Does Persistent Subclinical Hypothyroidism Put the Elderly at Cardiovascular Risk?
Does Persistent Subclinical Hypothyroidism Put the Elderly at Cardiovascular Risk?
Abstract & Commentary
By Rahul Gupta, MD, MPH, FACP, Clinical Assistant Professor, West Virginia University School of Medicine, Charleston, WV. Dr. Gupta reports no financial relationships relevant to this field of study.
Synopsis: In older adults, no association was found between subclinical hypothyroidism and coronary heart disease, heart failure, and cardiovascular mortality.
Source: Hyland KA, et al. Persistent subclinical hypothyroidism and cardiovascular risk in the elderly: The Cardiovascular Health Study. J Clin Endocrinol Metab 2012; Nov. 16. [Epub ahead of print.]
Hypothyroidism is quite common in elderly people. While screening patients for thyroid disease, clinicians often discover subclinical hypothyroidism, which is defined as having normal serum free thyroxine (T4) concentration in the presence of an elevated serum thyrotropin (TSH) concentration. Subclinical hypothyroidism is also a relatively common finding in the general population. In the National Health and Nutrition Examination Survey (NHANES III), 4.3% of the 16,533 Americans who did not report thyroid disease were found to have subclinical hypothyroidism.1 Generally, the prevalence of subclinical hypothyroidism rises with age, is higher in females than males, and is higher in whites than in blacks. Some patients with subclinical hypothyroidism have mild, non-specific symptoms of hypothyroidism, such as easy fatigability, dry skin, and constipation. While TSH levels may normalize or remain stable over time, a significant proportion of patients with subclinical hypothyroidism may eventually end up with clinical hypothyroidism.
Clinicians often cite the possible link of subclinical hypothyroidism to cardiovascular (CV) disease development and mortality as support for treatment in elderly individuals. However, the scientific evidence for the relationship between subclinical hypothyroidism and coronary heart disease (CHD), heart failure (HF), and CV mortality is mixed at best. Currently, most experts recommend treatment of patients with serum TSH concentrations > 10 mU/L, for which a case can be made from a recent meta-analysis which demonstrated that in patients with subclinical hypothyroidism, increased risk of CHD events occurred if TSH levels were ≥ 10 mU/L and increased risk of CHD mortality occurred if TSH levels were ≥ 7 mU/L.2 However, many such previous studies have used a single set of thyroid function tests to define subclinical hypothyroidism, which may lead to misclassification over time since an individual’s thyroid function may change over a period of years.
In their study, Hyland et al used data from the Cardiovascular Health Study, which is a large cohort of community-dwelling individuals ≥ 65 years and older. The researchers assessed the 10-year risk of incident CHD, HF, and CV mortality in individuals with persistently subclinical hypothyroidism. Included in the study were 679 subclinical hypothyroid and 4184 euthyroid Americans, none of whom were taking thyroid medications. Euthyroidism was defined as a TSH concentration of 0.45-4.50 mU/L and subclinical hypothyroidism was defined as a TSH concentration of > 4.50 mU/L and < 20 mU/L with a normal free T4 concentration. Employing repeated thyroid function testing over the 10-year period, subclinical hypothyroidism was modeled in three different ways, which allowed not only the initial subclinical hypothyroid individuals to be included but also those whose thyroid status changed over time. The researchers found no association between persistent subclinical hypothyroidism and incident CHD, HF, and CV death. The researchers also could not find any evidence of a gradient of risk or dose-response relationship by the degree of TSH elevation, although the number of subjects in the severe subclinical hypothyroidism subgroup was smaller.
Commentary
In patients with subclinical hypothyroidism, data linking CHD, HF, and CV to death have been conflicting. However, when higher-quality studies are pooled, the risk is found to be lower. The above study is a large population-based cohort study of the elderly specifically designed to examine CV factors long-term. Unlike several past studies, Hyland et al could not find an association between subclinical hypothyroidism, either transient or persistent, and incident CHD, HF, or CV mortality after repeatedly testing for thyroid function over a 10-year period in men and women ≥ 65 years. If these data are to be believed, then the treatment of this population with thyroid hormone is likely to cause no benefit (neutral) or harm, rather than benefit. In a joint statement issued on management of subclinical hypothyroidism from the American Association of Clinical Endocrinologists, the American Thyroid Association, and The Endocrine Society, the consensus panel recommended against routine treatment of patients with subclinical hypothyroidism with serum TSH levels of 4.5-10 mU/L, but indicated that treatment was reasonable for patients with TSH levels > 10 mU/L. So it seems that the current study’s findings directly conflict with the recommendations. Similar to debates on screening recommendations for hypothyroidism, treatment decisions may be equally controversial. The old saying that the absence of evidence is not evidence of absence supports my view that we should continue to screen our patients when clinically necessary, as well as treat them when we find it to be clinically necessary, at least until the controversy is put to rest!
References
1. Hollowell JG, 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;87:489-499.
2. Rodondi N, et al. Subclinical hypothyroidism and the risk of coronary heart disease and mortality. JAMA 2010;304:1365-1374.
3. Gharib H, et al. Subclinical thyroid dysfunction: A joint statement on management from the American Association of Clinical Endocrinologists, the American Thyroid Association, and the Endocrine Society. J Clin Endocrinol Metab 2005;90:581-585.
In older adults, no association was found between subclinical hypothyroidism and coronary heart disease, heart failure, and cardiovascular mortality.Subscribe Now for Access
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