Hakan KORKMAZ, Mürşide TAN, Hüseyin AYDIN, Duygu KUMBUL DOĞUÇ

FABP4 levels in hypothyroidism and its relationship with subclinical atherosclerosis

Background/aim: The aim of this study is to evaluate the relationship between serum fatty acid binding protein 4 (FABP4) levels andcarotid intima media thickness (CIMT) in patients with hypothyroidism.Materials and methods: Forty subclinical hypothyroidism patients, 40 overt hypothyroidism patients, and 40 healthy controls wereenrolled in the study. Blood pressure, body mass index, CIMT, fasting blood sugar, creatine, alanine aminotransferase, lipid parameters,insulin, free thyroxine, triiodothyronine, thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (anti-TPO), thyroglobulinantibody (anti-TG), high-sensitivity C-reactive protein (Hs-CRP), and FABP4 levels of all participants were measured.Results: Serum FABP4 levels were significantly higher in patients with subclinical and overt hypothyroidism than healthy controls(HCs) (P = 0.044 and P = 0.014, respectively). There was no significant difference in terms of FABP4 levels between patients withsubclinical and overt hypothyroidism (P = 0.641). Serum TSH levels and serum FABP4 levels were positively correlated (r = 0.201,P = 0.039). CIMT was found to be higher in patients with subclinical and overt hypothyroidism than in HCs (P = 0.042 and P

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1. Antunes TT, Gagnon A, Bell A, Sorisky A. Thyroid‐stimulating hormone stimulates interleukin‐6 release from 3T3‐L1 adipocytes through a cAMP‐protein kinase A pathway. Obesity Research 2005; 13 (12): 2066-2071. doi: 10.1038/oby.2005.256
2. Taddei S, Caraccio N, Virdis A, Dardano A, Versari D et al. Impaired endothelium-dependent vasodilatation in subclinical hypothyroidism: beneficial effect of levothyroxine therapy. Journal of Clinical Endocrinology & Metabolism 2003; 88 (8): 3731-3737. doi: 10.1210/jc.2003-030039
3. Lekakis J, Papamichael C, Alevizaki M, Piperingos G, Marafelia P et al. Flow-mediated, endothelium-dependent vasodilatation is impaired in subjects with hypothyroidism, borderline hypothyroidism, and high-normal serum thyrotropin (TSH) values. Thyroid 1997; 7 (3): 411-414. doi: 10.1089/thy.1997.7.411
4. Papaioannou GI, Lagasse M, Mather JF, Thompson PD. Treating hypothyroidism improves endothelial function. Metabolism 2004; 53 (3): 278-279. doi: 10.1016/j.metabol.2003.10.003
5. Giannotti G, Landmesser U. Endothelial dysfunction as an early sign of atherosclerosis. Herz 2007; 32 (7): 568-572. doi: 10.1007/s00059-007-3073-1
6. Milani AT, Khadem-Ansari MH, Rasmi Y. Effects of thyroidstimulating hormone on adhesion molecules and pro-inflammatory cytokines secretion in human umbilical vein endothelial cells. Research in Pharmaceutical Sciences 2018; 13 (6): 546-556. doi: 10.4103/1735-5362.245966
7. Ahn N, Kim HS, Kim K. Exercise training–induced changes in metabolic syndrome parameters, carotid wall thickness, and thyroid function in middle-aged women with subclinical hypothyroidism. Pflugers Archiv-European Journal of Physiology 2019; 471 (3): 479-489. doi: 10.1007/s00424-019-02254-7
8. Hak AE, Pols HA, Visser TJ, Drexhage HA et al. Subclinical hypothyroidism is an independent risk factor for atherosclerosis and myocardial infarction in elderly women: the Rotterdam Study. Annals of Internal Medicine 2000; 132 (4): 270-278. doi: 10.7326/0003-4819-132-4-200002150-00004
9. Bielecka-Dabrowa A, Godoy B, Suzuki T, Banach M, von Haehling S. Subclinical hypothyroidism and the development of heart failure: an overview of risk and effects on cardiac function. Clinical Research in Cardiology 2019; 108 (3): 225-233. doi: 10.1007/s00392-018-1340-1
10. Elbers LP, Squizzato A, Gerdes VEA. Thyroid disorders and hemostasis. Seminars in Thrombosis and Haemostasis 2018; 44 (7): 676-682. doi: 10.1055/s-0038-1666825
11. de Miranda ÉJFP, Bittencourt MS, Santos IS, Lotufo PA, Benseñor IM. Thyroid function and high-sensitivity C-reactive protein in cross-sectional results from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil): effect of adiposity and insulin resistance. European Thyroid Journal 2016; 5 (4): 240- 246. doi: 10.1159/000448683
12. Singh S, Sarkar PD. Serum lipids, tHcy, hs-CRP, MDA and PON-1 levels in SCH and overt hypothyroidism: effect of treatment. Acta Biomedica 2014; 85 (2): 127-134.
