Effects of ezetimibe add-on therapy for high-risk patients with dyslipidemia

Yamaoka‐Tojo, Minako; Tojo, Taiki; Kosugi, Rie; Hatakeyama, Yuko; Yoshida, Yuki; Machida, Yuichiro; Aoyama, Naoyoshi; Masuda, Takashi; Izumi, Tohru

doi:10.1186/1476-511x-8-41

Cited by 29 publications

(24 citation statements)

References 45 publications

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“…In addition, the period of improvement of RHI and d-ROMs by reducing some risk factor for the onset of cardiovascular disease (i.e. hypertension, diabetes, dyslipidemia) were generally 3-6 months in another clinical study [14,[16][17]38]. Therefore, we thought 24 weeks after demonstrating the normal range of IGF-1 levels might be adequate to verify the effects of GH replacement therapy.…”

Section: Discussionmentioning

confidence: 99%

Effect of growth hormone replacement therapy on plasma diacron-reactive oxygen metabolites and endothelial function in Japanese patients: The GREAT clinical study

et al. 2018

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Abstract. Patients with growth hormone deficiency (GHD) have an increased risk of atherosclerosis and vascular mortality. Evidence suggests that endothelial dysfunction is involved in all stages of atherogenesis. This study examined the effect of growth hormone (GH) replacement therapy on diacron-reactive oxygen metabolites (d-ROMs) and endothelial function in Japanese patients with GHD, using peripheral arterial tonometry. This was an open-label, prospective, case-control study. Nine patients with GHD who had not previously received any GH replacement therapy were enrolled. The following parameters were evaluated at baseline (before treatment), and after 24 weeks of GH replacement therapy: endothelial function using the reactive hyperemia index (RHI; EndoPAT ® system), d-ROMs, blood pressure, and fasting lipid levels. Plasma GH and insulin-like growth factor-1 (IGF-1) levels were measured at baseline and after 24 weeks of GH replacement therapy. We also enrolled eight controls with pituitary disease but no GH deficiency. Over 24 weeks of GH replacement therapy, the serum IGF-1 levels normalized with significant improvement in the RHI (from 1.65 ± 0.33 to 1.92 ± 0.26, p < 0.05) and decreased d-ROM levels (from 356.8 ± 64.1 to 303.1 ± 43.3 U.CARR, p < 0.05). There were no significant improvements in the RHI or d-ROM levels in controls. GH replacement therapy in Japanese patients with GHD may be mediated by the reduced oxidative stress and the d-ROMs associated with the treatment.

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Section: Discussionmentioning

confidence: 99%

Effect of growth hormone replacement therapy on plasma diacron-reactive oxygen metabolites and endothelial function in Japanese patients: The GREAT clinical study

et al. 2018

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“…None of these variables was significantly altered from baseline in the TLC group. Ezetimibe induced significant reductions in apoB and apoE levels by 16.5% (p \ 0.001 vs. baseline and p \ 0.01 vs. TLC To convert values for TC, LDL-C, non HDL-C and HDL-C levels to mmol/L, multiply by 0.02586; to convert TG levels to mmol/L multiply by 0.01129 TLC therapeutic lifestyle changes, TC total cholesterol, TAG triacylglycerols, HDL-C high-density lipoprotein cholesterol, LDL-C low-density lipoprotein cholesterol, apo apolipoprotein, ox-LDL oxidized low-density lipoprotein, 8-epiPGF2a 8-isoprostane, d-ROMs reactive oxygen metabolites * p \ 0.05 versus baseline, **p \ 0.01 versus baseline, ***p \ 0.001 versus baseline p \ 0.05 for the comparison with the TLC group, à p \ 0.001 for the comparison with the TLC group } p \ 0.01 for the comparison with the control group group) and 15.4% (p \ 0.001 vs. baseline and p \ 0.01 vs. TLC group), respectively, while apoA1 concentration remained unchanged (Table 1). No change in apolipoprotein levels was noted in the TLC group.…”

Section: Clinical Evaluationmentioning

confidence: 99%

“…To date, limited data suggest that ezetimibe may reduce various markers of oxidative stress [15][16][17]. As with other possible pleiotropic actions, it remains unclear whether these effects are associated with the LDL-C lowering capacity of this drug.…”

Section: Introductionmentioning

confidence: 99%

Ezetimibe Treatment Lowers Indicators of Oxidative Stress in Hypercholesterolemic Subjects with High Oxidative Stress

