Journal of Atherosclerosis and Thrombosis
Online ISSN : 1880-3873
Print ISSN : 1340-3478
ISSN-L : 1340-3478
Advance online publication
Showing 51-69 articles out of 69 articles from Advance online publication
  • Kimie Tanaka, Daiju Fukuda, Yasutomi Higashikuni, Yoichiro Hirata, Iss ...
    Type: Original Article
    Article ID: 52720
    Published: 2020
    [Advance publication] Released: February 26, 2020
    JOURNALS FREE ACCESS ADVANCE PUBLICATION

    Aim: Synthetic vascular grafts are widely used in surgical revascularization, mainly for medium- to large-sized vessels. However, synthetic grafts smaller than 6 mm in diameter are associated with a high incidence of thrombosis. In this study, we evaluated silk fibroin, a major protein of silk, with high biocompatibility and biodegradability, as a useful material for extremely-small-diameter vascular grafts.

    Methods: A small-sized (0.9 mm inner diameter) graft was braided from a silk fibroin thread. The right carotid arteries of 8- to 14-week-old male C57BL/6 mice were cut at the midpoint, and fibroin grafts (5- to 7-mm in length) were transplanted using a cuff technique with polyimide cuffs. The grafts were harvested at different time points and analyzed histologically.

    Results: CD31+ endothelial cells had already started to proliferate at 2 weeks after implantation. At 4 weeks, neointima had formed with α-smooth muscle actin+ cells, and the luminal surface was covered with CD31+endothelial cells. Mac3+ macrophages were accumulated in the grafts. Graft patency was confirmed at up to 6 months after implantation.

    Conclusion: This mouse model of arterial graft implantation enables us to analyze the remodeling process and biocompatibility of extremely-small-diameter vascular grafts. Biodegradable silk fibroin might be applicable for further researches using genetically modified mice.

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  • Fengzhi Wang, Jiaoqi Wang, Qiu He, Liyu Wang, Yumeng Cao, Hemin Zhang, ...
    Type: Original Article
    Article ID: 54221
    Published: 2020
    [Advance publication] Released: February 16, 2020
    JOURNALS FREE ACCESS ADVANCE PUBLICATION

    Aim: There is no randomized controlled trial to compare the effectiveness and safety of mechanical thrombectomy (MT) to intravenous thrombolysis in patients with posterior circulation occlusion (PCO). Hence, we firstly performed a meta-analysis to investigate the outcomes of MT in PCO and then compared these outcomes to anterior circulation occlusion (ACO) to provide fundamental data to further studies.

    Methods: We searched the PubMed, EMBASE, and Cochrane Library from dates of inception to June 2019 for relevant studies. Outcomes including functional independence at 90 days, successful recanalization, mortality, symptomatic intracranial hemorrhage (sICH), and futile recanalization were extracted.

    Results: Seven studies involving 474 patients with PCO thrombectomy were analyzed. There was a lower rate of functional independence at 90 days and a higher rate of mortality after thrombectomy in PCO versus ACO (odds ratios (OR) 0.72; 95% confidence interval (CI) 0.57–0.90; OR 2.03; 95% CI 1.30–3.18). Recanalization rates were comparable (OR 1.01; 95% CI 0.62–1.65), but a higher futile recanalization rate was found in basilar artery occlusion (BAO) (OR 1.75; 95% CI 1.30–2.37). There was a lower rate of sICH in MT for patients with PCO versus ACO (OR 0.54; 95% CI 0.29–0.99).

    Conclusions: We found that the outcomes of MT for patients with PCO were poorer than with ACO. On the other hand, MT appears to have lower rates of sICH and to increase successful recanalization. Given the high recanalization rate, MT may serve as an adjunct to standard treatment. The key point to improve outcomes is recognizing reliable factors associated with futile recanalization and optimizing the results of MT. But in view of the different characteristics of posterior circulation stroke and anterior circulation stroke, the results are far from robust.

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  • Congying Xia, Marleen Vonder, Grigory Sidorenkov, Matthijs Oudkerk, Ja ...
    Type: Original Article
    Article ID: 52928
    Published: 2020
    [Advance publication] Released: February 15, 2020
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    Aim: Coronary artery disease (CAD) and cognitive impairment are common in the elderly, with evidence for shared risk factors and pathophysiological processes. The coronary artery calcium (CAC) score is a marker of subclinical CAD, which may allow early detection of individuals prone to cognitive decline. Prior studies on associations of CAC and clinical CAD with cognitive impairment had discrepant results. This systematic review aims to evaluate the association of (sub)clinical CAD with cognitive function, cognitive decline, and diagnosis of mild cognitive impairment (MCI) or dementia.

