Journal of Atherosclerosis and Thrombosis
Online ISSN : 1880-3873
Print ISSN : 1340-3478
ISSN-L : 1340-3478
Volume 32, Issue 4
Displaying 1-11 of 11 articles from this issue
Review
  • Chinatsu Komiyama, Masanari Kuwabara, Ayako Harima, Takayoshi Kanie, T ...
    Article type: Review
    2025 Volume 32 Issue 4 Pages 395-404
    Published: April 01, 2025
    Released on J-STAGE: April 01, 2025
    Advance online publication: January 31, 2025
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    Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of morbidity and mortality worldwide, including in Japan, where the aging population intensifies its impact. This review evaluated the potential impact of digital healthcare on the prevention and management of ASCVD, covering both primary and secondary prevention strategies. Digital health tools, such as risk assessment applications remote monitoring, lifestyle modification support, and remote rehabilitation, have shown promise in improving patient engagement, adherence, and outcomes. However, while digital health interventions demonstrate significant benefits, challenges persist, including interoperability issues, privacy concerns, low digital literacy among older adults, and limited health insurance coverage for digital interventions. Through an analysis of recent advancements and case studies, this review demonstrates the need for user-centered design, enhanced regulatory frameworks, and expanded insurance support to facilitate the effective integration of digital health in ASCVD care. Furthermore, emerging technologies such as personalized healthcare modules offer promising directions for tailored and impactful care. Addressing these barriers is critical to unleashing the full potential of digital healthcare to reduce the burden of ASCVD and enhance patient outcomes.

Editorial
Original Article
  • Takaaki Kosugi, Masahiro Eriguchi, Hisako Yoshida, Hiroyuki Tamaki, Ta ...
    Article type: Original Article
    2025 Volume 32 Issue 4 Pages 407-420
    Published: April 01, 2025
    Released on J-STAGE: April 01, 2025
    Advance online publication: September 21, 2024
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    Aims: Both low and high serum levels of high-density lipoprotein cholesterol (HDL-C) were reported to be associated with adverse kidney outcomes. However, this association has not been well investigated in the general Japanese population.

    Methods: This nationwide longitudinal study used data from the Japan Specific Health Checkups Study conducted between 2008–2014. The association between serum HDL-C levels and 40% decline in estimated glomerular filtration rate (eGFR) was analyzed using Cox regression analysis. Trajectories of eGFR were compared using mixed-effects model.

    Results: Among 768,495 participants, 6,249 developed 40% decline in eGFR during the median follow-up period of 34.6 (interquartile range: 14.8–48.4) months. Using serum HDL-C levels of 40–59 mg/dL as a reference, the adjusted hazard ratios (95% confidence intervals) for the kidney outcome of serum HDL-C levels of <40, 60–79 and ≥ 80 mg/dL were 1.26 (1.14–1.39), 0.91 (0.86–0.96), and 0.86 (0.78–0.93), respectively. Restricted cubic spline analysis showed that HDL-C levels of less than approximately 60 mg/dL were associated with an increased risk of kidney outcomes. Subgroup analysis showed that baseline eGFR and proteinuria modified the effects of serum HDL-C levels on kidney outcomes. The mixed-effects model showed that the lower category of HDL-C level was associated with a higher eGFR decline rate (p for interaction <0.001).

    Conclusions: Low HDL-C levels were associated with kidney function decline; however, high HDL-C levels were not associated with adverse kidney outcomes in the general Japanese population.

  • Emi Fujii, Junya Ako, Yuri Takahashi, Mitsutoshi Toda, Kazuma Iekushi, ...
    Article type: Original Article
    2025 Volume 32 Issue 4 Pages 421-438
    Published: April 01, 2025
    Released on J-STAGE: April 01, 2025
    Advance online publication: October 05, 2024
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    Aims: To investigate the distribution of lipoprotein(a) (Lp(a)) and its association with atherosclerotic cardiovascular disease (ASCVD) in Japanese patients at high risk for ASCVD using a health insurance database.

    Methods: Between July 2013 and June 2021, patients eligible for ASCVD prevention according to the 2017 Japan Atherosclerosis Society (JAS) guidelines with documented Lp(a) test results were extracted from the Medical Data Vision claims database and divided into three groups: primary prevention high-risk (Group I), secondary prevention (Group II) and secondary prevention high-risk (Group III). Data on lipid levels, cardiovascular morbidity risk factors and lipid-lowering treatments were extracted.

