Journal of Atherosclerosis and Thrombosis
Online ISSN : 1880-3873
Print ISSN : 1340-3478
ISSN-L : 1340-3478
Volume 21 , Issue 10
Showing 1-10 articles out of 10 articles from the selected issue
  • Soo Lim, Philip Barter
    2014 Volume 21 Issue 10 Pages 997-1010
    Published: October 24, 2014
    Released: October 24, 2014
    [Advance publication] Released: August 15, 2014
    Redox systems are key players in vascular health. A shift in redox homeostasis-that results in an imbalance between reactive oxygen species (ROS) generation and endogenous antioxidant defenses has the potential to create a state of oxidative stress that subsequently plays a role in the pathogenesis of a number of diseases, including those of the cardiovascular and metabolic system. Statins, which are primarily used to reduce the concentration of low-density lipoprotein cholesterol, have also been shown to reduce oxidative stress by modulating redox systems.
    Studies conducted both in vitro and in vivo support the role of oxidative stress in the development of atherosclerosis and cardiovascular diseases. Oxidative stress may also be responsible for various diabetic complications and the development of fatty liver. Statins reduce oxidative stress by blocking the generation of ROS and reducing the NAD+/NADH ratio. These drugs also have effects on nitric oxide synthase, lipid peroxidation and the adiponectin levels.
    It is possible that the antioxidant properties of statins contribute to their protective cardiovascular effects, independent of the lipid-lowering actions of these agents. However, possible adverse effects of statins on glucose homeostasis may be related to the redox system. Therefore, studies investigating the modulation of redox signaling by statins are warranted.
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Original Article
  • Yuji Ueno, Ayami Okuzumi, Masao Watanabe, Yasutaka Tanaka, Yoshiaki Sh ...
    2014 Volume 21 Issue 10 Pages 1011-1021
    Published: October 24, 2014
    Released: October 24, 2014
    [Advance publication] Released: May 24, 2014
    Aim: Aortic arch calcification (AoAC) on chest X-rays represents systemic atherosclerosis and it is associated with ischemic cardiovascular diseases. However, the relationship between ischemic stroke and AoAC has yet to be fully elucidated.
    Methods: Patients with acute ischemic stroke who were undergoing chest X-ray, blood, and brain magnetic resonance imaging (MRI) examinations were prospectively studied. The extent of AoAC on chest X-ray was divided into four grades (0-3). Clinical characteristics, biochemical findings, white matter lesions on MRI, and AoAC extent were assessed in each stroke subtype, and the factors associated with AoAC were investigated.
    Results: A total of 175 patients (age, 70±13 years; 115 men) were enrolled in the study. According to the Trial of Org 10172 in Acute Stroke Treatment classification with minor modification, 33 patients (19%) had small artery occlusion (SAO), 42 (24%) had large artery atherosclerosis, 49 (28%) had cardioembolism, 24 (14%) had stroke with other determined etiologies, and 27 (17%) had stroke with undetermined etiologies. Compared to other stroke subtypes, the extent of AoAC was independently correlated with SAO (all p<0.05). Age (odds ratio [OR]: 1.14, 95% confidence interval [CI]: 1.08 to 1.19, p<0.001), hypertension, (OR: 3.44, 95% CI: 1.23 to 9.66, p=0.019), diabetes mellitus (OR: 2.19, 95% CI: 0.99 to 4.85, p=0.054), white matter lesions (OR: 1.54, 95% CI: 1.00 to 2.36, p=0.048), and SAO (OR: 1.38, 95% CI: 1.02 to 1.89, p=0.040) were significantly associated with AoAC.
    Conclusions: Age, hypertension, cerebral small artery disease, and possibly diabetes mellitus appear to be closely associated with AoAC in patients with acute ischemic stroke.
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  • Ji-Peng Zhou, Yong-Ping Bai, Xiao-Lei Hu, Da-Bin Kuang, Rui-Zheng Shi, ...
    2014 Volume 21 Issue 10 Pages 1022-1030
    Published: October 24, 2014
    Released: October 24, 2014
    [Advance publication] Released: May 16, 2014
    Aim: Asymmetric dimethylarginine (ADMA) is a nitric oxide synthase (NOS) inhibitor that decreases NO production and promotes the development of cardiovascular diseases. Alanine-glyoxylate aminotransferase 2 (AGXT2) plays an important role in ADMA metabolism. This study was designed to explore the association of the AGXT2 V140I (rs37369 G>A) polymorphism with risk for coronary heart disease (CHD) in a Chinese population.