Kostapanos

Spyrou

Tellis

et al. 2011

Lipids

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Ezetimibe effectively reduces low-density lipoprotein cholesterol (LDL-C). In this study, we tested the hypothesis that ezetimibe monotherapy may also decrease markers of oxidative stress in subjects with hypercholesterolemia. Subjects with hypercholesterolemia and no evidence of cardiovascular disease were randomly allocated to open-label ezetimibe monotherapy 10 mg/day (EZT group) or therapeutic lifestyle changes (TLC group). At baseline and 12 weeks post-treatment serum lipoprotein and apolipoprotein levels as well as oxidative stress parameters, including oxidized LDL (ox-LDL), 8-isoprostanes (8-epiPGF2a) and reactive oxygen metabolites (d-ROMs) levels, were blindly determined. A total of 60 patients were included; 30 in each group. Despite a significant decrease in ox-LDL levels (by 20.8%, p < 0.001 vs. baseline; p < 0.001 vs. TLC group) in the EZT group no change in the ratio ox-LDL to LDL-C was noticed following ezetimibe treatment. No significant change in 8-epiPGF2a and d-ROMs levels was observed in the EZT group. Of note, a significant decrease in 8-epiPGF2a and d-ROMs levels (by 20.4% and 18.2%, respectively, p < 0.01 vs. baseline for both), was noted among patients in the EZT group who exhibited 'high oxidative stress' at baseline. No change in any of oxidative stress parameters was noted in the TLC group. Ezetimibe may decrease markers of oxidative stress in hypercholesterolemic subjects. This benefit may be more profound among patients who exhibit 'high oxidative stress' at baseline.

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“…The high PAT-ratio observed in our study cohort may be explained by the fact that many patients were receiving treatment with statins or ACE inhibitors at the time of study inclusion. For both classes of drugs, an improvement in the endothelial function has been described [23][24][25] . Hovland et al 26) compared the PAT-ratios of patients with familial hypercholesterolemia under statin treatment with those of normal healthy controls and found no differences between the investigated groups, ascribing this finding to the use of statin pretreatment in the patients with familial hypercholesterolemia.…”

mentioning

confidence: 99%

Prognostic Value of Peripheral Arterial Tonometry in Patients with Coronary Artery Disease and a High Cardiovascular Risk Profile

Suessenbacher

Dörler

Wanitschek

et al. 2014

JAT

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Aim: Data regarding the prognostic value of peripheral endothelial function testing in patients with cardiovascular disease are conflicting. Peripheral arterial tonometry (PAT) is increasingly used to measure the peripheral endothelial function. The prognostic value of this method has not been investigated thus far in patients with cardiovascular disease and/or a high cardiovascular risk profile. Methods: In 96 patients with significant coronary artery disease (CAD) or ＜70% stenosis and ≥ three cardiovascular risk factors, reactive hyperemia was induced following upper arm occlusion and the PAT-ratio between baseline and hyperemia was calculated. The patients were followed for cardiovascular events (revascularization, acute coronary syndrome, ischemic stroke, cardiovascular death, repeat coronary angiography due to chest pain) for 44±14 months. The first event was included in the combined end point. Results: The study cohort was divided according to the median PAT-ratio (1.91). The combined end point occurred in 14 patients with a PAT-ratio below the median (1.91) and in 12 patients with a PAT-ratio of ≥ 1.91 (p= 0.65). In a subgroup of 76 patients, the PAT-ratio was reassessed after six months. No differences in the event rate were found between the patients who exhibited deterioration (n = 50) and those who exhibited an improvement in the PAT-ratio of ＞0.1 (n = 26; 22 vs. 32%, p = 0.32). The combined end point occurred earlier in the patients with a PAT-ratio within the 1st tertile than in those with a PAT-ratio within the 2nd/3rd tertile (11.3±11.0 vs. 27.5±18.6 months, p= 0.03). Conclusions: In patients with established CAD or a high cardiovascular risk profile, the PAT-ratio cannot be used to predict the risk of future cardiovascular events. However, a lower PAT-ratio may be associated with the earlier occurrence of cardiovascular events. J Atheroscler Thromb, 2014; 21:230-238.

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Effects of ezetimibe add-on therapy for high-risk patients with dyslipidemia

Cited by 29 publications

References 45 publications

Effect of growth hormone replacement therapy on plasma diacron-reactive oxygen metabolites and endothelial function in Japanese patients: The GREAT clinical study

Effect of growth hormone replacement therapy on plasma diacron-reactive oxygen metabolites and endothelial function in Japanese patients: The GREAT clinical study

Ezetimibe Treatment Lowers Indicators of Oxidative Stress in Hypercholesterolemic Subjects with High Oxidative Stress

Prognostic Value of Peripheral Arterial Tonometry in Patients with Coronary Artery Disease and a High Cardiovascular Risk Profile

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