Journal of atherosclerosis and thrombosis最新文献

{"title":"Efficacy and Safety of Bempedoic Acid for Hypercholesterolemia in Japan: A Phase 2 Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Dose-Finding Trial.","authors":"Shizuya Yamashita, Hitomi Fujita, Daisuke Yokota, Yuki Morikawa-Isogai, Ryuki Kitamoto","doi":"10.5551/jat.65336","DOIUrl":"https://doi.org/10.5551/jat.65336","url":null,"abstract":"<p><strong>Aim: </strong>We evaluated the efficacy and safety of bempedoic acid, an ATP-citrate lyase inhibitor, at doses of 60, 120, and 180 mg, administered for 12 weeks in conjunction with ongoing treatments (e.g., statin and/or other lipid-modifying therapy) and determined the phase 3 trial dosage in Japanese patients.</p><p><strong>Methods: </strong>This multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 2b trial included patients with hypercholesterolemia at risk for cardiovascular events and an inadequate response to statins/statin intolerance. The percentage change in low-density lipoprotein cholesterol (LDL-C) from baseline to week 12 was calculated.</p><p><strong>Results: </strong>The bempedoic acid 60 mg, 120 mg, 180 mg, and placebo groups included 47, 46, 48, and 47 patients, respectively; 79% of patients had an inadequate response to statins and 21% had statin intolerance. Relative to placebo (-1.9%), LDL-C reduction from baseline to week 12 was significantly greater in the bempedoic acid treatment groups (least squares mean: 60 mg, -10.6%; 120 mg, -21.9%; 180 mg, -21.3%; p＜0.01 vs. placebo). Patients with an inadequate response and statin intolerance who were treated with bempedoic acid showed improved LDL-C levels by week 12. The incidence of treatment-emergent adverse events was higher in the bempedoic acid-treated groups (60 mg, 57.4%; 120 mg, 54.3%; and 180 mg, 58.3%) than in the placebo group (38.3%). There was no increasing trend with increasing doses. Adverse events related to muscular and hepatic disorders were infrequent, and no new or worsening cases of diabetes were reported.</p><p><strong>Conclusions: </strong>The efficacy and safety of bempedoic acid in Japanese patients with elevated LDL-C levels were confirmed. The 180 mg dosage of bempedoic acid was found to be appropriate for a Japanese phase 3 trial.</p>","PeriodicalId":15128,"journal":{"name":"Journal of atherosclerosis and thrombosis","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Challenges of Pediatric Familial Hypercholesteremia Screening in Japan.","authors":"Toru Kikuchi","doi":"10.5551/jat.ED278","DOIUrl":"10.5551/jat.ED278","url":null,"abstract":"","PeriodicalId":15128,"journal":{"name":"Journal of atherosclerosis and thrombosis","volume":" ","pages":"306-307"},"PeriodicalIF":3.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883215/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and Validation of a Cardiovascular Disease Risk Prediction Model for the Japanese Working Population: The Japan Epidemiology Collaboration on Occupational Health Study.","authors":"Huan Hu, Tohru Nakagawa, Toru Honda, Shuichiro Yamamoto, Takeshi Kochi, Hiroko Okazaki, Toshiaki Miyamoto, Takayuki Ogasawara, Naoki Gommori, Makoto Yamamoto, Maki Konishi, Yosuke Inoue, Isamu Kabe, Seitaro Dohi, Tetsuya Mizoue","doi":"10.5551/jat.64919","DOIUrl":"10.5551/jat.64919","url":null,"abstract":"<p><strong>Aims: </strong>This study aimed to develop a cardiovascular disease (CVD) risk model using data from a large occupational cohort.</p><p><strong>Methods: </strong>A risk prediction model was developed using the routine health checkup data of 96,117 Japanese employees (84.0% men) who were 30-64 years of age and had no CVD at baseline. Cox proportional hazards regression models were employed to develop a risk model for assessing the 10-year CVD risk. Measures of discrimination and calibration were used to assess the predictive performance of the model and internal validation was used to examine potential overfitting.</p><p><strong>Results: </strong>During a mean follow-up period of 6.7 years (range, 0.1-11.0 years), 422 cases of incident CVD were confirmed. The final model, which included predictor variables of age, smoking, diabetes, systolic blood pressure, and low- and high-density lipoprotein cholesterol levels, demonstrated a good predictive ability (Harrell's C-statistic, 0.796; 95% confidence interval, 0.775-0.817) with excellent calibration between observed and predicted values. Internal validation revealed minimal overfitting.