Journal of Atherosclerosis and Thrombosis
Online ISSN : 1880-3873
Print ISSN : 1340-3478
ISSN-L : 1340-3478
早期公開論文
早期公開論文の63件中51~63を表示しています
  • Yoshimitsu Soga, Masahiko Fujihara, Yusuke Tomoi, Osamu Iida, Takayuki ...
    原稿種別: Original Article
    論文ID: 50369
    発行日: 2019年
    [早期公開] 公開日: 2019/06/29
    ジャーナル フリー 早期公開

    Aim: Paclitaxel-eluting stents' (Eluvia and Zilver PTX) effectiveness has been recently reported for femoropopliteeal (FP) lesions. However, there is no evaluation of one-year late lumen loss (LLL). Therefore, we evaluated one-year LLL after implantation with Eluvia or Zilver PTX.

    Methods: This was a multicenter, prospective study. Patients who had symptomatic de novo lesions in the native FP artery were enrolled. The primary endpoint was one-year angiographic LLL, and the secondary endpoints were binary restenosis and target lesion revascularization (TLR) at one year.

    Results: From December 2015 to December 2016, 48 patients (Eluvia, 36 patients; Zilver PTX, 12 patients) were enrolled. No significant difference was found in baseline and lesion characteristics between both groups. One-year, LLL was significantly lower in the Eluvia group (0.60 {plus minus}0.80 mm) than in the Zilver PTX group (1.74 {plus minus}0.89 mm) (P=0.0003). Negative LLL was observed only in the Eluvia group (0% vs. 23%, p=0.096). The binary restenosis rate was significantly lower than in the Zilver PTX group (0% vs. 16.7%, P=0.012). The one-year TLR in the Eluvia group tended to be lower (0% vs. 8.3%, P=0.08). Stent thrombosis was not observed in either group.

    Conclusion: One-year LLL in the Eluvia group was significantly lower than that in the Zilver PTX group for FP lesions.

  • Hidetaka Itoh, Hidehiro Kaneko, Hiroyuki Kiriyama, Yuriko Yoshida, Kok ...
    原稿種別: Original Article
    論文ID: 48728
    発行日: 2019年
    [早期公開] 公開日: 2019/06/22
    ジャーナル フリー 早期公開

    Aim: Obesity and metabolic syndrome (MetS) frequently coexist and are both important risk factors for cardiovascular disease. However, the pathophysiological role of obesity without MetS, also referred to as metabolically healthy obesity (MHO), remains unclear. In this study, we aim to clarify the effect of MHO on the development of carotid plaque using a community-based cohort.

    Methods: We examined 1,241 subjects who underwent health checkups at our institute. Obesity was defined by a body mass index of ≥ 25.0 kg/m2. Subjects were divided into three groups: non-obese, MHO, and metabolically unhealthy obesity (MUO).

    Results: The prevalence of carotid plaque, defined as intima-media thickness (IMT) ≥ 1.1 mm, was higher in subjects with MUO and MHO than in non-obese subjects. Multivariable analysis demonstrated that MHO (odds ratio 1.6, p=0.012) and MUO (odds ratio 1.9, p=0.003) as well as age of ≥ 65 years, male sex, hypertension, and diabetes mellitus were independently associated with carotid plaque formation. A similar trend was observed in each subgroup according to age and sex.

    Conclusions: MHO increased the prevalence of carotid plaque when compared with non-obese subjects, suggesting the potential significance of MHO in the development of subsequent cardiovascular diseases.

  • Hirofumi Tomiyama
    分野: Editorial
    論文ID: ED113
    発行日: 2019年
    [早期公開] 公開日: 2019/06/22
    ジャーナル フリー 早期公開
  • Yae Matsuo, Hisao Kumakura, Hiroyoshi Kanai, Toshiya Iwasaki, Shuichi ...
    分野: Original Article
    論文ID: 49767
    発行日: 2019年
    [早期公開] 公開日: 2019/06/19
    ジャーナル フリー 早期公開

    Aim: The Geriatric Nutritional Risk Index (GNRI) was developed to assess the nutritional risk and is associated with mortality. However, there are limited reports on the relationship between the GNRI and overall survival (OS) in peripheral artery disease (PAD). Therefore, the purpose of this study was to examine the relationship between GNRI and OS and cardiovascular or limb events in patients with PAD.

