Journal of Atherosclerosis and Thrombosis
Online ISSN : 1880-3873
Print ISSN : 1340-3478
ISSN-L : 1340-3478
Volume 26 , Issue 4
Showing 1-8 articles out of 8 articles from the selected issue
  • Hisanori Horiuchi, Tsuyoshi Doman, Koichi Kokame, Yoshikatsu Saiki, Ma ...
    2019 Volume 26 Issue 4 Pages 303-314
    Published: April 01, 2019
    Released: April 01, 2019
    [Advance publication] Released: March 12, 2019

    The blood glycoprotein von Willebrand factor (VWF) plays an important role in hemostasis and thrombosis.VWF is produced and secreted as large multimers by endothelial cells and megakaryocytes. It is then cleaved in a sheer-stress dependent manner by a specific protease, ADAMTS13, into multimers consisting of 2–80 subunits. Among VWF multimers, high molecular weight (HMW) multimers play important roles in platelet aggregation. Therefore, their loss induces a hemostatic disorder known as von Willebrand disease (VWD) type 2A. Various cardiovascular diseases, such as aortic stenosis, hypertrophic obstructive cardiomyopathy (HOCM), and several congenital structural diseases, as well as mechanical circulatory support systems, generate excessive high shear stress in the bloodstream. These cause excessive cleavage of VWF multimers resulting in a loss of HMW multimers, known as acquired von Willebrand syndrome (AVWS), a hemostatic disorder similar to VWD type 2A. Bleeding often occurs in the gastrointestinal tract since a fragile angiodysplasia develops associated with these diseases. Radical treatment for AVWS is to remove the pathological high shear causing AVWS.

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  • Akiomi Yoshihisa, Yasuchika Takeishi
    2019 Volume 26 Issue 4 Pages 315-327
    Published: April 01, 2019
    Released: April 01, 2019
    [Advance publication] Released: February 28, 2019

    Sleep disordered breathing (SDB), which causes sleep deprivation, intermittent hypoxia, and negative intrathoracic pressure swings, can be accompanied by other harmful pathophysiologies relating to cardiovascular diseases (CVD), including sudden death, atrial fibrillation, stroke, and coronary artery disease leading to heart failure. Continuous positive airway pressure (CPAP) therapy for SDB has been reported to provide favorable effects such as lowered systemic blood pressure and improved endothelial function. However, in recent randomized controlled trials, CPAP has failed to demonstrate its beneficial prognostic impact on the primary or secondary setting of CVD. In this review article, we describe the characteristics of SDB complicated with CVD, the prognostic impacts of SDB in CVD, and the beneficial effects of CPAP on CVD.

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Original Article
  • Hiroki Kobayashi, Hiromasa Otsuka, Mitsuru Yanai, Motohiko Hara, Mikan ...
    2019 Volume 26 Issue 4 Pages 328-339
    Published: April 01, 2019
    Released: April 01, 2019
    [Advance publication] Released: August 22, 2018

    Aim: Adiponectin exhibits its biological effects through adiponectin receptors (AdipoR1 and AdipoR2), which are distributed in the kidneys, and activation of those receptors could prevent or ameliorate diabetic nephropathy. This study aimed to evaluate the associations between AdipoR single nucleotide polymorphisms (SNPs) and kidney function in an elderly Japanese population.

    Methods: A total of 271 elderly Japanese volunteers underwent anthropometric and laboratory tests (cystatin C-based eGFR and total and high molecular weight adiponectin levels at baseline and a follow-up visit). Genotype data were obtained for the selected 7 and 5 AdipoR1 and AdipoR2 SNPs, respectively.

    Results: In a cross-sectional analysis at baseline, we found a significant association between the AdipoR2 SNP rs12230440 and kidney function; eGFRcys tended to increase as the number of carriers of T alleles increased after adjustment for covariates and Bonferroni correction, although the association of the SNP and annual eGFR decline could not be identified in the longitudinal data. Regarding the variants rs16850797, rs11061925, and rs10773983, each of the allele G, allele C, and allele G showed nominally significant associations with higher eGFRcys. However, this failed to reach significance after Bonferroni correction.

    Conclusion: Here, an AdipoR2 SNP was associated with kidney function, suggesting that the effects of this polymorphism on adiponectin receptor may affect kidney function in the elderly Japanese population.

