Ezetimibe Monotherapy Ameliorates Vascular Function in Patients with Hypercholesterolemia Through Decreasing Oxidative Stress

Abstract

Aim: Ezetimibe, an inhibitor of cholesterol intestinal absorption, is a lipid lowering agent. However, anti-atherogenic effects of ezetimibe have not been fully elucidated. Therefore, the objective in this study was to clarify the vascular protective effects of ezetimibe in patients with hypercholesterolemia. Methods: Ezetimibe was administered to 20 patients with hypercholesterolemia (group E), and 20 age-and sex-matched patients with hypercholesterolemia were followed as controls (group C). Difference in metabolic profiles and cardiovascular surrogate markers before ezetimibe treatment and after 12 weeks of ezetimibe treatment were statistically evaluated. Results: Ezetimibe treatment significantly reduced serum levels of low-density lipoprotein cholesterol (LDL-C) and malondialdehyde-modified low-density lipoprotein (MDA-LDL). In addition, the values of body mass index, body weight, waist circumference, plasma HbA1c and urinary albumin were significantly decreased in group E compared to those in group C. On the other hand, high-density lipoprotein cholesterol (HDL-C) and adiponectin levels were significantly increased in group E compared to those in group C. The values of brachial-ankle pulse wave velocity (ba-PWV), mean arterial blood pressure (m-ABP), and % of flow-mediated dilation (FMD) were significantly improved in group E. Furthermore, ultrasonic studies demonstrated amelioration of the vascular stiffness of common carotid arteries in group E but not in group C. These vascular protective effects of ezetimibe were statistically correlated with the decreased values of MDA-LDL and MDA-LDL-to-LDL-C ratio but not with those of LDL-C. Conclusion: Ezetimibe has a lipid lowering-independent vascular protective effect in patients with hypercholesterolemia through decreasing oxidative stress.

Cardiovascular protection by ezetimibe and influence on oxidative stress in mice exposed to intermittent hypoxia

“…This was probably because the control animals were relatively young and inflammatory changes of the LV myocardium were mild. It has been reported that ezetimibe can reduce the levels of TNF-α, high-sensitivity C-reactive protein, and 8-hydroxydeoxyguanosine (Kalogirou et al, 2007;Nakamura et al, 2009;Azar et al, 2010), suggesting that the anti-inflammatory effect of ezetimibe may be attributable to inhibition of oxidative stress and remnant lipoproteins (Fukuda et al, 2010;Kurobe et al, 2011;Tobaru et al, 2013). Futher investigation of other inflammatory genes should be needed.…”

Experimental research Influence of ezetimibe on selected parameters of oxidative stress in rat liver subjected to ischemia/reperfusion

“…The drug has become an increasingly popular therapeutic option for statin-resistant patients, as well as for statin-intolerant patients [14, 15]. The choice of ezetimibe for our experiment was also based on data from experimental [16, 17] and clinical studies [18, 19] suggesting antioxidant properties of this agent.…”

Circulating Adiponectin Levels and their Associated Factors in Young Lean Healthy Japanese Women

“…In this specified study population, we successfully eliminated the influence of age, and even that of adiposity, on adiponectin levels. Although adiponectin levels are reported to be associated with various health disorders [26][27][28][29][30][31][32] , it has been pointed out that their levels vary not only among ethnic groups [33][34][35] but also age groups 10,16) . It seems of clinical importance to evaluate their distribution with respect to each age group of a specific ethnic population.…”