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Is thyroid-stimulating hormone within the normal reference range a risk factor for atherosclerosis in women?

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Abstract

The relationship between overt hypothyroidism and cardiovascular risk has been well documented and some data also suggest an association between cardiovascular risk and subclinical hypothyroidism. The aim of our study was to investigate, in a large cohort of euthyroid women, the association of thyroid stimulating hormone (TSH) within the normal reference range with cardiovascular risk factors. The study was carried out on 744 women with normal thyroid function (TSH 0.3–4.9 μU/mL). Women with TSH above the median (≥2.1 μU/mL) were more obese, had greater waist girth, were more hypertensive and had higher levels of total cholesterol (TC), serum triglycerides (TG), blood sugar (BG) and lower levels of HDL-cholesterol (HDL-C) than women with TSH below the median. TSH was significantly correlated with body mass index (BMI), waist circumference, BG, TG, TC, HDL-C and hypertension. Multiple backward stepwise regression analysis with age, waist circumference and TSH as independent variables confirmed the strong association of TSH with BG, TG, HDL-C and hypertension. A total of 205 patients (28%) fulfilled the definition criteria of the metabolic syndrome and the prevalence of metabolic syndrome was significantly greater in patients with TSH above than in patients with TSH below the median. Results of logistic analysis, including age and TSH as predictor variables, confirmed the association of TSH with metabolic syndrome.The results of this study suggest that TSH in the upper limits of the reference range (above 2.1 μU/ml) is associated with a less favourable cardiometabolic profile and consequently with a higher risk of developing cardiovascular diseases.

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References

  1. Cappola AR, Ladenson PW (2003) Hypothyroidism and atherosclerosis. J Clin Endocrinol Metab 88:2438–2444

    Article  CAS  PubMed  Google Scholar 

  2. Hak AE, Pols HA, Visser TJ, Drexhage HA, Hofman A, Witteman JC (2000) Subclinical hypothyroidism is an independent risk factor for atherosclerosisand myocardial infarction in elderly women: the rotterdam Study. Ann Intern Med 132:270–278

    Article  CAS  PubMed  Google Scholar 

  3. Walsh JP, Bremner AP, Bulsara MK, O’Leary P, Leedman PJ, Feddema P, Michelangeli V (2005) Subclinical thyroid dysfunction as a risk factor for cardiovascular disease. Arch Intern Med 165:2467–2472

    Article  PubMed  Google Scholar 

  4. Rodondi N, Newman AB, Vittinghoff E, de Rekeneire N, Satterfield S, Harris TB, Bauer DC (2005) Subclinical hypothyroidism and the risk of heart failure, other cardiovascular events and death. Arch Intern Med 165:2460–2466

    Article  PubMed  Google Scholar 

  5. McDermott MT, Ridgway EC (2001) Subclinical hypothyroidism is mild thyroid failure and should be treated. J Clin Endocrinol Metab 86:4585–4590

    CAS  PubMed  Google Scholar 

  6. Kahaly GJ (2000) Cardiovascular and atherogenic aspects of subclinical hypothyroidism. Thyroid 10:665–679

    Article  CAS  PubMed  Google Scholar 

  7. Danese MD, Ladenson PW, Meinert CL, Powe NR (2000) Effect of thyroxine therapy on serum lipoproteins in patients with mild thyroid failure: a quantitative review of the literature. J Clin Endocrinol Metab 85:2993–3001

    CAS  PubMed  Google Scholar 

  8. Luboshitzky R, Aviv A, Herer P, Lavie L (2002) Risk factors for cardiovasculardisease in women with subclinical hypothyroidism. Thyroid 12:421–425

    Article  PubMed  Google Scholar 

  9. Åsvold BO, Vatten LJ, Nilsen TIL, Bjøro T (2007) The association between TSH within the reference range and serum lipid concentrations in a populated based study. The HUNT Study. Eur J Endocrinol 156:181–186

    Article  Google Scholar 

  10. Roos A, Bakker SJL, Links TP, Gans ROB, Wolffenbuttel BHR (2007) Thyroid function is associated with components of the metabolic syndrome in euthyroid subjects. J Clin Endocrinol Metab 92:491–496

    Article  CAS  PubMed  Google Scholar 

  11. Ruhla S, Weickert MO, Arafat AM, Osterhoff M, Isken F, Spranger J, Schofl C, Pfeiffer AFH, Möhlig M (2010) A high normal TSH is associated with the metabolic syndrome. Clin Endocrinol 72:696–701

