Impact of subclinical thyroid disorders on coronary heart disease, cardiovascular and all-cause mortality: A meta-analysis
Introduction
Subclinical hypothyroidism is defined as an elevated serum thyroid-stimulating hormone (TSH) level in the face of normal free thyroid hormone(free T4) values [1]. Previous studies have suggested that subclinical abnormalities in thyroid-stimulating hormone levels are associated with detrimental effects on the cardiovascular system [1]. Early clinical and autopsy studies had suggested an association between subclinical hypothyroidism and coronary heart disease, which has been subsequently confirmed by some, but not all, large cross-sectional and prospective studies [1]. Within the past three decades five large studies on this topic have produced conflicting results [2], [3], [4], [5], [6]. Four of them concluded that subjects with sub-clinical hypothyroidism had a significantly higher prevalence of coronary heart disease than euthyroid subjects(age and sex-adjusted prevalence odds ratio) [2], [3], [4], [5]. In the longitudinal analysis of subjects with sub-clinical hypothyroidism there were increased cardiovascular (CVS) deaths observed compared with expected and higher coronary heart disease (CHD) events in only one study implicating sub-clinical hypothyroidism as an independent risk factor for coronary heart disease [2]. Subclinical hypothyroidism was associated with an increase in the all-cause mortality in men only, in a 10-year follow-up study but not in other studies [5]. These discrepancies may have arisen from differences in the level of adjustment for other cardiovascular risk factors between included studies.
Subclinical hyperthyroidism has been defined as a low serum thyroid-stimulating hormone (TSH) level in the face of normal free thyroid hormone(free T4) values. Similarly a single measurement of low serum thyrotropin in individuals 60 yr or older has been reported to be associated with increased mortality from all causes and in particular due to circulatory and cardiovascular diseases in a 10-year follow-up study [7].
There have been no analyses performed to date on the relationship of sub-clinical thyroid disorders with CHD and their impact on mortality. We sought to produce a reliable and unbiased comparison of the relative risk for incident CHD events, cardiovascular-related and total mortality associated with sub-clinical thyroid abnormalities by utilizing data from the all large cross-sectional and prospective cohort studies published from 2000 till March 2006.
Section snippets
Identification of relevant trials
We searched the Medline, Ovid, Pubmed electronic databases. The medical literature was searched for all reports containing the key words, thyroid hormone, sub-clinical disease, coronary artery disease (CAD), and cardiovascular risk. We included cross-sectional and prospective cohort studies if by end of March 2006 they had published quantitative estimates and standard errors (or confidence limits) of the relative risk for fatal coronary heart disease associated with sub-clinical thyroid
Results
Our review yielded six large cohort studies [2], [3], [4], [5], [6], [7] (including subclinical hypothyroidism and subclinical hyperthyroidism) after exclusion of numerous articles either because there was no outcome of interest or because they reported duplicate data. These studies reported the number of patients with a diagnosis of sub-clinical thyroid dysfunction at baseline. The duration of follow-up varied from between 4 to 20 yr and the age range was between 17 and 89 yr (Table 1).
Discussion
Our findings are based on the information available on correlation of the sub-clinical thyroid disorder with cardiovascular disease making possible reliable quantitative estimates of the association between this condition and risk for coronary heart disease.
The results of our study report an association between subclinical hypothyroidism and prevalence of CHD that is independent of coronary risk factors such as blood pressure, BMI, total cholesterol, smoking status, ESR, presence of diabetes
Conclusion
Our meta-analysis indicates that sub-clinical hypothyroidism is associated with both, a significant risk of CHD at baseline and at follow-up. All-cause mortality from sub-clinical hypothyroidism is not increased, but mortality from cardiovascular causes is significantly higher at follow-up. Sub-clinical hyperthyroidism is not associated with a significant risk of either CHD at baseline or at follow-up (Fig. 6). In addition, mortality from cardiovascular causes is also not affected at long term
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