    Methods: A systematic search was conducted in MEDLINE, Embase, and Web of Science until February 2019, supplemented with citations tracking. Two reviewers independently screened studies and extracted information including odds ratios (ORs) and hazard ratios (HRs).

    Results: Forty-six studies, 10 on CAC and 36 on clinical CAD, comprising 1,248,908 participants were included in the systematic review. Studies about associations of (sub)clinical CAD with cognitive function and cognitive decline had heterogeneous methodology and inconsistent findings. Two population-based studies investigated the association between CAC and risk of dementia over 6–12.2 years using different CAC scoring methods. Both found a tendency toward higher risk of dementia as CAC severity increased. Meta-analysis in 15 studies (663,250 individuals) showed an association between CAD and MCI/dementia (pooled OR 1.32, 95%CI 1.17–1.48) with substantial heterogeneity (I2=87.0%, p<0.001). Pooled HR of CAD for incident MCI/dementia over 3.2–25.5 years in six longitudinal studies (70,060 individuals) was 1.51 (95%CI 1.24–1.85), with low heterogeneity (I2=14.1%, p=0.32). Sensitivity analysis did not detect any study that was of particular influence on the pooled OR or HR.

    Conclusions: Limited evidence suggests the CAC score is associated with risk of dementia. In clinical CAD, risk of MCI and dementia is increased by 50%, as supported by stronger evidence.

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  • Peiyang Zhou, Jincheng Liu, Lingyun Wang, Wenmin Feng, Zhihua Cao, Pu ...
    Type: Original Article
    Article ID: 53132
    Published: 2020
    [Advance publication] Released: February 15, 2020
    JOURNALS FREE ACCESS ADVANCE PUBLICATION

    Aim: To investigate the association of small dense low-density lipoprotein cholesterol (sdLDL-C) and acute ischemic stroke (AIS) in terms of risk, severity, and outcomes. Prediction models were established to screen high-risk patients and predict prognosis of AIS patients.

    Methods: We enrolled in this study 355 AIS patients and 171 non-AIS controls. AIS was subtyped according to TOAST criteria, and the severity and outcomes of AIS were measured. Blood glucose and lipid profiles including total cholesterol, triglyceride, and lipoproteins were measured in all patients using automatic measure. Lipoprotein subfractions were detected by the Lipoprint LDL system.

    Results: As compared with the non-AIS control group, the AIS group had higher sdLDL-C levels. Pearson correlation analysis revealed that the sdLDL-C level and risk of AIS, especially non-cardioembolic stroke, were positively correlated. The area under the curve of sdLDL-C for AIS risk was 0.665, better than that of other lipids. Additionally, the sdLDL-C level was significantly correlated with AIS severity and bad outcomes. A logistic regression model for assessing the probability of AIS occurrence and a prognostic prediction model were established based on sdLDL-C and other variables.

    Conclusions: Elevated levels of sdLDL-C were associated with a higher prevalence of AIS, especially in non-cardioembolic stroke subtypes. After adjustment for other risk factors, sdLDL-C was found to be an independent risk factor for AIS. Also, sdLDL-C level was strongly associated with AIS severity and poor functional outcomes. Logistic regression models for AIS risk and prognosis prediction were established to help clinicians provide better prevention for high-risk subjects and monitor their prognosis.

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  • Kexun Zhang, Yanfeng Jiang, Yingzhe Wang, Chen Suo, Kelin Xu, Zhen Zhu ...
    Type: Original Article
    Article ID: 52530
    Published: 2020
    [Advance publication] Released: February 08, 2020
    JOURNALS FREE ACCESS ADVANCE PUBLICATION

    Aims: We aimed to examine the associations of four extracranial artery indicators with cerebral small vessel disease (CSVD) and its total burden.

    Methods: A total of 904 individuals aged 55–65 years old were included from the Taizhou Imaging Study. CSVD markers, including lacunes (LAC), white matter hyperintensities (WMH), cerebral microbleeds (CMB), and perivascular spaces (PVS), were rated based on brain magnetic resonance imaging. We also measured extracranial artery indices, including the brachial-ankle pulse wave velocity (baPWV), the ankle-brachial index, the carotid intima-media thickness (IMT), and carotid plaque. Linear and binary logistic regressions were adopted to test the associations among these four artery indicators and each CSVD marker when appropriate. Additionally, ordinal and multinomial logistic regressions were performed to assess the relationships between artery indicators and total CSVD score (range from 0–4 points).