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  • Masato Nishimura, Toshiko Tokoro, Toru Takatani, Nodoka Sato, Tetsuya ...
    2019 Volume 26 Issue 4 Pages 340-350
    Published: April 01, 2019
    Released: April 01, 2019
    [Advance publication] Released: August 15, 2018

    Aim: Type Ⅲ collagen abundantly exists in the cardiovascular system, including the aorta and heart. We prospectively investigated whether serum levels of aminoterminal propeptide of type Ⅲ procollagen (PⅢNP), a circulating biomarker of cardiovascular fibrosis, could predict cardiovascular events in patients undergoing hemodialysis.

    Methods: Serum PⅢNP concentrations were measured in 244 patients undergoing maintenance hemodialysis (men, 126; women, 118; mean age, 64±11 years; dialysis duration, 11.5±7.8 years) by immunoradiometric assay in February 2005. The endpoint was cardiovascular events, and the patients were followed up until the endpoint was reached, or until January 31, 2011.

    Results: During the follow-up for 4.7±1.8 years, cardiovascular events occurred in 78 (30.3%) of 244 patients. Stepwise Cox hazard analysis revealed that cardiovascular events were associated with increased serum PⅢNP concentration (1 U/mL; hazard ratio, 1.616; P=0.0001). The median serum PⅢNP concentrations were higher in patients with cardiovascular events than in those without (2.30±0.19 U/mL vs 1.30±0.03 U/mL; P<0.0001). When the patients were assigned to subgroups based on serum PⅢNP cut-off value for cardiovascular events of 1.75 U/mL, defined by receiver operating characteristic analysis, cardiovascular event-free survival rates at 5 years were lower (P=0.0001) in the subgroup of serum PⅢNP ≥1.75 U/mL than in that of serum PⅢNP <1.75 U/mL (31.9% vs 88.2%).

    Conclusions: Serum PⅢNP could be a new biomarker for predicting the cardiovascular events in patients undergoing hemodialysis.

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  • Demet Ozkaramanli Gur, Ozcan Gur, Savas Guzel, Aydin Akyuz, Selami Gur ...
    2019 Volume 26 Issue 4 Pages 351-361
    Published: April 01, 2019
    Released: April 01, 2019
    [Advance publication] Released: September 25, 2018

    Aim: Peripheral artery disease (PAD) is a manifestation of atherosclerosis with poor prognosis. It is generally complicated by vascular calcification, which is located either in the intima as patchy infiltrates; or circumferentially in the media, also known as medial arterial calcification (MAC). Obstructive PAD is reflected by low anklebrachial index (ABI ≤ 0.9), whereas MAC is revealed by high ABI (ABI >1.4). Considering the increase in cardiovascular mortality at both ends of the ABI spectrum, this study aimed to explore the underlying pathology through cytokines with established prognostic significance; namely pentraxin-3(PTX3), high sensitivity C-reactive protein (hsCRP), copeptin, soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), NT-proBNP, and neopterin.

    Methods: We categorized 180 patients with previous multivessel coronary artery bypass grafting surgery into three groups based on their ABI measurements; 60 patients with ABI ≤ 0.9, 60 patients with ABI within 0.91 and 1.4 (normal ABI), and 60 patients with ABI >1.4 constituted the “PAD,” “normal,” “MAC” groups, respectively. The circulating levels of the biochemical markers were determined.

    Results: In the PAD group, the cytokine levels with predominantly proatherogenic actions such as PTX3, hsCRP, copeptin, and sTREM-1 were increased and these cytokine levels declined as the ABI increased. In the MAC group, the cytokine concentrations with pleiotropic actions such as NT-proBNP and neopterin increased and; NT-proBNP and neopterin concentrations decreased as ABI decreased. The linear regression analysis revealed that neopterin (β=0.72), PTX3 (β=-0.32), and copeptin (β=-0.48) were independent predictors of ABI.

    Conclusions: These findings suggest that different inflammatory pathways influence the pathology at the opposing ends of the ABI spectrum. Consequently, we suggest that PTX3, copeptin, and neopterin are promising biomarkers for future research.

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  • Yuichi Saito, Hideki Kitahara, Takashi Nakayama, Yoshihide Fujimoto, Y ...
    2019 Volume 26 Issue 4 Pages 362-367
    Published: April 01, 2019
    Released: April 01, 2019
    [Advance publication] Released: September 13, 2018

    Aim: Serum uric acid (SUA) level is known to have a prognostic value in patients with acute coronary syndrome (ACS). Endothelial function plays an important role in the development of cardiovascular disease. Although relation between SUA level and endothelial function has been previously studied in various populations, it is partially understood in patients with ACS.