    Methods: A prospective cohort study was performed on 1,219 patients with PAD. The baseline GNRI was calculated from the serum albumin level and body mass index obtained at the first visit. The patients were divided into four groups according to the GNRI: G0 (>98), G1 (92–98), G2 (82–91), and G3 (<82). The endpoints were OS and freedom from major adverse cardiovascular events (MACE) and MACE plus limb events (MACLE).

    Results: The median follow-up period was 73 months. There were 626 deaths (51.4%) during the follow-up. The rate of cardiovascular death was 51.3%. OS clearly depended on the GNRI (p<0.01), with five-year OS rates of 80.8% for G0, 62.0% for G1, 40.0% for G2, and 23.3% for G3. In multivariate analyses, the GNRI, age, ankle–brachial pressure index (ABPI), critical limb ischemia, estimated glomerular filtration rate (eGFR), and C-reactive protein (CRP) were independent factors associated with OS, and GNRI, age, ABPI, coronary artery disease, diabetes mellitus, eGFR, and CRP were associated with MACE and MACLE (all p<0.05). Statins were found to improve OS, MACE, and MACLE (p<0.01).

    Conclusions: GNRI is an independent predictor for OS, MACE, and MACLE in patients with PAD.

  • Daisuke Sugiyama, Tanvir Chowdhury Turin, Fahmida Yeasmin, Nahid Rum ...
    原稿種別: Original Article
    論文ID: 49098
    発行日: 2019年
    [早期公開] 公開日: 2019/06/18
    ジャーナル フリー 早期公開

    Aim: Lifetime risk (LTR) is a measure of disease burden, which presents the probability of occurrence of a specific disease in the remaining lifetime of a group of people for a given index age. This measure is useful for presenting the risk dynamics of a disease at the population level, which constitutes important public health information toward prevention. To date, there have been no studies investigating the LTR for coronary heart diseases (CHDs) in relation to hypercholesterolemia in Asian populations. Therefore, we estimated the LTR of CHDs according to serum low-density lipoprotein cholesterol (LDL-C).

    Methods: The participants included in this study were 2,559 men and 2,848 women, enrolled in the Suita Cohort Study of urban residents followed up from 1989 to 2007 for a total of 69,823 person-years. We estimated the sex- and index-age-specific LTR for the first CHD event among participants with or without hypercholesterolemia (LDL-C ≥ 160 mg/dL), accounting for the competing risk for mortality.

    Results: For men with hypercholesterolemia, the LTR was 47.2% (95% confidence interval [CI]: 29.3–65.1%) and 44.5% (95% CI: 21.4–68.5%) for those aged 45 and 75, respectively. The LTRs of women with hypercholesterolemia were also higher than of those without hypercholesterolemia. However, their LTRs were lower for all index ages compared to men. These results did not differ for hypercholesterolemia defined by non-high-density lipoprotein cholesterol.

    Conclusions: The presence of hypercholesterolemia increases the LTR for CHDs in the Japanese population, especially in men. This estimate can be used in preventive knowledge translation efforts at the population level.

  • Jong-Ho Park, Bruce Ovbiagele
    原稿種別: Original Article
    論文ID: 49304
    発行日: 2019年
    [早期公開] 公開日: 2019/06/12
    ジャーナル フリー 早期公開

    Aims: Low-density lipoprotein (LDL)-lowering statin therapy is an established secondary stroke prevention strategy. However, the differential impact of key non-LDL levels on recurrent stroke risk, while on lipid-modifying therapy (LT), remains unclear.

    Methods: We analyzed the dataset of a multicenter trial involving 3640 recent (<4 months) noncardioembolic stroke patients followed for 2 years. Participants were categorized into four groups of presumed improving lipid profile: level 0, no LT prescribed; level I, LT use with low high-density lipoprotein cholesterol (HDL-C) (<40 mg/dL for men; <50 mg/dL for women); level II, LT use with high HDL-C (≥ 40 mg/dL and ≥ 50 mg/dL, respectively); and level III, level II with low triglycerides (<150 mg/dL). Independent associations of LT category with stroke, major vascular events (MVEs; stroke/coronary heart disease/vascular death), and all-cause death were assessed.

