Download PDF
Horm Metab Res 2011; 43(09): 653-659
DOI: 10.1055/s-0031-1283162
Humans, Clinical
Georg Thieme Verlag KG Stuttgart · NewYork

Cardiovascular Events in Thyroid Disease: A Population Based, Prospective Study

M. Schultz
1   Department of Cardiology and Endocrinology E, Frederiksberg University Hospital, Frederiksberg, Denmark
,
C. Kistorp
1   Department of Cardiology and Endocrinology E, Frederiksberg University Hospital, Frederiksberg, Denmark
,
I. Raymond
1   Department of Cardiology and Endocrinology E, Frederiksberg University Hospital, Frederiksberg, Denmark
,
J. Dimsits
1   Department of Cardiology and Endocrinology E, Frederiksberg University Hospital, Frederiksberg, Denmark
,
C. Tuxen
1   Department of Cardiology and Endocrinology E, Frederiksberg University Hospital, Frederiksberg, Denmark
,
P. Hildebrandt
1   Department of Cardiology and Endocrinology E, Frederiksberg University Hospital, Frederiksberg, Denmark
,
J. Faber
1   Department of Cardiology and Endocrinology E, Frederiksberg University Hospital, Frederiksberg, Denmark
› Author Affiliations
Further Information

Publication History

received 13 January 2011

accepted 21 June 2011

Publication Date:
05 August 2011 (online)

Also available at
    Permissions and Reprints

Abstract

No consensus exists whether subclinical thyroid disease should be treated or just observed. Untreated overt thyroid disease is associated with increased risk of cardiovascular disease, and this study was conducted to assess the risk of cardiovascular events in subclinical thyroid disease. The population-based prospective study was conducted in Denmark. A total of 609 subjects from general practice aged 50 years or above with normal left ventricular function were examined. During a median of 5 years of follow-up, major cardiovascular events were documented. In subjects with abnormal TSH at baseline, information about potential thyroid treatment during follow-up was obtained from case reports and mailings. At baseline, 549 (90.7%) were euthyroid (TSH 0.40–4.00 mU/l), 31 (5.1%) were subclinical hypothyroid (TSH>4.00 mU/l), and 25 (4.1%) were subclinical hyperthyroid (TSH<0.40 mU/l). 1 overt hyperthyroid and 3 overt hypothyroid participants were excluded from the analyses. At baseline, the levels of NT-proBNP were inversely associated with the levels of TSH; the lower the levels of TSH, the higher the NT-proBNP concentration. During follow-up, 88 participants died, 81 had a major cardiovascular event, and 28 had a stroke. The incidence of stroke was increased among subjects with subclinical hyperthyroidism, HR 3.39 (95% CI 1.15–10.00, p=0.027) after adjusting for sex, age, and atrial fibrillation. Subclinical hypothyroidism was not related with any of the outcome measurements. Subclinical hyperthyroidism seems to be a risk factor of developing major cardiovascular events, especially stroke in older adults from the general population with normal left ventricular function.

