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Subclinical hypothyroidism is associated with elevated high-sensitive C-reactive protein among adult Taiwanese

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Abstract

Subjects with subclinical hypothyroidism (SCH) are at increased risk for cardiovascular disease (CVD). High-sensitivity C-reactive protein (hsCRP) is one of the inflammatory markers related to CVD. It is unclear whether inflammation is a mechanistic intermediary between SCH and CVD. We aimed to investigate the association between SCH and hsCRP in a Taiwanese population. A baseline cohort of 2,494 participants over the age of 19 was recruited in Taiwan from 2006 to 2008. SCH was defined as a serum thyroid-stimulating hormone (TSH) level of 5.61–19.9 mIU/L with normal thyroxine concentrations (a total T4 level of 4.9–12.0 μg/dL). Euthyroidism was defined as a serum TSH level of 0.34–5.60 mIU/L. HsCPR was grouped using quartiles. Multiple logistic and linear regression analyses were used to evaluate the relationship between hsCRP and SCH. After adjusting for gender and betel nut chewing, stepwise multiple logistic regression analyses revealed that hsCRP groups were significantly associated with SCH. Compared to the lowest hsCRP quartile, the adjusted odds ratio of having SCH for hsCRP quartile II, III, and IV were 1.38 (0.48–3.98), 1.48 (0.56–3.96), and 2.59 (1.01–6.67), respectively. The significant increase in odds ratios for SCH in progressive hsCRP quartiles reveals a dose–response effect (p < 0.05). Moreover, stepwise multiple linear regression analyses showed that hsCRP was significantly positively associated with serum TSH level after adjusting for potential confounders. Adult Taiwanese with SCH were associated with elevated hsCRP quartiles.

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References

  1. J.G. Hollowell, N.W. Staehling, W.D. Flanders, W.H. Hannon, E.W. Gunter, C.A. Spencer, L.E. Braverman, Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J. Clin. Endocrinol. Metab. 87, 489–499 (2002)

    Article  PubMed  CAS  Google Scholar 

  2. J. Karmisholt, S. Andersen, P. Laurberg, Variation in thyroid function tests in patients with stable untreated subclinical hypothyroidism. Thyroid 18, 303–308 (2008)

    Article  PubMed  Google Scholar 

  3. V. Fatourechi, Subclinical hypothyroidism: an update for primary care physicians. Mayo Clin. Proc. 84, 65–71 (2009)

    Article  PubMed  Google Scholar 

  4. T. Tzotzas, G.E. Krassas, T. Konstantinidis, M. Bougoulia, Changes in lipoprotein(a) levels in overt and subclinical hypothyroidism before and during treatment. Thyroid 10, 803–808 (2000)

    Article  PubMed  CAS  Google Scholar 

  5. H. Gharib, R.M. Tuttle, H.J. Baskin, L.H. Fish, P.A. Singer, M.T. McDermott, Subclinical thyroid dysfunction: a joint statement on management from the American Association of Clinical Endocrinologists, the American Thyroid Association, and the Endocrine Society. J. Clin. Endocrinol. Metab. 90, 581–585 (2005). discussion 586-587

    Article  PubMed  CAS  Google Scholar 

  6. A.E. Hak, H.A. Pols, T.J. Visser, H.A. Drexhage, A. Hofman, J.C. Witteman, Subclinical hypothyroidism is an independent risk factor for atherosclerosis and myocardial infarction in elderly women: the Rotterdam Study. Ann. Intern. Med. 132, 270–278 (2000)

    Article  PubMed  CAS  Google Scholar 

  7. V.N. Valentina, B. Marijan, D. Chedo, K. Branka, Subclinical hypothyroidism and risk to carotid atherosclerosis. Arq. Bras Endocrinol. Metabol. 55, 475–480 (2011)

    Article  PubMed  Google Scholar 

  8. B. Biondi, E.A. Palmieri, G. Lombardi, S. Fazio, Effects of subclinical thyroid dysfunction on the heart. Ann. Intern. Med. 137, 904–914 (2002)