13. Furuhashi M, Saitoh S, Shimamoto K, Miura T. Fatty acidbinding protein 4 (FABP4): pathophysiological insights and potent clinical biomarker of metabolic and cardiovascular diseases. Clinical Medicine Insights Cardiology 2014; 8 (Suppl. 3): 23-33. doi: 10.4137/CMC.S17067
14. Gürer MA, Gökalp H. Psoriasis and obesity. Turkish Archives of Dermatology and Venereology 2012; 46 (1): 3-6. doi: 10.4274/turkderm.98215
15. Makowski L, Boord JB, Maeda K, Babaev VR, Uysal KT et al. Lack of macrophage fatty-acid–binding protein aP2 protects mice deficient in apolipoprotein E against atherosclerosis. Nature Medicine 2001; 7 (6): 699-705. doi: 10.1038/89076
16. Obregon MJ. Adipose tissues and thyroid hormones. Frontiers in Physiology 2014; 5: 479. doi: 10.3389/fphys.2014.00479
17. Levy JC, Matthews DR, Hermans MP. Correct homeostasis model assessment (HOMA) evaluation uses the computer program. Diabetes Care 1998; 21 (12): 2191-2192. doi: 10.2337/diacare.21.12.2191
18. Hennessey JV, Espaillat R. Diagnosis and management of subclinical hypothyroidism in elderly adults: a review of the literature. Journal of American Geriatrics Society 2015; 63 (8): 1663-1673. doi: 10.1111/jgs.13532
19. Cappola AR, Ladenson PW. Hypothyroidism and atherosclerosis. Journal of Clinical Endocrinology & Metabolism 2003; 88 (6): 2438-2444. doi: 10.1210/jc.2003-030398
20. Mitu F, Cojocaru E, Tamba B, Leon M. Prevalence of cardiovascular diseases in patients with hypothyroidism. Revista Medico-Chirurgicala a Societatii de Medici si Naturalisti din Iasi 2012; 116 (2): 413-418.
