Endocrinol Metab.  2015 Sep;30(3):246-251. 10.3803/EnM.2015.30.3.246.

Subclinical Hypothyroidism and Cardiovascular Disease

• Suh S
• Kim DK

• KMID: 2407073
• DOI: http://doi.org/10.3803/EnM.2015.30.3.246

Abstract

Subclinical hypothyroidism (SCH) is a common disorder that is characterized by elevated thyroid-stimulating hormone levels in conjunction with free thyroxine concentrations within the normal reference range. Thyroid hormones are known to affect the heart and vasculature and, as a result, the impact of SCH on the cardiovascular (CV) system has recently become an important topic of research. Strong evidence points to a link between SCH and CV risk factors such as alterations in blood pressure, lipid levels, and atherosclerosis. Additionally, accumulating evidence indicates that SCH is associated with metabolic syndrome and heart failure. The present review proposes that SCH may be a potentially modifiable risk factor of CV disease and mortality. However, large-scale clinical trials with appropriate power investigating the risks and benefits of SCH treatment are required to determine whether these benefits can be achieved with levothyroxine therapy.

Keyword

Subclinical hypothyroidism; Cardiovascular diseases

MeSH Terms

Atherosclerosis
Blood Pressure
Cardiovascular Diseases*
Heart
Heart Failure
Hypothyroidism*
Mortality
Reference Values
Risk Assessment
Risk Factors
Thyroid Hormones
Thyrotropin
Thyroxine
Thyroid Hormones
Thyrotropin
Thyroxine

Reference

1. Cooper DS, Biondi B. Subclinical thyroid disease. Lancet. 2012; 379:1142–1154.

2. Leese GP, Flynn RV, Jung RT, Macdonald TM, Murphy MJ, Morris AD. Increasing prevalence and incidence of thyroid disease in Tayside, Scotland: the Thyroid Epidemiology Audit and Research Study (TEARS). Clin Endocrinol (Oxf). 2008; 68:311–316.

3. Surks MI, Ortiz E, Daniels GH, Sawin CT, Col NF, Cobin RH, et al. Subclinical thyroid disease: scientific review and guidelines for diagnosis and management. JAMA. 2004; 291:228–238.

4. Biondi B, Cooper DS. The clinical significance of subclinical thyroid dysfunction. Endocr Rev. 2008; 29:76–131.

5. Kim YA, Park YJ. Prevalence and risk factors of subclinical thyroid disease. Endocrinol Metab (Seoul). 2014; 29:20–29.

6. Canaris GJ, Manowitz NR, Mayor G, Ridgway EC. The Colorado thyroid disease prevalence study. Arch Intern Med. 2000; 160:526–534.

7. Kim TH, Choi HS, Bae JC, Moon JH, Kim HK, Choi SH, et al. Subclinical hypothyroidism in addition to common risk scores for prediction of cardiovascular disease: a 10-year community-based cohort study. Eur J Endocrinol. 2014; 171:649–657.

8. Knudsen N, Laurberg P, Rasmussen LB, Bulow I, Perrild H, Ovesen L, et al. Small differences in thyroid function may be important for body mass index and the occurrence of obesity in the population. J Clin Endocrinol Metab. 2005; 90:4019–4024.

9. Taylor PN, Razvi S, Pearce SH, Dayan CM. Clinical review: a review of the clinical consequences of variation in thyroid function within the reference range. J Clin Endocrinol Metab. 2013; 98:3562–3571.

10. Liu D, Jiang F, Shan Z, Wang B, Wang J, Lai Y, et al. A cross-sectional survey of relationship between serum TSH level and blood pressure. J Hum Hypertens. 2010; 24:134–138.

11. Asvold BO, Bjoro T, Nilsen TI, Vatten LJ. Association between blood pressure and serum thyroid-stimulating hormone concentration within the reference range: a population-based study. J Clin Endocrinol Metab. 2007; 92:841–845.

12. Ye Y, Xie H, Zeng Y, Zhao X, Tian Z, Zhang S. Association between subclinical hypothyroidism and blood pressure: a meta-analysis of observational studies. Endocr Pract. 2014; 20:150–158.

13. Pearce EN. Update in lipid alterations in subclinical hypothyroidism. J Clin Endocrinol Metab. 2012; 97:326–333.

14. Liu XL, He S, Zhang SF, Wang J, Sun XF, Gong CM, et al. Alteration of lipid profile in subclinical hypothyroidism: a meta-analysis. Med Sci Monit. 2014; 20:1432–1441.

