Journal of Atherosclerosis and Thrombosis
Online ISSN : 1880-3873
Print ISSN : 1340-3478
ISSN-L : 1340-3478
26 巻 , 3 号
選択された号の論文の8件中1~8を表示しています
Review
  • Rodrigo Alonso, Ada Cuevas, Alberto Cafferata
    2019 年 26 巻 3 号 p. 207-215
    発行日: 2019/03/01
    公開日: 2019/03/01
    [早期公開] 公開日: 2019/01/19
    ジャーナル フリー

    Statins are the main treatment for hypercholesterolemia and the cornerstone of atherosclerotic cardiovascular disease prevention. Many patients taking statins report muscle-related symptoms, one of the most important causes of statin treatment discontinuation, which is associated with an increased risk of cardiovascular events. Therefore, it is important to identify patients who are truly statin intolerant to avoid unnecessary discontinuation of this beneficial treatment. Some studies indicate that not all muscle complaints are caused by statins, and most patients can tolerate a statin upon re-challenge, down-titration of dose, or switching to another statin. In this paper, we review the definitions of statin intolerance and approaches to reducing cardiovascular risk among individuals reporting statin-associated muscle symptoms.

  • Masato Furuhashi
    2019 年 26 巻 3 号 p. 216-232
    発行日: 2019/03/01
    公開日: 2019/03/01
    [早期公開] 公開日: 2019/02/07
    ジャーナル フリー

    Fatty acid-binding proteins (FABPs), a family of lipid chaperones, contribute to systemic metabolic regulation via several lipid signaling pathways. Fatty acid-binding protein 4 (FABP4), known as adipocyte FABP (A-FABP) or aP2, is mainly expressed in adipocytes and macrophages and plays important roles in the development of insulin resistance and atherosclerosis in relation to metabolically driven low-grade and chronic inflammation, referred to as ‘metaflammation’. FABP4 is secreted from adipocytes in a non-classical pathway associated with lipolysis and acts as an adipokine for the development of insulin resistance and atherosclerosis. Circulating FABP4 levels are associated with several aspects of metabolic syndrome and cardiovascular disease. Ectopic expression and function of FABP4 in cells and tissues are also related to the pathogenesis of several diseases. Pharmacological modification of FABP4 function by specific inhibitors, neutralizing antibodies or antagonists of unidentified receptors would be novel therapeutic strategies for several diseases, including obesity, diabetes mellitus, atherosclerosis and cardiovascular disease. Significant roles of FABP4 as a lipid chaperone in physiological and pathophysiological conditions and the possibility of FABP4 being a therapeutic target for metabolic and cardiovascular diseases are discussed in this review.

Original Article
  • Kazuo Omori, Naoto Katakami, Yuichi Yamamoto, Hiroyo Ninomiya, Mitsuyo ...
    2019 年 26 巻 3 号 p. 233-245
    発行日: 2019/03/01
    公開日: 2019/03/01
    [早期公開] 公開日: 2018/08/01
    ジャーナル フリー

    Aim: Coronary artery disease (CAD) is the result of a complex metabolic disorder caused by various environmental and genetic factors. Metabolomics is a potential tool for identifying biomarkers for better risk classification and for understanding the pathophysiological mechanisms of CAD. With this background, we performed a pilot study to identify metabolites associated with the future onset of CAD in patients with type 2 diabetes.

    Methods: Sixteen subjects who suffered from CAD event during the observation period and 39 non-CAD subjects who were matched to the CAD subjects for Framingham Coronary Heart Disease Risk Score, diabetes duration, and HbA1c were selected. Capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS) was used to perform non-targeted metabolome analysis of serum samples collected in 2005.

    Results: A total of 104 metabolites were identified. Unsupervised principal component analysis (PCA) did not to reveal two distinct clusters of individuals. However, a significant association with CAD was found for 7 metabolites (pelargonic acid, glucosamine:galactosamine, thymine, 3-hydroxybutyric acid, creatine, 2-aminoisobutyric acid, hypoxanthine) and the levels of all these metabolites were significantly lower in the CAD group compared with the non-CAD group.

    Conclusions: We identified 7 metabolites related to long-term future onset of CAD in Japanese patients with diabetes. Further studies with large sample size would be necessary to confirm our findings, and future studies using in vivo or in vitro models would be necessary to elucidate whether direct relationships exist between the detected metabolites and CAD pathophysiology.

