pitavastatin and Atherosclerosis

Atherogenic dyslipidemia is characterised by high levels of triglycerides, low levels of high-density lipoprotein-cholesterol (HDL-C), and moderate to marked elevations in low-density lipoprotein-cholesterol (LDL-C) concentrations; such dyslipidemia is further characterised by high apolipoprotein B (apoB): apolipoprotein A1 (apoA1) ratios. Numerous clinical trials have demonstrated that statins are effective in lowering LDL-C and reducing cardiovascular (CV) risk in people with dyslipidemia. However, the most effective treatments should target all of the key atherogenic features, rather than LDL-C alone. Pitavastatin is a new member of the statin class whose distinct pharmacological features translate into a broad spectrum of action on both apoB-containing and apoA1-containing lipoprotein components of the atherogenic lipid profile. The efficacy and safety of this statin has been demonstrated by a large clinical development programme conducted both in Japanese and Caucasian populations. Phase III and IV studies in a wide range of patients with primary hypercholesterolemia or combined dyslipidemia showed that 12 weeks' treatment with pitavastatin l-4 mg was well tolerated, significantly improved lipid profiles (including LDL-C, TG, and HDL-C levels) and increased the EAS-/NCEP ATP Ill-recommended LDL-C target attainment rate to a similar or greater degree as comparable doses of atorvastatin, simvastatin, or pravastatin. Results were similar across all patient groups and were generally sustained after 52 weeks of treatment. However, whereas the effects of atorvastatin and simvastatin on HDL-C levels remained constant over the long term, pitavastatin-treated patients experienced progressive and maintained elevations in HDL-C, ultimately increasing by up to 14.3% vs. initial baseline. In this context, it is significant that the in vitro studies of Yamashita et al. [J Atheroscler Thromb 2010;17:436-51] have shown pitavastatin to be distinguished by its potent stimulation of apoA1 production in hepatocyte-like cells. These findings suggest that pitavastatin may be highly efficacious in raising levels of lipid-poor apoA1 particles, which are known to be highly active in ABCA1-mediated cellular cholesterol efflux, an observation which is pertinent to the excessive accumulation of cholesterol in macrophage foam cells of the atherosclerotic plaque. Indeed, the intravascular remodelling and maturation of lipid-poor apoA1 particles is known to drive flux of apoA1, ch

Topics: Apolipoprotein A-I; Apolipoproteins B; Atherosclerosis; Atorvastatin; Cholesterol, HDL; Cholesterol, LDL; Clinical Trials, Phase III as Topic; Clinical Trials, Phase IV as Topic; Coronary Artery Disease; Double-Blind Method; Dyslipidemias; Europe; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Japan; Lipids; Multicenter Studies as Topic; Plaque, Atherosclerotic; Pyrroles; Quinolines; Randomized Controlled Trials as Topic; Russia; Simvastatin; Triglycerides

Treatment for hypercholesterolemia aims to suppress the progression of early atherosclerotic changes and prevent the onset of future cardiovascular events. Drugs to treat hypercholesterolemia should thus have sufficient longterm lipid-lowering and direct antiatherosclerotic effects. Pitavastatin is a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor (statin) that was developed in Japan. In addition to its long-term lipid-lowering effects, pitavastatin also exerts pleiotropic effects against atherosclerotic changes. Although few studies have investigated the mechanism of pitavastatin, its pleiotropic effects have encouraged its use to treat both hypercholesterolemia and atherosclerosis. Pentraxin-related protein PTX3, a prototype protein of the pentraxin family, could serve as a novel useful blood marker to assess dynamic inflammation during the early atherosclerotic stages. This review clarifies the long-term lipid-lowering and antiatherosclerotic effects of pitavastatin.

Topics: Animals; Atherosclerosis; Clinical Trials as Topic; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Lipids; Quinolines

Type 2 diabetes mellitus is correlated with systemic atherosclerosis. Statin therapies have been proved to reduce low-density lipoprotein cholesterol (LDL-C) level, protecting type 2 diabetes mellitus patients from cardiovascular events. Recently, more interest has been focused on the regression of lower extremity atherosclerotic disease (LEAD) for the potential prevention of amputation. However, the effects of pitavastatin and atorvastatin on LEAD in type 2 diabetes mellitus patients have not been directly compared.. This study compared the effects of pitavastatin and atorvastatin on femoral total plaque areas (FTPA), and lipids and glucose metabolism in type 2 diabetes mellitus patients with elevated LDL-C level and LEAD. Type 2 diabetes mellitus patients with LDL-C level >2.6 mmol/L and LEAD were randomly assigned to receive either pitavastatin 2 mg/day or atorvastatin 10 mg/day for 48 weeks. FTPA were measured at baseline and the end of the study. Levels of glucose and lipids profile were measured periodically. The efficacy was evaluated in 63 patients.. The percentage change in FTPA measurements was similar between the pitavastatin group and atorvastatin group (-17.79 ± 21.27% vs -14.34 ± 16.33%), as were the changes in LDL-C (-44.0 ± 18.0% vs -40.3 ± 18.2%) and triglyceride (17.6 ± 20.0% vs 16.2 ± 17.0%). However, the level of high-density lipoprotein cholesterol was significantly higher in the pitavastatin group compared with the atorvastatin group after 48 weeks of treatment (12.9 ± 10.3% vs 7.2 ± 11.7%, P < 0.05). There were no significant differences between groups for the measurements of glucose metabolism.. In type 2 diabetes mellitus patients with elevated LDL-C level and LEAD, 48 weeks of treatment with either pitavastatin or atorvastatin was associated with significant regression of FTPA. Pitavastatin treatment resulted in a significantly higher high-density lipoprotein cholesterol level compared with atorvastatin treatment.

Topics: Aged; Atherosclerosis; Atorvastatin; Cholesterol, LDL; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Femur; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipids; Lower Extremity; Male; Middle Aged; Plaque, Atherosclerotic; Quinolines; Treatment Outcome

This study evaluates the effectiveness of pitavastatin in patients with atherosclerosis.. Sixty patients with atherosclerosis with lipid-rich carotid plaques were included and allocated into low-dose (2 mg/d) and high-dose (4 mg/d) pitavastatin groups with 48 weeks of treatment. Total cholesterol, LDL-C, HDL-C, triglycerides, apolipoprotein A1, apolipoprotein B, lipoprotein (a), and the inflammation-related factors interleukin 6, high-sensitivity C-reactive protein, and homocysteine were determined. High-resolution (3.0-T) magnetic resonance imaging was used to evaluate the lipid core area, plaque thickness, total vessel area, lumen area, wall area, and normalized wall index.. After the treatment period, the blood serum values were improved in both groups, but the improvement was significantly better for total cholesterol (P < 0.009), HDL-C, LDL-C, triglycerides, apolipoprotein A1, apolipoprotein B, lipoprotein (a), and homocysteine (all P < 0.001) in the high-dose group. The high-resolution magnetic resonance images revealed great improvements in both groups, although significantly better for the lipid core area (P < 0.001), plaque thickness (P < 0.001), wall area (P < 0.05), normalized wall index (P < 0.001), and lumen area (P < 0.05) in the HD group. Further analyses revealed a close correlation between lipid-rich plaques and changes in blood lipid components.. Pitavastatin had significant lipid-lowering and anti-inflammatory effects in patients with atherosclerosis. It also reduced the lipid components and plaques of lipid rich carotid plaques. The effect was obviously stronger in the high-dose than in the low-dose group.

