Subclinical hypothyroidism and cardiovascular risk: A reason to treat?

Treatments in Endocrinology

Volumn 3, Issue 4, 2004, Pages 233-244

  Palmieri, Emiliano A ^a   Fazio, Serafino ^a   Lombardi, Gaetano ^a   Biondi, Bernadette ^a,b  

^a UNIVERSITY OF NAPLES FEDERICO II   (Italy)

^b Dipto di Endocrinol/Oncol Molec   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

LEVOTHYROXINE; THYROTROPIN;

ADULT; AGED; ATHEROGENESIS; ATHEROSCLEROSIS; CARDIOVASCULAR RISK; DIASTOLE; EUTHYROIDISM; EXERCISE; FEMALE; HUMAN; HYPERCOAGULABILITY; HYPOTHYROIDISM; MAJOR CLINICAL STUDY; MALE; PRIORITY JOURNAL; REVIEW; THYROTROPIN BLOOD LEVEL; VASCULAR DISEASE;

CARDIOVASCULAR DISEASES; FEMALE; HOMOCYSTEINE; HUMANS; HYPOTHYROIDISM; LIPIDS; MALE; RISK FACTORS; THYROID GLAND; THYROXINE;

EID: 3142691997     PISSN: 11756349     EISSN: None     Source Type: Journal    
DOI: 10.2165/00024677-200403040-00005     Document Type: Review

References (106)