    Article  CAS  Google Scholar 

  12. Åsvold B, Bjøro T, Nilsen TIL, Vatten LJ (2007) Association between blood pressure and serum thyroid-stimulating hormone concentration within the reference range: A population-based study. J Clin Endocrinol Metab 92:841–845

    Article  PubMed  Google Scholar 

  13. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults.(2001) Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 285:2486–2497

    Google Scholar 

  14. Kim BJ, Kim TY, Koh JM, Park JY, Lee KU, Shong YK, Kim WB (2009) Relationship between serum free T4 (FT4) levels and metabolic syndrome (MS) and its components in healthy euthyroid subjects. Clin Endocrinol (Oxf) 70:152–160

    Article  CAS  Google Scholar 

  15. Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, Fruchart JC, James WP, Loria CM, Smith SC Jr (2009) Harmonizing the metabolic syndrome. a joint interim statement of the international diabetes federation task force on pidemiology and prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 120:1640–1645

    Article  CAS  PubMed  Google Scholar 

  16. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and bcell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419

    Article  CAS  PubMed  Google Scholar 

  17. Janssen I, Heymsfield SB, Allison DB, Kotler DP, Ross R (2002) Body mass index and waist circumference independently contribute to the prediction of nonabdominal, abdominal subcutaneous, and visceral fat. Am J Clin Nutr 75:683–688

    CAS  PubMed  Google Scholar 

  18. Rotondi M, Leporati P, La Manna A, Pirali B, Mondello T, Fonte R, Magri F, Chiovato L (2009) Raised serum TSH levels in patients with morbid obesity: is it enough to diagnose subclinical hypothyroidism? Eur J Endocrinol 160:403–408

    Article  CAS  PubMed  Google Scholar 

  19. Sari R, Balci MK, Altunbas H, Karayalcin U (2003) The effect of body weight andweight loss on thyroid volume and function in obese women. Clin Endocrinol (Oxf) 59:258–262

    Article  Google Scholar 

  20. Moulin de Moraes CM, Mancini MC, de Melo ME, Figueiredo DA, Villares SM, Raskovski A, Zilberstein B, Halpern A (2005) Prevalence of subclinical hypothyroidism in a morbidly obese population and improvement after weight loss induced by Roux-en-Y gastric bypass. Obes Surg 15:1287–1291

    Article  PubMed  Google Scholar 

  21. Radetti G, Longhi S, Baiocchi M, Cassar W, Buzi F. (2011) Changes in life style improve body composition, thyroid function and structure in obese children. J Endocrinol Invest Epub May 27

  22. Dall’Asta C, Paganelli M, Morabito A, Vedani P, Barbieri M, Paolisso G, Folli F, Pontiroli AE (2010) Weight loss through gastric banding: effects on TSH and thyroid hormones in obese subjects with normal thyroid function. Obesity 18:854–857

    Article  PubMed  Google Scholar 

  23. Lloyd RV, Jin L, Tsumanuma I, Vidal S, Kovacs K, Horvath E (2001) Leptin and leptin receptor in anterior pituitary function. Pituitary 4:33–47

    Article  CAS  PubMed  Google Scholar 

  24. Seoane LM, Carro E, Tovar S, Casanueva FF, Dieguez C (2000) Regulation of in vivo TSH secretion by leptin. RegulPept 92:25–29

    CAS  Google Scholar 

  25. Winter WE, Signorio MR (2001) Review: molecular thyroidology. Ann Clin Lab Sci 31:221–244

    CAS  PubMed  Google Scholar 

  26. Matthews KA, Meilahn E, Kuller LH, Kelsey SF, Caggiula AW, Wing RR (1989) Menopause and risk factors for coronary heart disease. N Engl J Med 321:641–646

    Article  CAS  PubMed  Google Scholar 

  27. Diekman T, Demacker PN, Kastelein JJ, Stalenhoef AF, Wiersinga WM (1998) Increased oxidizability of low-density lipoproteins in hypothyroidism. J Clin Endocrinol Metab 83:1752–1755

    CAS  PubMed  Google Scholar 

  28. Diekman MJ, Anghelescu N, Endert E, Bakker O, Wiersinga WM (2000) Changes in plasma low-density lipoprotein (LDL)- and high-density lipoprotein cholesterol in hypo- and hyperthyroid patients are related to changes in free thyroxine, not to polymorphisms in LDL receptor or cholesterol ester transfer protein genes. J Clin Endocrinol Metab 85:1857–1862