    Article  PubMed  Google Scholar 

  9. B. Biondi, M. Galderisi, L. Pagano, M. Sidiropulos, M. Pulcrano, D. E. A., S. Ippolito, A. Rossi, O. de Divitiis, G. Lombardi, Endothelial-mediated coronary flow reserve in patients with mild thyroid hormone deficiency. Eur. J. Endocrinol. 161, 323–329 (2009)

    Article  PubMed  CAS  Google Scholar 

  10. J. Jiskra, Z. Limanova, M. Antosova, Thyroid diseases, dyslipidemia and cardiovascular risk. Vnitr. Lek. 53, 382–385 (2007)

    PubMed  CAS  Google Scholar 

  11. T. Shavdatuashvili, Lipoprotein profile and endothelial function in patients with subclinical and overt hypothyroidism. Georgian Med. News 129, 57–60 (2005)

    PubMed  Google Scholar 

  12. P.J. Owen, R. Sabit, J.H. Lazarus, Thyroid disease and vascular function. Thyroid 17, 519–524 (2007)

    Article  PubMed  CAS  Google Scholar 

  13. E.N. Pearce, In people with subclinical hypothyroidism, TSH level >10 mIU/l may predict increased risk of coronary heart disease and related mortality. Evid. Based Med. 16, 31–32 (2011)

    Article  PubMed  Google Scholar 

  14. C. McQuade, M. Skugor, D.M. Brennan, B. Hoar, C. Stevenson, B.J. Hoogwerf, 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, 837–843 (2011)

    Article  PubMed  Google Scholar 

  15. N. Rodondi, W.P. den Elzen, D.C. Bauer, A.R. Cappola, S. Razvi, J.P. Walsh, B.O. Asvold, G. Iervasi, M. Imaizumi, T.H. Collet, A. Bremner, P. Maisonneuve, J.A. Sgarbi, K.T. Khaw, M.P. Vanderpump, A.B. Newman, J. Cornuz, J.A. Franklyn, R.G. Westendorp, E. Vittinghoff, J. Gussekloo, Subclinical hypothyroidism and the risk of coronary heart disease and mortality. JAMA 304, 1365–1374 (2010)

    Article  PubMed  CAS  Google Scholar 

  16. F.Y. Tseng, W.Y. Lin, C.C. Lin, L.T. Lee, T.C. Li, P.K. Sung, K.C. Huang, Subclinical hypothyroidism is associated with increased risk for all-cause and cardiovascular mortality in adults. J. Am. Coll. Cardiol. 60, 730–737 (2012)

    Article  PubMed  CAS  Google Scholar 

  17. G.J. Canaris, N.R. Manowitz, G. Mayor, E.C. Ridgway, The Colorado thyroid disease prevalence study. Arch. Intern. Med. 160, 526–534 (2000)

    Article  PubMed  CAS  Google Scholar 

  18. M.D. Danese, P.W. Ladenson, C.L. Meinert, N.R. Powe, Clinical review 115: effect of thyroxine therapy on serum lipoproteins in patients with mild thyroid failure: a quantitative review of the literature. J. Clin. Endocrinol. Metabol. 85, 2993–3001 (2000)

    Article  CAS  Google Scholar 

  19. S. Razvi, L. Ingoe, G. Keeka, C. Oates, C. McMillan, J.U. Weaver, The beneficial effect of l-thyroxine on cardiovascular risk factors, endothelial function, and quality of life in subclinical hypothyroidism: randomized, crossover trial. J. Clin. Endocrinol. Metabol. 92, 1715–1723 (2007)

    Article  CAS  Google Scholar 

  20. K. K. Xu, J., Murphy, S.L., Tejada-Vera, B.: Deaths: final data for 2007. National Vital Statistics Reports. 58, (2010)