    Methods: A case-control study including 1103 controls and 942 CHD patients was performed. The patients were genotyped for rs37369 using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Plasma ADMA concentration in healthy controls was measured by an enzyme-linked immunosorbent assay (ELISA).
    Results: The rs37369 GG genotype was significantly overrepresented in CHD patients compared to the controls (18.5% versus 14.8%, p=0.025), and it was significantly associated with increased risk for CHD in smokers (OR=2.21, 95% CI: 1.24-3.92, p=0.007) and marginally increased CHD risk for individuals with diabetes mellitus (OR=1.92; 95% CI: 0.94-3.91, p=0.074). The association between rs37369 and CHD risk was further increased in smokers with diabetes mellitus (OR=3.32, 95% CI:1.14-9.67, p=0.028). Patients who smoked and were rs37369 GG homozygous showed significantly higher plasma ADMA levels than carriers of the rs37369 A allele (p=0.004). However, in non-smokers, patients homozygous for rs37369 GG showed significantly lower plasma ADMA concentrations than carriers of the rs37369 A allele (p=0.003). Furthermore, smokers homozygous for rs37369 GG showed significantly higher plasma ADMA concentrations than non-smokers with the same genotype (p=0.012).
    Conclusion: The AGXT2 rs37369 polymorphism is associated with increased risk for CHD in smokers and in diabetes mellitus patients. This increased risk may be due to increased plasma ADMA levels.
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  • Takao Sato, Tomoki Kameyama, Takashi Ohori, Akira Matsuki, Hiroshi Ino ...
    2014 Volume 21 Issue 10 Pages 1031-1043
    Published: October 24, 2014
    Released: October 24, 2014
    [Advance publication] Released: May 16, 2014
    Aim: Epicardial adipose tissue (EAT) is a pathogenic fat depot that may be associated with coronary atherosclerosis and cardiovascular events. Because eicosapentaenoic acid (EPA) has been reported to exert cardiovascular protective effects, we aimed to assess the effects of EPA on the volume of visceral adipose tissue, including EAT and abdominal visceral adipose tissue (AVAT), using multislice computed tomography (CT).
    Methods: In 30 patients with coronary artery diseases (9 women; mean age, 67.2±5.4 years), EAT and AVAT volumes were compared between the control group (n=15, conventional therapy) and the EPA group (n=15, conventional therapy plus purified EPA 1800 mg/day) during a six-month period. EAT was defined as any pixel that had CT attenuation of -150 to -30 Hounsfield units (HU) within the pericardial sac.
    Results: After the six-month follow-up, the serum EPA level increased from 59.9±18.8 to 177.2± 3.3 μg/mL in the EPA group (p<0.01), but no increase was noted in the control group. Similarly, the EPA/arachidonic acid (AA) ratio increased from 0.39±0.12 to 1.22±0.28 in the EPA group (p<0.01), with no significant increase in the control group. The AVAT and EAT volumes decreased in the EPA group but were unchanged in the control group (AVAT, −11.6±17.0 vs. +8.8±13.6 cm2, p<0.01; EAT, −7.3±8.3 vs. +8.7±8.8 cm3, p<0.01). Moreover, the change in the AVAT volume negatively correlated with the change in EPA (r=−0.58, p<0.01) and EPA/AA levels (r=−0.53, p<0.01). A similar negative correlation in these parameters was also observed for the EAT volume.
    Conclusions: Oral intake of purified EPA appears to be associated with reductions in EAT and AVAT volumes.
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  • Kang-Ling Wang, Cheng-Hsueh Wu, Ko-Fan Wang, Chun-Chin Chang, Lung-Chi ...
    2014 Volume 21 Issue 10 Pages 1044-1054
    Published: October 24, 2014
    Released: October 24, 2014
    [Advance publication] Released: June 02, 2014
    Aim: Withholding effective treatment is clinically prevalent. The CEntralized Pan-Asian survey on tHE Under-treatment of hypercholeSterolemia (CEPHEUS-PA) indicated suboptimal low-density lipoprotein cholesterol (LDL-C) goal attainment in Taiwan, which may be attributable to clinical inertia. We herein analyzed the Taiwanese cohort in the CEPHEUS-PA to identify key elements regarding clinical inertia and unsatisfactory LDL-C control.