    CAS  PubMed  Google Scholar 

  29. Duntas LH (2002) Thyroid disease and lipids. Thyroid 12:287–293

    Article  CAS  PubMed  Google Scholar 

  30. Nikkila EA, Kekki M (1972) Plasma triglyceride metabolism in thyroid disease. J Clin Invest 51:2103–2114

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Tulloch BR, Lewis B, Fraser TR (1972) Triglyceride metabolism in thyroid disease. Lancet 1:391–394

    Google Scholar 

  32. Elkeles RS, Khan SR, Niththyananthan R, Seed M, Wynn V (1982) High density lipoprotein subfraction cholesterol in hypertriglyceridemia. Atherosclerosis 43:423–424

    Article  CAS  PubMed  Google Scholar 

  33. Duan Y, Peng W, Wang X, Tang W, Liu X, Xu S, Mao X, Feng S, Feng Y, Qin Y, Xu K, Liu C, Liu C (2009) Community-based study of the association of subclinical thyroid dysfunction with blood pressure. Endocrine 35:136–142

    Article  CAS  PubMed  Google Scholar 

  34. Klein I, Ojamaa K (2001) Thyroid hormone and the cardiovascular system. N Engl J Med 344:501–509

    Article  CAS  PubMed  Google Scholar 

  35. 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 103:1–6

    Article  PubMed  Google Scholar 

  36. Ambrosi B, Masserini B, Iorio L, Delnevo A, Malavazos AE, Morricone L, Sburlati LF, Orsi E (2010) Relationship of thyroid function with body mass index and insulin-resistance in euthyroid obese subjects. J Endocrinol Invest 33:640–643

    CAS  PubMed  Google Scholar 

  37. Garduño-Garcia Jde J, Alvirde-Garcia U, López-Carrasco G, Padilla Mendoza ME, Mehta R, Arellano-Campos O, Choza R, Sauque L, Garay-Sevilla ME, Malacara JM, Gomez-Perez FJ, Aguilar-Salinas CA (2010) TSH and free thyroxine concentrations are associated with differing metabolic markers in euthyroid subjects. Eur J Endocrinol 163:273–278

    Article  PubMed  Google Scholar 

  38. De Pergola G, Ciampolillo A, Alò D, Sciaraffia M, Guida P (2010) Free triiodothyronine is associated with smoking habit, independently of obesity, body fat distribution, insulin, and metabolic parameters. J Endocrinol Invest 33:815–818

    PubMed  Google Scholar 

  39. De Pergola G, Ciampolillo A, Paolotti S, Trerotoli P, Giorgino R (2007) Free triiodothyronine and thyroid stimulating hormone are associated with waist circumference, independently of insulin resistance, metabolic parameters and blood pressure in overweight and obese women. Clin Endocrinol 67:265–269

    Article  Google Scholar 

  40. Bakker SJ, terMaaten JC, Popp-Snijders C, Slaets JP, Heine RJ, Gans RO (2001) The relationship between thyrotropin and low density lipoprotein cholesterol is modified by insulin sensitivity in healthy euthyroid subjects. J Clin Endocrinol Metab 86:1206–1211

    CAS  PubMed  Google Scholar 

  41. Ortega E, Koska J, Pannacciulli N, Bunt JC, Krakoff J (2008) Free triiodothyronine plasma concentrations are positively associated with insulin secretion in euthyroid individuals. Eur J Endocrinol 158:217–221

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  42. Brabant G, Beck-Peccoz P, Jarzab B, Laurberg P, Orgiazzi J, Szabolcs I, Weetman AP, Wiersinga WM (2006) Is there a need to redefine the upper normal limit of TSH? Eur J Endocrinol 154:633–637

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Dietetic and Clinical Nutrition Unit, “Luigi Sacco” University Hospital, Milan, Italy

    Anna Boggio, Fulvio Muzio & Michela Fiscella

  2. Centro per lo Studio e la Prevenzione dell ‘Aterosclerosi, Department of Internal Medicine,IRCCS Cà Granda, Ospedale Maggiore Policlinico Foundation, University of Milan, Milan, Italy

    Domenico Sommariva & Adriana Branchi

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  1. Anna Boggio
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  2. Fulvio Muzio
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Correspondence to Anna Boggio.

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Boggio, A., Muzio, F., Fiscella, M. et al. Is thyroid-stimulating hormone within the normal reference range a risk factor for atherosclerosis in women?. Intern Emerg Med 9, 51–57 (2014). https://doi.org/10.1007/s11739-011-0743-z

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  • DOI: https://doi.org/10.1007/s11739-011-0743-z

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