    Methods: A total of 55 patients with ACS with measurements of SUA level and reactive hyperemia index (RHI) to evaluate endothelial function were included. They were classified into three groups according to the tertiles of SUA level. The tertiles of SUA level were as follows: low tertile, ≤ 5.2 mg/dl; intermediate tertile, 5.3 to 6.5 mg/dl; and high tertile, ≥ 6.6 mg/dl.

    Results: Mean SUA level and RHI were 5.8±1.5 mg/dl and 1.88±0.58. There was a significant negative correlation between SUA level and RHI (r=0.41, p=0.002). RHI was stepwisely observed in favor of the higher tertile groups (2.14±0.74 vs. 1.84±0.45 vs. 1.67±0.38, p=0.04). Multivariate analysis showed elevated SUA level as an independent predictor of reduced RHI.

    Conclusion: Elevated SUA level was significantly associated with endothelial dysfunction in patients with ACS, possibly leading to subsequent poor outcomes following ACS.

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  • Atsushi Nohara, Yoshihiko Otsubo, Koji Yanagi, Masayuki Yoshida, Katsu ...
    2019 Volume 26 Issue 4 Pages 368-377
    Published: April 01, 2019
    Released: April 01, 2019
    [Advance publication] Released: September 26, 2018

    Aim: Lomitapide is an approved lipid-lowering agent indicated as adjunct to low-fat diet and standard lipid-lowering therapies (LLTs) including lipoprotein apheresis for the treatment of homozygous familial hypercholesterolemia (HoFH). Clinical data from Phase 3 studies have demonstrated the prolonged lipid-lowering capacity of lomitapide in patients with HoFH. We assessed the long-term lipid-lowering capacity of daily oral lomitapide in a cohort of Japanese patients with HoFH enrolled in a Phase 3 extension study.

    Methods: Five of 8 Japanese HoFH patients completing a 56-week Phase 3 dose-escalation and safety study of lomitapide continued their maximum tolerated dose (MTD) until study drug was approved or commercially available or until treatment was discontinued. Lipid parameters were measured at Day 1 and at 12-week intervals through study end. Safety and tolerability were assessed.

    Results: Daily lomitapide treatment with permitted LLTs maintained approximately 50% mean reductions in plasma low-density lipoprotein cholesterol (LDL-C) levels from baseline for >60 weeks. Reductions in LDL-C levels varied across patients and were not associated with the HoFH genotype. Four patients achieved >25% reductions and 1 patient achieved >50% reduction in LDL-C; 2 patients achieved reduction in LDL-C to <100 mg/dL. Lomitapide significantly reduced total cholesterol (-26.5%), triglycerides (-54.8%), and non-high-density lipoprotein cholesterol (non-HDL-C) (-37.4%). All 5 patients continued their individual MTD of lomitapide throughout the extension study with acceptable safety and tolerability, and no deaths were reported.

    Conclusion: Results from this extension study support the long-term safety and efficacy of lomitapide in significantly reducing plasma levels of atherosclerotic lipids in patients with HoFH.

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  • Xuewei Xie, Xianwei Wang, Zixiao Li, Xingquan Zhao, Zhongrong Miao, Li ...
    2019 Volume 26 Issue 4 Pages 378-387
    Published: April 01, 2019
    Released: April 01, 2019
    [Advance publication] Released: October 12, 2018

    Aim: The impact of international normalized ratio (INR) on prognosis after acute ischemic stroke without anticoagulation therapy is unclear. Herein, the association between baseline INR and stroke outcomes in patients without anticoagulation therapy was investigated.

    Methods: A total of 14,782 ischemic stroke patients from the China National Stroke Registry Ⅱ were included in this analysis. The period of follow-up was 1 year after stroke onset. Multivariate logistic regression models were used to estimate the relationship between INR and stroke outcomes including all-cause death, recurrent stroke, composite end point, and poor functional outcome.

    Results: Of 14,782 patients with stroke, all-cause death occurred in 1080 (7.3%), recurrence stroke in 538 (3.9%), combined end point in 1319 (8.9%), and poor functional outcome in 3001 (20.3%). Compared with the medium INR group (0.9–1.1), the odds ratios with confidence intervals of 95% for the high INR group (>1.1) were 1.58 (1.32–1.98) for all-cause death, 1.40 (1.10–1.79) for stroke recurrence, 1.52 (1.29–1.79) for combined end point, and 1.21 (1.06–1.39) for poor functional outcome. No association between low INR (<0.9) and any stroke outcomes was found compared with the medium group.

    Conclusions: Increased admission INR was associated with adverse stroke outcomes among acute ischemic stroke patients without atrial fibrillation or anticoagulation therapy.

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