  • Hisataka Yamazaki, Manabu Takahashi, Tetsuji Wakabayashi, Kent Sakai, ...
    2019 年 26 巻 3 号 p. 246-259
    発行日: 2019/03/01
    公開日: 2019/03/01
    [早期公開] 公開日: 2018/10/04
    ジャーナル フリー

    Aim: Acyl-CoA cholesterol acyltransferase 1 (ACAT1) esterifies free cholesterol to cholesteryl esters (CE), which are subsequently hydrolyzed by neutral cholesterol ester hydrolase 1 (NCEH1). The elimination of ACAT1 in vitro reduces the amounts of CE accumulated in Nceh1-deficient macrophages. The present study aimed at examining whether the loss of ACAT1 attenuates atherosclerosis which is aggravated by the loss of NCEH1 in vivo.

    Methods: Low density lipoprotein receptor (Ldlr)-deficient mice were transplanted with bone marrow from wild-type mice and mice lacking ACAT1, NCEH1, or both. The four types of mice were fed a high-cholesterol diet and, then, were examined for atherosclerosis.

    Results: The cross-sectional lesion size of the recipients of Nceh1-deficient bone marrow was 1.6-fold larger than that of the wild-type bone marrow. The lesions of the recipients of Nceh1-deficient bone marrow were enriched with MOMA2-positive macrophages compared with the lesions of the recipients of the wild-type bone marrow. The size and the macrophage content of the lesions of the recipients of bone marrow lacking both ACAT1 and NCEH1 were significantly smaller than the recipients of the Nceh1-deficient bone marrow, indicating that the loss of ACAT1 decreases the excess CE in the Nceh1-deficient lesions. The collagen-rich and/or mucin-rich areas and en face lesion size were enlarged in the recipients of the Acat1-/- bone marrow compared with those of the recipients of the WT bone marrow.

    Conclusion: The loss of ACAT1 in bone marrow-derived cells attenuates atherosclerosis, which is aggravated by the loss of NCEH1, corroborating the in vitro functions of ACAT1 (formation of CE) and NCEH1 (hydrolysis of CE).

  • Yaping Yuan, Jiajia Yang, Xu Zhang, Renfang Han, Mengya Chen, Xingxing ...
    2019 年 26 巻 3 号 p. 260-271
    発行日: 2019/03/01
    公開日: 2019/03/01
    [早期公開] 公開日: 2018/08/08
    ジャーナル フリー

    Aim: Inflammatory arthritis (IA) diseases are relevant with subclinical atherosclerosis, but the data in ankylosing spondylitis (AS) were inconsistent. Therefore, we performed this meta-analysis to explore the relationship between the marker of subclinical atherosclerosis (carotid intima-media thickness (IMT)) and AS.

    Methods: We performed a systematic literature review using PubMed, Web of Science, Chinese National Knowledge Infrastructure (CNKI) and Chinese Biomedical Database (CBM) databases up to March 2018. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated to assess the association between carotid IMT and AS. Subgroup analysis, sensitivity analysis, and meta-regression were applied to explore the sources of heterogeneity, and publication bias was calculated to access the quality of pooled studies.

    Results: A total of 24 articles were collected. The carotid IMT was significantly increased in AS compared with healthy controls (SMD=0.725, 95% CI=0.443–1.008, p<0.001). Subgroup analyses showed the Bath Ankylosing Spondylitis Activity Index (BASDAI) was the source of heterogeneity. Notably, IMT was not significantly increased in those studies that included >50% patients treated with anti-TNF. Meta-regression revealed severe inflammation status (BASDAI and C-reactive protein (CRP)) could significantly impact carotid IMT in AS.

    Conclusions: Carotid IMT was significantly increased in patients with AS compared with healthy controls, which suggested subclinical atherosclerosis is related to AS.

  • Shusuke Yagi, Daisuke Kondo, Takayuki Ise, Daiju Fukuda, Koji Yamaguch ...
    2019 年 26 巻 3 号 p. 272-281
    発行日: 2019/03/01
    公開日: 2019/03/01
    [早期公開] 公開日: 2018/08/21
    ジャーナル フリー

    Aim: It is speculated that statin therapy modulates the synthesis of polyunsaturated fatty acids (PUFA), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). However, the data available on the effects of statin therapy on the serum levels of PUFA and the subsequent impact on in-stent restenosis (ISR) in patients with acute coronary syndrome (ACS) are limited.

    Methods: A total of 120 ACS patients who received emergent coronary stent implantation, follow-up coronary angiography to evaluate ISR, and new statin therapy were enrolled. We measured the serum levels of the PUFA and lipids at the onset of ACS and at the follow-up coronary angiography.

