Original contributionIntegrated Backscatter and Intima-Media Thickness of the Thoracic Aorta Evaluated by Transesophageal Echocardiography in Hypercholesterolemic Patients: Effect of Pitavastatin Therapy
Introduction
Plaque in the thoracic aorta is a risk factor of coronary artery disease and transesophageal echocardiography (TEE), magnetic resonance imaging (MRI) or computed tomography (CT) are useful tools for evaluation of atherosclerosis of the thoracic aorta (Tomochika et al 1996, Fayad et al 2000, Momiyama et al 2006, Okane et al 2006). With respect to ultrasound imaging, the integrated backscatter (IBS) signal obtained from ultrasound examination of the carotid arteries can discriminate the tissue characteristics of arterial plaques (Kawasaki et al 2001, Kawasaki et al 2005). In the arterial intima, fibrosis and calcification give high IBS values while deposition of lipid gives low IBS values. Other investigators showed that measurements of IBS values of carotid arteries are clinically useful for risk assessment of patients with coronary artery disease (Honda et al. 2004). However, there are few studies of tissue characterization of the thoracic aorta by use of IBS-TEE.
Atherosclerotic changes consist of two components: atherosis as a structural change and sclerosis as a functional change. We previously reported that the IBS values of the arterial media were correlated with the stiffness parameter β and pulse wave velocity (PWV), indices of arterial stiffness (sclerosis) (Yokoyama et al. 2005). As the stiffness parameter β and PWV increased, the IBS values of the arterial media increased. An increase in arterial stiffness has been reported as an early sign of atherosclerosis and arterial stiffness has been shown to be a useful index for risk stratification of mortality from cardiovascular disease (Hirai et al 1989, Willum-Hansen et al 2006). Therefore, an improvement of arterial stiffness results in a reduction of the mortality from cardiovascular disease.
When considering therapies for atherosclerosis, several clinical trials have demonstrated that HMG-CoA reductase inhibitor (statins) can alter plaque volume and tissue characteristics of coronary and carotid arterial plaques (Nissen et al 2004, Okazaki et al 2004, Smilde et al 2001, Kawasaki et al 2005). A newly developed strong, lipophilic statin (pitavastatin), which was launched in Japan in 2003 exhibits a favorable and promising safety profile, as it is hardly metabolized by the cytochrome P-450 (CYP) system (Kajinami et al 2003, Hayashi et al 2007). It was reported that pitavastatin had an excellent lipid-lowering effect in Watanabe Heritable Hyperlipidemic rabbits, suppressing the progression of atherosclerosis and stabilizing atherosclerotic plaques (Suzuki et al. 2003). However, the effects of pitavastatin on the human thoracic aorta with respect to tissue characterization have not yet been assessed by IBS-TEE. The purpose of this study was to evaluate the effect of pitavastatin therapy on plaque components and morphology in the thoracic aorta by use of IBS-TEE and clarify the impact of the therapy on “arterial media” and “intimal plaque” separately in patients with hypercholesterolemia.
Section snippets
Subjects and study protocol
This study was designed as a simple randomized, single-center, open-label prospective study that included 32 hypercholesterolemic patients with atrial fibrillation (AF), who underwent TEE to evaluate mural thrombus in the left atrium, cardiac function and valvular disease. These patients had not been previously treated with statin therapy. They were randomized to a statin-treatment group with oral administration of pitavastatin (P: 1-2 mg/d, n = 16) or a diet group (D: n = 16). Patients in the
Reproducibility and reliability of data
We determined interobserver variability of c-IBS values and IMT in 30 recordings that were measured by two observers at randomly selected thoracic cross-sections. The interobserver variability of c-IBS values and IMT was 1.1 ± 3.0% and 0.5 ± 4.0%, respectively. The interobserver correlation coefficient was 0.98 for c-IBS values and 0.99 for IMT. Likewise, we determined intraobserver variability of c-IBS values and IMT in 30 recordings that were measured two times by one observer at randomly
Ultrasound parameters in aortic media
We previously demonstrated that c-IBS values of the arterial media increased in proportion to the degree of fragmentation of the elastic fiber and reflected the stiffness of carotid arteries (Kawasaki et al. 2005). The thoracic aorta and carotid arteries are similar since they are elastic arteries. Therefore, we thought that we could evaluate the effect of the statin on arterial intima and arterial media separately using IBS-TEE. In the 168 patients with AF, who were not enrolled in the
Conclusions
Oral administration of pitavastatin significantly decreased the c-IBS values and IMT in arterial media in the thoracic aorta. Alternatively, in intimal plaques, pitavastatin therapy significantly decreased IMT but increased c-IBS values. These data suggest that pitavastatin not only lowers the total cholesterol and LDL-cholesterol but also inhibits the progression of sclerosis of the thoracic aorta, as well as inducing regression and stabilization of plaques. We also conclude that measurement
Acknowledgments
The authors acknowledge the help of Ms. Maki Nagaya, Mr. Noriaki Sato and Ms. Satoko Kanada for ultrasound investigations, and Mr. Keisuke Moriya for preparation of the manuscript.
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