</p><p><strong>Conclusions: </strong>The developed model can accurately predict the 10-year CVD risk. Because it is based on routine health checkup data, the prediction model can be easily implemented in the workplace. Further studies are required to assess the external validity and transferability of the proposed CVD risk model.</p>","PeriodicalId":15128,"journal":{"name":"Journal of atherosclerosis and thrombosis","volume":" ","pages":"334-344"},"PeriodicalIF":3.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883218/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142287967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Severity, Outcomes, and their Secular Changes in 33,870 Ischemic Stroke Patients with Atrial Fibrillation in a Hospital-Based Registry: Japan Stroke Data Bank.","authors":"Kazunori Toyoda, Sohei Yoshimura, Michikazu Nakai, Shinichi Wada, Kaori Miwa, Junpei Koge, Takashi Yoshida, Kenji Kamiyama, Tatsuya Mizoue, Taketo Hatano, Yasuhisa Yoshida, Yusuke Sasahara, Akiko Ishigami, Yoshitaka Iwanaga, Yoshihiro Miyamoto, Kazuo Minematsu, Shotai Kobayashi, Masatoshi Koga","doi":"10.5551/jat.65117","DOIUrl":"10.5551/jat.65117","url":null,"abstract":"<p><strong>Aim: </strong>Severity, functional outcomes, and their secular changes in acute atrial fibrillation (AF)-associated stroke patients were determined.</p><p><strong>Methods: </strong>Acute ischemic stroke patients with AF in a hospital-based, multicenter, prospective registry from January-2000 through December-2020, were compared with those without AF. The co-primary outcomes were the initial severity assessed by the NIH Stroke Scale (NIHSS) score and favorable outcome assessed by the modified Rankin Scale scores 0-2 at hospital discharge.</p><p><strong>Results: </strong>Of the 142,351 patients studied, 33,870 had AF. AF patients had higher NIHSS scores (median 9 vs. 3, adjusted coefficient 5.468, 95% CI 5.354-5.582) than non-AF patients. Favorable outcome was less common in AF patients than in non-AF patients in the unadjusted analysis (48.4% vs. 70.4%), but it was more common with adjustment for the NIHSS score and other factors (adjusted OR 1.110, 95% CI 1.061-1.161). In AF patients, the NIHSS score decreased throughout the 21-year period (adjusted coefficient -0.088, 95% CI -0.115 - -0.061 per year), and the reduction was steeper than in non-AF patients (P＜0.001). In AF patients, favorable outcome became more common over the period (adjusted OR 1.018, 95% CI 1.010-1.026), and the increase was steeper than in non-AF patients (P＜0.001); the increase was no longer significant after further adjustment by reperfusion therapy.</p><p><strong>Conclusions: </strong>Initial stroke severity became milder and functional outcomes improved in AF patients over the 21-year period. These secular changes were steeper than in non-AF patients, suggesting that AF-associated stroke seemed to reap more benefit of recent development of stroke care than stroke without AF.</p>","PeriodicalId":15128,"journal":{"name":"Journal of atherosclerosis and thrombosis","volume":" ","pages":"308-320"},"PeriodicalIF":3.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142093190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Action Required to Maximize Protection against Ischemic Stroke among Patients with Atrial Fibrillation.","authors":"Hisatomi Arima","doi":"10.5551/jat.ED274","DOIUrl":"10.5551/jat.ED274","url":null,"abstract":"","PeriodicalId":15128,"journal":{"name":"Journal of atherosclerosis and thrombosis","volume":" ","pages":"304-305"},"PeriodicalIF":3.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883217/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adequate Vegetable Intake Improves Metabolic Indices in Healthy Japanese Participants: A Randomized Crossover Study.","authors":"Yuka Kawakami-Shinoda, Megumi Sato, Alima Bao, Xiangna Zheng, Mana Kamiya, Ge Li, Toshio Hosaka, Toshinao Goda, Hidekazu Arai","doi":"10.5551/jat.64509","DOIUrl":"10.5551/jat.64509","url":null,"abstract":"<p><strong>Aim: </strong>We aimed to elucidate the effect of a healthy diet containing adequate amounts of protein and vegetables on metabolic indices.