    Results: A total of 443 (49.0%) participants were found to have at least one of the CSVD markers, including 172 (19.0%) with WMH, 184 (20.4%) with LAC, 147 (16.3%) with CMB, and 226 (25.0%) with PVS. Increased baPWV was significantly associated with each CSVD marker, increasing carotid IMT was associated with LAC and PVS, and the presence of carotid plaque was associated with WMH volume and PVS. Moreover, per SD increment of baPWV (odds ratio [OR]: 1.29, 95% confidence interval [CI]: 1.11–1.50) and the presence of carotid plaque (OR: 1.42, 95% CI: 1.05–1.92) were significantly associated with greater total CSVD scores.

    Conclusion: Increased baPWV and the presence of carotid plaque appear to be associated with total CSVD burden in rural regions in China.

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  • Yandong Liu, Wei Huan, Jianjin Wu, Sili Zou, Lefeng Qu
    Type: Original Article
    Article ID: 52993
    Published: 2020
    [Advance publication] Released: February 08, 2020
    JOURNALS FREE ACCESS ADVANCE PUBLICATION

    Aims: To investigate the differentially expressed genes (DEGs) and molecular interaction in unstable atherosclerotic carotid plaques.

    Methods: Gene expression datasets GSE41571, GSE118481, and E-MTAB-2055 were analyzed. Co-regulated DEGs in at least two datasets were analyzed with the enrichment of Gene Ontology Biological Process (GO-BP), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein–protein interaction (PPI) networks, interrelationships between miRNAs/transcriptional factors, and their target genes and drug–gene interactions. The expression of notable DEGs in human carotid artery plaques and plasma was further identified.

    Results: The GO-BP enrichment analysis revealed that genes associated with inflammatory response, and extracellular matrix organization were altered. The KEGG enrichment analysis revealed that upregulated DEGs were enriched in the tuberculous, lysosomal, and chemokine signaling pathways, whereas downregulated genes were enriched in the focal adhesion and PI3K/Akt signaling pathway. Collagen type I alpha 2 chain (COL1A2), adenylate cyclase 3 (ADCY3), C-X-C motif chemokine receptor 4 (CXCR4), and TYRO protein tyrosine kinase binding protein (TYROBP) might play crucial roles in the PPI networks. In drug–gene interactions, colonystimulating factor-1 receptor had the most drug interactions. Insulin-like growth factor binding protein 6 (IGFBP6) was markedly downregulated in unstable human carotid plaques and plasma. Under a receiver operating characteristic curve analysis, plasma IGFBP6 had a significant discriminatory power (AUC, 0.894; 95% CI, 0.810–0.977), with a cutoff value of 142.08 ng/mL.

    Conclusions: The genes COL1A2, ADCY3, CXCR4, and TYROBP are promising targets for the prevention of unstable carotid plaque formation. IGFBP6 may be an important biomarker for predicting vulnerable plaques.

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  • Michikazu Nakai, Makoto Watanabe, Yoshihiro Kokubo, Kunihiro Nishimura ...
    Type: Original Article
    Article ID: 48843
    Published: 2020
    [Advance publication] Released: February 06, 2020
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    Aim: To construct a risk prediction model for cardiovascular disease (CVD) based on the Suita study, an urban Japanese cohort study, and compare its accuracy against the Framingham CVD risk score (FRS) model.

    Methods: After excluding participants with missing data or those who lost to follow-up, this study consisted of 3,080 men and 3,470 women participants aged 30–79 years without CVD at baseline in 1989–1999. The main outcome of this study was incidence of CVD, defined as the incidence of stroke or coronary heart disease. Multivariable Cox proportional hazards models with stepwise selection were used to develop the prediction model. To assess model performance, concordance statistics (C-statistics) and their 95% confidence intervals (CIs) were calculated using a bootstrap procedure. A calibration test was also conducted.

    Results: During a median follow-up period of 16.9 years, 351 men and 241 women developed CVD. We formulated risk models with and without electrocardiogram (ECG) data that included age, sex, systolic blood pressure, diastolic blood pressure, high-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, diabetes mellitus, smoking, and urinary protein as risk factors. The C-statistics of the Suita CVD risk models with ECG data (0.782; 95% CI, 0.766–0.799) and without ECG data (0.781; 95% CI, 0.765–0.797) were significantly higher than that of the FRS model (0.768; 95% CI, 0.750–0.785).