Topics: Aged; Apolipoprotein A-I; Apolipoproteins B; Atherosclerosis; C-Reactive Protein; Cholesterol; Female; Humans; Lipids; Magnetic Resonance Imaging; Male; Middle Aged; Plaque, Atherosclerotic; Prospective Studies; Quinolines; Triglycerides

HMG-CoA reductase inhibitors, also termed statins, are used to reduce the risk of coronary artery disease. Two oxidatively modified low-density lipoprotein (LDL) complexes, serum amyloid A-LDL (SAA-LDL) and α1-antitrypsin-LDL (AT-LDL), serve as atherosclerotic, inflammatory, and cardiovascular risk markers. In this study, we examined the effects of hydrophilic rosuvastatin (RSV) and lipophilic pitavastatin (PTV) on these markers in patients with hypercholesterolemia.. The present study was a sub-analysis of our previous STAT-LVDF study. The subjects were treated with RSV or PTV for 24weeks. Changes in glucose-lipid metabolism, serum levels of SAA-LDL and AT-LDL, and C-reactive protein (CRP) level were assessed.. In total, 53 patients were analyzed in the present study. RSV and PTV significantly decreased SAA-LDL (RSV: p=0.003, PTV: p=0.012) and AT-LDL levels (RSV: p=0.013, PTV: p=0.037). Changes in SAA-LDL level were significantly and positively correlated with those in CRP in both the RSV (r=0.549, p=0.003) and PTV (r=0.576, p=0.004) groups. Moreover, a positive correlation between changes of SAA-LDL levels and those of HbA1c levels was observed in the PTV group (r=0.442, p=0.030) but not in the RSV group (r=-0.100, p=0.611).. Both hydrophilic rosuvastatin and lipophilic pitavastatin reduce serum levels of atherosclerotic and inflammatory markers. These findings also indicate differential effects of RSV and PTV on glucose tolerance.

Topics: Adult; Aged; Aged, 80 and over; alpha 1-Antitrypsin; Atherosclerosis; Biomarkers; Dyslipidemias; Female; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipoproteins, LDL; Male; Middle Aged; Quinolines; Rosuvastatin Calcium; Serum Amyloid A Protein; Treatment Outcome; Ventricular Dysfunction, Left

We sought to evaluate the effects of a strong lipophilic statin (pitavastatin) on plaque components and morphology assessed by transesophageal echocardiography (TEE) and transthoracic echocardiography (TTE), as well as plaque inflammation assessed by 18F-fluorodeoxyglucose (FDG) PET/CT in the thoracic aorta and the carotid artery. Furthermore, we compared the effects of pitavastatin with those of mild hydrophilic statin (pravastatin).. We examined atherosclerotic plaques in the thoracic aorta by TEE and those in the carotid artery by integrated backscatter (IBS)-TTE and PET/CT. We identified the target plaque, where there was macrophage infiltration and inflammation, by strong FDG uptake in the thoracic aorta and carotid arteries and measured maximum standard uptake values (max SUV) by PET/CT. We measured the intima-media thickness (IMT) and the corrected IBS (cIBS) values in the intima-media complex by TEE and TTE at the same site of FDG accumulation by PET/CT.. Patients were randomly divided into two treatment groups: a pitavastatin group (PI group: n =10, 68.4 ± 5.1 years) and a pravastatin group (PR group: n =10, 63.9 ± 11.2 years). The same examinations were performed after six months at the same site in each patient. We used calculated target-to-background ratio (TBR) to measure max SUV of plaques and evaluated percent change of TBR. There was no significant difference in low density lipoprotein-cholesterol, TBR, IMT and cIBS values in plaques at baseline between the PI and PR groups. After treatment, there was greater improvement in TBR, cIBS values and IMT in the PI group than the PR group.. The pravastatin treatment was less effective on plaque inflammation than pitavastatin treatment. This trend was the same in the carotid arteries and the thoracic aorta. Pitavastatin not only improved the atherosis as measured by IMT and cIBS values but also attenuated inflammation of plaques as measured by max SUV at the same site. The present study indicated that pitavastatin has stronger effects on the regression and stabilization of plaques in the thoracic aorta and carotid arteries compared with pravastatin.

Topics: Aged; Anti-Inflammatory Agents; Atherosclerosis; Carotid Arteries; Echocardiography, Transesophageal; Female; Humans; Male; Multimodal Imaging; Positron-Emission Tomography; Pravastatin; Quinolines; Reproducibility of Results; Sensitivity and Specificity; Systems Integration; Thoracic Arteries; Tomography, X-Ray Computed; Treatment Outcome

Statins have proven efficacy in inhibiting the onset and progress of atherosclerosis. The effectiveness of pitavastatin in reversing carotid atherosclerosis associated with hypercholesterolemia (HC) is unknown.. To explore the simultaneous effects of pitavastatin calcium on brachial arterial flow-mediated vasodilatation (FMD), carotid intima-media thickness (IMT), and arterial stiffness (β), three surrogate markers of atherosclerosis were studied in HC patients.. A randomized, double-blind trial was performed with 40 HC subjects who fulfilled the inclusion/exclusion criteria. Patients were given pitavastatin calcium 1 mg/d (Group 1) or 2 mg/d (Group 2) for 8 weeks. There were 20 patients in each group, and 30 gender- and age-matched healthy subjects as controls were recruited. FMD of the brachial artery, carotid IMT, and arterial stiffness indicated by β were measured at baseline and at 8 weeks after starting pitavastatin calcium therapy using ultrasound techniques. Biochemical tests were also made on all subjects.. At baseline, higher total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), reduced FMD, and increased β and IMT were observed in HC patients (P<0.001 for all) compared with controls. After 8 weeks, TC was decreased by 20.59%/27.56% and LDL-C 30.92%/35.64%, respectively, in comparison to baseline groups; the HC groups had reduced β and improved endothelial function over the 8-week follow-up (P<0.05-0.001); nonetheless, no significant alterations of IMT were found (P>0.05). Significant negative interactions between TC/LDL and FMD (P<0.05-0.001), positive interactions between TC and IMT (P=0.003) and between TC/LDL and β (P<0.001-0.000) were found.. Treatment with pitavastatin calcium exerted favorable effects on endothelial function and arterial stiffness. It also improved carotid atherosclerosis in patients with HC.