Key words

CV-risk - subclinical thyroid diseases - TSH - NT-proBNP - stroke
 

  • References

  • 1 Cooper DS. Approach to the Patient with Subclinical Hyperthyroidism. J Clin Endocrinol Metab 2007; 92: 3-9
    PubMedGoogle Scholar
  • 2 Klein I, Ojamaa K. Thyroid hormone and the cardiovascular system. N Engl J Med 2001; 344: 501-509
    CrossrefPubMedGoogle Scholar
  • 3 Osman F, Franklyn JA, Holder RL, Sheppard MC, Gammage MD. Cardiovascular manifestations of hyperthyroidism before and after antithyroid therapy: a matched case-control study. J Am Coll Cardiol 2007; 49: 71-81
    CrossrefPubMedGoogle Scholar
  • 4 Faber J, Wiinberg N, Schifter S, Mehlsen J. Haemodynamic changes following treatment of subclinical and overt hyperthyroidism. Eur J Endocrinol 2001; 145: 391-396
    CrossrefPubMedGoogle Scholar
  • 5 Klein I, Levey GS. The cardiovascular system in thyrotoxicosis. In: Braverman LE, Utiger RD. ed Werner and Ingbar’s The Thyroid. Philadelphia: Lippincott-Raven Publisher; 1996: 607-615
    Google Scholar
  • 6 Faber J, Petersen L, Wiinberg N, Schifter S, Mehlsen J. Haemodynamic changes after levothyroxine treatment in subclinical hypothyroidism. Thyroid 2002; 12: 319-324
    CrossrefPubMedGoogle Scholar
  • 7 Klein I, Ojamaa K. The cardiovascular system in hypothyroidism. In: Braverman LE, Utiger RD. ed Werner and Ingbar’s The Thyroid. Philadelphia: Lippincott-Raven Publisher; 1996: 799-804
    Google Scholar
  • 8 Wang C, Crapo LM. The epidemiology of thyroid disease and implication for screening. Endocrinol Metab Clin North Am 1997; 26: 189-218
    CrossrefPubMedGoogle Scholar
  • 9 Samuels MH. Subclinical thyroid disease in the elderly. Thyroid 1998; 8: 803-813
    CrossrefPubMedGoogle Scholar
  • 10 Marqusee E, Haden ST, Utiger RD. Subclinical thyrotoxicosis. Endocrinol Metab Clin North Am 1998; 27: 37-49
    CrossrefPubMedGoogle Scholar
  • 11 Biondi B, Palmieri EA, Lombardi G, Fazio S. Effects of subclinical thyroid dysfunction on the heart. Ann Intern Med 2002; 137: 904-914
    PubMedGoogle Scholar
  • 12 Parle JV, Franklyn JA, Cross KW, Jones SC, Sheppard MC. Prevalence and follow-up of abnormal thyrotrophin (TSH) concentrations in elderly in the United Kingdom. Clin Endocrinol (Oxf) 1991; 34: 77-83
    CrossrefPubMedGoogle Scholar
  • 13 Stott DJ, McLellan AR, Finlayson J, Chu P, Alexander WD. Elderly patients with suppressed serum TSH but normal free thyroid hormone levels usually have mild thyroid overactivity and are at increased risk of developing overt hyperthyroidism. Q J Med 1991; 78: 77-84
    PubMedGoogle Scholar
  • 14 Sawin CT, Geller A, Kaplan MM, Bacharach P, Wilson PW, Hershman JM. Low serum thyrotropin (thyroid-stimulating hormone) in older persons without hyperthyroidism. Arch Intern Med 1991; 151: 165-168
    CrossrefPubMedGoogle Scholar
  • 15 Sundbeck G, Jagenburg R, Johansson PM, Eden S, Lindstedt G. Clinical significance of low serum thyrotropin concentration by chemiluminometric assay in 85-year-old women and men. Arch Intern Med 1991; 151: 549-556
    CrossrefPubMedGoogle Scholar
  • 16 Forfar JC, Muir AL, Sawer SA, Toft AD. Abnormal left ventricular function in hyperthyroidism. Evidence for possible reversible cardiomyopathy. N Engl J Med 1982; 307: 1165-1170
    CrossrefPubMedGoogle Scholar