    Conclusions: The Suita CVD risk model is feasible to use and improves predictability of the incidence of CVD relative to the FRS model in Japan.

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  • Atsushi Takahashi, Tetsuya Ohira, Kanako Okazaki, Seiji Yasumura, Akir ...
    Type: Original Article
    Article ID: 52225
    Published: 2020
    [Advance publication] Released: January 31, 2020
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    Aim: The Fukushima Daiichi Nuclear Power Plant accident dramatically changed the lifestyle of residents who lived near the plant. We evaluated the association of metabolic syndrome (MetS) with specific lifestyle- and disaster-related factors in residents following the accident.

    Methods: This cross-sectional study included 20,920 residents who underwent both the Comprehensive Health Check and the Mental Health and Lifestyle Survey from June 2011 to March 2012. Associations between MetS and lifestyle- and disaster-related factors, including psychological distress (post-traumatic stress disorder [PTSD]), were estimated using logistic regression analysis, adjusted for demographic and lifestyle factors, in 2019.

    Results: MetS was present in 30.4% of men and 11.5% of women. There were significant differences in smoking, drinking status, and PTSD prevalence between subjects with and without MetS. Multivariable logistic regression analysis showed that age, quitting smoking, light to moderate drinking, and low physical activity were significantly associated with MetS. Moreover, PTSD was also significantly associated with MetS in women.

    Conclusions: Lifestyle- and disaster-related factors, including PTSD, were associated with MetS among subjects who lived near the Fukushima Daiichi Nuclear Power Plant accident.

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  • Kazuo Omori, Naoto Katakami, Shoya Arakawa, Yuichi Yamamoto, Hiroyo Ni ...
    Type: Original Article
    Article ID: 52506
    Published: 2020
    [Advance publication] Released: January 25, 2020
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    Aim: An identification of the high-risk group of atherosclerotic cardiovascular disease (CVD) is important in the management of patients with diabetes. Metabolomics is a potential tool for the discovery of new biomarkers. With this background, we aimed to identify metabolites associated with atherosclerosis in patients with type 2 diabetes mellitus (T2DM).

    Methods: A total of 176 patients with T2DM who have never had a CVD event and 40 who were survivors of coronary artery disease (CAD) events were enrolled. Non-targeted metabolome analysis of fasting plasma samples was performed using gas chromatography coupled with mass spectrometry (GC/MS) highly optimized for multiple measurement of blood samples. First, metabolites were screened by analyzing the association with the established markers of subclinical atherosclerosis (i.e., carotid maximal intima-media thickness (max-IMT) and flow-mediated vasodilation (FMD)) in the non-CVD subjects. Then, the associations between the metabolites detected and the history of CAD were investigated.

    Result: A total of 65 annotated metabolites were detected. Non-parametric univariate analysis identified inositol and indoxyl sulfate as significantly (p<0.05) associated with both max-IMT and FMD. These metabolites were also significantly associated with CAD. Moreover, inositol remained to be associated with CAD even after adjustments for traditional coronary risk factors.

    Conclusions: We identified novel biomarker candidates for atherosclerosis in Japanese patients with T2DM using GC/MS-based non-targeted metabolomics.

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  • Yuri Shojima, Yuji Ueno, Ryota Tanaka, Kazuo Yamashiro, Nobukazu Miyam ...
    Type: Original Article
    Article ID: 52373
    Published: 2020
    [Advance publication] Released: January 23, 2020
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    Aims: The ratio of eicosapentaenoic acid (EPA) to arachidonic acid (AA) is related to major adverse events and death in cardiovascular diseases. The association between long-term prognosis of ischemic stroke and EPA/AA ratio has not been clarified.

    Methods: Acute ischemic stroke patients who had undergone blood examinations for polyunsaturated fatty acids were enrolled. Major cardiovascular events, including recurrence of ischemic stroke, occurrence of cardiovascular and peripheral artery diseases and hemorrhagic stroke, and death, were analyzed, retrospectively. Cox proportional hazards regression analysis was used to explore factors, including clinical characteristics, laboratory data including EPA/AA ratio, and treatments associated with major cardiovascular events and death.