1. Cooper DS. Clinical practice: subclinical hypothyroidism. N Engl J Med 2001; 345: 260-5
2. Tunbridge WMG, Evered DC, Hall R, et al. The spectrum of thyroid disease in a community: the Whickham survey. Clin Endocrinol (Oxf) 1977; 7: 481-93
3. Ladenson PW, Wilson MC, Gardin J, et al. Relationship of subclinical hypothyroidism to cardiovascular risk factors and disease in an elderly population [abstract]. Thyroid 1994; 4: S-18
4. Bauer DC, Ettinger B, Browner WS. Thyroid function and serum lipids in older women: a population-based study. Am J Med 1998; 104: 546-51
5. Liendman RD, Schade DS, LaRue A, et al. Subclinical hypothyroidism in biethnic, urban community. J Am Geriatr Soc 1999; 47: 703-9
6. Canaris GJ, Manowitz NR, Mayor G, et al. The Colorado thyroid disease prevalence study. Arch Intern Med 2000; 160: 526-34
7. Hak AE, Pols HAP, Visser TJ, et al. Subclinical hypothyroidism is an independent risk factor for atherosclerosis and myocardial infarction in elderly women: the Rotterdam Study. Ann Intern Med 2000; 132: 270-8
8. Pirich C, Mullner M, Sinzinger H. Prevalence and relevance of thyroid dysfunction in 1922 cholesterol screening participants. J Clin Epidemiol 2000; 53: 623-9
9. Kanaya AM, Harris F, Volpato S, et al. Association between thyroid dysfunction and total cholesterol level in an older biracial population: the health, aging and body composition study. Arch Intern Med 2002; 162: 773-9
10. Hollowell JG, Staehling NW, Flanders WD, et al. 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 2002; 87: 489-99
11. Cappola AR, Ladenson PW. Hypothyroidism and atherosclerosis. J Clin Endocrinol Metab 2003; 88: 2438-44
12. Andersen S, Pedersen KM, Brunn NH, et al. Narrow individual variations in serum T4 and T3 in normal subjects: a clue to the understanding of subclinical thyroid disease. J Clin Endocrinol Metab 2002; 87: 1068-72
13. Carr D, McLeod DT, Parry G, et al. Fine adjustment of thyroxine replacement dosage: comparison of the thyrotropin releasing hormone test using sensitive thyrotropin assay with measurement of free thyroid hormone and clinical assessment. Clin Endocrinol 1988; 28: 325-33
14. Spencer CA, Lopresti JS, Patel A, et al. Applications of a new chemiluminescent thyrotropin assay to subnormal measurement. J Clin Endocrinol Metab 1990; 70: 453-60
15. Meier CA, Maisen MN, Lowry A, et al. Interindividual differences in the pituitary-thyroid axis influence the interpretation of thyroid function tests. Clin Endocrinol 1993; 39: 101-7
16. Huber G, Staub JJ, Meier C, et al. Prospective study of the spontaneous course of subclinical hypothyroidism: prognostic value of thyrotropin, thyroid reserve, and thyroid antibodies. J Clin Endocrinol Metab 2002; 87: 3221-6
17. Series JJ, Biggert EM, O'Reilly DSJ, et al. The thyroid dysfunction and hypercholesterolemia in the general population of Glasgow. Clin Chim Acta 1988; 172: 217-22
18. Ball MJ, Griffiths D, Thorogood M. Asymptomatic hypothyroidism and hypercholesterolemia. J R Soc Med 1991; 84: 527-9
19. Pallas D, Koutras DA, Adamopulos P, et al. Increased mean serum thyrotropin in apparently euthyroid hypercholesterolemic patients: does it mean occult hypothyroidism? J Endocrinol Invest 1991; 14: 743-6
20. Oettgen P, Ginsburg GS, Horowitz GL, et al. Frequency of hypothyroidism in adults with serum cholesterol levels > 200 mg/dl. Am J Cardiol 1994; 73: 955-7
21. Diekman T, Lansberg PJ, Kastelein JJ, et al. Prevalence and correction of hypothyroidism in a large cohort of patients referred for dyslipidemia. Arch Intern Med 1995; 155: 1490-5
22. Bindels AJ, Westendorp RG, Frolich M, et al. The prevalence of subclinical hypothyroidism at different total plasma cholesterol levels in middle aged men and women: a need for case finding? Clin Endocrinol 1999; 50: 217-20
23. Tsimihodimos V, Bairaktari E, Tzallas C, et al. The incidence of thyroid abnormalities in patients attending an outpatient lipid clinic. Thyroid 1999; 9: 356-68
24. Tunbridge WMG, Evered DC, Hall R, et al. Lipid profiles and cardiovascular disease in the Whickham area with particular reference to thyroid failure. Clin Endocrinol 1977; 7: 495-508
25. Valdemarsson S, Hansson P, Hedner P, et al. Relations between thyroid function, hepatic and lipoprotein lipase activities, and plasma lipoprotein concentrations. Acta Endocrinol 1983; 104: 50-6
