Journal of atherosclerosis and thrombosis (J Atherosclerosis Thromb )

Publisher: Nihon Dōmyaku Kōka Gakkai

Description

  • Impact factor
    2.93
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    Impact factor
  • 5-year impact
    2.99
  • Cited half-life
    3.60
  • Immediacy index
    0.41
  • Eigenfactor
    0.01
  • Article influence
    0.77
  • Website
    Journal of Atherosclerosis and Thrombosis website
  • Other titles
    Journal of atherosclerosis and thrombosis (Online)
  • ISSN
    1340-3478
  • OCLC
    53835682
  • Material type
    Document, Internet resource
  • Document type
    Internet Resource, Computer File, Journal / Magazine / Newspaper

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Aim: The goal of the study was to investigate the relationships between coronary artery disease (CAD) and risk factors, including the serum levels of high-sensitivity C-reactive protein (hs-CRP), lipoprotein(a) (Lp(a)) and homocysteine, in Japanese patients with peripheral arterial disease (PAD). Methods: Coronary angiography was performed in 451 patients with PAD, among whom the prevalence and clinical characteristics of CAD were analyzed. A multiple logistic analysis was used to evaluate the relationships between CAD and the risk factors. The relationships between the severity of coronary arterial lesions and the risk factors were evaluated using multiple regression analysis. Results: The prevalence of CAD (≥70% luminal diameter narrowing or a history of CAD) and coronary artery stenosis (≥50%) was 55.9% and 74.1%, respectively, and the rate of CAD (≥70%) with single-, double- and triple-vessel disease was 25.9%, 13.5% and 10.6%, respectively. The prevalence of diabetes was higher among the patients with CAD than among those without. The serum levels of hs-CRP, Lp(a), and homocysteine were higher in the patients with CAD, whereas the estimated glomerular filtration rates and HDL-cholesterol levels were lower in these patients. According to the multiple logistic analysis, CAD was related to diabetes (hazard ratio [HR]: 2.253; 95% confidence interval [CI]: 1.137-4.464, p=0.020), hs-CRP (HR: 1.721; 95% CI: 1.030-2.875, p=0.038), Lp(a) (HR: 1.015; 95% CI: 1.001-1.029, p=0.041) and homocysteine (HR: 1.084; 95% CI: 1.012-1.162, p=0.021). Furthermore, diabetes and the D-dimer and LDL-cholesterol levels exhibited significant relationships with the number of stenotic coronary lesions in the stepwise multiple regression analysis (p<0.05). Conclusions: Diabetes, hs-CRP, Lp(a), homocysteine and lipid abnormalities are critical risk factors for CAD in Japanese patients with PAD.
    Journal of atherosclerosis and thrombosis 10/2014;
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    ABSTRACT: Aims: Acquired Von Willebrand syndrome (AVWS) is an acquired bleeding disorder that has been reported to aggravate bleeding complications in patients with ventricular assist devices or aortic stenosis. AVWS is characterized by the loss of the high-molecular-weight (HMW) multimers of Von Willebrand factor (VWF) with consequent impaired VWF binding to platelets and collagen. The aim of this study was to investigate the development of AVWS in patients treated with veno-venous ECMO (extracorporeal membrane oxygenation) support.Methods: We examined the presence of AVWS in adult patients receiving ECMO support (n=18) and control subjects treated without ECMO support (n=18). The diagnosis of AVWS was made based on the ratio of collagen-binding capacity to VWF-antigen (VWF:CB/VWF:Ag) and a VWF multimeric analysis. In addition, bleeding episodes were monitored. Results: All patients supported with ECMO developed AVWS. AVWS was identified in the early period after ECMO implantation, i.e. within 24 hours after ECMO implantation. In 17 patients, the VWF:CB/VWF:Ag ratio was significantly reduced and HMW multimers were severely missing, and 17 of the 18 patients developed bleeding complications and required transfusions of blood, FFP and/or platelet concentrates.In addition, nine patients without an ECMO device were investigated (prior to ECMO implantation: n=2, after ECMO explantation: n=7). Conclusions: In this study, all patients treated with ECMO support developed AVWS, and AVWS was detectable within 24 hours after ECMO implantation. However, the AVWS was reversible after ECMO explantation. Making an early diagnosis of AVWS and providing appropriate treatment may reduce the incidence of life-threatening bleeding.
