colesterol y LDL colesterol, TSH, Tiroxina libre, ON y fibrinógeno. Resultados: Se encontró una disminución en la concentración de ON (p <0.001), acompañado de un incremento en la concentración de colesterol total (p <0.0001), LDL colesterol (p <0.01) y fibrinógeno (p <0.0001) en los pacientes con HSC vs los controles. Se realiza una correlación negativa (p <0.0001; r = -0.5020) entre la TSH y el ON y una correlación positiva (p <0.0001; r = 5412) entre la TSH y el fibrinógeno plasmático en los pacientes con HSC. Conclusión: los pacientes con HSC envío una disminución en los niveles séricos de ON y una elevación en la concentración plasmática de fibrinógeno.Ambas mediciones se correlacionaron significativamente con la concentración de TSH.
Citas
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.