  21. Department of Health, Executive Yuan, TAIWAN, 2009 Statistics of Major Causes of Death. http://www.doh.gov.tw/CHT2006/DM/DM2_p01.aspx?class_no=387&level_no=1&doc_no=76103. Accessed 3 March 2013

  22. P. Jeemon, D. Prabhakaran, L. Ramakrishnan, R. Gupta, F. Ahmed, K. Thankappan, C. Kartha, V. Chaturvedi, K. Reddy, Association of high sensitive C-reactive protein (hsCRP) with established cardiovascular risk factors in the Indian population. Nutr Metab (Lond). 8, 19 (2011)

    Article  PubMed  CAS  Google Scholar 

  23. M. Saito, T. Ishimitsu, J. Minami, H. Ono, M. Ohrui, H. Matsuoka, Relations of plasma high-sensitivity C-reactive protein to traditional cardiovascular risk factors. Atherosclerosis 167, 73–79 (2003)

    Article  PubMed  CAS  Google Scholar 

  24. S. La Vignera, R. Condorelli, E. Vicari, A.E. Calogero, Endothelial dysfunction and subclinical hypothyroidism: a brief review. J. Endocrinol. Invest. 35, 96–103 (2012)

    PubMed  Google Scholar 

  25. W.J. Hueston, D.E. King, M.E. Geesey, Serum biomarkers for cardiovascular inflammation in subclinical hypothyroidism. Clin Endocrinol (Oxf). 63, 582–587 (2005)

    Article  PubMed  CAS  Google Scholar 

  26. M.P. Vanderpump, The epidemiology of thyroid disease. Br. Med. Bull. 99, 39–51 (2011)

    Article  PubMed  Google Scholar 

  27. J.J. Haggerty, R.N. Golden, J. Garbutt, C. Pedersen, J.S. Simon, D.L. Evans, C.B. Nemeroff, Subclinical hypothyroidism: a review of neuropsychiatric aspects. Int. J. Psychiatr. Med. 20, 193–208 (1990)

    Article  Google Scholar 

  28. C.C. Chuang, S.T. Wang, P.W. Wang, M.L. Yu, Prevalence study of thyroid dysfunction in the elderly of Taiwan. Gerontology 44, 162–167 (1998)

    Article  PubMed  CAS  Google Scholar 

  29. A. Tuzcu, M. Bahceci, D. Gokalp, Y. Tuzun, K. Gunes, Subclinical hypothyroidism may be associated with elevated high-sensitive C-reactive protein (low grade inflammation) and fasting hyperinsulinemia. Endocr. J. 52, 89–94 (2005)

    Article  PubMed  CAS  Google Scholar 

  30. M. Christ-Crain, C. Meier, M. Guglielmetti, P.R. Huber, W. Riesen, J.J. Staub, B. Muller, Elevated C-reactive protein and homocysteine values: cardiovascular risk factors in hypothyroidism? A cross-sectional and a double-blind, placebo-controlled trial. Atherosclerosis 166, 379–386 (2003)

    Article  PubMed  CAS  Google Scholar 

  31. B.O. Asvold, L.J. Vatten, T.I. Nilsen, T. Bjoro, The association between TSH within the reference range and serum lipid concentrations in a population-based study. The HUNT study. Eur. J. Endocrinol. 156, 181–186 (2007)

    Article  PubMed  Google Scholar 

  32. J.P. Walsh, A.P. Bremner, M.K. Bulsara, P. O’Leary, P.J. Leedman, P. Feddema, V. Michelangeli, Subclinical thyroid dysfunction as a risk factor for cardiovascular disease. Arch. Intern. Med. 165, 2467–2472 (2005)

    Article  PubMed  Google Scholar 

  33. K. Ashizawa, M. Imaizumi, T. Usa, T. Tominaga, N. Sera, A. Hida, E. Ejima, K. Neriishi, M. Soda, S. Ichimaru, E. Nakashima, S. Fujiwara, R. Maeda, S. Nagataki, K. Eguchi, M. Akahoshi, Metabolic cardiovascular disease risk factors and their clustering in subclinical hypothyroidism. Clin. Endocrinol. (Oxf). 72, 689–695 (2010)