    Journal of atherosclerosis and thrombosis 09/2014;
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    ABSTRACT: Aims: Recently, a number of studies have shown an increased red blood cell distribution width (RDW) to be a strong and independent predictor of the prognosis of coronary artery disease. The aim of this study was to investigate the underlying mechanisms responsible for the relationship between the RDW and a poor prognosis of coronary artery disease.Methods: Four hundred and twenty-four patients with ST elevation myocardial infarction treated with primary percutaneous coronary intervention (pPCI) were analyzed retrospectively. We evaluated the relationships between the RDW and the high-sensitivity C-reactive protein (hsCRP) N-terminal pro-brain natriuretic peptide (NTpro-BNP), fasting blood glucose and lipid levels, as well as other parameters of blood examinations and angiographic manifestations. Results: There were 85 patients in the RDW ≥14% group (mean age 60.62±11.29 years, and men: 87%) and 339 patients in the RDW <14% group (mean age: 59.74±11.55 years, and men: 78%). The RDW ≥14% group had higher platelet distribution width (PDW), NTpro-BNP and hsCRP values on admission, a heavier intracoronary thrombotic burden and a higher incidence of three-branch vascular lesions than the RDW <14% group. In the multiple logistic regression analysis, the associations between the RDW and the NTpro-BNP level, incidence of three-branch and left main lesions and intracoronary thrombotic burden remained. Conclusions: A high RDW may be associated with the severity and instability of acute myocardial infarction.
    Journal of atherosclerosis and thrombosis 09/2014;
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    ABSTRACT: Aims: The population-attributable fraction (PAF) is an indicator of the disease burden. In Western countries, the PAF of hypercholesterolemia in cardiovascular disease (CVD) is the highest among that for traditional risk factors; however, data for Asian populations are limited. Methods: A 24-year cohort study was conducted among 9,209 randomly selected patients who were not taking statins. We estimated the hazard ratio (HR) after adjusting for covariates and PAF associated with the serum total cholesterol (TC) levels in relation to CVD mortality. Results: The TC level was found to be positively associated with an increased risk of CVD, coronary heart disease (CHD) and cardiac death (CHD plus heart failure), with an HR of 1.08 (95% confidence interval [CI]: 1.00-1.16), 1.33 (95% CI: 1.14-1.55) and 1.21 (95% CI: 1.08-1.35) for a 1-SD increment in the serum TC level, respectively. Similar positive associations between the TC level and both CHD and cardiac death were observed after classifying the patients by age and sex. Furthermore, the highest serum TC level (≥6.72 mmol/L) was positively associated with CVD death, with an HR of 1.76 (95% CI: 1.25-2.47), as well as both CHD death and cardiac death. In contrast, no significant relationships were observed between the serum TC level and stroke. Meanwhile, the PAF for CVD, CHD, and cardiac deaths due to hypercholesterolemia (serum TC level ≥5.69 mmol/L, defined by the Japan Atherosclerosis Society) was 1.7%, 10.6% and 5.6%, respectively. Conclusions: The estimated PAF of CVD death due to hypercholesterolemia is moderately high, but lower than that for other risk factors, such as hypertension.
    Journal of atherosclerosis and thrombosis 09/2014;
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    ABSTRACT: Aim: Previous clinical trials have demonstrated the effectiveness of eicosapentaenoic acid (EPA) in preventing cardiovascular events. The aim of the present study was to investigate the effects of EPA treatment on the accumulation of coronary atherosclerotic plaque using optical coherence tomography (OCT). Methods: A total of 46 acute coronary syndrome (ACS) patients without dyslipidemia were divided into two groups: those who received 1,800 mg/day of EPA (n=15) or the control group (n=31). Serial OCT examinations were performed at baseline and after eight months of follow-up. The target for the OCT analysis was non-culprit plaque with a percent diameter of stenosis of 30% to 70% in non-culprit vessels of ACS. Results: Between the baseline and follow-up visits, the serum EPA levels increased (50±26 mg/dL to 200±41 mg/dL, p<0.001) in the EPA group, although they did not change in the control group. According to the OCT analysis, the lipid arc did not change in the EPA group (131±52 degrees to 126±54 degrees, p=0.106) or the control group (137±50 degrees to 138±50 degrees, p=0.603). In contrast, the fibrous cap thickness significantly increased in both the EPA group (169±70 μm to 201±49 μm, p<0.001) and the control group (164±63 μm to 174±72 μm, p=0.018); however, the relative change in the fibrous cap thickness was significantly greater in the EPA group than in the control group (131±35% vs. 106±15%, p=0.001). Conclusions: In the present study, the administration of EPA for eight months significantly increased the fibrous cap thickness in patients with coronary atherosclerotic plaque.