26. Althaus BU, Staub JJ, Ryff-de Leche A, et al. LDL/HDL-changes in subclinical hypothyroidism: possible risk factors for coronary heart disease. Clin Endocrinol 1988; 28: 157-63
27. Caron P, Calazel C, Parra HJ, et al. Decreased HDL cholesterol in subclinical hypothyroidism: the effect of L-thyroxine therapy. Clin Endocrinol 1990; 33: 519-23
28. Elder J, McLelland A, O'Reilly DS, et al. The relationship between serum cholesterol and serum thyrotropin, thyroxine and tri-iodothyronine concentrations in suspected hypothyroidism. Ann Clin Biochem 1990; 27: 110-3
29. Staub JJ, Althaus BU, Engler H, et al. Spectrum of subclinical and overt hypothyroidism: effect on thyrotropin, prolactin, and thyroid reserve, and metabolic impact on peripheral target tissues. Am J Med 1992; 92: 631-42
30. Parle JV, Franklyn JA, Cross KW, et al. Circulating lipids and minor abnormalities of thyroid function. Clin Endocrinol 1992; 37: 411-4
31. Geul KW, van Sluisveld IL, Grobbee DE, et al. The importance of thyroid microsomal antibodies in the development of elevated serum TSH in middle-aged women: associations with serum lipids. Clin Endocrinol 1993; 39: 275-80
32. Bogner U, Arntz HR, Peters H, et al. Subclinical hypothyroidism and hyperlipoproteinaemia: indiscriminate L-thyroxine treatment not justified. Acta Endocrinol 1993; 128: 202-6
33. Johnston J, McLelland A, O'Reilly DS. The relationship between serum cholesterol and serum thyroid hormones in male patients with suspected hypothyroidism. Ann Clin Biochem 1993; 30: 256-9
34. Miura S, litaka M, Yoshimura H, et al. Disturbed lipid metabolism in patients with subclinical hypothyroidism: effect of L-thyroxine therapy. Intern Med 1994; 33: 413-7
35. Kung AW, Pang RW, Janus ED. Elevated serum lipoprotein(a) in subclinical hypothyroidism. Clin Endocrinol 1995; 43: 445-9
36. Müller B, Zulewski H, Huber P, et al. Impaired action of thyroid hormone associated with smoking in women with hypothyroidism. N Engl J Med 1995; 333: 964-9
37. Yildirimkaya M, Ozata M, Yilmaz K, et al. Lipoprotein(a) concentration in subclinical hypothyroidism before and after levo-thyroxine therapy. Endocr J 1996; 43: 731-6
38. 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: 803-8
39. Vierhapper H, Nardi A, Grosser P, et al. Low-density lipoprotein cholesterol in subclinical hypothyroidism. Thyroid 2000; 10: 981-4
40. Müller B, Tsakiris DA, Roth CB, et al. Haemostatic profile in hypothyroidism as potential risk factor for vascular or thrombotic disease. Eur J Clin Invest 2001; 31: 131-7
41. Efstathiadou Z, Bitsis S, Milionis HJ, et al. Lipid profile in subclinical hypothyroidism: is L-thyroxine substitution beneficial? Eur J Endocrinol 2001; 145: 705-10
42. Caraccio N, Ferranini E, Monzani F. Lipoprotein profile in subclinical hypothyroidism: response to levothyroxine replacement, a randomized placebo-controlled study. J Clin Endocrinol Metab 2002; 87: 1533-8
43. Duntas LH, Mantzou E, Koutras DA. Circulating levels of oxidized low-density lipoprotein in overt and mild hypothyroidism. Thyroid 2002; 12: 1003-7
44. Luboshitzky R, Aviv A, Herer P, et al. Risk factors for cardiovascular disease in women with subclinical hypothyroidism. Thyroid 2002; 12: 421-5
45. 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: 379-86
46. 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: 2099-106
47. Nilsson G, Nordlander S, Levin K. Studies on subclinical hypothyroidism with special reference to the serum lipid pattern. Acta Med Scand 1976; 200: 63-7
48. Lithell H, Boberg J, Hellsing K, et al. Serum lipoprotein and apolipoprotein concentrations and tissue lipoprotein-lipase activity in overt and subclinical hypothyroidism: the effect of substitution therapy. Eur J Clin Invest 1981; 11: 3-10
49. Ridgway EC, Cooper DS, Walker H, et al. Peripheral responses to thyroid hormone before and after L-thyroxine therapy in patients with subclinical hypothyroidism. J Clin Endocrinol Metab 1981; 53: 1238-42
50. Cooper DS, Halpern R, Wood LC, et al. L-thyroxine therapy in subclinical hypothyroidism: a double-blind, placebo-controlled trial. Ann Intern Med 1984: 101: 18-24
51. Bell GM, Todd WT, Forfar JC, et al. End-organ responses to thyroxine therapy in subclinical hypothyroidism. Clin Endocrinol 1985; 22: 83-9
52. Nystrom E, Caidahl K, Fager G, et al. A double-blind cross-over 12-month study of L-thyroxine treatment of women with 'subclinical' hypothyroidism. Clin Endocrinol 1988; 29: 63-75