    Results: A total of 269 patients (mean age, 70±13 years; 179 men) were enrolled. During follow-up (mean, 2.3 ±1.0 years), 64 patients exhibited major cardiovascular events and death (annualized rate, 10.5% per person-year). Multivariate Cox analysis revealed that EPA/AA ratio (hazard ratio, 0.26; 95% confidence interval, 0.07– 0.99; p=0.048) and statin therapy (hazard ratio, 0.43; 95% confidence interval, 0.25–0.73; p=0.002) correlated inversely with major cardiovascular events and death. In the Kaplan–Meier analysis, cumulative event-free rates were significantly lower among patients with EPA/AA ratio <0.33 and patients without statin therapy (p=0.006).

    Conclusions: Low EPA/AA ratio at baseline and treatment without statins could predict mortality, recurrent ischemic stroke, cardiovascular and peripheral artery diseases, and hemorrhagic stroke among patients with acute ischemic stroke. The combination of baseline EPA/AA ratio and statin therapy could be critical in predicting the long-term prognosis of ischemic stroke patients.

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  • Md Maruf Haque Khan, Akira Fujiyoshi, Akihiko Shiino, Takashi Hisamats ...
    Type: Original Article
    Article ID: 51284
    Published: 2020
    [Advance publication] Released: January 22, 2020
    JOURNALS FREE ACCESS ADVANCE PUBLICATION

    Aim: Coronary artery calcification (CAC) is an independent predictor of stroke and dementia, in which subclinical cerebrovascular diseases (SCVDs) play a vital pathogenetic role. However, few studies have described the association between CAC and SCVDs. Therefore, the aim of this study was to assess the clinical relationship between CAC and SCVDs in a healthy Japanese male population.

    Methods: In this observational study, 709 men, free of stroke, were sampled from a city in Japan from 2010 to 2014. CAC was scored using the Agatston method. The following SCVDs were assessed using magnetic resonance imaging: intracranial arterial stenosis (ICAS), lacunar infarction, deep and subcortical white matter hyperintensity (DSWMH), periventricular hyperintensity (PVH), and microbleeds. The participants were categorized according to CAC scores as follows: no CAC (0), mild CAC (1–100), and moderate-to-severe CAC (>100). The adjusted odds ratios of prevalent SCVDs were computed in reference to the no-CAC group using logistic regression.

    Results: The mean (standard deviation) age of the participants was 68 (8.4) years. Participants in the moderate-to-severe-CAC category showed significantly higher odds of prevalent lacunar infarction, DSWMH, and ICAS in age-adjusted and risk-factor-adjusted models. Microbleeds and PVH, in contrast, did not show any significant associations. The trends for CAC with lacunar infarction, DSWMH, and ICAS were also significant (all P-values for trend ≤ 0.02).

    Conclusions: Higher CAC scores were associated with higher odds of lacunar infarction, DSWMH, and ICAS. The presence and degree of CAC may be a useful indicator for SCVDs involving small and large vessels.

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  • Xingyang Yi, Ling Zhu, Guo Sui, Jie Li, Hua Luo, Ming Yu, Chun Wang, X ...
    Type: Original Article
    Article ID: 53074
    Published: 2020
    [Advance publication] Released: January 17, 2020
    JOURNALS FREE ACCESS ADVANCE PUBLICATION

    Aim: To examine the association between carotid plaque and variants in genes involved in inflammation and endothelial function.

    Methods: This was a multicenter, cross-sectional survey in southwestern China. The residents aged ≥ 40 years volunteered to participate in the face-to-face survey in eight communities. A total of 2,377 subjects with high stroke risk were enrolled. Carotid plaque and plaque phenotype were assessed by carotid ultrasound. Genotypes of 19 variants in 10 genes related to inflammation and endothelial function were examined. Gene–gene interaction was analyzed by generalized multifactor dimensionality reduction (GMDR).

    Results: Carotid plaques were found in 852 (35.8%) subjects, and 454 (53.3%) had stable plaques, whereas 398 (46.7%) had vulnerable plaques. PPARA rs4253655, HABP2 rs7923349, and IL1A rs1609682 were associated with the presence of carotid plaque, and NOS2A rs2297518 and PPARA rs4253655 were associated with vulnerable plaque in univariate analysis. The GMDR analysis revealed that there was a significant gene–gene interaction among HABP2 rs7923349, ITGA2 rs1991013, IL1A rs1609682, and NOS2A rs8081248, and the high-risk interactive genotype among the four variants was independently associated with a higher risk of carotid vulnerable plaque after adjusting the covariates (OR, 2.86, 95% CI: 1.32–7.13, P=0.003).