    Journal of atherosclerosis and thrombosis 08/2014;
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    ABSTRACT: Aim: Vitamin A plays a major role in lipid metabolism. Previously, we reported that chronic vitamin A feeding (129 mg/kg) for two months normalized the abnormally high plasma HDL-cholesterol (HDL-C) levels in hypercholesterolemic obese rats by upregulating the hepatic scavenger receptor class B type 1 (SR-BI) expression. In this report, we hypothesize that the administration of a dose less than 129 mg of vitamin A/kg would also be effective in lowering the plasma HDL-C levels in these rats. Methods: Changes in the activity and expression of proteins related to RCT were analyzed together with blood parameters in five-month-old male lean and obese rats supplemented with 2.6 (control group), 26, 52 and 129 mg of vitamin A/kg as retinyl palmitate for 20 weeks. Results: Vitamin A supplementation in the obese rats decreased the plasma HDL-C levels with a concomitant increase in the hepatic SR-BI expression and lipase activity compared to that observed in the control diet-fed obese rats treated with 2.6 mg of vitamin A/kg diet. Furthermore, vitamin A supplementation at doses of 52 and 129 mg/kg diet reduced the plasma lecithin cholesterol acyltransferase activity and increased the hepatic ATP-binding cassette transporter protein A1 expression in the obese rats. Interestingly, most of these changes were not observed in the lean rats fed a vitamin A-enriched diet. Conclusions: Chronic feeding of a vitamin A-enriched diet in hypercholesterolemic obese rats normalizes the plasma HDL-C level and presumably improves RCT, with an effective dose of 52 mg/kg diet. Further studies should focus on the pharmacological potential of vitamin A supplementation to correct an abnormal human obesity-associated lipoprotein metabolism.
    Journal of atherosclerosis and thrombosis 08/2014;
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    ABSTRACT: Aim: We used quantitative coronary angiography (QCA) to investigate whether coronary plaque progression can be inhibited by controlling lipids with rosuvastatin at Japanese standard doses following elective percutaneous coronary intervention (PCI). Methods: A total of 143 patients who underwent elective PCI were randomized to either the rosuvastatin (5 or 2.5mg/day) or non-statin group. Changes from baseline in the minimal lumen diameter (MLD) and average lumen diameter (ALD) measured using QCA were analyzed in both target and non-target lesions. Results: The changes in MLD and ALD from baseline to 24 months in the non-target lesions were significantly smaller in the rosuvastatin group than in the non-statin group (-0.079±0.014 mm vs.-0.135±0.019 mm, p=0.022; -0.062±0.012 mmvs. -0.109±0.016mm, p=0.025). The changes in MLD from six to 24 months in the target lesions were significantly lower in the rosuvastatin group than in the non-statin group among the patients treated with drug-eluting stents (-0.046± 0.108 mm vs. -0.133±0.108 mm, p=0.009) versus those treated with bare-metal stents (-0.011± 0.094 mm vs. -0.015±0.040 mm, p=0.255). Conclusions: The present study demonstrated that the administration of a standard dose of rosuvastatin slows coronary plaque progression and may prevent the late catch-up phenomenon associated with drug-eluting stents in patients who undergo elective PCI.
    Journal of atherosclerosis and thrombosis 08/2014;
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    ABSTRACT: Aim: Patients with peripheral artery disease (PAD) are at a high risk of cardiovascular disease (CVD) among Western populations. However, evidence for an elevated risk in Asian populations is limited. Methods: This prospective cohort study examined 939 Japanese men 60-74 years of age at the time of the baseline survey. A total of 115 cases of CVD were detected during a median 9.3 years of follow-up, and the ankle brachial blood pressure index (ABI) functioned as a surrogate measurement of PAD. Results: The age-adjusted risks of coronary heart disease, ischemic stroke and ischemic CVD (coronary heart disease and ischemic stroke) were higher among men in the lowest ABI tertile compared with that observed in the men in the highest tertile (<1.08 vs. >1.17). These associations did not change substantially after adjusting for cardiovascular risk factors. The respective multivariable hazard ratios (HRs, 95% CI) for the three conditions were as follows: 2.48 (1.08-5.71), p for trend=0.03; 1.95 (0.94-4.02), p for trend=0.04; and 2.16 (1.25-3.72), p for trend=0.004. These results did not vary based on a comparison of the three ABI categories: ≤0.90, 0.91-1.10 and >1.10. The multivariable HRs (95% CI) for an ABI ≤0.90 versus >1.10 were as follows: 2.04 (0.67-6.20), p for trend=0.14 for coronary heart disease; 3.39 (1.10-10.5), p for trend=0.006 for ischemic stroke; and 2.61 (1.19-5.76), p for trend=0.003 for ischemic CVD. There were no associations between the ABI and the risk of hemorrhagic stroke. Conclusions: A low ABI is associated with the risk of coronary heart disease, ischemic stroke and ischemic CVD in elderly Japanese men.