53. Powell JT, Wiseman SA, Carter G, et al. Can thyroxine halt the progression of peripheral arterial disease? Eur J Vasc Surg 1989; 3: 85-7
54. Arem R, Patsch W. Lipoprotein and apolipoprotein levels in subclinical hypothyroidism: effect of levothyroxine therapy. Arch Intern Med 1990; 150: 2097-100
55. Franklyn JA, Daykin J, Betteridge J, et al. Thyroxine replacement therapy and circulating lipid concentrations. Clin Endocrinol 1993; 38: 453-9
56. 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: 1559-63
57. Romaldini JH, Biancalana MM, Figueiredo DI, et al. Effect of L-thyroxine administration on antithyroid antibody levels, lipid profile, and thyroid volume in patients with Hashimoto's thyroiditis. Thyroid 1996; 6: 183-8
58. Jaeschke R, Guyatt G, Gerstein H, et al. Does treatment with L-thyroxine influence health status in middle-aged and older adults with subclinical hypothyroidism? J Gen Intern Med 1996; 11: 744-9
59. Paoli M, Bellabarba G, Velazquez E, et al. Sex steroids, lipids, and lipoprotein cholesterols in women with subclinical and overt hypothyroidism before and after L-thyroxine therapy. Clin Chim Acta 1998; 275: 81-91
60. Meier C, Staub JJ, Roth CB, et al. TSH-controlled L-thyroxine therapy reduces cholesterol levels and clinical symptoms in subclinical hypothyroidism: a double blind, placebo-controlled trial (Basel Thyroid Study). J Clin Endocrinol Metab 2001; 86: 4860-6
61. Kong WM, Sheikh M, Lumb P, et al. A 6-month randomized trial of thyroxine treatment in women with mild subclinical hypothyroidism. Am J Med 2002; 112: 348-54
62. Bakker SJL, Ter Matten JC, Popp-Snijders C, et al. The relationship between thyrotropin and low density lipoprotein cholesterol is modified by insulin sensitivity in healthy euthyroid subjects. J Clin Endocrinol Metab 2001; 86: 1206-11
63. Deicher R, Vierehapper H. Homocysteine: a risk factor for cardiovascular disease in subclinical hypothyroidism? Thyroid 2002; 12: 733-6
64. Bough EW, Crowley WF, Ridgway C, et al. Myocardial function in hypothyroidism: relation to disease severity and response to treatment. Arch Intern Med 1978; 138: 1476-80
65. Tseng KH, Walfish PG, Persand JA, et al. Concurrent aortic and mitral valve echocardiography permits measurement of systolic time intervals as an index of peripheral tissue thyroid function status. J Clin Endocrinol Metab 1989; 69: 633-8
66. Kahaly GJ. Cardiovascular and atherogenic aspects of subclinical hypothyroidism. Thyroid 2000; 10: 665-79
67. Foldes J, Istvanfy M, Halmagyi H, et al. Hypothyroidism and the heart: examination of left ventricular function in subclinical hypothyroidism. Acta Med Hung 1987; 44: 337-47
68. Biondi B, Fazio S, Palmieri EA, et al. Left ventricular diastolic dysfunction in patients with subclinical hypothyroidism. J Clin Endocrinol Metab 1999; 84: 2064-7
69. Di Bello V, Monzani F, Giorgi D, et al. Ultrasonic myocardial textural analysis in subclinical hypothyroidism. J Am Soc Echocardiogr 2000; 13: 832-40
70. Monzani F, Di Bello V, Caraccio N, et al. Effects of levo-thyroxine on cardiac function and structure in subclinical hypothyroidism: a double blind, placebo-controlled study. J Clin Endocrinol Metab 2001; 86: 1110-5
71. Vitale G, Galderisi M, Luppoli GA, et al. Left ventricular myocardial impairment in subclinical hypothyroidism assessed by a new ultrasound tool: pulsed tissue Doppler. J Clin Endocrinol Metab 2002; 87: 4350-5
72. Brenta G, Mutti LA, Schnitman M, et al. 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: 1327-30
73. Forfar JC, Wathen CG, Todd WT, et al. Left ventricular performance in subclinical hypothyroidism. Q J Med 1985; 57: 857-65
74. Arem R, Rokey R, Kiefe C, et al. Cardiac systolic and diastolic function at rest and exercise in subclinical hypothyroidism: effect of thyroid hormone therapy. Thyroid 1996; 6: 397-402
75. Lekakis J, Papamichael C, Alevizaki M, et al. Flow-mediated, endothelium-dependent vasodilatation is impaired in subjects with hypothyroidism, borderline hypothyroidism, and high-normal serum thyrotropin (TSH) values. Thyroid 1997; 7: 411-4
76. Taddei S, Caraccio N, Virdis A, et al. Impaired endothelium-dependent vasodilation in subclinical hypothyoidism: beneficial effect of levothyroxine therapy. J Clin Endocrinol Metab 2003; 88: 3731-7
77. Faber J, Petersen L, Wiinberg N, et al. Hemodynamic changes after levothyroxine treatment in subclinical hypothyroidism. Thyroid 2002; 12: 319-24