    Article  PubMed  CAS  Google Scholar 

  34. A.R. Cappola, L.P. Fried, A.M. Arnold, M.D. Danese, L.H. Kuller, G.L. Burke, R.P. Tracy, P.W. Ladenson, Thyroid status, cardiovascular risk, and mortality in older adults. JAMA 295, 1033–1041 (2006)

    Article  PubMed  CAS  Google Scholar 

  35. G. Vitale, M. Galderisi, G.A. Lupoli, A. Celentano, I. Pietropaolo, N. Parenti, O. De Divitiis, G. Lupoli, Left ventricular myocardial impairment in subclinical hypothyroidism assessed by a new ultrasound tool: pulsed tissue Doppler. J. Clin. Endocrinol. Metabol. 87, 4350–4355 (2002)

    Article  CAS  Google Scholar 

  36. A. Haribabu, V.S. Reddy, C. Pallavi, A.R. Bitla, A. Sachan, P. Pullaiah, V. Suresh, P.V. Rao, M.M. Suchitra, Evaluation of protein oxidation and its association with lipid peroxidation and thyrotropin levels in overt and subclinical hypothyroidism. Endocrine. Epub Date: 2012/12/12. doi:10.1007/s12020-12012-19849-y (2012)

  37. P.H. Dessein, B.I. Joffe, S. Singh, Biomarkers of endothelial dysfunction, cardiovascular risk factors and atherosclerosis in rheumatoid arthritis. Arthr. Res. Ther. 7, R634–R643 (2005)

    Article  CAS  Google Scholar 

  38. B. Biondi, D.S. Cooper, The clinical significance of subclinical thyroid dysfunction. Endocr. Rev. 29, 76–131 (2008)

    Article  PubMed  CAS  Google Scholar 

  39. F. Alibaz Oner, S. Yurdakul, E. Oner, A. Kubat Uzum, M. Erguney, Evaluation of the effect of l-thyroxin therapy on endothelial functions in patients with subclinical hypothyroidism. Endocrine 40, 280–284 (2011)

    Article  PubMed  Google Scholar 

  40. F. Montecucco, F. Mach, New evidences for C-reactive protein (CRP) deposits in the arterial intima as a cardiovascular risk factor. Clin. Interv. Aging 3, 341–349 (2008)

    PubMed  CAS  Google Scholar 

  41. P.W. Ladenson, P.A. Singer, K.B. Ain, N. Bagchi, S.T. Bigos, E.G. Levy, S.A. Smith, G.H. Daniels, H.D. Cohen, American Thyroid Association guidelines for detection of thyroid dysfunction. Arch. Intern. Med. 160, 1573–1575 (2000)

    Article  PubMed  CAS  Google Scholar 

  42. M. Helfand, C.C. Redfern, Clinical guideline, part 2. Screening for thyroid disease: an update. American College of Physicians. Ann. Intern. Med. 129, 144–158 (1998)

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We thank all the staff and subjects who participated in this study. The study is supported by Grants from China Medical University Hospital (DMR-101-058) and from Taiwan Department of Health Clinical Trial and Research Center for Excellence (DOH102-TD-B-111-004).

Conflict of interest

We certify that all my affiliations with or financial involvement in, within the past 5 years and foreseeable future, any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript are completely disclosed.

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Correspondence to Wen-Yuan Lin.

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Ya-Ting Yu and Chih-Te Ho have contributed equally to this work and are to be considered as joint first authors.

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Yu, YT., Ho, CT., Hsu, HS. et al. Subclinical hypothyroidism is associated with elevated high-sensitive C-reactive protein among adult Taiwanese. Endocrine 44, 716–722 (2013). https://doi.org/10.1007/s12020-013-9915-0

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