    Results: Of 700,580 patients with documented low-density lipoprotein cholesterol (LDL-C), 2,967 (0.42%) were tested for Lp(a). In 2,170 eligible patients, the median [interquartile range] serum concentration of Lp(a) was 13.9 [7.5-24.6] mg/dL, with 151 patients (7.0%) above the recommended risk threshold of ≥ 50 mg/dL. Lp(a) levels increased with risk across all prevention groups. Being in the highest Lp(a) quintile (Q5) was associated with an increased frequency of ASCVD (28.9% versus 18.9% in the lowest quintile (Q1) for unstable angina; 18.7% versus 10.1% for myocardial infarction; 27.9% versus 17.0% for ischemic stroke). In the secondary prevention groups, the proportion of patients meeting an LDL-C target of <70 mg/dL decreased from 30.2% in Q1 to 19.0% in Q5 for Group II and from 32.9% to 16.3% for Group III.

    Conclusions: Despite a high prevalence of Lp(a) ≥ 50mg/dL in Japanese patients at high risk for ASCVD, it found that the Lp(a) testing rate was very low.

  • Jiaxin Zeng, Jiaming Feng, Yuanming Luo, Hailong Wei, Huiqing Ge, Huig ...
    Article type: Original Article
    2025 Volume 32 Issue 4 Pages 439-457
    Published: April 01, 2025
    Released on J-STAGE: April 01, 2025
    Advance online publication: October 30, 2024
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    Aim: Venous thromboembolism (VTE) risk significantly increases in patients with an acute exacerbation of chronic obstructive pulmonary disease (AECOPD), which is characterized by an enhanced inflammatory response. This study aimed to evaluate the predictive value of inflammatory biomarkers for VTE in AECOPD.

    Methods: A prospective, multicenter study was conducted to include patients hospitalized for AECOPD. Inflammatory biomarkers on admission were compared between the patients who developed VTE during hospitalization and the patients without VTE. A logistic regression analysis was used to identify inflammatory biomarkers with an independently predictive value.

    Results: Among the 13,531 AECOPD inpatients, 405 (2.99%) developed VTE during hospitalization. Patients who developed VTE had higher levels of inflammatory biomarkers, including the white blood cell count, neutrophil percentage, systemic immune/inflammatory index, neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio, C-reactive protein (CRP), procalcitonin (PCT), and lactate dehydrogenase (LDH), and lower lymphocyte and eosinophil ratios (ESOR), platelet, and albumin (p all <0.05). NLR, LDH, CRP, PCT, and ESOR were identified as independent predictors of VTE (odds ratios (ORs) were 2.22, 1.95, 1.64, 1.59, and 1.37, respectively). The incidence of VTE increased with increasing NLR, LDH, CRP, and PCT quartiles, and a decreasing ESOR quartile. Among them, NLR and LDH had predictive capabilities for VTE that were comparable to the widely used Padua and IMPROVE scores.

    Conclusion: Easily available inflammatory parameters, such as NLR and LDH, can identify AECOPD patients at increased risk for VTE who may therefore be candidates for thromboprophylaxis.

  • Lamia M’barek, Aoming Jin, Yuesong Pan, Jinxi Lin, Yong Jiang, Xia Men ...
    Article type: Original Article
    2025 Volume 32 Issue 4 Pages 458-473
    Published: April 01, 2025
    Released on J-STAGE: April 01, 2025
    Advance online publication: October 26, 2024
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    Aim: D-dimer, lipoprotein (a) (Lp(a)), and high-sensitivity C-reactive protein (hs-CRP) are known predictors of vascular events; however, their impact on the stroke prognosis is unclear. This study used data from the Third China National Stroke Registry (CNSR-III) to assess their combined effect on functional disability and mortality after acute ischemic stroke (AIS).

    Methods: In total, 9,450 adult patients with AIS were enrolled between August 2015 and March 2018. Patients were categorized based on a cutoff value for D-dimer, Lp(a), and hs-CRP in the plasma. Adverse outcomes included poor functional outcomes (modified Rankin Scale (mRS score ≥ 3)) and one- year all-cause mortality. Logistic and multivariate Cox regression analyses were performed to investigate the relationship between individual and combined biomarkers and adverse outcomes.

    Results: Patients with elevated levels of all three biomarkers had the highest odds of functional disability (OR adjusted: 2.01; 95% CI (1.47-2.74); P<0.001) and mortality (HR adjusted: 2.93; 95% CI (1.55-5.33); P<0.001). The combined biomarkers improved the predictive accuracy for disability (C-statistic 0.80 vs.0.79, P<0.001) and mortality (C-statistic 0.79 vs.0.78, P=0.01).

    Conclusion: Elevated D-dimer, Lp(a), and hs-CRP levels together increase the risk of functional disability and mortality one-year post-AIS more than any single biomarker.