Topics: Aged; Atherosclerosis; Body Mass Index; Brachial Artery; Calcium; Carotid Arteries; Carotid Intima-Media Thickness; Cholesterol, LDL; Double-Blind Method; Endothelium, Vascular; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Male; Middle Aged; Quinolines; Vascular Stiffness; Vasodilation

A low n-3 to n-6 polyunsaturated fatty acid (PUFA) ratio is associated with cardiovascular events. However, the effects of this ratio on coronary atherosclerosis have not been fully examined, particularly in patients treated with different types of statins. This study compared the effects of n-3 to n-6 PUFA ratios on coronary atherosclerosis in patients treated with pitavastatin and pravastatin. Coronary atherosclerosis in nonculprit lesions in the percutaneous coronary intervention vessel was evaluated using virtual histology intravascular ultrasound in 101 patients at the time of percutaneous coronary intervention and 8 months after statin therapy. Pitavastatin and pravastatin were used to treat 51 and 50 patients, respectively. Changes in the docosahexaenoic acid (DHA)/arachidonic acid (AA) and eicosapentaenoic acid+DHA/AA ratios were not correlated with the percentage change in plaque volume in the pitavastatin group, whereas the percentage change in plaque volume and the changes in the DHA/AA ratio (r = -0.404, p = 0.004) and eicosapentaenoic acid+DHA/AA ratio (r = -0.350, p = 0.01) in the pravastatin group showed significant negative correlations. Multivariate regression analysis showed that age (β = 0.306, p = 0.02), the presence of diabetes mellitus (β = 0.250, p = 0.048), and changes in the DHA/AA ratio (β = -0.423, p = 0.001) were significant predictors of the percentage change in plaque volume in patients treated with pravastatin. In conclusion, decreases in n-3 to n-6 PUFA ratios are associated with progression in coronary atherosclerosis during pravastatin therapy but not during pitavastatin therapy.

Topics: Aged; Atherosclerosis; Biomarkers; Coronary Artery Disease; Dose-Response Relationship, Drug; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Female; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Percutaneous Coronary Intervention; Pravastatin; Prospective Studies; Quinolines; Severity of Illness Index; Treatment Outcome; Ultrasonography, Interventional

Inflammatory reactions and oxidative stress, which are important in progression of atherosclerosis, are reported to be increased in individuals with metabolic syndrome (MetS). On the other hand, adiponectin levels are lowered. Since effects of pitavastatin on these parameters have not been reported in hypercholesterolemic patients with MetS, the present study was conducted.. To evaluate the effects of pitavastatin on inflammatory reaction, oxidative stress, and plasma adiponectin levels in hypercholesterolemic MetS patients in a multicenter trial.. This open-label, single group study was performed at 7 hospitals in Japan. Pitavastatin (2mg/day) was administered to 103 consecutive patients with hypercholesterolemia, subdivided into MetS and non-MetS for 12 weeks. Blood samples were collected after overnight fasting at the start of treatment (baseline) and after 12 weeks.. In the patients with MetS (n=69), mean values of plasma high-sensitivity C-reactive protein (hs-CRP) were significantly higher and mean values of plasma high-molecular-weight (HMW)-adiponectin significantly lower than in their counterparts without MetS (n=34). The baseline HMW-adiponectin and high-density lipoprotein cholesterol (HDL-C) values significantly correlated only in the MetS patients (r=0.318; p=0.01). In an effectiveness analysis including 94 patients (62 with MetS, 32 without MetS), the level of hs-CRP was significantly decreased in patients with MetS during the drug treatment, whereas HMW-adiponectin did not change. When patients with MetS were divided into two subgroups according to the percent changes in HDL-C, significantly greater increase in HMW-adiponectin by pitavastatin treatment was observed in the HDL-C ≥10% increase subgroup than in the HDL-C <10% increase subgroup (p=0.009).. Twelve weeks administration of pitavastatin, in addition to the antihyperlipidemic effects, may be beneficial as an anti-atherosclerotic therapy in hypercholesterolemic patients with MetS, taking changes in hs-CRP and HMW-adiponectin into consideration. ClinicalTrials.gov identifier: NCT00444717.

Topics: Adiponectin; Atherosclerosis; C-Reactive Protein; Cholesterol, HDL; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Inflammation; Metabolic Syndrome; Molecular Weight; Oxidative Stress; Quinolines; Time Factors

It remains unclear whether the decrease in the ADMA level associated with statin treatment results from the LDL-C-lowering effect or the pleiotropic effects of statins. A prospective, controlled study was conducted to examine whether statin treatment affects serum ADMA concentrations in ischemic stroke patients.. Consecutive outpatients with non-cardiogenic ischemic stroke who had never been treated with statins and whose LDL-cholesterol level was higher than 140 mg/dL were enrolled and compared with control patients whose LDL-cholesterol level was lower than 140 mg/dL. Overall, 114 patients were enrolled in the study (56 and 58 in statin-treated and non-statin-treated groups, respectively). Patients in the statin group were treated with pravastatin 10 mg/day (n=15), fluvastatin 20 mg/day (n=14), pitavastatin 1 mg/day (n=14), or atorvastatin 10 mg/day (n=13).. The serum ADMA concentration and LDL-C level were significantly decreased by statin treatment (p=0.003 and p< 0.001, respectively), and the ADMA concentration in subjects treated with statins was significantly lower than that of the control (p=0.028). Multiple linear regression analysis showed that age (β=0.26, p< 0.05) and statin use (β=-0.20, p< 0.05) were independently associated with the ADMA level.. A significant relation between statin treatment and decreased levels of ADMA was demonstrated in ischemic stroke patients with an adequately controlled lipid profile, suggesting the statin treatment might prevent atherosclerotic disease in ischemic stroke patients through suppression of ADMA concentration.

Topics: Aged; Aged, 80 and over; Arginine; Atherosclerosis; Atorvastatin; Brain Ischemia; Cholesterol, LDL; Fatty Acids, Monounsaturated; Female; Fluvastatin; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Linear Models; Male; Middle Aged; Pravastatin; Prospective Studies; Pyrroles; Quinolines; Stroke

The present study was undertaken to compare the efficacy of pitavastatin and colestimide in patients with diabetes mellitus complicated by hyperlipidemia and metabolic syndrome. 48 diabetic patients with metabolic syndrome were randomly assigned to a pitavastatin group or colestimide group. The clinical parameters, serum lipids, fasting (FPG) and postprandial plasma glucose(PPG), HOMA-IR, hemoglobin A1c(HbA1c), hs-CRP and urinary albumin were measured before/after 24-week administration. Treatment with pitavastatin reduced LDL-C and TG, while that with colestimide significantly reduced waist circumference, BMI, LDL-C, HbA1c, FPG, PPG, HOMA-R , hs-CRP and urinary albumin. Percent improvement in LDL-C was greater in the pitavastatin group than in the colestimide group. Colestimide appeared to be useful in the management of Japanese patients with diabetes mellitus complicated by metabolic syndrome, since it alleviates obesity and insulin resistance in addition to exhibiting lipid profile-improving effects, and can thus improve markers of atherosclerosis.