    Conclusion: The prevalence of carotid plaque was very high in the high-risk stroke population in southwestern China. Variants in genes involved in the endothelial function and inflammation were associated with the carotid plaque. The high-risk interactive genotype among rs7923349, rs1991013, rs1609682, and rs8081248 was independently associated with a higher risk of vulnerable plaque.

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  • Hongbing Liu, Kai Liu, Lulu Pei, Yuan Gao, Lu Zhao, Shilei Sun, Jun Wu ...
    Type: Original Article
    Article ID: 51151
    Published: 2020
    [Advance publication] Released: January 16, 2020
    JOURNALS FREE ACCESS ADVANCE PUBLICATION

    Aim: Monocyte-to-high-density lipoprotein ratio (MHR) recently emerged as an inflammatory marker and has been reported to be a novel prognostic indicator of cardiovascular diseases. However, the relationship between MHR and prognosis of acute ischemic stroke (AIS) remains unclear.

    Methods: Consecutive AIS patients were prospectively identified from January 2015 to December 2017. Functional outcome was evaluated by the modified Rankin Scale (mRS). Poor outcome was defined as of mRS 3-6. Multivariate logistic regression analysis was conducted to evaluate the relationship between MHR and poor outcome.

    Results: A total of 1090 AIS patients within 24 hours of the onset of symptoms were recruited. MHR was higher in poor outcome group compared to that in good outcome group [0.53 (0.37-0.69) vs. 0.48 (0.33-0.60), P=0.007]. Multivariate logistic regression analysis indicated that higher MHR level was independently associated with the poor outcome at 3 months (OR 2.58, 95% CI, 1.21-5.51, P=0.015), especially the stroke subtype of large artery atherosclerosis (OR 2.52, 95% CI, 1.03-6.19, P=0.034). Receiver operating curve (ROC) analysis showed that the area under the ROC curves for MHR was 0.67 and the best predictive cutoff value of MHR was 0.51,with a sensitivity of 62.3% and a specificity of 66.5%.

    Conclusions: MHR may be a significant and independent predictor of poor functional outcome in patients with AIS.

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  • Kenji Ebihara, Kazumasa Yamagishi, Mitsumasa Umesawa, Isao Muraki, Ren ...
    Type: Original Article
    Article ID: 52241
    Published: 2020
    [Advance publication] Released: January 11, 2020
    JOURNALS FREE ACCESS ADVANCE PUBLICATION

    Aim: N-terminal pro-B-type natriuretic peptide (NT-proBNP), frequently used as a biochemical marker for detecting and monitoring heart failure, is also a risk marker for development of coronary heart disease and total stroke. However, studies that explore subtypes of ischemic stroke with regard to NT-proBNP are scarce. Here, we examined NT-proBNP and its impact upon subtypes of ischemic stroke (lacunar stroke, large-artery occlusive stroke and embolic stroke) among Japanese.

    Methods: We measured NT-proBNP and categorized 4,393 participants of the Circulatory Risk in Communities Study into four groups (<55, 55-124, 125-399, and ≥ 400 pg/ml). We used a multivariable Cox proportional hazards model to examine association with risks of stroke and subtypes.

    Results: During 4.7 years of follow-up, we identified 50 strokes, including 35 ischemic (15 lacunar, 6 largeartery occlusive, 10 embolic strokes) and 14 hemorrhagic strokes. NT-proBNP was associated with stroke risk: the multivariable hazard ratio of total strokes was 7.29 (2.82-18.9) for the highest and 2.78 (1.25-6.16) for the second highest NT-proBNP groups compared with the lowest group. The respective hazard ratios for the highest NT-proBNP group were 9.37 (3.14–28.0) for ischemic stroke and 6.81 (1.11–41.7) for lacunar stroke. Further adjustment for atrial fibrillation did not attenuate these associations. The associations were similarly observed for large-artery occlusive and embolic strokes.

    Conclusion: We found that even moderate serum levels of NT-proBNP were associated with the risk of total and ischemic strokes among Japanese whose NT-proBNP levels were relatively low compared with Westerners.