</p><p><strong>Methods: </strong>In this randomized crossover study, twenty-two healthy Japanese participants ingested two different test meals: fish diet (F) or fish diet with adequate vegetable content (FV). Each 5-day diet load test was separated by a washout period of at least seven days. Metabolic indices were measured in fasting blood and 24-h urine samples.</p><p><strong>Results: </strong>The delta (Δ) plasma glucose and Δserum low-density lipoprotein (LDL) cholesterol concentrations were significantly larger in the participants in group FV than in group F (p=0.042, p=0.013, respectively). The urinary pH in participants in group F on day 6 was significantly lower than on day 1 (p=0.008), and the Δurinary pH and Δnet gastrointestinal absorption of alkali of participants in group FV tended to be smaller than in group F (p=0.070, p=0.075, respectively).</p><p><strong>Conclusions: </strong>This study showed that a healthy diet containing adequate protein and vegetables reduced the dietary acid load and improved plasma glucose and serum LDL concentrations in healthy Japanese participants.</p>","PeriodicalId":15128,"journal":{"name":"Journal of atherosclerosis and thrombosis","volume":" ","pages":"356-366"},"PeriodicalIF":3.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142287965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New Approaches to Lipoproteins for the Prevention of Cardiovascular Events.","authors":"Masashi Fujino, Giuseppe Di Giovanni, Stephen J Nicholls","doi":"10.5551/jat.RV22031","DOIUrl":"10.5551/jat.RV22031","url":null,"abstract":"<p><p>Atherosclerotic cardiovascular disease (ASCVD) is a leading global cause of mortality, and recent research has underscored the critical role of lipoproteins in modulating cardiovascular (CV) risk. Elevated low-density lipoprotein cholesterol (LDL-C) levels have been linked to increased CV events, and while numerous trials have confirmed the efficacy of lipid-lowering therapies (LLT), significant gaps remain between recommended LDL-C targets and real-world clinical practice. This review addresses care gaps in LLT, emphasizing the necessity for innovative approaches that extend beyond LDL-C management. It explores combination therapy approaches such as statins combined with ezetimibe or PCSK9 inhibitors, which have shown promise in enhancing LDL-C reduction and improving outcomes in high-risk patients. Additionally, this review discusses new approaches in lipid modification strategies, including bempedoic acid, inclisiran, and drugs that lower Lp(a), highlighting their potential for CV risk reduction. Furthermore, it emphasizes the potential of polygenic risk scores to guide LLT and lifestyle changes despite challenges in implementation and genetic testing ethics. This article discusses the current guidelines and proposes innovative approaches for optimizing lipoprotein management, ultimately contributing to improved patient outcomes in ASCVD prevention.</p>","PeriodicalId":15128,"journal":{"name":"Journal of atherosclerosis and thrombosis","volume":" ","pages":"265-280"},"PeriodicalIF":3.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Apolipoprotein E Variants: A Review of Naturally Occurring Variants and Clinical Features.","authors":"Akira Matsunaga, Takao Saito","doi":"10.5551/jat.65393","DOIUrl":"10.5551/jat.65393","url":null,"abstract":"<p><p>Apolipoprotein E (apoE) is a key apoprotein in lipid transport and is susceptible to genetic mutations. ApoE variants have been studied for four decades and more than a hundred of them have been reported. This paper presents an up-to-date review of the function and structure of apoE in lipid metabolism, the E2, E3, and E4 isoforms, the APOE gene, and various pathologies, such as familial type III hyperlipidemia and lipoprotein glomerulopathy, caused by apoE variants. Alzheimer's disease was barely mentioned in this paper. But this review should help researchers obtain a comprehensive overview of human apoE in lipid metabolism.</p>","PeriodicalId":15128,"journal":{"name":"Journal of atherosclerosis and thrombosis","volume":" ","pages":"281-303"},"PeriodicalIF":3.