Topics: Adult; Aged; Albuminuria; Atherosclerosis; Biomarkers; C-Reactive Protein; Cholesterol, LDL; Diabetes Complications; Epichlorohydrin; Female; Glycated Hemoglobin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperglycemia; Hyperlipidemias; Hypolipidemic Agents; Imidazoles; Insulin Resistance; Japan; Male; Metabolic Syndrome; Middle Aged; Obesity; Quinolines; Resins, Synthetic; Triglycerides; Weight Loss

To compare the long-term efficacy and safety of pitavastatin with atorvastatin in patients with type 2 diabetes and combined (mixed) dyslipidaemia.. Randomised, double-blind, active-controlled, multinational non-inferiority study. Patients were randomised 2 : 1 to pitavastatin 4 mg (n = 279) or atorvastatin 20 mg (n = 139) daily for 12 weeks. Patients completing the core study could continue on pitavastatin 4 mg (n = 141) or atorvastatin 20 mg (n = 64) [40 mg (n = 7) if lipid targets not reached by week 8] for a further 44 weeks (extension study). The primary efficacy variable was the change in low-density lipoprotein cholesterol (LDL-C).. Reductions in LDL-C were not significantly different at week 12 between the pitavastatin (-41%) and atorvastatin (-43%) groups. Attainment of National Cholesterol Education Program and European Atherosclerosis Society targets for LDL-C and non-high-density lipoprotein cholesterol (non-HDL-C) was similarly high for both treatment groups. Changes in secondary lipid variables (e.g. HDL-C, apolipoprotein B and triglycerides) were similar between treatments. Post hoc analysis showed that adjusted mean treatment differences for pitavastatin vs. atorvastatin were within the non-inferiority margin at weeks 16 (+0.11%; 95% confidence interval (CI), -5.23 to 5.44) and 44 (-0.02%; 95% CI, -5.46 to 5.41) of the extension study. Both treatments were well tolerated; atorvastatin increased fasting blood glucose from baseline (+7.2%; p < 0.05), whereas pitavastatin had no significant effect (+2.1%).. Reductions in LDL-C and changes in other lipids were not significantly different in patients treated with pitavastatin 4 mg or atorvastatin 20 or 40 mg. Pitavastatin may, however, have a more favourable effect on the glycaemic status.

Topics: Adolescent; Adult; Aged; Anticholesteremic Agents; Atherosclerosis; Atorvastatin; Cholesterol, LDL; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Double-Blind Method; Dyslipidemias; Female; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Pyrroles; Quinolines; Treatment Outcome; Young Adult

To clarify whether the effects of statin treatment on plaque regression vary according to the presence or absence of polyvascular disease (PVD) in patients with acute coronary syndrome (ACS).. 307 patients with ACS who underwent percutaneous coronary intervention for the culprit lesion at 33 centers were treated with atorvastatin or pitavastatin. Noncoronary atherosclerosis was defined as coexistent, clinically recognized arterial disease other than coronary artery disease (CAD) (cerebral, aortic, or lower extremity). Intravascular ultrasound (IVUS) was performed to assess non-culprit coronary atherosclerosis at baseline and at 8-12 months follow-up. Serial IVUS examinations were obtained in 252 patients. Atheroma volume and percent change in atheroma volume of the target plaque was assessed.. Patients of the CAD+PVD (n = 19) were older (68 vs. 62 years, p = 0.02), had lower low-density lipoprotein cholesterol (LDL-C) levels at baseline (116 vs. 134 mg/dL, p=0.03) than those of the CAD-only group (n = 233), whereas LDL-C levels at follow-up were similar (81 vs. 83 mg/dL). Although the baseline plaque volume was similar in the two groups (59 vs. 57 mm(3)), patients of the CAD+PVD group showed milder regression of atherosclerosis than those of the CAD-only group (-8.9% vs. -18.2%, p = 0.005). This difference remained significant even after adjustment for coronary risk factors including age and serum LDL-C (p = 0.047).. Statin treatment results in milder regression of coronary atherosclerosis in CAD patients with polyvascular disease compared to those with CAD only.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Atherosclerosis; Atorvastatin; Chi-Square Distribution; Coronary Artery Disease; Female; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Japan; Male; Middle Aged; Multivariate Analysis; Predictive Value of Tests; Prospective Studies; Pyrroles; Quinolines; Regression Analysis; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Ultrasonography, Interventional

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.

Topics: Aged; Aorta, Thoracic; Atherosclerosis; Atrial Fibrillation; Diet; Echocardiography, Transesophageal; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Middle Aged; Observer Variation; Prospective Studies; Quinolines; Scattering, Radiation; Treatment Outcome; Tunica Intima; Tunica Media

Many clinical trials have shown that 3-hydroxy-3-methylglutaryl-conenzyme A reductase inhibitors (statins) can significantly reduce the incidence of coronary artery disease in both primary and secondary prevention. A recent study showed that aggressive lipid-lowering therapy with statins could achieve regression of coronary artery plaque evaluated with gray-scale intravascular ultrasound (IVUS). However, the actual changes in coronary artery plaque composition produced by statin therapy have not been well delineated.. This study will be a prospective, open-label, randomized multicenter study of 160 patients with stable or unstable angina who have undergone percutaneous coronary intervention with Virtual Histology IVUS (VH-IVUS). Patients will be randomly assigned to either the pitavastatin or pravastatin group. After treatment for 24-40 weeks, VH-IVUS will be performed again in the same segment of the coronary artery. The primary endpoint will be quantitative changes in each of the 4 components measured by VH-IVUS.. The treatment with statin on atheroma regression evaluated by intravascular ultrasound with Virtual Histology (TRUTH) study will be the first multicenter study using VH-IVUS to evaluate the effects of statins on changes in coronary artery plaque composition and the findings will clarify the mechanisms of coronary artery plaque stabilization.

Topics: Atherosclerosis; Coronary Artery Disease; Coronary Vessels; Endpoint Determination; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Japan; Pravastatin; Prospective Studies; Quinolines; Ultrasonography, Interventional; User-Computer Interface

The effects of statins on platelet activation markers, chemokines and adiponectin, were investigated in 135 patients with hyperlipidemia. Of the 135 hyperlipidemic patients, 63 were allocated to the simvastatin group, treated with simvastatin at the dose of 10 mg daily, and the remaining 72 were allocated to the pitavastatin group, treated with pitavastatin at the dose of 2 mg daily. Plasma levels of platelet-derived microparticles (PDMP), cell adhesion molecules (sCD40L and sP-selectin), chemokines [monocyte chemoattractant protein-1 (MCP-1) and regulated on activation normally T-cell expressed and secreted] and adiponectin were measured at the baseline and after 6 months of treatment in both the groups. In addition, we carried out a basic study to investigate the MCP-1-dependent induction of tissue factor expression on a histiocytic cell line (U937 cells). The plasma levels of PDMP, sCD40L, sP-selectin, regulated on activation normally T-cell expressed and secreted and MCP-1 were higher, whereas those of adiponectin were lower, in the hyperlipidemic patients than in the normolipidemic controls. Plasma PDMP and sCD40L were positively correlated, whereas plasma adiponectin was negatively correlated, with the plasma levels of MCP-1. No significant differences in the plasma levels of PDMP, sCD40L, sP-selectin, regulated on activation normally T-cell expressed and secreted and MCP-1 measured before and after treatment were observed in either the simvastatin or pitavastatin group. A significant increase of the plasma adiponectin levels was observed after 6 months of treatment with pitavastatin but not after an equal duration of treatment with simvastatin. When pitavastatin-treated patients were divided into two groups according to the adiponectin response to pitavastatin treatment, significant decreases of the plasma MCP-1, PDMP and sCD40L levels were observed after pitavastatin treatment in the responder group. In the aforementioned basic study, MCP-1 by itself did not induce the expression of tissue factor on the U937 cells. However, the recombinant sCD40L-induced expression of tissue factor on U937 was enhanced by the addition of MCP-1. These findings suggest that PDMP, sCD40L and MCP-1 may participate in the development of atherothrombosis in patients with hyperlipidemia and that pitavastatin may exert an adiponectin-dependent antiatherothrombotic effect in hyperlipidemic patients.

