Original contribution
Integrated Backscatter and Intima-Media Thickness of the Thoracic Aorta Evaluated by Transesophageal Echocardiography in Hypercholesterolemic Patients: Effect of Pitavastatin Therapy

https://doi.org/10.1016/j.ultrasmedbio.2008.08.011Get rights and content

Abstract

The effect of a strong, lipophilic statin (pitavastatin) on the thoracic aorta has not yet been elucidated. The purpose of the present study was to evaluate the effects of pitavastatin (P) therapy on plaque components and morphology in the thoracic aorta by transesophageal echocardiography (TEE) and clarify the impact of the therapy on media and intima in patients with hypercholesterolemia. Sixty-four media and 64 intima of the thoracic aorta were investigated in 32 patients with hypercholesterolemia. The corrected integrated backscatter (c-IBS) values in the thoracic aortic wall and intima-media thickness (IMT) at the same site were measured before and after P therapy or diet (D) for 7 mo. Moreover, c-IBS values in media were measured in 168 patients without hypercholesterolemia to estimate age-dependent changes. C-IBS values in media were correlated with age (r = 0.84, p < 0.001). C-IBS and IMT of media in the P group significantly decreased from −17.8 ± 2.4 to −20.1 ± 3.7 dB and from 1.7 ± 0.3 to 1.5 ± 0.3 mm, respectively (p < 0.001), whereas those in the D group significantly increased from −18.3 ± 2.0 to −16.7 ± 2.1 dB and from 1.6 ± 0.3 to 1.7 ± 0.2 mm, respectively (p < 0.001). IMT in intima in the P group significantly decreased from 3.7 ± 0.4 to 3.3 ± 0.4 mm (p < 0.001). C-IBS in intima in the P group significantly increased from −10.2 ± 2.2 to −6.9 ± 1.7 dB, which indicated plaque stabilization. Pitavastatin improved the atherosis measured by IMT and sclerosis measured by c-IBS values in the media and induced stabilization and regression of plaques in the intima of the thoracic aorta. (E-mail: [email protected])

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.

References (32)

  • T.J. Smilde et al.

    Effect of aggressive versus conventional lipid lowering on atherosclerosis progression in familial hypercholesterolemia (ASAP): A prospective, randomized, double-blind trial

    Lancet

    (2001)
  • K. Watanabe et al.

    Stabilization of carotid atheroma assessed by quantitative ultrasound analysis in nonhypercholesterolemic patients with coronary artery disease

    J Am Coll Cardiol

    (2005)
  • H. Yokoyama et al.

    Effects of fluvastatin on the carotid arterial media as assessed by integrated backscatter ultrasound compared with pulse-wave velocity

    J Am Coll Cardiol

    (2005)
  • A. Yonemura et al.

    Effect of lipid-lowering therapy with atorvastatin on atherosclerotic aortic plaques detected by noninvasive magnetic resonance imaging

    J Am Coll Cardiol

    (2005)
  • P. Amarenco et al.

    Statin in stroke prevention and carotid atherosclerosisSystem review and up-to-date meta-analysis

    Stroke

    (2004)
  • R. Corti et al.

    Lipid lowering by simvastatin induces regression of human atherosclerotic lesions: Two years' follow-up by high-resolution noninvasive magnetic resonance imaging

    Circulation

    (2002)
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