21. Garber AM, Avins AL. Triglyceride concentration and coronary heart disease. British Medical Journal 1994; 309 (6966): 1440-1441. doi: 10.1136/bmj.309.6966.1440a
22. Manninen V, Elo MO, Frick MH, Haapa K, Heinonen OP et al. Lipid alterations and decline in the incidence of coronary heart disease in the Helsinki Heart Study. Journal of the American Medical Association 1998; 260 (5): 641-651. doi: 10.1001/ jama.1988.03410050061031
23. Kahaly GJ. Cardiovascular and atherogenic aspects of subclinical hypothyroidism. Thyroid 2000; 10 (8): 665-679. doi: 10.1089/10507250050137743
24. Tunbridge W, Evered D, Hall R, Appleton D, Brewis M et al. The spectrum of thyroid disease in a community: the Whickham survey. Clinical Endocrinology 1977; 7 (6): 481-493. doi: 0.1111/j.1365-2265.1977.tb01340.x
25. Razvi S, Weaver JU, Vanderpump MP, Pearce SH. The incidence of ischemic heart disease and mortality in people with subclinical hypothyroidism: reanalysis of the Whickham Survey cohort. Journal of Clinical Endocrinology & Metabolism 2010; 95 (4): 1734-1740. doi: 10.1210/jc.2009-1749
26. Nagasaki T, Inaba M, Kumeda Y, Ueda M, Hiura Y et al. Decrease of arterial stiffness at common carotid artery in hypothyroid patients by normalization of thyroid function. Biomedicine & Pharmacotherapy 2005; 59 (1-2): 8-14. doi: 10.1016/j.biopha.2004.11.001
27. Saric MS, Jurasic MJ, Sovic S, Kranjcec B, Glivetic T et al. Dyslipidemia in subclinical hypothyroidism requires assessment of small dense low density lipoprotein cholesterol (sdLDL-C). Romanian Journal of Internal Medicine 2017; 55 (3): 159-166. doi: 10.1515/rjim-2017-0015
28. Abreu IM, Lau E, de Sousa Pinto B, Carvalho D (2017). Subclinical hypothyroidism: to treat or not to treat, that is the question! A systematic review with meta-analysis on lipid profile. Endocrine Connections 2017; 6 (3): 188-199. doi: 10.1530/EC-17-0028
29. Kanaya AM, Harris F, Volpato S, Pérez-Stable EJ, Harris T et al. Association between thyroid dysfunction and total cholesterol level in an older biracial population: the health, aging and body composition study. Archives of Internal Medicine 2002; 162 (7): 773-779. doi: 10.1001/archinte.162.7.773
30. Tognini S, Polini A, Pasqualetti G, Ursino S, Caraccio N et al. Age and gender substantially influence the relationship between thyroid status and the lipoprotein profile: results from a large cross-sectional study. Thyroid 2012; 22 (11): 1096-1103. doi: 10.1089/thy.2012.0013
31. Badimon L, Peña E, Arderiu G, Padró T, Slevin M et al. C-reactive protein in atherothrombosis and angiogenesis. Frontiers in Immunology 2018; 9: 430. doi: 10.3389/fimmu.2018.00430
32. Kang ES, Kim HJ, Kim YM, Lee S, Cha BS et al. Serum high sensitivity C-reactive protein is associated with carotid intima-media thickness in type 2 diabetes. Diabetes Research and Clinical Practice 2004; 66 (Suppl. 1): 115-120. doi: 10.1016/j. diabres.2004.05.009
33. Yadav R. Dyslipidemia associated with subclinical hypothyroidism in Eastern Nepal. American Journal of the Medical Sciences 2014; 5: 23-25. doi: 10.3126/ajms.v5i3.9251
34. Bell RJ, Rivera‐Woll L, Davison SL, Topliss DJ, Donath S et al. Well‐being, health‐related quality of life and cardiovascular disease risk profile in women with subclinical thyroid disease– a community‐based study. Clinical Endocrinology 2007; 66 (4): 548-556. doi: 10.1111/j.1365-2265.2007.02771.x
35. Tuzcu A, Bahceci M, Gokalp D, Tuzun Y, Gunes K. Subclinical hypothyroidism may be associated with elevated high-sensitive c-reactive protein (low grade inflammation) and fasting hyperinsulinemia. Endocrine Journal 2005; 52 (1): 89-94. doi: 10.1507/endocrj.52.89
36. Zeng J, Zhang Y, Hao J, Sun Y, Liu S et al. Stearic acid induces CD11c expression in proinflammatory macrophages via epidermal fatty acid binding protein. Journal of Immunology 2018; 200 (10): 3407-3419. doi: 10.4049/jimmunol.1701416