Topics: Adiponectin; Adult; Aged; Atherosclerosis; CD40 Ligand; Cell-Derived Microparticles; Chemokine CCL2; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Male; Middle Aged; P-Selectin; Quinolines; T-Lymphocytes; Thrombophilia; Thromboplastin; U937 Cells

Topics: Atherosclerosis; Atorvastatin; Diabetes Mellitus, Type 2; Glucose Intolerance; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Pyrroles; Quinolines; Treatment Outcome

To compare the efficacy and safety of pitavastatin and atorvastatin in Japanese patients with hypercholesterolemia.. Japanese patients with total cholesterol (TC) > or = 220 mg/dL were randomized to receive pitavastatin 2 mg (n=126) or atorvastatin 10 mg (n=125) for 12 weeks. The primary endpoint was percent change from baseline in non-HDL-C level after 12 weeks of treatment. Reduction of non-HDL-C by pitavastatin treatment (39.0%, P=0.456 vs. atorvastatin) was non-inferior to that by atorvastatin (40.3%). Both pitavastatin and atorvastatin also significantly reduced LDL-C by 42.6% and 44.1%, TC by 29.7% and 31.1%, and TG by 17.3% and 10.7%, respectively, at 12 weeks without intergroup differences. HDL-C showed a significant increase at 12 weeks with pitavastatin treatment (3.2%, P=0.033 vs. baseline) but not with atorvastatin treatment (1.7%, P=0.221 vs. baseline). Waist circumference, body weight and BMI were significantly correlated with percent reduction of non-HDL-C in the atorvastatin group, whereas pitavastatin showed consistent reduction of non-HDL-C regardless of the body size. In patients with metabolic syndrome, LDL-C was reduced significantly more in patients receiving pitavastatin when compared with those receiving atorvastatin. AST, ALT and gammaGTP increased significantly in patients receiving atorvastatin but not in those receiving pitavastatin. Both treatments were well tolerated.. Pitavastatin 2 mg and atorvastatin 10 mg are equally effective in improving the lipid profile and were well tolerated in Japanese patients with hypercholesterolemia.

Topics: Aged; Anticholesteremic Agents; Atherosclerosis; Atorvastatin; Body Mass Index; Body Weight; Cholesterol, LDL; Female; Heptanoic Acids; Humans; Hypercholesterolemia; Japan; Male; Middle Aged; Pyrroles; Quinolines; Waist Circumference

The effects of treatment with pitavastatin on inflammatory and platelet activation markers and adiponectin in 117 patients with hyperlipidemia were investigated to determine whether pitavastatin may prevent the progression of atherosclerotic changes in hyperlipidemic patients. Adiponectin levels prior to pitavastatin treatment in hyperlipidemic patients with and without diabetes were lower than levels in normolipidemic controls. Both total cholesterol and the low-density lipoprotein cholesterol decreased significantly after pitavastatin administration. Additionally, hyperlipidemic patients with or without type 2 diabetes exhibited a significant increase in adiponectin levels 6 months after pitavastatin treatment (diabetes: 3.52 +/- 0.80 vs. 4.52 +/- 0.71 microg/ml, p < 0.001; no diabetes: 3.48 +/- 0.71 vs. 4.23 +/- 0.82 microg/ml, p < 0.05). However, high-sensitivity C-reactive protein, platelet-derived microparticle and soluble P-selectin did not exhibit any differences before or after pitavastatin administration. Levels of adiponectin significantly increased after pitavastatin administration in the group of lower soluble P-selectin (soluble P-selectin before pitavastatin treatment <200 ng/ml). These results suggest that pitavastatin possesses an adiponectin-increasing effect in patients with hyperlipidemia and this effect is influenced by intensive platelet activation.

Topics: Adiponectin; Aged; Atherosclerosis; C-Reactive Protein; Cholesterol; Cholesterol, LDL; Diabetes Mellitus, Type 2; Disease Progression; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Male; Middle Aged; Oxidative Stress; P-Selectin; Quinolines

Statins play a major role in reducing circulating cholesterol levels and are widely used to prevent coronary artery disease. Although they are recently confirmed to up-regulate mitophagy, little is known about the molecular mechanisms and its effect on endothelial progenitor cell (EPC). Here, we explore the role and mechanism underlying statin (pitavastatin, PTV)-activated mitophagy in EPC proliferation. ApoE

Topics: Animals; Atherosclerosis; Calcium; Calcium Signaling; Calcium-Calmodulin-Dependent Protein Kinase Type 1; Cell Proliferation; Endothelial Progenitor Cells; Mice; Mitophagy; Protein Kinases; Quinolines; Ubiquitin-Protein Ligases

Cardiovascular diseases are responsible for the majority of deaths on a global scale. Atherosclerosis is the main risk factor for cardiovascular disorders and represents a complex phenomenon associated with endothelial dysfunction and inflammation. Statins, especially atorvastatin (ATV) and pitavastatin (PTV), are common agents used to control ongoing atherosclerotic events in the body to minimize cardiovascular disease-based deaths.. The present study aimed at comparing the efficacy of ATV and PTV in a cell line model of inflammation. Human saphenous vein cells were treated with TNF-alpha to mimic atherosclerotic conditions, and the cells were divided into 7 groups, including control, DMSO, TNF-alpha (10 ng/mL-6 hours), ATV (50 μM/24 hours), PTV (2 μM/24 hours), ATV (50 μM/24 hours)+TNF-alpha (10 ng/mL-6 hours) and PTV (2 μM/24 hours)+TNF-alpha (10 ng/mL-6 hours). The expression levels of 20 proinflammatory cytokines and chemokines were investigated in these groups using a human atherosclerosis antibody array.. Possible pathway interactions were determined by STRING and PANTHER analyses. Comparison with the effect of ATV indicated that PTV reduced the levels of 4 proinflammatory cytokines: CCL11, CSF2, CCL20, and TGFB1 (p<0.05).. Pleiotropic effects of pitavastatin against cardiovascular diseases appeared to be better; however, additional studies are required to compare statins and to identify new drugs that maintain broader protection from the risks of cardiovascular diseases.