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142949402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Changes in Lifestyle and Psychological Factors on the Incidence of Metabolic Syndrome after the Great East Japan Earthquake: Follow-up of the Fukushima Health Management Survey.","authors":"Atsushi Takahashi, Fumikazu Hayashi, Tetsuya Ohira, Michio Shimabukuro, Akira Sakai, Masaharu Maeda, Mitsuaki Hosoya, Junichiro J Kazama, Koichi Hashimoto, Shiho Sato, Hironori Nakano, Masanori Nagao, Kanako Okazaki, Hitoshi Ohto, Seiji Yasumura, Hiromasa Ohira","doi":"10.5551/jat.64923","DOIUrl":"10.5551/jat.64923","url":null,"abstract":"<p><strong>Aim: </strong>The Fukushima Daiichi Nuclear Power Plant accident caused lifestyle changes and psychological distress in residents living near the plant. This study clarified the associations between changes in residents' lifestyles and psychological factors with the onset of metabolic syndrome (METs) after the accident.</p><p><strong>Methods: </strong>This longitudinal study included 10,373 residents who underwent the Comprehensive Health Check and Mental Health and Lifestyle Survey in Fiscal Year (FY) 2013. Follow-up surveys were conducted between FY 2014 and FY 2017. Lifestyle changes and the METs incidence were evaluated using a logistic regression model.</p><p><strong>Results: </strong>METs developed in 14.0% of subjects. In addition to metabolic factors, such as the body mass index, hypertension, dyslipidemia, and diabetes mellitus, there were differences in physical activity, fast walking, eating fast, eating habits before bedtime, skipping breakfast, current smoking, and alcohol intake between subjects with and without new-onset METs. Eating fast, current smoking, and drinking alcohol were positively associated with new-onset METs, whereas starting physical activity and fast walking were inversely associated with new-onset METs.</p><p><strong>Conclusions: </strong>Disaster-related lifestyle changes, such as eating fast, starting to smoke, and continued alcohol intake, were risk factors for new-onset METs after the Fukushima Daiichi Nuclear Power Plant accident.</p>","PeriodicalId":15128,"journal":{"name":"Journal of atherosclerosis and thrombosis","volume":" ","pages":"345-355"},"PeriodicalIF":3.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142287968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel ELISA System for Measuring Modified LDL-Adiponectin Complex.","authors":"Mai Sasaoka, Akemi Kakino, Roberto Villalobos-Labra, Yuki Yamashita, Floor Spaans, Satoru Joshita, Hiroshi Hosoda, Takeshi Uehara, Chu-Huang Chen, Sandra T Davidge, Tatsuya Sawamura","doi":"10.5551/jat.65377","DOIUrl":"https://doi.org/10.5551/jat.65377","url":null,"abstract":"<p><strong>Aim: </strong>Adiponectin is an anti-diabetic and anti-atherogenic protein secreted primarily from adipose tissue. Adiponectin and modified LDL (mLDL) form a complex to modulate their biological activity. To elucidate the significance of the complex formation, we analyzed its effects on vascular tissue and developed and verified novel quantifying methods for adiponectin.</p><p><strong>Methods: </strong>To study the significance of the mLDL-adiponectin complex (MAC) formation, we used the wire-myography method on rat mesenteric artery. We developed a method to measure MAC by using LOX-1 as the capture protein and anti-adiponectin antibody for detection. We compared serum MAC levels between hemodialysis patients and control subjects.</p><p><strong>Results: </strong>Administering mLDL alone to rat mesenteric artery impaired endothelium-dependent vasorelaxation, whereas simultaneously administering adiponectin with mLDL protected rat mesenteric artery from the mLDL-induced impairment of vasorelaxation. This finding indicates MAC formation prevents endothelium from mLDL-induced dysfunction in tissue. Using our novel ELISA for MAC, we found that MAC was increasingly detectable depending on the doses of mLDL and adiponectin in vitro. In serum, hemodialysis patients showed a significantly higher ratio of MAC-high patients (higher than the median level of MAC) than did healthy controls. Furthermore, the MAC-high hemodialysis group had lower mLDL activity measured as LOX-1 ligand containing apoB.</p><p><strong>Conclusion: </strong>Using our ELISA, we detected MAC in human serum that protected blood vessels from the deleterious effects of oxidized LDL.</p>","PeriodicalId":15128,"journal":{"name":"Journal of atherosclerosis and thrombosis","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}