  • Yusuke Kawachi, Yuya Fujishima, Hitoshi Nishizawa, Atsushi Tanaka, His ...
    Article type: Original Article
    2025 Volume 32 Issue 4 Pages 474-490
    Published: April 01, 2025
    Released on J-STAGE: April 01, 2025
    Advance online publication: October 03, 2024
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    Aims: The effect of uric acid (UA)-lowering therapy with xanthine oxidoreductase (XOR) inhibitors on the development of cardiovascular disease requires further investigation. This study aimed to evaluate the long-term effects of febuxostat on arterial stiffness, focusing on liver function.

    Methods: The PRIZE study involved random assignment of patients with asymptomatic hyperuricemia to receive either add-on febuxostat treatment (febuxostat group) or non-pharmacological treatment (control group). Of the 514 participants, 23 and 14 patients in the febuxostat and control groups, respectively, underwent assessment of arterial stiffness using the cardio-ankle vascular index (CAVI). The participants in each group were further grouped on the basis of their baseline alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels (above or below the media value or 30 U/L). The primary endpoint was the change in the CAVI from baseline to 12 and 24 months.

    Results: Overall, no significant differences were found between the control and febuxostat groups in the least-squares mean estimates of changes in CAVI at 24 months (mean between-group difference, −0.41 [95% CI, −1.05 to 0.23]; p=0.204). However, there were significant differences in participants with higher baseline ALT or AST levels above 30 U/L at 24 months (mean between-group difference, −1.12 [95% CI, −2.23 to −0.01]; p=0.048 for ALT ≥ 30 U/L and −1.08 [95% CI, −2.13 to −0.03]; p=0.044 for AST ≥ 30 U/L).

    Conclusions: Two-year treatment with febuxostat demonstrated a beneficial effect on CAVI in patients with hyperuricemia and liver dysfunction.

  • Itaru Hisauchi, Tetsuya Ishikawa, Kota Yamada, Tomoaki Ukaji, Masatosh ...
    Article type: Original Article
    2025 Volume 32 Issue 4 Pages 491-501
    Published: April 01, 2025
    Released on J-STAGE: April 01, 2025
    Advance online publication: October 24, 2024
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    Aim: We aimed to determine whether baseline high-density lipoprotein (HDL) cholesterol efflux capacity (CEC) at the time of coronary angiography (CAG) could serve as a prognostic marker for future major adverse cardiovascular events (MACE) in patients with coronary artery disease (CAD) through a systematic review and meta-analysis.

    Methods: The MEDLINE, Cochrane, and Embase databases were used for data collection. As of April 2024, 2,871 studies have been identified. Clinical studies comparing MACEs over an observational interval exceeding 12 months in patients with angiographically defined CAD with estimated hazard ratios (HRs) of MACEs in the higher or top-quartile HDL-CEC (H-HDL-CEC) group compared with the lower or bottom-quartile HDL-CEC (L-HDL-CEC) group, after adjusting for six confounding variables, including HDL-C, were included. HRs of 1) overall cardiovascular outcomes, composite of cardiovascular mortality, myocardial infarction, any coronary revascularization, and all-cause mortality (Model-1), and 2) cardiovascular outcomes excluding all-cause mortality from Model-1 (Model-2), compared between the L-HDL-CEC and H-HDL-CEC groups, were estimated using a random-effects model, respectively.

    Results: In five studies, 5,725 patients with CAD with a mean observational interval of 4.9 years were included. The H-HDL-CEC group had significantly lower risks for both estimates (Model-1: HR: 0.34, 95% confidence interval [CI]: 0.18–0.63 [p=0.0005], and I2=59.8% [p=0.04]; Model-2: HR: 0.28, 95% CI: 0.13–0.60 [p=0.0013], and I2=64% [p=0.04]).

    Conclusion: This is the first systematic review and meta-analysis to demonstrate a significant inverse relationship between the baseline HDL-CECs on CAG and long-term MACEs in CAD patients.

  • Nozomi Shimizu, Hiroshige Jinnouchi, Katsuhito Kato, Kazumasa Yamagish ...
    Article type: Original Article
    2025 Volume 32 Issue 4 Pages 502-512
    Published: April 01, 2025
    Released on J-STAGE: April 01, 2025
    Advance online publication: October 24, 2024
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    Aims: Few studies have investigated the impact of sleep duration at night and daytime napping on mortality from aortic disease. In this study, we examined the associations of sleep duration at night with daytime napping and mortality from aortic disease.