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  • Wei-Ting Wang, Pai-Feng Hsu, Chung-Chi Lin, Yuan-Jen Wang, Yaw-Zon Din ...
    Type: Original Article
    Article ID: 51425
    Published: 2019
    [Advance publication] Released: December 27, 2019
    JOURNALS FREE ACCESS ADVANCE PUBLICATION

    Aim: Coronary atherosclerotic plaques can be detected in asymptomatic subjects and are related to low-density lipoprotein cholesterol (LDL) levels in patients with coronary artery disease. However, researchers have not yet determined the associations between various plaque characteristics and other lipid parameters, such as HDL-C and TG levels, in low-risk populations.

    Methods: One thousand sixty-four non-diabetic subjects (age, 57.86±9.73 years; 752 males) who underwent coronary computed tomography angiography (CCTA) were enrolled and the severity and patterns of atherosclerotic plaques were analyzed.

    Results: Statin use was reported by 25% of the study population, and subjects with greater coronary plaque involvement (segment involvement score, SIS) were older and had a higher body mass index (BMI), blood pressure, unfavorable lipid profiles and comorbidities. After adjusting for comorbidities, only age (β=0.085, p<0.001), the male gender (β=1.384, p<0.001), BMI (β=0.055, p=0.019) and HbA1C levels (β=0.894, p<0.001) were independent factors predicting the greater coronary plaque involvement in non-diabetic subjects. In the analysis of significantly different (>50%) stenosis plaque patterns, age (OR: 1.082, 95% CI: 10.47-1.118) and a former smoking status (OR: 2.061, 95% CI: 1.013-4.193) were independently associated with calcified plaques. For partial calcified (mixed type) plaques, only age (OR: 1.085, 95% CI: 1.052-1.119), the male gender (OR: 7.082, 95% CI: 2.638-19.018), HbA1C levels (OR: 2.074, 95% CI: 1.036-4.151), and current smoking status (OR: 1.848, 95% CI: 1.089-3.138) were independently associated with the risk of the presence of significant stenosis in mixed plaques.

    Conclusions: A higher HbA1c levels is independently associated with the presence and severity of coronary artery atherosclerosis in non-diabetic subjects, even when LDL-C levels are tightly controlled.

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  • Haixin Bo, Yilin Li, Ge Liu, Yufen Ma, Zhen Li, Jing Cao, Ying Liu, Ji ...
    Type: Original Article
    Article ID: 51359
    Published: 2019
    [Advance publication] Released: December 17, 2019
    JOURNALS FREE ACCESS ADVANCE PUBLICATION

    Aim: We sought to validate the 2010 Caprini risk assessment model (RAM) in risk stratification for deep vein thrombosis (DVT) prophylaxis among Chinese bedridden patients.

    Methods: We performed a prospective study in 25 hospitals in China over 9 months. Patients were risk-stratified using the 2010 Caprini RAM.

    Results: We included a total 24,524 patients. Fresh DVT was found in 221 patients, with overall incidence of DVT 0.9%. We found a correlation of DVT incidence with Caprini score according to risk stratification (χ2 =196.308, P<0.001). Patients in the low-risk and moderate-risk groups had DVT incidence <0.5%. More than half of patients with DVT were in the highest risk group. Compared with the low-risk group, risk was 2.10-fold greater in the moderate-risk group, 3.34-fold greater in the high-risk group, and 16.12-fold greater in the highest-risk group with Caprini scores ≥ 9. The area under the receiver operating characteristic curve was 0.74 (95% confidence interval, 0.71–0.78; P<0.01) for all patients. A Caprini score of ≥ 5 points was considered the criterion of a reliably increased risk of DVT in surgical patients with standard thromboprophylaxis. Predicting DVT using a cumulative risk score ≥ 4 is recommended for nonsurgical patients.

    Conclusions: Our study suggested that the 2010 Caprini RAM can be effectively used to stratify hospitalized Chinese patients into DVT risk categories, based on individual risk factors. Classification of the highest risk levels using a cumulative risk score ≥ 4 and ≥ 5 provides significantly greater clinical information in nonsurgical and surgical patients, respectively.

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  • Masako Miyashima, Tetsuo Shoji, Yoshinori Kakutani, Yuko Yamazaki, Aki ...
    Type: Original Article
    Article ID: 52886
    Published: 2019
    [Advance publication] Released: December 06, 2019
    JOURNALS FREE ACCESS ADVANCE PUBLICATION

    Aim: Inter-arm blood pressure difference (IAD) is known to be associated with a composite of cardiovascular disease (CVD) and with CVD risk factors. However, only limited information is available regarding the contribution of diabetes mellitus to IAD and the association of IAD with individual CVDs, such as coronary artery disease (CAD), stroke, and peripheral artery disease (PAD).