15. Park YJ, Lee YJ, Choi SI, Chun EJ, Jang HC, Chang HJ. Impact of subclinical hypothyroidism on the coronary artery disease in apparently healthy subjects. Eur J Endocrinol. 2011; 165:115–121.

16. Marfella R, Ferraraccio F, Rizzo MR, Portoghese M, Barbieri M, Basilio C, et al. Innate immune activity in plaque of patients with untreated and L-thyroxine-treated subclinical hypothyroidism. J Clin Endocrinol Metab. 2011; 96:1015–1020.

17. Razvi S, Ingoe L, Keeka G, Oates C, McMillan C, Weaver JU. 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 Metab. 2007; 92:1715–1723.

18. Takamura N, Akilzhanova A, Hayashida N, Kadota K, Yamasaki H, Usa T, et al. Thyroid function is associated with carotid intima-media thickness in euthyroid subjects. Atherosclerosis. 2009; 204:e77–e81.

19. Suh S, Lee MK. Metabolic syndrome and cardiovascular diseases in Korea. J Atheroscler Thromb. 2014; 21:Suppl 1. S31–S35.

20. Iwen KA, Schroder E, Brabant G. Thyroid hormones and the metabolic syndrome. Eur Thyroid J. 2013; 2:83–92.

21. Nakajima Y, Yamada M, Akuzawa M, Ishii S, Masamura Y, Satoh T, et al. Subclinical hypothyroidism and indices for metabolic syndrome in Japanese women: one-year follow-up study. J Clin Endocrinol Metab. 2013; 98:3280–3287.

22. Lee YK, Kim JE, Oh HJ, Park KS, Kim SK, Park SW, et al. Serum TSH level in healthy Koreans and the association of TSH with serum lipid concentration and metabolic syndrome. Korean J Intern Med. 2011; 26:432–439.

23. Oh JY, Sung YA, Lee HJ. Elevated thyroid stimulating hormone levels are associated with metabolic syndrome in euthyroid young women. Korean J Intern Med. 2013; 28:180–186.

24. Monzani F, Di Bello V, Caraccio N, Bertini A, Giorgi D, Giusti C, et al. Effect of levothyroxine on cardiac function and structure in subclinical hypothyroidism: a double blind, placebo-controlled study. J Clin Endocrinol Metab. 2001; 86:1110–1115.

25. Brenta G, Mutti LA, Schnitman M, Fretes O, Perrone A, Matute ML. Assessment of left ventricular diastolic function by radionuclide ventriculography at rest and exercise in subclinical hypothyroidism, and its response to L-thyroxine therapy. Am J Cardiol. 2003; 91:1327–1330.

26. Nanchen D, Gussekloo J, Westendorp RG, Stott DJ, Jukema JW, Trompet S, et al. Subclinical thyroid dysfunction and the risk of heart failure in older persons at high cardiovascular risk. J Clin Endocrinol Metab. 2012; 97:852–861.

27. Biondi B, Fazio S, Palmieri EA, Carella C, Panza N, Cittadini A, et al. Left ventricular diastolic dysfunction in patients with subclinical hypothyroidism. J Clin Endocrinol Metab. 1999; 84:2064–2067.

28. Madathil A, Hollingsworth KG, Blamire AM, Razvi S, Newton JL, Taylor R, et al. Levothyroxine improves abnormal cardiac bioenergetics in subclinical hypothyroidism: a cardiac magnetic resonance spectroscopic study. J Clin Endocrinol Metab. 2015; 100:E607–E610.

29. Gencer B, Collet TH, Virgini V, Bauer DC, Gussekloo J, Cappola AR, et al. Subclinical thyroid dysfunction and the risk of heart failure events: an individual participant data analysis from 6 prospective cohorts. Circulation. 2012; 126:1040–1049.

30. Asvold BO, Bjoro T, Platou C, Vatten LJ. Thyroid function and the risk of coronary heart disease: 12-year follow-up of the HUNT study in Norway. Clin Endocrinol (Oxf). 2012; 77:911–917.

31. Ceresini G, Ceda GP, Lauretani F, Maggio M, Usberti E, Marina M, et al. Thyroid status and 6-year mortality in elderly people living in a mildly iodine-deficient area: the aging in the Chianti Area Study. J Am Geriatr Soc. 2013; 61:868–874.