    Results: LTs were mostly statins (>95%). The unadjusted recurrent stroke rate declined with LT category level (9.2% for level 0; 8.4% for level I; 7.5% for level II; and 5.7% for level III). Compared with level 0, the adjusted hazard ratio of stroke for level I was 0.78 (95% confidence interval (CI), 0.59–1.03), level II 0.80 (0.54–1.18), and level III 0.63 (0.43–0.91). Multivariable analyses of MVEs and all-cause death followed a similar pattern of declining risk with higher LT category level.

    Conclusions: Compared with the nonuse of LT, there may be a hierarchy of residual vascular risk after stroke by non-LDL type and target, while on LT. Particularly, stroke patients with low HDL-C levels on LT may benefit from additional therapeutic strategies to improve their outcomes.

  • Hideki Ishii
    原稿種別: Editorial
    論文ID: ED114
    発行日: 2019年
    [早期公開] 公開日: 2019/06/12
    ジャーナル フリー 早期公開
  • Xin-Wei He, Ying Zhao, Yan-Hui Shi, Rong Zhao, Yi-Sheng Liu, Yue Hu, M ...
    原稿種別: Original Article
    論文ID: 47704
    発行日: 2019年
    [早期公開] 公開日: 2019/05/30
    ジャーナル フリー 早期公開

    Aim: Studies have suggested that genetic and environmental factors do not account for all risks and mechanisms of intracranial atherosclerotic stenosis (ICAS). DNA methylation may play a role in the progression of ICAS.

    Methods: DNA methylation profiles of peripheral blood leucocytes from 7 patients with early-onset ICAS and 7 perfectly matched controls were interrogated for the first time using the Illumina Infinium Human MethylationEPIC BeadChip. Afterward, functional analysis for differentially methylated genes was conducted. In addition, pyrosequencing verification was performed in an independent cohort comprising 21 patients with early-onset ICAS and 21 age- and gender-matched controls.

    Results: A total of 318 cytosine-phosphate-guanine sites were found to be differentially methylated based on the established standards. Functional analysis annotated differentially methylated sites to atherosclerosis-related processes and pathways, such as the negative regulation of hydrolase activity (GO 0051346), type II diabetes mellitus (KEGG hsa04930), and the insulin signaling pathway (KEGG hsa04910). In addition, a differentially methylated site was also validated, cg22443212 in gene Rnf213, which showed significant hypermethylation in patients with early-onset ICAS compared with controls 59.56% (49.77%, 88.55%) vs. 44.65% (25.07%, 53.21%), respectively; P=0.010). Receiver operating characteristic curve analysis showed that the area under the curve value of cg22443212 was 0.744 (95% confidence interval, 0.586–0.866; P=0.002).

    Conclusions: We revealed that altered DNA methylation may play a role in the occurrence and development of ICAS. These results provided new epigenetic insights into ICAS.

  • Yuichi Sasaki, Yoshiyuki Ikeda, Takahiro Miyauchi, Yoshihiro Uchikado, ...
    原稿種別: Original Article
    論文ID: 47993
    発行日: 2019年
    [早期公開] 公開日: 2019/05/18
    ジャーナル フリー 早期公開

    Aim: Menopause causes arterial senescence and atherosclerotic development through decrease of estrogen. Recently, histone deacetylase SIRT1 has been reported to have protective effects against arterial senescence and atherosclerosis. However, the relationship between estrogen and SIRT1 in the context of menopause-induced arterial senescence is not well understood. The present study aims to investigate whether SIRT1 is involved in the etiology of menopause-induced arterial senescence and atherosclerotic development.

    Methods: Twelve-week old female apolipoprotein E-knockout (ApoE-KO) mice underwent ovariectomy (OVX) or sham surgery.