    Methods: We addressed these issues in this cross-sectional study of 2580 participants who had simultaneous blood pressure measurements in both arms using an automated device.

    Results: Compared with 1,264 nondiabetic subjects, 1316 patients with diabetes mellitus had a greater IAD (P=0.01) and a higher prevalence of IAD of ≥ 10 mmHg (8.4% vs. 5.4%, P=0.002). However, such difference was not significant after the adjustment for potential confounders. Among CAD, stroke, and PAD, only PAD was significantly associated with IAD in a model adjusted for the CVD risk factors. Age was found to modify the association between IAD and PAD, with the association being more prominent in the younger subgroup.

    Conclusion: Thus, diabetes mellitus itself was not an independent factor associated with IAD. A larger IAD was preferentially associated with the presence of PAD, and this association was modified by age.

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  • Mitsuyoshi Takahara, Osamu Iida, Shun Kohsaka, Yoshimitsu Soga, Masahi ...
    Type: Original Article
    Article ID: 53330
    Published: 2019
    [Advance publication] Released: November 21, 2019
    JOURNALS FREE ACCESS ADVANCE PUBLICATION

    Aim: The aim of the current study is to describe the presentation pattern of symptomatic peripheral artery disease undergoing endovascular therapy (EVT) in comparison to symptomatic coronary artery disease undergoing percutaneous coronary intervention (PCI) based on data from nationwide databases.

    Methods: Data were extracted from the nationwide procedural databases of EVT and PCI in Japan (J-EVT and J-PCI) between 2012 and 2017. The presentation pattern was investigated using a Poisson regression model, including the month, seasonality, and weekend (versus weekday) as the explanatory variables. Seasonality was expressed as a cosine function of a 12-month period, and its significance was evaluated using the Fisher–Yates shuffle method.

    Results: A total of 41,906 and 62,585 cases underwent EVT for critical limb ischemia (CLI) and intermittent claudication (IC), respectively, whereas 518,858 and 504,139 cases underwent PCI for acute coronary syndrome (ACS) and stable angina (SA). The procedural volume increased by 21.6%, 12.3%, 4.5%, and 3.6% per year in CLI, IC, ACS, and SA. CLI and ACS, but not IC or SA, showed a significant volume seasonality. Compared with ACS, CLI demonstrated a larger peak-to-trough ratio of seasonality (1.75 versus 1.21; P<0.001), and a later peak appearance (February–March versus January–February by 1.37 months; P<0.001). The procedural volume on weekends relative to weekdays was smaller for SA, IC, and CLI than for ACS. These distinct features were observed in a diabetic population and a non-diabetic population.

    Conclusions: The current study analyzed nationwide procedural databases and demonstrated the presentation pattern of symptomatic PAD and CAD warranting revascularization.

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  • Toshiyuki Ko, Michiaki Higashitani, Yukari Uemura, Makoto Utsunomiya, ...
    Type: Original Article
    Article ID: 52647
    Published: 2019
    [Advance publication] Released: November 12, 2019
    JOURNALS FREE ACCESS ADVANCE PUBLICATION

    Aim: Previous studies on peripheral artery disease (PAD) only enrolled patients with atherosclerotic lesion limited to any one of isolated locations (aortoiliac [AI], femoropopliteal [FP], and below the knee [BTK]). However, the interventions for PAD in a real-world clinical setting are often simultaneously performed for several different locations.

    Methods: We conducted a prospective multicenter study that included 2,230 patients with PAD who received intervention for lower extremity lesions in each area and across different areas. Patients were divided into 7 groups according to the combination of treatment locations. Overall survival (OS), major adverse limb events (MALEs), and risk factors for OS and MALEs were statistically analyzed.

    Results: After adjustment for confounding factors, the attributable risk for OS was similar among isolated AI, FP, and BTK treatments. MALEs increased in correlation with the number of treatment locations. Dialysis, critical limb ischemia, and cardiac contractile dysfunction were the common risk factors for OS and MALEs. However, the contribution of other factors such as type of drug usage was different according to treatment locations.

    Conclusions: In patients with PAD, OS was largely defined by comorbidities but not by lesion location. The background risk factors, underlying comorbidities, and event rates were different according to PAD location, suggesting that stratified treatment should be established for different patient populations.

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