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 relaxing 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 .
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