    Results: SIRT1 expression and endothelial nitric oxide synthase (eNOS) activation in the aorta were significantly lower in OVX mice than they were in sham mice (OVX vs. sham, n=5 per group). Senescence-associated β-galactosidase activity, protein expression of Ac-p53 and PAI-1, and aortic atherosclerosis lesions were significantly greater in OVX mice than they were in sham mice. Administration of 17β-estradiol (E2) for eight weeks to OVX mice restored aortic SIRT1 expression, activated eNOS, and retarded OVX-induced arterial senescence and atherosclerotic development (E2 vs. control, n=5 per group). The effects of E2 on SIRT1 upregulation, anti-senescence and anti-atherosclerosis were attenuated by administration of a SIRT1 inhibitor, sirtinol. In vitro experiment using human endothelial cells demonstrated that E2 also increased SIRT1 expression and retarded oxidized low density lipoprotein-induced premature senescence, which were also abolished by sirtinol. These results suggested that estrogen modulated arterial senescence and atherosclerosis through SIRT1. Additionally a selective estrogen receptor modulator (SERM), bazedoxifene, also augmented SIRT1 and inhibited arterial senescence and atherosclerotic development (SERM vs. control, n=3 per group).

    Conclusions: Downregulation of SIRT1 causes OVX-induced arterial senescence and atherosclerosis in ApoE-KO mice. Administration of estrogen or SERM enables OVX mice to restore these alterations by SIRT1 induction.

  • Hayato Tada, Tamami Nakagawa, Hirofumi Okada, Takuya Nakahashi, Mika M ...
    原稿種別: Original Article
    論文ID: 49551
    発行日: 2019年
    [早期公開] 公開日: 2019/05/18
    ジャーナル フリー 早期公開

    Aim: Carotid plaque score (cPS) reflecting throughout the carotid artery plaque burden may be a better marker than carotid intima–media thickness (cIMT) is. We aimed to compare the prognostic utility of these measurements in patients with atherosclerotic cardiovascular disease (ASCVD).

    Methods: We retrospectively examined 2,035 Japanese patients with ASCVD who underwent carotid ultrasonography between January 2008 and December 2015 at Kanazawa University Hospital. Median follow-up period was 4 years. We used Cox models that adjusted for established risk factors of ASCVD, including age, gender, hypertension, diabetes, smoking, and serum lipids to assess the association of cIMT as well as cPS with major adverse cardiac events (MACE). MACE was defined as all-cause mortality or rehospitalization for a cardiovascular-related illness.

    Results: During follow-up, 243 participants experienced MACE. After adjustment for established risk factors, cPS was associated with MACE (hazard ratio [HR]=3.38 for top quintile vs. bottom quintile of cPS; 95% confidence interval [CI] 1.82–6.27; P trend <0.001), while cIMT was not (HR=0.88, P=0.57). Addition of the cPS to established risk factors significantly improved risk discrimination (C-index 0.726 vs. 0.746; P=0.017).

    Conclusion: These results suggest that cPS, rather than cIMT may be a better marker to identify increased risk for recurrence of MACE among patients with secondary prevention setting.

  • Kazuki Ueda, Eriko Morishita, Hironaga Shiraki, Shunzo Matsuoka, Shins ...
    原稿種別: Case Report
    論文ID: 48819
    発行日: 2019年
    [早期公開] 公開日: 2019/05/15
    ジャーナル フリー 早期公開

    Thrombophilia increases the risk of venous thrombosis, but is rarely responsible for aortic thrombosis. Aortic mural thrombus (AMT) may be associated with a protein C deficiency. However, it is necessary to determine whether the protein C deficiency is congenital/hereditary or secondary/acquired (consumption of protein C during the process of thrombus formation). This study describes a 77-year-old Japanese woman with incidentally diagnosed AMT, who had a protein C deficiency (activity 54%, antigen 42%). Sequencing of the protein C gene revealed a heterozygous mutation of c.1268delG, p.Gly423Valfs82 in exon 9, indicating a congenital protein C deficiency. These findings indicate that very late onset AMT can occur in an adult with congenital protein C deficiency.