Topics: Atherosclerosis; Atorvastatin; Cardiovascular Diseases; Cytokines; Endothelial Cells; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inflammation; Pilot Projects; Quinolines; Saphenous Vein; Tumor Necrosis Factor-alpha

People living with HIV (PLHIV) have an elevated risk of atherosclerotic cardiovascular disease (CVD) compared to their HIV-negative peers. Expanding statin use may help alleviate this burden. However, the choice of statin in the context of antiretroviral therapy is challenging. Pravastatin and pitavastatin improve cholesterol levels in PLHIV without interacting substantially with antiretroviral therapy. They are also more expensive than most statins. We evaluated the cost-effectiveness of pravastatin and pitavastatin for the primary prevention of CVD among PLHIV in Thailand who are not currently using lipid-lowering therapy.. We developed a discrete-state microsimulation model that randomly selected (with replacement) individuals from the TREAT Asia HIV Observational Database cohort who were aged 40 to 75 years, receiving antiretroviral therapy in Thailand, and not using lipid-lowering therapy. The model simulated each individual's probability of experiencing CVD. We evaluated: (1) treating no one with statins; (2) treating everyone with pravastatin 20mg/day (drug cost 7568 Thai Baht ($US243)/year) and (3) treating everyone with pitavastatin 2 mg/day (drug cost 8182 Baht ($US263)/year). Direct medical costs and quality-adjusted life-years (QALYs) were assigned in annual cycles over a 20-year time horizon and discounted at 3% per year. We assumed the Thai healthcare sector perspective.. Pravastatin was estimated to be less effective and less cost-effective than pitavastatin and was therefore dominated (extended) by pitavastatin. Patients receiving pitavastatin accumulated 0.042 additional QALYs compared with those not using a statin, at an extra cost of 96,442 Baht ($US3095), giving an incremental cost-effectiveness ratio of 2,300,000 Baht ($US73,812)/QALY gained. These findings were sensitive to statin costs and statin efficacy, pill burden, and targeting of PLHIV based on CVD risk. At a willingness-to-pay threshold of 160,000 Baht ($US5135)/QALY gained, we estimated that pravastatin would become cost-effective at an annual cost of 415 Baht ($US13.30)/year and pitavastatin would become cost-effective at an annual cost of 600 Baht ($US19.30)/year.. Neither pravastatin nor pitavastatin were projected to be cost-effective for the primary prevention of CVD among PLHIV in Thailand who are not currently using lipid-lowering therapy. We do not recommend expanding current use of these drugs among PLHIV in Thailand without substantial price reduction.

Topics: Adult; Atherosclerosis; Cost-Benefit Analysis; Drug Costs; Female; HIV Infections; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Pravastatin; Quality-Adjusted Life Years; Quinolines; Thailand

It has been demonstrated that pitavastatin can significantly reduce low-density lipoprotein (LDL) cholesterol (LDL-C), but its impact on lipoprotein subfractions and oxidized low-density lipoprotein (oxLDL) has not been determined. The aim of the present study was to investigate the potential effects of pitavastatin on subfractions of LDL and high-density lipoprotein (HDL) as well as oxLDL in untreated patients with coronary atherosclerosis (AS). Thirty-six subjects were enrolled in this study. Of them, 18 patients with AS were administered pitavastatin 2 mg/day for 8 weeks and 18 healthy subjects without therapy served as controls. The plasma lipid profile, lipoprotein subfractions and circulating oxLDL were determined at baseline and 8 weeks respectively. The results showed that pitavastatin treatment indeed not only decreased LDL-C, total cholesterol (TC), triglycerides (TG) and apolipoprotein B (ApoB) levels, and increased HDL cholesterol (HDL-C), but also reduced the cholesterol concentration of all of the LDL subfractions and the percentage of intermediate and small LDL subfractions. Meanwhile, pitavastatin could decrease plasma oxLDL levels. Furthermore, a more close correlation was found between oxLDL and LDL-C as well as LDL subfractions after pitavastatin treatment. We concluded that a moderate dose of pitavastatin therapy not only decreases LDL-C and oxLDL concentrations but also improves LDL subfractions in patients with AS.

Topics: Adolescent; Adult; Aged; Atherosclerosis; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Female; Humans; Lipoproteins, LDL; Male; Middle Aged; Quinolines; Triglycerides; Young Adult

Statins inhibiting 3-hydroxy-3-methylglutaryl-CoA reductase are the standard treatment for hypercholesterolemia in atherosclerotic cardiovascular disease (ASCVD), mediated by inflammatory reactions within vessel walls. Several studies highlighted the pleiotropic effects of statins beyond their lipid-lowering properties. However, few studies investigated the effects of statins on T cell activation. This study evaluated the immunomodulatory capacities of three common statins, pitavastatin, atorvastatin, and rosuvastatin, in activated human T cells. The enzyme-linked immunosorbent assay (ELISA) and quantitative real time polymerase chain reaction (qRT-PCR) results demonstrated stronger inhibitory effects of pitavastatin on the cytokine production of T cells activated by phorbol 12-myristate 13-acetate (PMA) plus ionomycin, including interleukin (IL)-2, interferon (IFN)-γ, IL-6, and tumor necrosis factor α (TNF-α). Molecular investigations revealed that pitavastatin reduced both activating protein-1 (AP-1) DNA binding and transcriptional activities. Further exploration showed the selectively inhibitory effect of pitavastatin on the signaling pathways of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK), but not c-Jun N-terminal kinase (JNK). Our findings suggested that pitavastatin might provide additional benefits for treating hypercholesterolemia and ASCVD through its potent immunomodulatory effects on the suppression of ERK/p38/AP-1 signaling in human T cells.

Topics: Anti-Inflammatory Agents; Atherosclerosis; Cytokines; Gene Expression Regulation; Humans; Immunologic Factors; Inflammation; Inflammation Mediators; Lymphocyte Activation; Models, Biological; Phorbol Esters; Quinolines; Signal Transduction; T-Lymphocytes; Transcription Factor AP-1

Activation of macrophage adipocyte fatty acid-binding protein (FABP4) induces development of atherosclerosis in animal models. We previously reported that statin inhibited while dexamethasone activated macrophage FABP4 expression. However, co-treatment of macrophages with statin and dexamethasone induced FABP4 expression in a synergistic manner, which implies that this co-treatment may exacerbate high-fat diet (HFD)-induced atherosclerosis. In this study, we fed apoE-deficient (apoE) mice with HFD or HFD containing dexamethasone or pitavastatin or both for 16 weeks. Compared with HFD alone, pitavastatin or dexamethasone had little effect on lesions in both en face aortas and aortic root cross sections. However, the co-treatment exacerbated HFD-induced lesions. In addition, the co-treatment decreased collagen content and disturbed the integrity of lesion caps. Both serum total cholesterol and LDL cholesterol levels were reduced by pitavastatin and increased by dexamethasone, respectively. However, the co-treatment had little effect on both total cholesterol and LDL cholesterol levels, indicating that the exacerbation of lesions is independent of total cholesterol or LDL cholesterol levels. FABP4 expression in aortic lesion area was significantly induced by the co-treatment, suggesting that activation of FABP4 expression is a main contributor to lesions. In conclusion, our study demonstrates that co-treatment of pitavastatin and dexamethasone exacerbates HFD-induced atherosclerosis and defines a potential risk to use the dual treatment for patients in clinics.

