Skip to main content
SpringerLink
Log in

Risk factors for cardiovascular disease in patients with subclinical hypothyroidism

  • Original Research
  • Published:
Advances in Therapy Aims and scope Submit manuscript

Abstract

Introduction

The relationship between subclinical hypothyroidism (SCH) and cardiovascular disease is not fully understood. We investigated risk factors for cardiovascular disease (lipid profile, lipoproteins, insulin resistance, C-reactive protein [CRP] homocysteine [Hcy] and fibrinogen levels) and their relationships with thyroid hormones in SCH patients and controls.

Methods

Thirty-eight SCH patients and 44 controls were enrolled in this study. No patients had any substantial confounding medical conditions (including diabetes mellitus or coronary heart disease) or were taking thyroidrelated medication.

Results

Serum total cholesterol (P<0.05), low-density lipoprotein cholesterol (P<0.05) and triglycerides (P<0.001) were higher in patients with SCH than in controls. Serum lipoprotein(a) (Lp[a]) levels were higher in SCH subjects but this difference did not reach statistical significance (P=0.07). No significant differences were noted in CRP, Hcy, fibrinogen, high-density lipoprotein cholesterol, apolipoprotein A-1, apolipoprotein B (Apo B) or insulin resistance between patients with SCH and controls (in all cases, P>0.05). Free triiodothyronine (FT3) negatively correlated with Apo B (r=.0.46, P=0.005) and Lp(a) (r=.0.31, P=0.03) in patients with SCH and negatively correlated with Lp(a) (r=.0.30, P=0.04) in controls. All of these parameters were comparable between patients with thyroid-stimulating hormone (TSH) >10 μIU/ml and TSH <10 μIU/ml (in SCH patients, P>0.05).

Conclusion

Our results suggest that SCH is associated with some lipid and lipoprotein abnormalities. Our results also suggest that this association does not depend on the subject’s TSH level.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Franklyn J. ’subclinical hypothyroidism’: to treat or not to treat, that is the question. Clin Endocrinol (Oxf). 1995;43:443–444.

    Article  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  3. Owen PJ, Lazarus JH. Subclinical hypothyroidism: the case for treatment. Trends Endocrinol Metab. 2003;14:257–261.

    Article  PubMed  CAS  Google Scholar 

  4. Biondi B, Klein I. Hypothyroidism as a risk factor for cardiovascular disease. Endocrine. 2004;24:1–13.

    Article  PubMed  CAS  Google Scholar 

  5. Vanderpump MP, Tunbridge WM, French JM, et al. The development of ischemic heart disease in relation to autoimmune thyroid disease in a 20-year follow-up study of an English community. Thyroid. 1996;6:155–160.

    PubMed  CAS  Google Scholar 

  6. Lindeman RD, Romero LJ, Schade DS, et al. 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. 2003;13:595–600.

    Article  PubMed  CAS  Google Scholar 

  7. Mya MM, Aronow WS. Subclinical hypothyroidism is associated with coronary artery disease in older persons. J Gerontol A Biol Sci Med Sci. 2002;57:M658–M659.

    PubMed  Google Scholar 

  8. Tieche M, Lupi GA, Gutzwiller F, et al. Borderline low thyroid function and thyroid autoimmunity. Risk factors for coronary heart disease? Br Heart J. 1981;46:202–206.

    Article  PubMed  CAS  Google Scholar 

  9. Lekakis J, Papamichael C, Alevizaki M, et al. Flow-mediated, endothelium-dependent vasodilation is impaired in subjects with hypothyroidism, borderline hypothyroidism, and high-normal serum thyrotropin (TSH) values. Thyroid. 1997;7:411–414.

    PubMed  CAS  Google Scholar 

  10. Monzani F, Caraccio N, Kozakowa M, 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.

    Article  PubMed  CAS  Google Scholar 

  11. Danese MD, Ladenson PW, Meinert CL, et al. 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.

    Article  PubMed  CAS  Google Scholar 

  12. Tanis BC, Westendorp GJ, Smelt HM. Effect of thyroid substitution on hypercholesterolaemia in patients with subclinical hypothyroidism: a reanalysis of intervention studies. Clin Endocrinol (Oxf). 1996;44:643–649.

    Article  CAS  Google Scholar 

  13. Christ-Crain M, Meier C, Guglielmetti M, et al. Elevated C-reactive protein and homocysteine values: cardiovascular risk factors in hypothyroidism? A cross-sectional and a double-blind, placebo-controlled trial. Atherosclerosis. 2003;166:379–386.

    Article  PubMed  CAS  Google Scholar 

  14. Perez A, Cubero JM, Sucunza N, et al. Emerging cardiovascular risk factors in subclinical hypothyroidism: lack of change after restoration of euthyroidism. Metabolism. 2004;53:1512–1515.

    Article  PubMed  CAS  Google Scholar 

  15. Deicher R, Vierhapper H. Homocysteine: a risk factor for cardiovascular disease in subclinical hypothyroidism? Thyroid. 2002;12:733–736.

    Article  PubMed  CAS  Google Scholar 

  16. Sengul E, Cetinarslan B, Tarkun I, et al. Homocysteine concentrations in subclinical hypothyroidism. Endocr Res. 2004;30:351–359.

    Article  PubMed  CAS  Google Scholar 

  17. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18:499–502.