    Methods: We followed 67,269 participants (26,826 men and 40,443 women, aged 40–79 years) who were not night shift workers and had no history of stroke, heart disease, or cancer. The baseline survey was conducted in 1988–1990, and follow-up continued until the end of 2009. Sleep duration at night was classified into three categories: ≤ 6, 7, and ≥ 8 hours/day. We also asked the presence or absence of daytime napping. Hazard ratios (HRs) for mortality from aortic disease with 95% confidence intervals (CIs) were estimated using the Cox proportional hazards model.

    Results: During an average 16.3-year follow-up period, we observed 87 deaths from aortic dissection and 82 from aortic aneurysms. There was no association between sleep duration at night and mortality from aortic disease, but daytime napping was associated with an increased risk of mortality from total aortic disease; the multivariable-adjusted HRs were 1.48 [95% CIs: 1.08–2.02]. Furthermore, the stratified analysis revealed a stronger association with medium sleep duration (7 hours at night) compared to the other shorter and longer sleep duration: the multivariable-adjusted HR for aortic disease, 2.02 [1.16–3.52].

    Conclusion: Daytime napping but not sleep duration at night was associated with an increased risk of mortality from aortic disease.

  • Ping-ting Yang, Li Tang, Hui-rong Guo, Yong-mei He, Yue-xiang Qin, Lei ...
    Article type: Original Article
    2025 Volume 32 Issue 4 Pages 513-524
    Published: April 01, 2025
    Released on J-STAGE: April 01, 2025
    Advance online publication: October 22, 2024
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    Aims: Lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD), and its level is genetically determined. Although guidelines and consensuses in various cardiovascular fields have emphasized the importance of Lp(a), screening for Lp(a) in China has not been well studied.

    Methods: A cross-sectional study was conducted using a random sample of 30,000 medical examiners from each of the five health check-up centres. The distribution of Lp(a) was described for those who completed Lp(a) testing, and logistic regression modelling was used to evaluate the relationship between Lp(a) levels and vascular structure and function in the population who underwent carotid ultrasound and brachial‒ankle pulse wave velocity (baPWV) measurements.

    Results: Lp(a) was measured in only 4400 (3.02%) of the 150,000 participants. Among those tested for Lp(a), the median concentration was 15.85 mg/dL. The proportion of participants with Lp(a) levels ≥ 30 mg/dL was 15.00%. Multiple logistic regression analysis revealed a significant correlation between Lp(a) and cIMT ≥ 1.0 mm (OR: 1.008, 95% CI: 1.001-1.014, P=0.020) and carotid artery plaques (OR: 1.010, 95% CI: 1.004-1.016, P=0.001) but no correlation with baPWV ≥ 1400 (OR: 0.999, 95% CI: 0.993-1.005, P=0.788) or baPWV ≥ 1800 (OR: 1.002, 95% CI: 0.993-1.011, P=0.634).

    Conclusions: The detection rate of Lp(a) at health checkups is low, and Lp(a) is positively associated with cervical vascular sclerosis and plaque but not with baPWV. Therefore, the testing rate of Lp(a) and the awareness of the risk of vascular structural changes due to Lp(a) should be further improved.

  • Jiaxu Weng, Xin Qiu, Yingyu Jiang, Hong-Qiu Gu, Xia Meng, Xingquan Zha ...
    Article type: Original Article
    2025 Volume 32 Issue 4 Pages 525-534
    Published: April 01, 2025
    Released on J-STAGE: April 01, 2025
    Advance online publication: November 23, 2024
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    Aims: Clonal hematopoiesis of indeterminate potential (CHIP), which has recently been shown to be an age-related phenomenon, is associated with cardiovascular diseases, including atherosclerosis and stroke. This study focused on the association between CHIP and short- and long-term stroke recurrence in patients with acute ischemic stroke and intracranial atherosclerotic stenosis (ICAS).

    Methods: This study included 4,699 patients with acute ischemic stroke based on data from the Third China National Stroke Registry (CNSR-III), a nationwide prospective hospital-based registry. The ICAS assessment followed the criteria established by the Warfarin-Aspirin Symptomatic Intracranial Disease Study and Brain Imaging. Atherosclerosis Scores (AS) were used to assess the atherosclerosis burden, as determined by the number and severity of steno-occlusions in the intracranial arteries. The primary outcome was stroke recurrence three months and one year after the event.

    Results: Among the 4,699 patients, 3,181 (67.7%) were female, and the median age was 63.0 (55.0–71.0) years. We found that CHIP significantly increased the risk of stroke recurrence at the 1-year follow-up in patients with ICAS (adjusted hazard ratio [HR] 2.71, 95% confidence interval [CI] (1.77–4.16), P for interaction, 0.008).

    Conclusions: Our results revealed that CHIP might have a significant impact on the long-term risk of recurrent stroke, particularly in patients with a higher atherosclerotic burden.

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