Topics: Animals; Apolipoproteins E; Atherosclerosis; Dexamethasone; Diet, High-Fat; Drug Therapy, Combination; Female; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Mice; Mice, Knockout; Quinolines

Chronic renal disease (CRD) accelerates atherosclerosis and cardiovascular calcification. Statins reduce low-density lipoprotein-cholesterol levels in patients with CRD, however, the benefits of statins on cardiovascular disease in CRD remain unclear. This study has determined the effects of pitavastatin, the newest statin, on arterial inflammation and calcification in atherogenic mice with CRD.. CRD was induced by 5/6 nephrectomy in cholesterol-fed apolipoprotein E-deficient mice. Mice were randomized into three groups: control mice, CRD mice, and CRD mice treated with pitavastatin. Ultrasonography showed that pitavastatin treatment significantly attenuated luminal stenosis in brachiocephalic arteries of CRD mice. Near-infrared molecular imaging and correlative Mac3 immunostaining demonstrated a significant reduction in macrophage accumulation in pitavastatin-treated CRD mice. Pitavastatin treatment reduced levels of osteopontin in plasma and atherosclerotic lesions in CRD mice, but did not produce a significant reduction in calcification in atherosclerotic plaques as assesses by histology. CRD mice had significantly higher levels of phosphate in plasma than did control mice, which did not change by pitavastatin. In vitro, pitavastatin suppressed the expression of osteopontin in peritoneal macrophages stimulated with phosphate or calcium/phosphate in concentrations similar to those found in human patients with CRD.. Our study provides in vivo evidence that pitavastatin reduces inflammation within atherosclerotic lesions in CRD mice.

Topics: Animals; Apolipoproteins E; Atherosclerosis; Calcium; Cholesterol; Humans; Kidney Failure, Chronic; Macrophages, Peritoneal; Mice; Mice, Knockout; Osteopontin; Phosphates; Plaque, Atherosclerotic; Quinolines; Ultrasonography

Reducing the expression of endothelial cell adhesion molecules is conducive to the decrease of inflammation-induced vascular complications. In this study, we observed pitavastatin on expression of vascular cell adhesion molecule-1 (VCAM-1) and its influence on VCAM-1's target gene miR-126 in endothelial cells. The purpose of this study is to explore the mechanism of pitavastatin in prevention and treatment of atherosclerosis.. HUVEC were cultured in M1640 and passages 2-5 were used in experiments. The cells were randomly divided into three groups, control, TNF-α and pitavastatin group. Cells of TNF-α group were co-incubated with different concentrations (10, 20, 30 μg/L) of TNF-α for 24 h. Cells of pitavastatin group were firstly coincubated with (0.01, 0.1, 1 μmol/L) pitavastatin, respectively, for 1 h, then coincubated with 30 μg/L TNF-α for 24 h. VCAM-1 and miR-126 mRNA were detected by RT-PCR, and Western blotting was used to detect protein expression of VCAM-1.. Both detection methods have showed that TNF-α stimulation significantly increased the mRNA and protein expression of VCAM-1 in a dose-dependent manner, and miR-126 mRNA expression exhibited a decreasing trend. The increase of VCAM-1 mRNA and protein expression induced by TNF-α was inhibited by pitavastatin in a dose-dependent manner, too. However, there were no differences of the expression of miR-126 among three groups.. These effects may explain the ability of pitavastatin to reduce the progression of atherosclerosis. The findings further suggest that inhibitory effect of pitavastatin on VCAM-1 is not related to miR-126 but depends on other ways.

Topics: Atherosclerosis; Cells, Cultured; Human Umbilical Vein Endothelial Cells; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; MicroRNAs; Quinolines; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1

To examine the impact of the plasma homocysteine level on the anti-atherosclerotic effects of pitavastatin treatment, we retrospectively examined 59 patients who had a history of stroke and had been prescribed pitavastatin for the treatment of dyslipidemia at the Neurology department of Toho University Ohashi Medical Center Hospital. The patients were classified into two groups according to their homocysteine levels. Carotid artery plaque progression was determined before and after pitavastatin treatment. Plasma levels of high-sensitivity C-reactive protein, platelet molecular markers, and von Willebrand factor were measured. Pitavastatin treatment had beneficial effects on the lipid profiles of these patients and slowed atherosclerosis progression. These effects were observed in both the high and low homocysteine groups. Proactive lipid intervention using pitavastatin may inhibit the progression of atherosclerosis and contribute to secondary prevention of stroke in high-risk patients. We conclude that this statin could inhibit progression at any stage of disease and should therefore be proactively administered to these patient groups, regardless of disease severity.

Topics: Aged; Aged, 80 and over; Atherosclerosis; Biomarkers; C-Reactive Protein; Carotid Arteries; Demography; Female; Homocysteine; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipids; Male; Middle Aged; Platelet Activation; Quinolines; Retrospective Studies; Risk Factors; Stroke; Ultrasonography; von Willebrand Factor

Although statins increase the plasma concentration of high-density lipoprotein cholesterol (HDL-C), it has not been elucidated whether the increased HDL particles possess normal antiatherosclerotic properties. Pitavastatin functions to increase the plasma HDL-C level and decrease the lowdensity lipoprotein cholesterol (LDL-C) level. In the present study, we sought to examine the qualitative changes in HDL during pitavastatin treatment.. A total of 30 patients with dyslipidemia were treated with 2 mg of pitavastatin for four weeks. The cholesterol efflux capacity and activities of the antioxidative enzymes paraoxonase-1 (PON-1) and platelet-activating factor acetylhydrolase (PAF-AH) were evaluated using polyethethylene glycol-treated HDL fractions before and after pitavastatin treatment.. Pitavastatin treatment decreased the serum LDL-C level by 39% and increased the serum HDL-C level by 9% (p＜0.05). In addition, pitavastatin increased the phospholipid content of HDL by 7.8% (p＜0.05). The pitavastatin-induced increase in the HDL-C level coincided with an increase in the cholesterol efflux capacity of the isolated HDL fraction of 8.6% (p＜0.05). The post-pitavastatin treatment activity of HDL-associated PON-1 (paraoxonase and arylesterase) was increased by 9% (p＜0.05) and 11% (p＜0.05), respectively, while the HDL-associated PAF-AH activity was not affected by pitavastatin.. In addition to its LDL-C-lowering effects, pitavastatin elevates the HDL-C level and enhances the cholesterol efflux capacity and antioxidative properties of HDL. Pitavastatin therefore increases the amount of functional HDL without attenuating HDL quality.