    Journal of atherosclerosis and thrombosis 07/2014;
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    ABSTRACT: Aim: Population studies have shown obesity and diabetes to be risk factors for atherosclerosis. We assessed changes in the common carotid arteries in rat models of obesity and diabetes without hypertension. Methods: Twenty 30-week-old male spontaneously diabetic and obese model Otsuka Long-Evans Tokushima Fatty (OLETF) and 20 control Long-Evans Tokushima Otsuka (LETO) rats were used in the experiments. The animals were considered diabetic if the plasma glucose level peaked at >300 mg/dL and remained at >200 mg/dL for 120 minutes. Blood gas physiological parameters were continuously monitored under anesthesia, and the flow of the carotid artery was assessed with ultrasonography. All animals were sacrificed with an overdose of anesthesia at the end of the experiment. Sections of the middle portion of the internal carotid artery were cut and stained with hematoxylin and eosin to assess the overall morphology. Results: All OLETF rats were diabetic, and all LETO rats were non-diabetic. The physiological parameters did not differ significantly between the control and model rats, whereas the carotid artery wall thickness (19.3±3.2 vs. 6.1±4.5 μm) was significantly different between the two groups. The blood flow velocity in the common carotid artery determined using ultrasonography and color Doppler sonography was significantly increased during systole in the model rats compared with that observed in the control rats (203±20.3 vs. 55.3±21.4 cm/sec). Conclusions: The OLETF rats were obese, and diabetes worsened the degree of carotid artery stenosis. These results indicate the possibility of new therapies for carotid artery stenosis in obese and diabetic patients.
    Journal of atherosclerosis and thrombosis 07/2014;
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    ABSTRACT: Aim: Venous stasis is a well-known risk factor for the development of venous thromboembolism. It is likely that stasis increases the risk of thrombosis by inducing hypercoagulability via the hypoxic procoagulant activation of endothelial and mononuclear cells and the accumulation of activated clotting factors. However, increased rates of thrombin formation have not been demonstrated in response to venous stasis in vivo. Methods: In this study, we used the venous occlusion (VO) test to determine, if stasis triggers thrombin formation in healthy individuals (n=25) and patients with additional thrombotic risk factors, such as inherited thrombophilia (n=19) and symptomatic atherosclerosis (n=15). Thrombin formation was monitored by measuring plasma levels of free thrombin using a highly sensitive oligonucleotide enzyme capture assay (OECA) in addition to the plasma levels of prothrombin fragment 1+2 (F1+2) and thrombin-antithrombin-complexes (TAT). The plasma levels of activated protein C (APC) were additionally measured using an APC-OECA. Results: VO induced a significant (p<0.05) increase in the levels of tissue-type plasminogen activator and plasmin-α2-antiplasmin-complexes. In all three cohorts, the majority of samples obtained during VO showed no quantifiable thrombin or APC levels. Consistent with these findings F1+2 and TAT did not change. Conclusions: We conclude that short-term venous stasis induces a profibrinolytic response due to the activation of endothelial cells, but not a prothrombotic response, even in the presence of additional thrombophilic risk factors. Furthermore, our results support the hypothesis that the stasis-induced profibrinolytic activation of endothelial cells occurs independently from thrombin formation.
