Elsevier

Biomedicine & Pharmacotherapy

Volume 59, Issues 1–2, January–February 2005, Pages 8-14
Biomedicine & Pharmacotherapy

Dossier: Hypertension and cardiovascular diseases: the rational approach
Decrease of arterial stiffness at common carotid artery in hypothyroid patients by normalization of thyroid function

https://doi.org/10.1016/j.biopha.2004.11.001Get rights and content

Abstract

This study examined the effect of hypothyroidism on arterial stiffening and the effect of levothyroxine (l-T4) replacement. The arterial stiffness index beta (stiffness β) and intima-media thickness (IMT), a parameter of arterial stiffening and thickening, respectively, were determined in common carotid artery (CCA) by ultrasonography in 30 hypothyroid patients before and after 1 year of normalization of thyroid function by l-T4 replacement. Baseline CCA stiffness β and IMT was significantly higher in the hypothyroid patients than in age- and sex-matched normal controls [9.46 ± 0.93 vs. 8.02 ± 0.91 (mean ± SE); P < 0.05, 0.635 ± 0.018 mm vs. 0.541 ± 0.019 mm; P < 0.005, respectively]. In multivariate analysis, baseline stiffness β was significantly associated with baseline levels of IMT (r = 0.457, P = 0.0311), FT4 (r = –0.413, P = 0.0169), and a plasma vascular injury marker, von Willebrand factor (vWF) (r = 0.412, P = 0.0261). During 1 year of euthyroidism, 22 and 29 out of 30 patients showed significant decreases of stiffness β and IMT to normal respective level, from 9.46 ± 0.93 to 7.58 ± 0.34 and from 0.635 ± 0.018 to 0.552 ± 0.015 mm, respectively. Change in stiffness β during l-T4 therapy correlated significantly in a negative manner with baseline levels of age (r = –0.465, P = 0.011) and IMT (r = –0.406, P = 0.029). Stiffness β after but not before l-T4 therapy showed a tendency towards a positive correlation with age. This study suggested that increases of arterial thickening, and plasma vWF, and a reduction in serum FT4 might have an important role independently in the increased arterial stiffening in hypothyroid patients. Furthermore, it was demonstrated that sustained euthyroidism might have the potential to reverse arterial stiffening in addition to thickening in hypothyroid patients.

Introduction

Hypothyroidism, even in its latent form, is associated with increased morbidity from cardiovascular disease [1], [2], [3], [4], [5]. Accelerated atherosclerosis in hypothyroidism is accounted for by multiple mechanisms such as hyperlipidemia [2], [6] hypercoagulable state [4], impaired endothelium-dependent vasodilation [7], and obesity [8].

We recently reported that hypothyroid patients exhibited increased intima-media thickness (IMT) in the common carotid artery (CCA) [9], a good predictor for increased cardiovascular events [10], [11], [12], [13], and that normalization of thyroid function for 1 year by l-T4 replacement significantly decreased CCA IMT to levels comparable to normal controls [9].

Although arterial stiffening has emerged as one of major factors causing caridiovascular events independent of arterial thickening, few studies have yet been performed on the influence of normalization of thyroid function on arterial stiffening at CCA in hypothyroid patients [14]. The recent development of phase-locked echo-tracking sonography allows easy and reproducible measurement of the distensibility of the walls of CCA as stiffness β [15], [16], [17], which is reported to increase in patients with diabetes [15], hypertension [17], and coronary heart disease [18].

This background scenario prompted us to examine whether (i) normalization of thyroid function by l-T4 therapy during 1 year in hypothyroid patients might decrease arterial stiffening in CCA as well as arterial thickening and (ii) the factor independently associated with increased arterial stiffening in hypothyroid patients.

Section snippets

Patients and study design

The present study was designed as an open prospective study. Written informed consent was obtained from each patient, and the study was approved by the ethical committee of Osaka City University Hospital. Hypothyroid patients (5 males and 25 females) were selected consecutively and were studied during the 20-month period. The diagnosis of overt hypothyroidism was established on the basis of suppression of serum free thyroxine (FT4) and free triiodothyronine (FT3) to below the normal lower limit

Statistical analysis

Data are expressed as mean ± SE unless otherwise indicated. Statistical analysis was performed with the Stat View V system (Abacus Concepts, Berkeley, CA) for the Apple computer. Differences in basal values between hypothyroid patients and normal controls were examined using Wilcoxon test for the assessment of mean value. The difference in each parameter between before and after treatment was compared using the two-tailed Student’s t test for paired data. Independent association between one

Basal levels of CCA stiffness β and IMT, and clinical variables in hypothyroid state

Clinical characteristics of hypothyroid patients and normal controls are shown in Table 1. Serum levels of metabolic markers of thyroid function including serum total cholesterol and LDL-cholesterol differed significantly between the two groups. No significant difference existed between the two groups in age, gender, body height, body weight, body mass index (BMI), smoking index (daily cigarettes multiplied smoking years), systolic and diastolic and mean blood pressures, pulse pressure, pulse

Discussion

In the present study, we demonstrated that CCA stiffness β, which is an index of arterial stiffening [15], [16], [17], [18], is significantly higher in hypothyroid patients than in normal controls (Table 1), and that CCA stiffness β is normalized by sustained normalization of thyroid function (Table 2, Fig. 1). Our findings also suggested that in hypothyroid patients, baseline stiffness β in the CCA showed a significant association in a positive fashion with baseline CCA IMT and serum vWF, and

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