Topics: 1-Alkyl-2-acetylglycerophosphocholine Esterase; Adult; Aged; Antioxidants; Aryldialkylphosphatase; Atherosclerosis; Cholesterol; Cholesterol, HDL; Dyslipidemias; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Platelet Activating Factor; Polyethylene Glycols; Quinolines

It is not clear if the new 3-hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor pitavastatin prevents atherogenesis by a direct effect. Statins have a cholesterol-lowering effect, so an accessible animal model of atherosclerosis showing only moderate hypercholesterolaemia as in humans, is needed. The effects of pitavastatin were evaluated on atherosclerotic lesions accumulating foam cells derived from macrophages, produced in rabbits with moderate hypercholesterolaemia by chronic inhibition of nitric oxide synthase (NOS).. White New Zealand rabbits were fed a 0.2% cholesterol diet with the NOS inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) in the same diet. Pitavastatin (0.1 and 0.3 mg x kg(-1)) was given orally once a day for 8 weeks. The aortic arch and thoracic aorta were analysed by histochemistry and atherosclerotic lesions were quantified. The effect of pitavastatin on adhesion of THP-1 cells to endothelial cells, and cholesterol content in RAW264.7 cells incubated with oxidized or acetylated LDL were also investigated.. Atherosclerotic lesions containing foam cells were induced in a model of atherosclerosis in rabbits with moderate hypercholesterolaemia by chronic inhibition of NOS. The area of atherosclerotic lesions was diminished by pitavastatin administration. The adhesion of THP-1 cells and cholesteryl ester content in RAW macrophages were decreased by pitavastatin treatment.. Atherosclerosis induced by chronic inhibition of NOS in moderately hypercholesterolaemic rabbits was suppressed by pitavastatin via inhibition of macrophage accumulation and macrophage foam cell formation.

Topics: Animals; Atherosclerosis; Cell Adhesion; Endothelium, Vascular; Enzyme Inhibitors; Humans; Hypercholesterolemia; Immunohistochemistry; Male; Monocytes; Nitric Oxide; Quinolines; Rabbits

Atherosclerosis with hypoadiponectinemia can be further aggravated by intestinal ischemia/reperfusion (II/R)-induced injuries, such as bacterial translocation and lung injury. We investigated the effect of statin administration on the risk of II/R-induced injury in atherosclerotic rats with hypoadiponectinemia.. Wistar rats were divided into 4 groups: (1) the Normal group (normal diet), (2) the Chol group (2% high cholesterol diet), (3) the St-1w group, and (4) the St-2w group (Chol group plus pitavastatin administration for 1 or 2 weeks, respectively). The serum concentrations of lipids and adiponectin were measured preoperatively. After midline laparotomy (time, T0), the superior mesenteric artery was occluded with a microvascular clamp for 30 min, followed by 360 min of reperfusion (T1). Intestinal and lung nitric oxide (NO) concentrations were measured. Intestinal injury was assessed by microcirculatory flow, histology, and permeability. Bacterial translocation was assessed by analysis of serum peptidoglycan concentration. Lung injury was assessed by histologic examination, pulmonary permeability index, and wet/dry lung weight ratio.. The 2-week administration of statins with high-cholesterol feeding (St-2w group) improved hypoadiponectinemia to levels similar to those of the Normal group. Intestinal and lung NO concentrations were significantly lower at T1 in the Normal and St-2w groups than in the Chol group. Statin administration improved poor recovery of intestinal microcirculatory flow in the Chol group. At T1, intestinal and lung injuries were significantly aggravated and serum peptidoglycan concentration was significantly elevated in the Chol group compared with the Normal and St-2w groups. The 1-week administration of statins had no significant influence on serum adiponectin levels, tissue NO concentration, or tissue injury.. Administration of pitavastatin reduces the risk of II/R-induced injury in atherosclerotic rats with hypoadiponectinemia by improving hypoadiponectinemia and inhibiting inducible NO synthase-produced NO. Furthermore, preoperative improvement of hypoadiponectinemia may be important as an index of the protective effect of pitavastatin for II/R-induced injury in atherosclerotic rats with hypoadiponectinemia.

Topics: Adiponectin; Animals; Atherosclerosis; Bacterial Translocation; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Intestinal Diseases; Lung Injury; Male; Nitric Oxide; Peptidoglycan; Quinolines; Rats; Rats, Wistar; Reperfusion Injury

To investigate the effect of pitavastatin on asymptomatic atherosclerosis in patients with hypercholesterolemia.. Thirty-five outpatients with hypercholesterolemia (61.5+/-12.8 yr) were administered 2 mg oral pitavastatin daily for 6 months. Plasma pentraxin 3 (PTX3), a novel inflammatory marker of atherosclerosis, was measured together with the serum hsCRP and carotid-artery intima-media thickness (IMT).. Significant improvement of the LDL-C/HDL-C and log (TG/HDL-C) ratios began to be observed from 1 month after using pitavastatin. Significant correlation of the initial PTX3 value was observed with the initial plaque score (PS) (p=0.038, r=0.246), but not between the hsCRP and plasma PTX3 or PS. When patients were divided into 3 groups based on the initial PTX3 values, a significant decrease of the plasma PTX3 was obtained in the highest PTX3 group alone (p=0.034). The change in the plasma PTX3 value (DeltaPTX3) was significantly correlated with the Delta mean IMT during the study period (p=0.008, r=0.456).. Pitavastatin significantly reduced the elevated plasma levels of PTX3 in patients with hypercholesterolemia by its pleiotropic effect against atherosclerotic inflammation. This study showed for the first time that the plasma PTX3 might be a useful blood parameter for direct detection of active atherosclerotic change.

Topics: Aged; Atherosclerosis; C-Reactive Protein; Female; Humans; Hypercholesterolemia; Inflammation; Male; Middle Aged; Quinolines; Serum Amyloid P-Component; Vascular Resistance

We investigated the effects of co-administration of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor and angiotensin II type 1 receptor blocker (ARB) on nitric oxide (NO) bioavailability in genetically hyperlipidemic rabbits with our newly developed NO sensor. A total of 36 myocardial infarction-prone Watanabe heritable hyperlipidemic (WHHLMI) rabbits equally derived (n=6 per group) were treated with 1) vehicle (control), 2) hydralazine (15 mg/kg/d), 3) the HMG-CoA reductase inhibitor pitavastatin (P: 0.5 mg/kg/d), 4) the ARB valsartan (V: 5 mg/kg/d), and 5) pitavastatin+valsartan (P+V) together without or 6) with N(G)-nitro-L-arginine methyl ester (L-NAME) for 8 weeks. After treatment, acetylcholine (ACh)-induced NO production was measured as a surrogate for endothelium protective function, and vascular peroxynitrite (a product of superoxide and NO) was measured for assessing dysfunctional endothelial NO synthase activity. Plaque area was quantified by histology as well as optical coherence tomography (OCT). Intra-aortic infusion of ACh produced an increase in plasma NO concentration, which was significantly greater with all drug treatments than with the control. P+V increased ACh-induced NO by 4.1 nmol/L significantly more than either P or V singly. The vascular peroxynitrite concentration was 1.6 pmol/mg protein in the control group and significantly less than those in the P- and V-monotherapy-groups. The lowest peroxynitrite concentration was observed in the P+V group (0.4 pmol/mg protein), which was significantly lower than those in the P- and the V-monotherapy-groups. OCT and histology of the thoracic aorta revealed that the plaque area decreased significantly more with the combination than with the monotherapy. In conclusion, the combined treatment with an HMG-CoA reductase inhibitor and an ARB may have additive protective effects on endothelial function as well as atherosclerotic change.

Topics: Acetylcholine; Angiotensin II Type 1 Receptor Blockers; Animals; Atherosclerosis; Biological Availability; Drug Therapy, Combination; Echocardiography; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Myocardial Infarction; Nitric Oxide; Quinolines; Rabbits; Reactive Oxygen Species; Tetrazoles; Tyrosine; Valine; Valsartan