    Journal of atherosclerosis and thrombosis 07/2014;
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    ABSTRACT: Optical coherence tomography (OCT) is a catheter-based imaging system that uses near-infrared light to produce cross-sectional images of the coronary arteries. With its extraordinarily high resolution (10-20 μm), OCT allows clinicians to observe various morphological features of coronary atherosclerosis in vivo. For example, intimal thickening presents as homogeneous, signal-rich regions on OCT, while fibroatheroma with a lipid-rich necrotic core is characterized by the presence of signal-poor regions with a diffuse border. Furthermore, plaque rupture is detected in 50〜70% of culprit lesions of acute coronary syndrome (ACS), and plaque erosion develops over areas of intimal thickening and/or thick-cap fibroatheroma. Meanwhile, calcified nodules are common in older patients with hypertension and chronic renal disease. Platelet-rich thrombi are visualized as low backscattering structures and often detected in patients with unstable angina, whereas red blood cell-rich thrombi exhibit a high backscattering structure with signal-free shadowing and are frequently noted in patients with acute myocardial infarction. Moreover, OCT-derived thin cap fibroatheroma has been shown to be a predictor of subsequent plaque progression and acute coronary events, while vasa vasorum and the macrophage density are associated with a thin fibrous cap and large necrotic core as well as increased serum levels of inflammatory biomarkers. One current challenge of OCT examinations is to detect morphologic characteristics capable of discriminating vulnerable from stable plaques. The ability to detect vulnerable plaques in vivo would allow physicians to identify patients at high risk for adverse coronary events, thus significantly helping to prevent ACS.
    Journal of atherosclerosis and thrombosis 07/2014;
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    ABSTRACT: Aim: Nocturnal intermittent hypoxia (NIH), a primary marker of obstructive sleep apnea, has increasingly been linked with cardiovascular morbidity and mortality. The purpose of this study was to investigate the association between NIH and arterial stiffness as measured according to the cardio-ankle vascular index (CAVI) based on cardiovascular risk factors in a Japanese community-dwelling population. Methods: We conducted a cross-sectional study in Toon city among 684 men and 1,241 women 30-79 years of age. The severity of NIH was defined as mild or moderate-to-severe according to five or 15 events/hour on the 3% oxygen desaturation index (ODI), respectively. Increased arterial stiffness was diagnosed according to a CAVI of ≥9. Results: The number of subjects with no, mild and moderate-to-severe NIH was 1,348 (70%), 451 (23%) and 126 (7%), respectively. Increased arterial stiffness was detected in 21.9% of the participants. The multivariable-adjusted odds ratio (95% CI) of severe NIH related to an increased CAVI in comparison with a 3% ODI of <5 was 1.36 (0.82-2.23). The stratified logistic regression analysis showed that the multivariable-adjusted OR of severe NIH for an increased CAVI was remarkably increased in the individuals with a BMI of ≥25 (OR=2.53, 1.08-5.96; p=0.03). An interaction test showed a trend for an overweight status to be a modifier of the association between OSA and increased arterial stiffness (p=0.05). Conclusions: NIH has a tendency to promote increased arterial stiffness as measured according to the CAVI, especially in overweight subjects.
    Journal of atherosclerosis and thrombosis 07/2014;
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    ABSTRACT: Sitosterolaemia is caused by mutations in either ABCG5 or ABCG8. Chinese and Japanese individuals usually have mutations in ABCG5. We herein report a known and a novel mutation in ABCG8 and their potential interaction with NPC1L1 polymorphisms in a Chinese family with sitosterolaemia. We sequenced ABCG5 and ABCG8 and measured the levels of plasma plant sterols in a 15-year-old Chinese girl with clinical sitosterolaemia (xanthomas with elevated low-density lipoprotein cholesterol (LDL-C) and plant sterols) and her apparently healthy family members. NPC1L1 was sequenced in the genetically affected sibling and other family members. A known mutation, c.490C>T (p. Arg164(*)), in exon 4 and a novel mutation, c.1949T>G (p.Leu650Arg), in exon 13 of ABCG8 were detected in the proband and her sister, who had elevated sterols but low LDL-C levels and no xanthomas. The genetically affected sister, but not the proband, carried two additional heterozygous changes in NPC1L1 (rs2072183 C>G, rs2301935 A>C), which were inherited from the mother, who also had a low LDL-C level. In this study, we detected a known and a novel mutation in ABCG8 in a Chinese patient with sitosterolaemia. The same mutations were found in her clinically normal sister, suggesting that the contrasting features with the proband may be related to different variants in NPC1L1 and/or some other undetermined lipid-related genetic factors.