    Methods: A questionnaire regarding the attitudes and perceptions for each physician and patient was included in the CEPHEUS-PA. Physicians completed the physician questionnaire before enrolling patients, who completed the patient questionnaire before the assessment.
    Results: The National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) guideline was used by 81.8% of physicians to establish the individual therapeutic targets; 50.2% of patients failed to take medications persistently. Regarding perceptions to hypercholesterolemia management, 75.9% of physicians were confident of having a sufficient number of patients at cholesterol targets; 80.2% and 65.9% of patients felt satisfied and motivated, respectively, but 46.0% had no strong feeling. The healthcare reimbursement policy used for treatment guidance was a significant determinant for LDL-C goal attainment (OR=0.32, 95% CI: 0.15-0.69, P=0.006) in addition to patient compliance. Low patient involvement indexed by having no strong feeling was associated with poor LDL-C control (OR=0.73, 95% CI: 0.56-0.95, P=0.020).
    Conclusions: The referenced healthcare reimbursement policy, poor patient compliance, and low patient involvement with hypercholesterolemia management were associated with failure of LDL-C control. Our findings highlight the need to overcome those barriers to improve the under-treatment of hypercholesterolemia.
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  • Yasushi Ishigaki, Suminori Kono, Hideki Katagiri, Yoshitomo Oka, Shini ...
    2014 Volume 21 Issue 10 Pages 1055-1065
    Published: October 24, 2014
    Released: October 24, 2014
    [Advance publication] Released: June 13, 2014
    Aim: Atherosclerosis is strongly associated with an increased mortality in subjects with diabetes. The carotid intima-media thickness (IMT) is commonly measured as a surrogate marker for cardiovascular risk. Statins are well-established protective agents against atherosclerosis and reportedly suppress IMT progression in subjects with diabetes. To clarify the effects of statins on subclinical atherosclerosis, we herein investigated changes in the carotid IMT and lipid profiles in a multi-center, prospective, randomized trial.
    Methods: Hypercholesterolemic subjects with type 2 diabetes were randomly assigned to open-label treatment with either pravastatin or pitavastatin. The primary endpoint of this study was the IMT change after 36 months of statin treatment.
    Results: A total of 97 subjects (51 pitavastatin; 46 pravastatin) completed this 36-month study. The LDL-C decreased significantly from 163.4±27.9 mg/dl at baseline to 100.4±19.6 mg/dl at 36 months in the pitavastatin group and from 159.7±25.6 mg/dl to 118.5±22.1 mg/dl in the pravastatin group. The mean IMT showed moderate regression in both the pitavastatin (−0.070±0.215 mm, P<0.05) and the pravastatin (−0.067±0.260 mm) group. However, there was no significant difference in the IMT change between the two groups. When the two groups were combined, the 36-month change in the mean IMT was significantly associated with HDL-C change (r=−0.24, P= 0.03). Multiple linear regression analysis revealed the change in HDL-C to be an independent variable showing a positive correlation with the carotid IMT reduction.
    Conclusion: The administration of statins for 3 years to subjects with type 2 diabetes resulted in a significant regression of the carotid IMT. An elevation of the plasma HDL-C with statin treatment was closely related to a regression of atherosclerosis.
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  • Ismail Kocyigit, Ozkan Gungor, Aydin Unal, Mustafa Yasan, Ozcan Orscel ...
    2014 Volume 21 Issue 10 Pages 1066-1074
    Published: October 24, 2014
    Released: October 24, 2014
    [Advance publication] Released: June 05, 2014
    Aim: Cardiovascular disease is a major cause of mortality in dialysis patients. Epicardial adipose tissue (EAT) has been proposed as a cardiovascular risk marker in this population. Subclinical hypothyroidism and low free triiodothyronine (fT3) levels are associated with EAT in patients without chronic renal failure. The aim of this study was to investigate the relationship between EAT and low free T3 levels in peritoneal dialysis (PD) patients.
    Methods: A total of 125 prevalent PD patients were enrolled in this cross-sectional study. The epicardial fat thickness (EFT) was measured by echocardiography, and the endothelial function was assessed by flow mediated dilatation (FMD). Thyroid function tests were performed by an enzyme immunoassay.