    Results: The follow-up coronary angiography revealed 38 ISR cases. New statin therapy significantly reduced the serum levels of DHA and low-density lipoprotein cholesterol (LDL-C), while it did not affect EPA level. Single regression analysis revealed that a decreased serum level of LDL-C was associated with decreased DHA level. The multiple logistic regression analysis revealed that the decreased DHA level after statin therapy and low serum level of EPA on admission were determinants of prevalence of ISR.

    Conclusion: Statin therapy decreased the serum level of DHA with a parallel reduction in LDL-C level in patients with ACS. Decreased DHA level after statin therapy and low EPA level on admission are risk factors for ISR, indicating that in patients with ACS, decreased serum levels of DHA may be a residual target for the prevention of ISR.

  • Tamio Teramoto, Makiko Usami, Yoshiharu Takagi, Marie T. Baccara-Dinet ...
    2019 年 26 巻 3 号 p. 282-293
    発行日: 2019/03/01
    公開日: 2019/03/01
    [早期公開] 公開日: 2018/08/01
    ジャーナル フリー

    Aim: To examine the efficacy and safety of alirocumab in Japanese patients with dyslipidemia with or without diabetes mellitus (DM).

    Methods: Patients (n=216) with heterozygous familial hypercholesterolemia (heFH), non-FH at high cardiovascular risk with coronary artery disease (CAD), or category III (primary prevention) were enrolled; 148 (68.5%) patients had a diagnosis of DM at baseline. Patients were randomized (2:1), with stratification factor (heFH, non-FH), to alirocumab (75 mg every 2 weeks [Q2W] with increase to 150 mg if week 8 LDL-C was above predefined limits) or placebo subcutaneously for 52 weeks on top of stable statin therapy.

    Results: At Week 24, least square (LS) mean±standard error changes in low-density lipoprotein cholesterol (LDL-C) concentration from baseline in alirocumab-treated patients were -63.1±1.6% and -60.8±2.7% in those with and without DM. These LDL-C reductions were maintained to Week 52: -63.0±1.6% (LS mean difference vs placebo -62.4±3.0%; P<0.0001) with DM and -61.3±2.8% (LS mean difference vs placebo -53.4±4.0%; P<0.0001) without DM. The most common adverse events in the alirocumab group were nasopharyngitis, back pain, injection site reaction, and fall. No particular safety signals or concerns were noted between DM and non-DM groups at 52 weeks. A dose-increase in alirocumab from 75 to 150 mg Q2W was necessary in two heFH patients, neither of whom had DM.

    Conclusions: In high-cardiovascular-risk Japanese patients with hypercholesterolemia on stable statin therapy, alirocumab produced substantial and sustained LDL-C reductions throughout the 52-week study regardless of DM status at baseline, with a similar safety profile to placebo.

  • Masashi Fukunaga, Daizo Kawasaki, Machiko Nishimura, Masanao Yamagami, ...
    2019 年 26 巻 3 号 p. 294-301
    発行日: 2019/03/01
    公開日: 2019/03/01
    [早期公開] 公開日: 2018/08/21
    ジャーナル フリー

    Aim: The aim of this study was to investigate the clinical effect of planned endovascular therapy (EVT) for critical limb ischemia (CLI) patients with tissue loss. Although several rounds of EVT for CLI patients are required for complete wound healing, time required for complete wound healing depends on the wound severity. We hypothesized that planned EVT might reduce the time to wound healing.

    Methods: A total of 89 limbs of 76 CLI patients with tissue loss, who had undergone more than at least two EVTs were included in this study. From January 2013 through December 2015 (Conventional-EVT-group, 52 limbs), indication of target lesion revascularization (TLR) was decided based on decreased skin perfusion pressure (SPP) values or delayed wound healing. From January 2016 through October 2016 (Planned-EVT-group, 37 limbs), TLR were done every two months regardless of the SPP values until complete wound healing was obtained. Time to wound healing and complete wound healing rates were compared between the two groups.

    Results: No significant differences existed in baseline patients and lesion characteristics between the two groups. There was no significant difference in total EVT numbers between the two groups (2.0; interquartile range, 2.0–3.0 versus 2.0; interquartile range, 2.0–3.0; P=0.9). Although complete wound healing rate was similar in both groups (71.2% versus 73.0%, p=1.0), time to wound healing was significantly shorter (95 days versus 143 days, p=0.025) in the Planned-EVT-group than in the Conventional-EVT-group.

    Conclusions: Planned-EVT is a useful strategy to shorten the time to wound healing for CLI patients with tissue loss.

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