32. Gussekloo J, van Exel E, de Craen AJ, Meinders AE, Frolich M, Westendorp RG. Thyroid status, disability and cognitive function, and survival in old age. JAMA. 2004; 292:2591–2599.

33. Pereg D, Tirosh A, Elis A, Neuman Y, Mosseri M, Segev D, et al. Mortality and coronary heart disease in euthyroid patients. Am J Med. 2012; 125:826.e7–826.e12.

34. Tseng FY, Lin WY, Lin CC, Lee LT, Li TC, Sung PK, et al. Subclinical hypothyroidism is associated with increased risk for all-cause and cardiovascular mortality in adults. J Am Coll Cardiol. 2012; 60:730–737.

35. Ittermann T, Haring R, Sauer S, Wallaschofski H, Dorr M, Nauck M, et al. Decreased serum TSH levels are not associated with mortality in the adult northeast German population. Eur J Endocrinol. 2010; 162:579–585.

36. Parle JV, Maisonneuve P, Sheppard MC, Boyle P, Franklyn JA. Prediction of all-cause and cardiovascular mortality in elderly people from one low serum thyrotropin result: a 10-year cohort study. Lancet. 2001; 358:861–865.

37. Westerink J, van der Graaf Y, Faber DR, Spiering W, Visseren FL. SMART study group. Relation between thyroid-stimulating hormone and the occurrence of cardiovascular events and mortality in patients with manifest vascular diseases. Eur J Prev Cardiol. 2012; 19:864–873.

38. Selmer C, Olesen JB, Hansen ML, von Kappelgaard LM, Madsen JC, Hansen PR, et al. Subclinical and overt thyroid dysfunction and risk of all-cause mortality and cardiovascular events: a large population study. J Clin Endocrinol Metab. 2014; 99:2372–2382.

39. Hyland KA, Arnold AM, Lee JS, Cappola AR. Persistent subclinical hypothyroidism and cardiovascular risk in the elderly: the cardiovascular health study. J Clin Endocrinol Metab. 2013; 98:533–540.

40. Rodondi N, den Elzen WP, Bauer DC, Cappola AR, Razvi S, Walsh JP, et al. Subclinical hypothyroidism and the risk of coronary heart disease and mortality. JAMA. 2010; 304:1365–1374.

41. Ochs N, Auer R, Bauer DC, Nanchen D, Gussekloo J, Cornuz J, et al. Meta-analysis: subclinical thyroid dysfunction and the risk for coronary heart disease and mortality. Ann Intern Med. 2008; 148:832–845.

42. Zhang Y, Chang Y, Ryu S, Cho J, Lee WY, Rhee EJ, et al. Thyroid hormones and mortality risk in euthyroid individuals: the Kangbuk Samsung health study. J Clin Endocrinol Metab. 2014; 99:2467–2476.

43. Li M, Tang Z. Subclinical hypothyroidism: to treat or not to treat? Med Princ Pract. 2015; 24:99–100.

44. Adrees M, Gibney J, El-Saeity N, Boran G. Effects of 18 months of L-T4 replacement in women with subclinical hypothyroidism. Clin Endocrinol (Oxf). 2009; 71:298–303.

45. Danese MD, Ladenson PW, Meinert CL, Powe NR. 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 Metab. 2000; 85:2993–3001.

46. Monzani F, Caraccio N, Kozakowa M, Dardano A, Vittone F, Virdis A, et al. Effect of levothyroxine replacement on lipid profile and intima-media thickness in subclinical hypothyroidism: a double-blind, placebo-controlled study. J Clin Endocrinol Metab. 2004; 89:2099–2106.

47. Razvi S, Weaver JU, Butler TJ, Pearce SH. Levothyroxine treatment of subclinical hypothyroidism, fatal and nonfatal cardiovascular events, and mortality. Arch Intern Med. 2012; 172:811–817.

48. Villar HC, Saconato H, Valente O, Atallah AN. Thyroid hormone replacement for subclinical hypothyroidism. Cochrane Database Syst Rev. 2007; (3):CD003419.

49. Helfand M. U.S. Preventive Services Task Force. Screening for subclinical thyroid dysfunction in nonpregnant adults: a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med. 2004; 140:128–141.