37. Aragonès G, Saavedra P, Heras M, Cabré A, Girona J et al. Fatty acid-binding protein 4 impairs the insulin-dependent nitric oxide pathway in vascular endothelial cells. Cardiovascular Diabetology 2012; 11: 72. doi: 10.1186/1475-2840-11-72
38. Lee MY, Li H, Xiao Y, Zhou Z, Xu A et al. Chronic administration of BMS309403 improves endothelial function in apolipoprotein E‐deficient mice and in cultured human endothelial cells. British Journal of Pharmacology 2011; 162 (7): 1564- 1576. doi: 10.1111/j.1476-5381.2010.01158.x
39. Rodríguez‐Mañas L, El‐Assar M, Vallejo S, López‐Dóriga P, Solís J et al. Endothelial dysfunction in aged humans is related with oxidative stress and vascular inflammation. Aging Cell 2009; 8 (3): 226-238. doi: 10.1111/j.1474-9726.2009.00466.x
40. Saif A, Mousa S, Assem M, Tharwat N, Abdelhamid A. Endothelial dysfunction and the risk of atherosclerosis in overt and subclinical hypothyroidism. Endocrine Connections 2018; 7 (10): 1075-1080. doi: 10.1530/EC-18-0194
41. Singh B, Sinha R, Yen P. Novel transcriptional mechanisms for regulating metabolism by thyroid hormone. International Journal of Molecular Sciences 2018; 19 (10): 3284. doi: 10.3390/ijms19103284
42. Ota H, Furuhashi M, Ishimura S, Koyama M, Okazaki Y et al. Elevation of fatty acid-binding protein 4 is predisposed by family history of hypertension and contributes to blood pressure elevation. American Journal of Hypertension 2012; 25 (10): 1124-1130. doi: 10.1038/ajh.2012.88
43. Xu A, Wang Y, Xu JY, Stejskal D, Tam S et al. Adipocyte fatty acid–binding protein is a plasma biomarker closely associated with obesity and metabolic syndrome. Clinical Chemistry 2006; 52 (3): 405-413. doi: 10.1373/clinchem.2005.062463
44. Chow WS, Tso AWK, Xu A, Yuen MMA, Fong CHY et al. Elevated circulating adipocyte-fatty acid binding protein levels predict incident cardiovascular events in a community-based cohort: a 12-year prospective study. Journal of the American Heart Association 2013; 2 (1): e004176. doi: 10.1161/ JAHA.112.004176
45. Furuhashi M, Tuncman G, Görgün CZ, Makowski L, Atsumi G et al. Treatment of diabetes and atherosclerosis by inhibiting fatty-acid-binding protein aP2. Nature 2007; 447 (7147): 959. doi: 10.1038/nature05844
46. Kahaly GJ. Cardiovascular and atherogenic aspects of subclinical hypothyroidism. Thyroid 2000; 10 (8): 665-679. doi: 10.1089/10507250050137743
47. Walsh JP, Bremner AP, Bulsara MK, O’Leary P, Leedman PJ et al. Subclinical thyroid dysfunction as a risk factor for cardiovascular disease. Archives of Internal Medicine 2005; 165 (21): 2467-2472. doi: 10.1001/archinte.165.21.2467
48. Selmer C, Olesen JB, Hansen ML, von Kappelgaard LM, Madsen JC et al. Subclinical and overt thyroid dysfunction and risk of all-cause mortality and cardiovascular events: a large population study. Journal of Clinical Endocrinology & Metabolism 2014; 99 (7): 2372-2382. doi: 10.1210/jc.2013-4184
49. Moon S, Kim MJ, Yu JM, Yoo HJ, Park YJ. Subclinical hypothyroidism and the risk of cardiovascular disease and all-cause mortality: a meta-analysis of prospective cohort studies. Thyroid 2018; 28 (9): 1101-1110. doi: 10.1089/thy.2017.0414
50. Ebrahim S, Papacosta O, Whincup P, Wannamethee G, Walker M et al. Carotid plaque, intima media thickness, cardiovascular risk factors, and prevalent cardiovascular disease in men and women: the British Regional Heart Study. Stroke 1999; 30 (4): 841-850. doi: 10.1161/01.str.30.4.841
51. Önder E, Aydın Y, Güngör A, Celbek G, Kır S et al. Carotis intima media thickness in female patiens with subclinical hypothyroidism. Turkish Journal of Endocrinology and Metabolism 2010; 14: 89-94 (in Turkish with English abstract).