78. Bastenie PA, Vanhaelst L, Bonnyns M, et al. Preclinical hypothyroidism: a risk factor for coronary artery disease. Lancet 1971; 1: 203-4
79. Bastenie PA, Bonnyns M, Neve P, et al. Asymptomatic atrophic thyroiditis in coronary artery disease. Lancet 1972; 1: 1072-3
80. Powell J, Zadeh JA, Carter G, et al. Raised serum thyrotropin in women with peripheral arterial disease. Br J Surg 1987; 74: 1139-41
81. Ponte E, Ursu HI. Overt and subclinical hypothyroidism and atherosclerotic arteriopathy of the lower limbs (clinical and subclinical). Rom J Endocrinol 1993; 31: 71-9
82. Tièche 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: 202-6
83. Dean JW, Fowler PB. Exaggerated responsiveness to thyrotropin releasing hormone: a risk factor in women with coronary artery disease. Br Med J (Clin Res Ed) 1985; 290: 1555-61
84. Heinonen OP, Gordin A, Aho K, et al. Symptomless autoimmune thyroiditis in coronary heart disease. Lancet 1972; 1: 785-6
85. Miura S, Itaka M, Suzuki S, et al. Decrease in serum levels of thyroid hormone in patients with coronary heart disease. Endocr J 1996; 43: 657-63
86. 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: 155-60
87. Mya MM, Aronow WS. Subclinical hypothyroidism is associated with coronary artery disease in older persons. J Gerontol A Biol Sci Med 2002; 57: M658-9
88. Manowitz NR, Mayor GH, Klepper MJ, et al. Subclinical hypothyroidism and euthyroid sick syndrome in patients with moderate-to-severe congestive heart failure. Am J Ther 1996; 3: 797-801
89. McDermott MM, Feinglass J, Sy J, et al. Hospitalized congestive heart failure patients with preserved versus abnormal left ventricular systolic function: clinical characteristics and drug therapy. Am J Med 1995; 99: 629-35
90. Danese MD, Ladenson PW, Meinert CL, et al. 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
91. Michalopoulou G, Alevizaki M, Piperingos G, et al. High serum cholesterol levels in persons with 'high normal' TSH levels: should one extend the definition of subclinical hypothyroidism? Eur J Endocrinol 1998; 138: 141-5
92. Faber J, Galloe AM. Changes in bone mass during prolonged subclinical hyperthyroidism due to L-thyroxine treatment: a meta-analysis. Eur J Endocrinol 1994; 130: 350-6
93. Perk M, O'Neill BJ. The effect of thyroid hormone therapy on angiographic coronary artery disease progression. Can J Cardiol 1997; 13: 273-6
94. Vanderpump MP, Tunbridge WM, French JM, et al. The incidence of thyroid disease in the community: a twenty-year follow-up of the Whickham Survey. Clin Endocrinol 1995; 43: 55-69
95. Kannel WB, Neaton JD, Wentworth D, et al. Overall and CHD mortality in relation to major risk factors in 325,348 men screened for the MRFIT. Am Heart J 1987; 8: 77-88
96. LaRosa JC, He J, Vupputuri S. Effects of statins on risk of coronary artery disease. JAMA 1999; 282: 2340-6
97. Law MR, Wald NJ, Thompson SG. By how much and how quickly does reduction in serum cholesterol lower risk of ischemic heart disease? BMJ 1994; 308: 367-72
98. Parle JV, Franklyn JA, Cross KW, et al. Thyroxine prescription in the community: serum thyroid hormone stimulating level assays as an indicator of undertreatment or overtreatment. Br J Gen Pract 1993; 43: 107-9
99. Bemben DA, Winn P, Hamm RM, et al. Thyroid disease in the elderly. Part 1: prevalence of undiagnosed hypothyroidism. J Fam Pract 1994; 38: 577-82
100. Watsky JG, Koeniger MA. Prevalence of iatrogenic hyperthyroidism in a community hospital. J Am Board Fam Pract 1998; 11: 175-9
101. Sawin CT, Geller A, Wolf PA, et al. Low serum thyrotropin concentrations as a risk factor for atrial fibrillation in older persons. N Engl J Med 1994; 331: 1249-52
102. Biondi B, Fazio S, Carella C, et al. Cardiac effects of long term thyrotropin-suppressive therapy with levothyroxine. J Clin Endocrinol Metab 1993; 77: 334-8
103. De Whalley P. Do abnormal thyroid stimulating hormone level values result in treatment changes? A study of patients on thyroxine in one general practice. Br J Gen Pract 1995; 45: 93-5
104. Kasagi K, Takeuchi R, Misaki T, et al. Subclinical Graves' disease as a cause of subnormal TSH levels in euthyroid subjects. J Endocrinol Invest 1997; 20: 183-8
105. Figge J, Leinung M, Goodman AD, et al. The clinical evaluation of patients with subclinical hyperthyroidism and free triiodothyronine (free T3) toxicosis. Am J Med 1994; 96: 229-34
106. Weetman AP. Hypothyroidism: screening and subclinical disease. BMJ 1997; 314: 1175-8