In a multivariate analysis, carotid IMT values were significantly greater in the higher TSH decile women group (0.92±0.02 vs. 0.86±0.01 mm; P=0.037) compared with women in the other deciles. Women in the upper TSH decile had an increased risk of carotid IMT (odds ratio 16.0, 95% confidence interval 1.08–237.9, P=0.04), after adjustment for comorbidities.
The prevalence of carotid plaques was not significantly different in the two groups (75 vs. 68%, P=0.29), whereas the total number of plaques was higher in the group of women in the upper TSH decile (2.3±0.3 vs. 1.7±0.1; P=0.025) (Fig. 1).
In a Mediterranean female population, we found a positive, independent association of TSH levels with carotid artery IMT and the number of atherosclerotic plaques, indicators of subclinical atherosclerosis.
Previous studies have examined a possible association between thyroid function and atherosclerotic risk, mainly in patients with overt or subclinical hyperthyroidism or hypothyroidism 14–17. A few data have been obtained in a population-based sample. Our results are in agreement with and complement the findings of a recent analysis carried out in 643 Japanese adults with euthyroid status, showing that both free thyroxine and TSH levels were associated with carotid IMT and suggesting an increased cardiovascular risk in participants with low normal thyroid function 19. In contrast to these results, in the Tromso study, no significant relationship was found between carotid IMT and serum TSH levels in normal, nonthyroxine-taking individuals, whereas carotid IMT was increased in participants taking thyroxine 18.
Our finding of a different association of THS levels with carotid IMT and plaque has no clear explanation, but could be related to the evidence that processes leading to IMT and plaque formation may not be similar 30, and patterns of risk factors may be different. In a population of hyperlipidemic patients, average IMT was significantly greater in patients having overt hypothyroidism than in patients with subclinical hypothyroidism, whereas the prevalence of carotid plaques was higher in patients with subclinical hypothyroidism than in patients having overt hypothyroidism 31.
The mechanism that could link TSH levels with carotid IMT and plaque number within our euthyroid population remains to be elucidated. The positive relationship remained statistically significant after adjustment for lipid parameters, smoking, and other traditional atherosclerotic risk factors. In patients with elevated TSH levels (subclinical hypothyroidism), recent evidences indicate a high mean platelet volume and platelet distribution width values 32, an increased oxidative stress 33, and a reduced endothelium-dependent vasodilation 34, all factors potentially involved in the pathogenesis of atherosclerosis.
Some major limitations of the present study should be taken into account. Small transient increases in TSH are common within the population and often revert to normal; thus, whether these individuals have a sustained increase in TSH is not known. As an association with TSH would likely be mediated by changes in circulating thyroid hormone concentrations, the lack of measurement of total or free T4 on the same specimens is a limitation of our study, as are lack of thyroid antibodies and evaluation of the iodine status of the population. In a cross-sectional and relatively small epidemiological study, an association may be found, and it is only longitudinal data with hard outcomes that will determine whether this is a true association. We are carrying out a follow-up study in these women and, in the near future, this information could be available.
The ‘Progetto Atena’ was supported by funds from the Consiglio Nazionale delle Ricerche (Rome, Italy), ‘Progetto finalizzato Biotecnologie’, and ‘Progetto finalizzato FATMA’; the Ministero dell’Università e della Ricerca Scientifica e Tecnologica (MURST) 1998, no. 9806174392-008; Fondazione Banco di Napoli.
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