    Journal of atherosclerosis and thrombosis 07/2014;
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    ABSTRACT: Aim: It has been reported that oxidized low-density lipoprotein (oxLDL) forms a stable and non-dissociable complex with β2-glycoprotein I (β2GPI) and that IgG anti-β2GPI autoantibodies are able to recognize this complex, thus facilitating macrophage-derived foam cell formation in patients with antiphospholipid syndrome (APS). However, the immunopathological mechanisms of oxLDL/β2GPI complexes in promoting foam cell formation are not fully understood. In this study, we examined the role of toll-like receptor 4 (TLR4) in the oxLDL/β2GPI/anti-β2GPI complex-induced transformation of mouse peritoneal macrophages to foam cells. Methods: Oil red O staining and optical density (OD) measurements of intracellular stained oil red O solution were used to monitor the transformation of peritoneal macrophages to foam cells in TLR4-competent C3H/HeN and TLR4-mutant C3H/HeJ mice. During foam cell formation induced by the oxLDL/β2GPI/anti-β2GPI complex, the expression of TLR4 and activation of nuclear factor kappa B (NF-κB) were confirmed by analyzing the protein and mRNA levels of these compounds. Furthermore, the related active molecule expression during foam cell formation induced by the oxLDL/β2GPI/anti-β2GPI complex was examined in the presence or absence of TLR4. Results: The data showed that treatment with the oxLDL/β2GPI/anti-β2GPI complex markedly increased foam cell formation, the TLR4 expression, NF-κB activation, the tissue factor (TF) expression and tumor necrosis factor-α (TNF-α) and monocyte chemotactic protein-1 (MCP-1) secretion in the C3H/HeN mice. However, the transformation of macrophages to foam cells and the expression levels of phosphorylated NF-κB, TF, TNF-α and MCP-1 were significantly reduced in the C3H/HeJ mice treated with the oxLDL/β2GPI/anti-β2GPI complex. In addition, compared with that achieved by oxLDL alone, the oxLDL/β2GPI complex decreased foam cell formation and the related signaling molecule expression in the C3H/HeN mice. Conclusions: Our results indicate that TLR4 plays an important role in the process of oxLDL/β2GPI/anti-β2GPI complex-induced transformation of macrophages to foam cells, which may accelerate the development of atherosclerosis in the setting of APS. However, β2GPI alone functions as an antiatherogenic protein by preventing the foam cell formation induced by oxLDL.
    Journal of atherosclerosis and thrombosis 07/2014;
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    ABSTRACT: 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.
    Journal of atherosclerosis and thrombosis 06/2014;
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    ABSTRACT: 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.
    Journal of atherosclerosis and thrombosis 06/2014;
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    ABSTRACT: 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.
    Journal of atherosclerosis and thrombosis 05/2014;
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    ABSTRACT: Aim: Vascular calcification is a critical problem in patients with chronic kidney disease (CKD). In this study, we examined the effects of a HMG Co-A reductase inhibitor (statin) and an angiotensin Ⅱ type 1 receptor blocker (ARB) on renal failure-induced vascular calcification. Method and Result: Severe renal failure was induced in rats by feeding a 0.75% adenine diet for six weeks. These rats had hyperphosphatemia, hypertension and hypercholesterolemia. A histological assessment showed extensive linear calcification in the aortic media and a significant increase in the aortic content of calcium and phosphorus. Oral administration of pravastatin (a statin; 1-10 mg/kg/day) or olmesartan (an ARB; 1-10 mg/kg/day) dose-dependently inhibited the aortic calcification in parallel with their renoprotective, lipid-lowering and blood pressure-lowering effects. Of note, the lowest dose of pravastatin inhibited aortic calcification with no influence on the renal function, BP and cholesterol, suggesting that it has direct vasoprotective properties. Intriguingly, the combined administration of pravastatin and olmesartan at the lowest doses synergistically ameliorated the aortic calcification, and the protective effect was at least partly attributable to the inhibition of RF-induced apoptosis in the aortic wall. An in vitro model of inorganic phosphate (Pi)-induced vascular smooth muscle cell calcification mimicked these effects of pravastatin and olmesartan, and the beneficial effect of the combination was attributable to the inhibitory effects on Pi-induced apoptosis via the restoration of the Gas6/Axl-mediated anti-apoptotic pathway. Conclusion: A statin and an ARB exerted potent protective effects against vascular calcification due to CKD, probably through their pleiotropic effects. In addition, combination therapy with pravastatin and olmesartan may provide a new therapeutic strategy for the prevention of vascular calcification.
    Journal of atherosclerosis and thrombosis 05/2014;
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    ABSTRACT: 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.
    Journal of atherosclerosis and thrombosis 05/2014;