  • 17 Spencer CA, LoPresti JS, Patel A, Guttler RB, Eigen A, Shen D, Gray D, Nicoloff JT. Applications of a new chemiluminometric thyrotropin assay to subnormal measurement. J Clin Endocrinol Metab 1990; 70: 453-460
    CrossrefPubMedGoogle Scholar
  • 18 Davis PH, Franklyn JA, Daykin J, Sheppard MC. The significance of TSH values measured in a sensitive assay in the follow-up of hyperthyroid patients treated with radioiodine. J Clin Endocrinol Metab 1992; 74: 1189-1194
    CrossrefPubMedGoogle Scholar
  • 19 Raymond I, Pedersen F, Busch-Sørensen M, Green A, Hildebrandt PR. The Frederiksberg Heart Failure Study: Rationale, design and methodology, with special emphasis on the sampling procedure for the study population and its comparison to the background population. HeartDrug 2002; 4: 67-174
    PubMedGoogle Scholar
  • 20 Rose G, Blackburn H, Gillum RF, Prineas RJ. Cardiovascular Survey Methods. In: World Health Organisation Monograph series. Geneva: World Health Organization; (ed. 2) 1982: 56
    Google Scholar
  • 21 Karl J, Borgya A, Gallusser A, Huber E, Krueger K, Rollinger W, Schenk J. Development of a novel, N-terminal-proBNP (NT-proBNP) assay with a low detection limit. Scand J Clin Lab Invest 1999; 230: 177-181
    PubMedGoogle Scholar
  • 22 Kistorp C, Raymond I, Pedersen F, Gustafsson F, Faber J, Hildebrandt P. N-terminal pro-brain natriuretic peptide, C-reactive protein, and urinary albumin levels as predictors of mortality and cardiovascular events in older adults. J Am Med Assoc 2005; 293: 1609-1616
    CrossrefPubMedGoogle Scholar
  • 23 Richards AM, Troughton R, Lainchbury J, Doughty R, Wright S. 2005; Guiding and Monitorering of Heart Failure Therapy with NT-ProBNP: Concepts and Clinical Studies. J Card Fail 2005; 11: S34-S37
    CrossrefPubMedGoogle Scholar
  • 24 Andersen TF, Madsen M, Jorgensen J, Mellemkjoer L, Olsen JH. The Danish National Hospital Register. A valuable source of data for modern health sciences. Dan Med Bull 1999; 46: 263-268
    PubMedGoogle Scholar
  • 25 Sawin CT, Geller A, Wolf PA, Belanger AJ, Baker E, Bacharach P, Wilson PW, Benjamin EJ, D’Agostino RB. Low serum thyrotropin concentrations as a risk factor for atrial fibrillation in older persons. N Engl J Med 1994; 331: 1249-1252
    CrossrefPubMedGoogle Scholar
  • 26 Presti C, Hart RG. Thyrotoxicosis atrial fibrillation and embolism, revisited. Am Heart J 1989; 117: 976-977
    CrossrefPubMedGoogle Scholar
  • 27 Staffurth JS, Gibberd MC, Fui SN. Arterial embolism in thyrotoxicosis with atrial fibrillation. Br Med J 1977; 2: 688-690
    CrossrefPubMedGoogle Scholar
  • 28 Bar-Sela S, Ehrenfeld M, Eliakim M. Arterial embolism in thyrotoxicosis with atrial fibrillation. Arch Intern Med 1981; 141: 1191-1192
    CrossrefPubMedGoogle Scholar
  • 29 Squizzato A, Gerdes VE, Brandjes DP, Buller HR, Stam J. Thyroid diseases and cerebrovascular disease. Stroke 2005; 36: 2302-2310
    CrossrefPubMedGoogle Scholar
  • 30 Tenerz A, Forberg R, Jansson R. 1990; Is a more active attitude warranted in patients with subclinical thyrotoxicosis?. J Intern Med 1990; 228: 229-233
    PubMedGoogle Scholar
  • 31 Auer J, Scheibner P, Mische T, Langsteger W, Eber O, Eber B. Subclinical hyperthyroidism as a risk factor for atrial fibrillation. Am Heart J 2001; 142: 838-842