    PubMed  CAS  Google Scholar 

  18. Matthews DR, Hosker JP, Rudenski AS, et al. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28:412–419.

    Article  PubMed  CAS  Google Scholar 

  19. Efstathiadou Z, Bitsis S, Milionis HJ, et al. Lipid profile in subclinical hypothyroidism: is L-thyroxine substitution beneficial? Eur J Endocrinol. 2001;145:705–710.

    Article  PubMed  CAS  Google Scholar 

  20. Walsh JP, Bremner AP, Bulsara MK et al. Thyroid dysfunction and serum lipids: a community-based study. Clin Endocrinol (Oxf). 2005;63:670–675.

    Article  CAS  Google Scholar 

  21. Hueston WJ, Pearson WS. Subclinical hypothyroidism and the risk of hypercholesterolemia. Ann Fam Med. 2004;2:351–355.

    Article  PubMed  Google Scholar 

  22. Gullu S, Sav H, Kamel N. Effects of levothyroxine treatment on biochemical and hemostasis parameters in patients with hypothyroidism. Eur J Endocrinol. 2005;152:355–361.

    Article  PubMed  CAS  Google Scholar 

  23. Tzotzas T, Krassas GE, Konstantinidis T, et al. Changes in lipoprotein(a) levels in overt and subclinical hypothyroidism before and during treatment. Thyroid. 2000;10:803–808.

    Article  PubMed  CAS  Google Scholar 

  24. Maas R, Boger RH. Old and new cardiovascular risk factors: from unresolved issues to new opportunities. Atheroscler Suppl. 2003;4:5–17.

    Article  PubMed  Google Scholar 

  25. Valdemarsson S, Hedner P, Nilsson-Ehle P. Reversal of decreased hepatic lipase and lipoprotein lipase activities after treatment of hypothyroidism. Eur J Clin Invest. 1982;12:423–428.

    Article  PubMed  CAS  Google Scholar 

  26. Duntas LH. Thyroid disease and lipids. Thyroid. 2002;12:287–293.

    Article  PubMed  CAS  Google Scholar 

  27. Kung AW, Pang RW, Janus ED. Elevated serum lipoprotein(a) in subclinical hypothyroidism. Clin Endocrinol (Oxf). 1995;43:445–449.

    Article  CAS  Google Scholar 

  28. Arem R, Escalante DA, Arem N, et al. Effect of L-thyroxine therapy on lipoprotein fractions in overt and subclinical hypothyroidism, with special reference to lipoprotein(a). Metabolism. 1995;44:1559–1563.

    Article  PubMed  CAS  Google Scholar 

  29. Yildirimkaya M, Ozata M, Yilmaz K, et al. Lipoprotein(a) concentration in subclinical hypothyroidism before and after levo-thyroxine therapy. Endocr J. 1996;43:731–736.

    Article  PubMed  CAS  Google Scholar 

  30. Lee WY, Suh JY, Rhee EJ, et al. Plasma CRP, apolipoprotein A-1, apolipoprotein B and Lpa levels according to thyroid function status. Arch Med Res. 2004;35:540–545.

    Article  PubMed  CAS  Google Scholar 

  31. Gullberg H, Rudling M, Salto C, et al. Requirement for thyroid hormone receptor beta in T3 regulation of cholesterol metabolism in mice. Mol Endocrinol. 2002;16:1767–1777.

    Article  PubMed  CAS  Google Scholar 

  32. Grover GJ, Mellstrom K, Ye L, et al. Selective thyroid hormone receptor-beta activation: a strategy for reduction of weight, cholesterol, and lipoprotein (a) with reduced cardiovascular liability. Proc Natl Acad Sci U S A. 2003;100:10067–10072.

    Article  PubMed  CAS  Google Scholar 

  33. Hueston WJ, King DE, Geesey ME. Serum biomarkers for cardiovascular inflammation in subclinical hypothyroidism. Clin Endocrinol (Oxf). 2005;63:582–587.

    Article  CAS  Google Scholar 

  34. Surks MI, Ortiz E, Daniels GH, et al. Subclinical thyroid disease: scientific review and guidelines for diagnosis and management. JAMA. 2004;291:228–238.

    Article  PubMed  CAS  Google Scholar 

  35. Gharib H, Tuttle RM, Baskin HJ, et al. American Association of Clinical Endocrinologists; American Thyroid Association; The Endocrine Society. Consensus statement #1: subclinical thyroid dysfunction: a joint statement on management from the American Association of Clinical Endocrinologists, the American Thyroid Association, and The Endocrine Society. Thyroid. 2005;15:24–28.

    Article  PubMed  Google Scholar 

  36. Monzani F, Dardano A, Caraccio N. Does treating subclinical hypothyroidism improve markers of cardiovascular risk? Treat Endocrinol. 2006;5:65–81.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Endocrinology and Metabolism, Gazi University, Faculty of Medicine, Ankara, Turkey

    Fusun Toruner, Alev E. Altinova, Ayhan Karakoc, Ilhan Yetkin, Goksun Ayvaz, Nuri Cakir & Metin Arslan

Authors
  1. Fusun Toruner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alev E. Altinova
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ayhan Karakoc
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ilhan Yetkin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Goksun Ayvaz
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Nuri Cakir
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Metin Arslan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alev E. Altinova.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Toruner, F., Altinova, A.E., Karakoc, A. et al. Risk factors for cardiovascular disease in patients with subclinical hypothyroidism. Adv Therapy 25, 430–437 (2008). https://doi.org/10.1007/s12325-008-0053-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12325-008-0053-7

Keywords

Search

Navigation