Is Subclinical Hypothyroidism a Cardiovascular Risk Factor in the Elderly?

Abstract

Context:The negative impact of subclinical hypothyroidism (sHT) on cardiovascular risk, widely recognized in young adults (aged Ͻ55-60 y), is still debated in the elderly (Ͼ65 y), especially in the oldest olds (Ͼ80 y).Evidence Acquisition: We searched Medline for reports published with the following search terms: "hypothyroidism," "subclinical hypothyroidism," "ageing," "elderly," "L-thyroxin," "thyroid," "guidelines," "treatment," "quality of life," "cardiovascular risk," "heart failure," "coronary heart disease" (CHD), "atherosclerosis," and "endothelial dysfunction." We limited our search to reports in English published after 1980, although we incorporated some reports published before 1980. We supplemented the search with records from personal files, textbooks, and relevant articles. Analyzed parameters included the epidemiology of thyroid failure, the effect of thyroid hormone on the aging process, cardiovascular function, and CHD risk factors. We also included the potential benefits of L-T 4 therapy on the quality of life, cardiovascular events, and survival.Evidence Synthesis: TSH levels increase with age, even in older people without thyroid disease. Most longitudinal studies show an increased risk for CHD events and mortality in sHT participants. This increase is less evident in the elderly, mainly in cases of serum TSH values above 10 mIU/L. Lower mortality rate in a cohort of the oldest olds (Ͼ85 y) has been reported. Conclusions: sHT in older people should be not regarded as a unique condition, and moderately old patients (aged Ͻ70 -75 y) could be considered clinically similar to the adult population, albeit with a higher optimal TSH target value. Conversely, the oldest old subjects should be carefully followed with a wait-and-see strategy, generally avoiding hormonal treatment. The decision to treat elderly people is still an unresolved clinical challenge-first, due to a lack of appropriately powered randomized controlled trials of L-T 4 in sHT patients, examining cardiovascular hard endpoints in various classes of age; and second, because of the negative effects of possible overtreatment. (J Clin Endocrinol Metab 98: 2256 -2266, 2013) S ubclinical hypothyroidism (sHT), defined as serum TSH concentration above the upper limit of the reference range in the face of normal free T 4 (FT 4 ) and free T 3 (FT 3 ) levels, is common in the elderly (1-3). This biochemical condition encompasses several pathological entities, mainly represented by chronic autoimmune thyroiditis even if increasing TSH may represent a physiological aging process (4).Depending on the degree of TSH elevation, sHT has been related to hyperlipidemia, intermediary metabolism changes, arterial hypertension, reduced glomerular filtration rate, and neuropsychiatric alterations (5-11). The negative impact of sHT in terms of coronary heart disease (CHD) and global cardiovascular (CV) risk is mostly acknowledged in young adults, whereas it remains to be established in the elderly, especially in the oldest old (aged Ͼ 80 y) (4). Moreover, t...

Major adverse cardiovascular and cerebral events in hypothyroid patients undergoing percutaneous coronary intervention

“…Although the study had some limitations mainly represented by the study design (observational), the definition of hypothyroidism (only based on a single TSH measurement without taking into account the level of serum free thyroxin) and the lack of age specific serum TSH reference ranges, the results are robust and consistent with previous experiences confirming the important role of thyroid function on the cardiovascular system especially in adult population younger than 65-70 years (2,3). In this regard, the link between thyroid function and cardiovascular risk factors is widely recognized and some meta-analyses documented an increased risk for CV events and mortality only in young adult population (<65 years).…”

“…In order to obtain an accurate diagnosis of SCH in the elderly, we have to consider the observed shift of serum TSH level toward upper values during age (19). In this setting, data from scientific literature obtained in disease free, oldest old population (>80-85 years) suggested that well ageing is characterized by a certain degree of down regulation of the hypothalamus-pituitary-thyroid peripheral axis, and this finding might lead to the idea that a mild decline of thyroid activity at the tissue level has favourable effect (2,20). However, sharing this interpretation with older people at all should be done with caution since a mild elevation of serum TSH may occur by either the aging process itself or an actual thyroid disease.…”

“…Indeed, we should also consider that the prevalence of circulating anti-thyroid autoantibody levels increases with ageing (21), suggesting actual subclinical thyroid impairment as the cause of TSH raise in the elderly. Therefore, a correct diagnosis of SCH is challenging in the oldest old population (i.e., elevated serum TSH according to age related reference ranges and documented thyroid disease) but crucial in avoiding significant misclassification of patients with abnormal TSH value, who may or may not have an actual thyroid failure and may receive unnecessary or even harmful therapy (2,3,22,23). Keeping in mind these considerations, the fundamental clinical question regarding older persons with slightly elevated serum TSH value is how they have to be dealt with and, in the case of confirmed thyroid failure, whether they need hormone replacement therapy (2,19,23).…”

“…Therefore, a correct diagnosis of SCH is challenging in the oldest old population (i.e., elevated serum TSH according to age related reference ranges and documented thyroid disease) but crucial in avoiding significant misclassification of patients with abnormal TSH value, who may or may not have an actual thyroid failure and may receive unnecessary or even harmful therapy (2,3,22,23). Keeping in mind these considerations, the fundamental clinical question regarding older persons with slightly elevated serum TSH value is how they have to be dealt with and, in the case of confirmed thyroid failure, whether they need hormone replacement therapy (2,19,23). The study by Zhang et al demonstrated in an indirect way that an adequate L-thyroxin replacement may reverse the CV risk of SCH, however this is not easily to obtain in clinical practice since in a certain number of cases (mainly older women) the treatment could be detrimental if an excess of therapy is administered and a strict monitoring of serum TSH value is warranted (1,24).…”

Cardiovascular Risk and Mild Thyroid Hormone Deficiency: Are there some Differences in the Elderly?

“…Nonetheless, the term sHT is recognized worldwide and will be utilized in the present editorial. Since 90s, a relationship between sHT and increased cardio-vascular (CV) risk (both heart failure and coronary heart disease events) has been reported, although some experiences suggest that the risk may depend on the degree of TSH elevation [1,[3][4][5]. Moreover, several reports from elderly population (>65 years old) showed that this relationship seems no longer evident in such individuals especially in the oldest old (>85 years old) [6][7][8][9].…”