The relationship between hypothyroidism and atherosclerosis has been confirmed by case-control studies and autopsy; the relationship is much clearer in patients with overt hypothyroidism than in patients with subclinical disease. Overt hypothyroidism increases low-density lipoprotein (LDL) cholesterol levels, induces diastolic hypertension, alters coagulability, and negatively affects vascular smooth muscle function. Treatment of overt hypothyroidism can moderate these negative effects, but the effect of treatment is less clear in patients with subclinical hypothyroidism. Reductions in total cholesterol levels are highest in patients who had the highest pretreatment thyroid-stimulating hormone (TSH) and lipid levels. Hypothyroidism treatment also can reduce hypertension and improve vascular smooth muscle function. Treatment of subclinical hypothyroidism may lower cholesterol levels in patients with hypercholesterolemia. Cappola and Ladenson reviewed the most recent information about hypothyroidism and cardiovascular risk factors.
Patients with hypothyroidism appear to have elevated homocysteine and C-reactive protein (CRP) levels and altered flow-mediated, endothelium-dependent vasodilatation; coagulation capacity also may be affected. Thyroxine (T4) therapy can reduce homocysteine and CRP levels significantly in persons with overt hypothyroidism, but it may not be as useful in patients with subclinical disease.
Hypothyroidism may benefit patients with atherosclerotic disease because decreased peripheral oxygen utilization and bradycardia result in decreased cardiac work. Thyroid hormone replacement may reverse this benefit and increase myocardial ischemia. However, closer examination reveals that hormone therapy may be beneficial in these patients because of decreased peripheral vascular resistance, improved myocardial contractility, reduced preload, and decreased risk of left ventricular dilation. These effects result in improved myocardial efficiency. Hormone replacement should be started at a low dosage (12.5 to 25 mcg per day) and slowly titrated (in 12.5- to 25-mcg increments at four- to six-week intervals) until serum TSH reaches normal levels. Angina symptoms can be treated by revascularization, pharmacotherapy, or a temporary reduction in thyroid hormone dosage.
The authors conclude that overt hypothyroidism can cause atherosclerosis and other cardiac risk factors. Careful management of hypothyroidism can improve morbidity resulting from cardiac events.
editor's note: The benefit of treating patients with overt hypothyroidism is clear. Although there are many advocates for treating subclinical hypothyroidism, cardiovascular benefits are unclear. Physicians have a variety of preparations available to use for thyroid hormone supplementation. A study by Dong and associates1 showed that two brand-name preparations, Levoxyl and Synthroid, and two generic preparations distributed by Geneva Generics and Rugby Laboratories were bioequivalent. Each product, when taken over a six-week period in a four-way crossover design study, demonstrated similar bioavailability parameters of total T4, triiodothyronine, and resin thyroxine uptake. Although not all brands were tested, it appears that thyroid hormone supplementation can be offered reliably with generic preparations.—R.S.