Cardiovascular effects of hypothyroidism
- Irwin Klein, MD
Irwin Klein, MD
- Professor of Medicine and Endocrinology
- NYU School of Medicine
Hypothyroidism is characterized by a decrease in oxygen and substrate utilization by all the major organ systems of the body. As a result, the demands for cardiac output decrease; in addition, hypothyroidism directly alters cardiac function through changes in myocyte-specific gene expression . This topic will review the cardiovascular manifestations of overt hypothyroidism. Other symptoms of hypothyroidism and cardiovascular manifestations of subclinical hypothyroidism are discussed separately. (See "Clinical manifestations of hypothyroidism" and "Subclinical hypothyroidism in nonpregnant adults".)
The major cardiovascular changes that occur in hypothyroidism include a decrease in cardiac output and cardiac contractility, a reduction in heart rate, and an increase in peripheral vascular resistance (figure 1) [2,3]. There are also significant changes in modifiable atherosclerotic risk factors, including hypercholesterolemia, diastolic hypertension, carotid intimal media thickness, and endothelial derived relaxation factor (nitric oxide), which accompany overt hypothyroidism [1-5].
Cardiac contractility — All measures of left ventricular performance are impaired in both short and long-term hypothyroidism, leading to a reduction in cardiac output [4,5]. There is also a decrease in the rate of ventricular diastolic relaxation; as a result, compliance and diastolic filling are impaired .
The reduced ventricular performance is probably multifactorial. Possible mechanisms include increases in afterload and changes in expression of the genes for myocardial calcium regulatory proteins [1,6]. Several enzymes involved in regulating calcium fluxes in the heart are controlled by thyroid hormone, including the calcium-dependent adenosine triphosphatase and phospholamban [3,7]. Hypothyroidism-dependent decreases in the expression and activity of these enzymes could potentially impair systolic performance and diastolic relaxation . Beta adrenergic receptor expression is also decreased, resulting in a blunted response to catecholamine mediated increases in inotropy.
Vascular resistance — Thyroid hormone relaxes vascular smooth muscle cells, thereby reducing peripheral vascular resistance . Conversely, hypothyroidism causes a decrease in the release of endothelial-derived relaxation factor (EDRF), which in turn promotes contraction of these cells thereby increasing peripheral vascular resistance . This change results in reductions in cardiac output (in part because the heart cannot increase contractility to compensate) and tissue perfusion. Tissue oxygen utilization is also decreased; thus, arteriovenous (A-V) oxygen extraction is not different from that in normal subjects .
- Klein I, Danzi S. Thyroid disease and the heart. Circulation 2007; 116:1725.
- Taddei S, Caraccio N, Virdis A, et al. Impaired endothelium-dependent vasodilatation in subclinical hypothyroidism: beneficial effect of levothyroxine therapy. J Clin Endocrinol Metab 2003; 88:3731.
- Klein I, Ojamaa K. Thyroid hormone and the cardiovascular system. N Engl J Med 2001; 344:501.
- GRAETTINGER JS, MUENSTER JJ, CHECCHIA CS, et al. A correlation of clinical and hemodynamic studies in patients with hypothyroidism. J Clin Invest 1958; 37:502.
- Crowley WF Jr, Ridgway EC, Bough EW, et al. Noninvasive evaluation of cardiac function in hypothyroidism. Response to gradual thyroxine replacement. N Engl J Med 1977; 296:1.
- Klein I. Endocrine disorders and cardiovascular disease. In: Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine, 8th, Libby P, Bonow RO, Mann DL, Zipes DP (Eds), Saunders Elsevier, Philadelphia 2008. p.2033.
- Dillmann WH. Cellular action of thyroid hormone on the heart. Thyroid 2002; 12:447.
- Fredlund BO, Olsson SB. Long QT interval and ventricular tachycardia of "torsade de pointe" type in hypothyroidism. Acta Med Scand 1983; 213:231.
- Fommei E, Iervasi G. The role of thyroid hormone in blood pressure homeostasis: evidence from short-term hypothyroidism in humans. J Clin Endocrinol Metab 2002; 87:1996.
- Gumieniak O, Perlstein TS, Hopkins PN, et al. Thyroid function and blood pressure homeostasis in euthyroid subjects. J Clin Endocrinol Metab 2004; 89:3455.
- Kabadi UM, Kumar SP. Pericardial effusion in primary hypothyroidism. Am Heart J 1990; 120:1393.
- 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.
- Biondi B, Klein I. Hypothyroidism as a risk factor for cardiovascular disease. Endocrine 2004; 24:1.
- Smith TJ, Bahn RS, Gorman CA. Connective tissue, glycosaminoglycans, and diseases of the thyroid. Endocr Rev 1989; 10:366.
- Parving HH, Hansen JM, Nielsen SL, et al. Mechanisms of edema formation in myxedema--increased protein extravasation and relatively slow lymphatic drainage. N Engl J Med 1979; 301:460.
- O'Brien T, Dinneen SF, O'Brien PC, Palumbo PJ. Hyperlipidemia in patients with primary and secondary hypothyroidism. Mayo Clin Proc 1993; 68:860.
- Thompson GR, Soutar AK, Spengel FA, et al. Defects of receptor-mediated low density lipoprotein catabolism in homozygous familial hypercholesterolemia and hypothyroidism in vivo. Proc Natl Acad Sci U S A 1981; 78:2591.
- Diekman T, Lansberg PJ, Kastelein JJ, Wiersinga WM. Prevalence and correction of hypothyroidism in a large cohort of patients referred for dyslipidemia. Arch Intern Med 1995; 155:1490.
- Catargi B, Parrot-Roulaud F, Cochet C, et al. Homocysteine, hypothyroidism, and effect of thyroid hormone replacement. Thyroid 1999; 9:1163.
- Klein I, Mantell P, Parker M, Levey GS. Resolution of abnormal muscle enzyme studies in hypothyroidism. Am J Med Sci 1980; 279:159.
- KEATING FR Jr, PARKIN TW, SELBY JB, DICKINSON LS. Treatment of heart disease associated with myxedema. Prog Cardiovasc Dis 1961; 3:364.
- Polikar R, Feld GK, Dittrich HC, et al. Effect of thyroid replacement therapy on the frequency of benign atrial and ventricular arrhythmias. J Am Coll Cardiol 1989; 14:999.
- Flynn RW, Macdonald TM, Jung RT, et al. Mortality and vascular outcomes in patients treated for thyroid dysfunction. J Clin Endocrinol Metab 2006; 91:2159.