    CrossrefPubMedGoogle Scholar
  • 32 Cappola AR, Fried LP, Arnold AM, Danese MD, Kuller LH, Burke GL, Tracy RP, Ladenson PW. Thyroid status, cardiovascular risk, and mortality in older adults. J Am Med Assoc 2006; 295: 1033-1041
    CrossrefPubMedGoogle Scholar
  • 33 Hoogendoorn EH, den Heijer M, van Dijk AP, Hermus AR. Subclinical hyperthyroidism: to treat or not to treat?. Postgrad Med J 2004; 80: 394-398
    CrossrefPubMedGoogle Scholar
  • 34 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
    CrossrefPubMedGoogle Scholar
  • 35 Gussekloo J, Exel EV, AJMD Craen, Meinders AE, Frölich M, Westerndorp RGJ. Thyroid status, disability and cognitive function, and survival in old age. J Am Med Assoc 2004; 292: 2591-2599
    CrossrefPubMedGoogle Scholar
  • 36 Walsh JP, Bremner AP, Bulsara MK, O’Leary P, Leedman PJ, Feddema P, Michelangeli V. Subclinical Thyroid Dysfunction as a Risk Factor for Cardiovascular Disease. Arch Intern Med 2005; 165: 2467-2472
    CrossrefPubMedGoogle Scholar
  • 37 Rodondi N, Aujesky D, Vittinghoff E, Cornuz J, Bauer DC. Subclinical Hypothyroidism and the Risk of Coronary Heart Disease: A Meta-Analysis. Am J Med 2006; 119: 541-551
    CrossrefPubMedGoogle Scholar
  • 38 Hak AE, Pols HA, Visser TJ, Drexhage HA, Hofman A, Witterman JC. Subclinical hypothyroidism is an independent risk factor for atherosclerosis and myocardial infarction in elderly women: the Rotterdam Study. Ann Intern Med 2000; 132: 270-278
    PubMedGoogle Scholar
  • 39 Imaizumi M, Akahoshi M, Ichimaru S, Nakashima E, Hida A, Soda M, Usa T, Ashizawa K, Yokoyama N, Maeda R, Nagataki S, Eguchi K. Risk for ischemic heart disease and all-cause mortality in subclinical hypothyroidism. J Clin Endocrinol Metab 2004; 89: 3365-3370
    CrossrefPubMedGoogle Scholar
  • 40 Kvetny J, Heldgaard PE, Bladbjerg EM, Gram J. Subclinical hypothyroidism is associated with low-grade inflammation, increased triglyceride levels and predicts cardiovascular disease in males below 50 years. Clin Endocrinol 2004; 61: 232-238
    CrossrefPubMedGoogle Scholar
  • 41 Nyirenda MJ, Clark DN, Finlayson AR, Read J, Elders A, Bain M, Fox KA, Toft AD. Thyroid Disease and Increased Cardiovascular Risk. Thyroid 2005; 15: 718-724
    CrossrefPubMedGoogle Scholar
  • 42 Col NF, Surks MI, Daniels GH. Subclinical Thyroid Disease: Clinical Applications. J Am Med Assoc 2004; 291: 239-243
    CrossrefPubMedGoogle Scholar
  • 43 Schultz M, Faber J, Kistorp C, Jarlov A, Pedersen F, Wiinberg N, Hildebrandt P. N-terminal-pro-b-type natriuretic peptide (NT-pro-BNP) in different thyroid function states. Clin Endocrinol (Oxf) 2004; 60: 54-59
    CrossrefPubMedGoogle Scholar
  • 44 Schultz M, Kistorp C, Langdahl B, Raymond I, Hildebrandt P, Faber J. N-terminal-pro-b-type natriuretic peptide in acute hyperthyroidism. Thyroid 2007; 17: 237-241
    CrossrefPubMedGoogle Scholar
  • 45 Biondi B, Cooper DS. The Clinical Significance in Subclinical Thyroid Dysfunction. Endocr Rev 2008; 29: 76-131
    CrossrefPubMedGoogle Scholar
  • 46 Knudsen N, Bülow I, Jørgensen T, Laurberg P, Ovesen L, Perrild H. Comparative study of thyroid function and types of thyroid dysfunction in two areas in Denmark with slightly different iodine status. Eur J Endocrinol 2000; 143: 485-491
    CrossrefPubMedGoogle Scholar