    Results: The mean age of the patients was 51±13, and the time on PD was 36 months. The mean EFT was 6.7±2.9 mm. The EFT correlated positively with the patient age, systolic blood pressure (BP), mean BP, high sensitivity C-reactive protein (hs-CRP) level and body mass index (BMI), and negatively with the fT3 level and FMD. The median fT3 value was 2.53, and patients were divided according to their serum fT3 values (within the normal range and below the reference level). Compared with patients in the low fT3 group, the subjects in the normal fT3 group had higher serum albumin levels and FMD, but a lower BMI, plasma fasting glucose level, EFT, TSH level, hs-CRP level, low density lipoprotein (LDL) cholesterol level and mean BP in office measurements, and both the diastolic BP and mean BP by ambulatory blood pressure measurement. A multivariate linear regression analysis showed that the EFT was predicted by the hs-CRP and fT3 levels.
    Conclusion: Low free T3 levels are associated with the epicardial fat thickness in PD patients. Further studies are needed to evaluate the pathogenesis and to support these findings.
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  • Haixia Liu, Jingbo Hou, Sining Hu, Xiumin Du, Yan Fang, Haibo Jia, Lin ...
    2014 Volume 21 Issue 10 Pages 1075-1086
    Published: October 24, 2014
    Released: October 24, 2014
    [Advance publication] Released: June 05, 2014
    Aim: Inflammation plays a critical role in the development of atherosclerotic plaque, and lipopolysaccharide (LPS) is a potentially important source of inflammation. The aim of this study was to develop a rabbit model of spontaneous thrombosis mimicking the pathophysiological and morphological characteristics of atherosclerotic plaque in humans.
    Methods: The rabbits were randomized into four groups: group A (n=10) received a normal diet; group B (n=10) received a regular diet and weekly LPS injections (1 μg/kg, Escherichia coli); group C (n=15) received a cholesterol-enriched diet before and after sustaining a balloon injury to the right common carotid artery; and group D (n=15) was treated the same as group C in addition to receiving LPS injections. The morphological characteristics of the resulting lesions were evaluated using optical coherence tomography (OCT) and histology.
    Results: No significant atherosclerotic plaque was observed in groups A or B. Group D exhibited a higher incidence of spontaneous luminal thrombi than group C or B (60% vs. 20% vs. 10%, p<0.05). All of the thrombi detected with OCT were confirmed on histology. A good correlation between the fibrous cap thickness and thrombus arc was obtained on OCT and the histological evaluations.
    Conclusions: A rabbit model of LPS-induced spontaneous thrombosis was developed in which OCT was used to follow changes in plaque morphology.
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  • Mitsunobu Kubota, Shuhei Nakanishi, Masatoshi Hirano, Shusaku Maeda, M ...
    2014 Volume 21 Issue 10 Pages 1087-1097
    Published: October 24, 2014
    Released: October 24, 2014
    [Advance publication] Released: June 18, 2014
    Aim: Serum cholesterol efflux has been suggested to be a key anti-atherogenic function of reverse cholesterol transport. Meanwhile, the quantitative and qualitative alteration of the levels of lipoproteins in the serum has been reported in patients with diabetes, although it remains unclear whether the serum cholesterol efflux capacity is impaired in cases of newly diagnosed glucose intolerance. We thus assessed the relationship between the serum cholesterol efflux capacity and glucose intolerance as detected using oral glucose tolerance tests (OGTTs).
    Methods: We measured the capacity of whole serum to mediate cholesterol efflux from human THP-1 macrophages in a cohort of 439 Japanese-Americans who underwent 75-g OGTTs. A multiple regression analysis was performed to examine the relationship between the serum cholesterol efflux capacity and glucose intolerance.
    Results: The serum cholesterol efflux capacity was found to be negatively correlated with the area under the curve for the serum glucose concentration during the 75-g OGTTs in all subjects. In addition, the serum cholesterol efflux capacity was found to be modestly but significantly lower in the glucose intolerance group (31.4±6.2%) than in the normal glucose tolerance group (33.2±6.1%). There was also a negative association between the serum cholesterol efflux capacity and glucose intolerance after adjusting for age and sex. Moreover, this association remained significant even after further adjustments for serum total cholesterol, high-density lipoprotein cholesterol, apolipoprotein AI and C-reactive protein.
    Conclusions: The serum cholesterol efflux capacity is impaired in Japanese-Americans newly diagnosed with glucose intolerance. This impairment may contribute in some manner to increasing the risk of atherosclerotic disease in subjects with glucose intolerance.
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