  • Masakatsu Nishikawa, Yoshihiro Takeda, Naoei Isomura, Takashi Tanigawa ...
    原稿種別: Original Article
    論文ID: 48934
    発行日: 2019年
    [早期公開] 公開日: 2019/05/14
    ジャーナル フリー 早期公開

    Aim: Although high on-treatment platelet reactivity (HTPR) with dual antiplatelet therapy (DAPT) correlates with long-term adverse outcomes in patients undergoing percutaneous coronary intervention, the correlation in Japanese patients remains unclear. Therefore, we examined the relationship between platelet reactivity during DAPT with aspirin and clopidogrel and 1-year clinical outcomes following successful coronary stent implantation.

    Methods: A prospective, multicenter registry study (j-CHIPS) was conducted in patients undergoing coronary stenting and receiving aspirin and clopidogrel at 16 hospitals in Japan. A VerifyNow point-of-care assay was used to assess platelet reactivity, and a cutoff value to define HTPR was established.

    Results: Between February 2011 and May 2013, 1047 patients were prospectively enrolled, of which 854 patients with platelet function evaluation at 12–24 h after PCI were included in the final analysis. After 1 year of follow-up, the incidence of the primary endpoint (a composite of all-cause mortality, myocardial infarction, stent thrombosis, and ischemic stroke) was significantly higher in patients with HTPR than in those without (5.9% vs. 1.5%, p=0.008), and HTPR showed a modest ability to discriminate between patients who did and did not experience major adverse cardiac and cerebrovascular events (area under the curve, 0.60; 95% confidence interval, 0.511–0.688, p=0.039). HTPR status did not identify patients at risk for major or minor bleeding events.

    Conclusion: HTPR was significantly associated with adverse ischemic outcomes at 1 year after PCI in Japanese patients receiving maintenance DAPT, indicating its potential as a prognostic indicator of clinical outcomes in this high-risk patient population.

  • Maki Tsujita, Nobukatsu Akita, Tomo Yokota, Fumihiko Kobayashi, Shinji ...
    原稿種別: Original Article
    論文ID: 48967
    発行日: 2019年
    [早期公開] 公開日: 2019/05/14
    ジャーナル フリー 早期公開

    Aim: Probucol is a controversial drug to inhibit ATP-binding cassette transporter A1 (ABCA1) and to exhibit some positive clinical effects such as regression of xanthomas. It reportedly rescues female infertility in scavenger receptor BI-deficient mice. Here, we investigated the effect of probucol on propagation in HDL-deficient mice as alternative models for impaired HDL-mediated cholesterol delivery.

    Methods: Propagation of ABCA1-deficient (Abca1-/-) mice and lecithin: cholesterol acyltransferase (LCAT)-deficient (Lcat-/-) mice were quantitatively observed under the probucol treatment.

    Results: Abca1-/- and Lcat-/- mice appear with negligible plasma HDL concentration. Upon backcrossing Abc1+/- with the Abc1-/- mice and cross-breeding between Abc1+/- mice, the numbers of Abc1-/- weaned pups were reduced to 54.7% and to 57.1% from those expected by Mendelian genetics, respectively. Similarly, Lcat-/- weaned pups decreased to 67.7% and to 35.9% but only in the male. Probucol severely reduced plasma HDL-cholesterol to 5% in the wild-type mice, but showed no effects on their propagation. Probucol corrected the deflections of the genotype distribution in the weaned pups recovery in the LCAT-deficient mice propagation but not in the ABCA1-deficient mice while plasma HDL was kept negligible. Probucol had no effect on cholesterol content in the steroidogenic organs of the HDL-deficient mice, while it somewhat increased plasma corticosterone and expression of adrenal cortex HMG-CoA reductase, StAR, cytochrome P450scc, and VKORC1 indicating increase in the synthesis of cholesterol and steroid hormones and in vitamin K turn-over. However, no evident mechanistic background was indicated.

    Conclusions: Probucol corrected deflection of genotype distribution in propagation of the LCAT-deficient mice but not the ABCA1-deficient mice at the weaning stage, apparently not through normalization of hypoalphalipoproteinemia.

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