Kerollos Abdelsayed, Qasi Najah, Ahmed Almahdy Mohamed, Basma Ehab Amer, Ahmed Eltanbedawi, Basel Abdelazeem, Arvind Kunadi, Daniel Brito
{"title":"Prognostic implications of factor VIII levels in African Americans: insights from a propensity-matched US-based multicenter retrospective analysis.","authors":"Kerollos Abdelsayed, Qasi Najah, Ahmed Almahdy Mohamed, Basma Ehab Amer, Ahmed Eltanbedawi, Basel Abdelazeem, Arvind Kunadi, Daniel Brito","doi":"10.1007/s11239-025-03119-w","DOIUrl":"https://doi.org/10.1007/s11239-025-03119-w","url":null,"abstract":"<p><p>Elevated levels of coagulation factor VIII (FVIII) are more commonly observed in African Americans (AAs) and have been linked to higher risks of thromboembolism and other cardiovascular comorbidities. However, the prognostic implications of elevated FVIII levels in AAs have not been well-studied. We queried the TriNetX (August 2005 to August 2019) to compare AAs with FVIII > 200% to those with 50-200%. A propensity score match (PSM) was used to adjust for potential confounders. Primary outcomes were assessed within five years after the index FVIII and included major adverse cardiovascular events (MACE), while exploratory outcomes included venous thromboembolism (VTE), cerebrovascular events, new-onset heart failure (HF), HF exacerbations, and all-cause mortality. A survival analysis using log-rank tests, Kaplan-Meier curves, and a univariate Cox regression was performed to investigate the association of FVIII with the time to development of each outcome after PSM through the hazard ratio (HR). A multivariate-adjusted analysis was performed before PSM for select outcomes. An E-sensitivity analysis was implemented to assess the association of unmeasured confounders post-PSM. Initially, 11,199 patients were identified from the TriNetX database. After PSM, 3,833 patients with balanced baseline characteristics were included in each cohort. Patients with elevated FVIII had a higher 5-year risk of MACE (HR: 1.14, 95% CI: 1.02-1.27, P = 0.017), VTE (HR: 1.23, 95% CI: 1.11-1.35, P < 0.001), new-onset HF (HR: 1.41, 95% CI: 1.14-1.74, P = 0.001), and mortality (HR: 1.37, 95% CI: 1.20-1.57, P < 0.001). In adjusted models, the association between FVIII and new-onset HF attenuated after accounting for vWF and comorbidities, while the mortality risk remained significant (HR: 1.53, 95% CI: 1.34-1.73, P < 0.001). No significant association was found between FVIII and HF exacerbation. Elevated FVIII levels in AAs are linked to a higher risk of adverse cardiovascular outcomes, including new-onset HF. Future research should explore the dynamic interaction of FVIII with these outcomes, including its potential causal role and its use as a marker for the development of these conditions.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Philipp Drees, Irene Schmidtmann, Manuel Herbst, Dorothea Becker, Stefano Barco, Frederikus A Klok, Karsten Keller, Lukas Hobohm, Konstantinos C Christodoulou, Christina Abele, Rupert Bauersachs, Walter Ageno, Erik Lerkevang Grove, Henrik Kehlet, Friedhelm Hufen, Thomas Klonschinski, Yama Afghanyar, Lukas Eckhard, Nadine Martin, Susanne Fischer, Stanislav Gorbulev, Dominik Rath, Anna C Mavromanoli, Claude Jabbour, Irene Lang, Francis Couturaud, Christian Heiss, Harald Binder, Stavros Konstantinides
{"title":"Enhanced recovery and abbreviated length of anticoagulation for thromboprophylaxis after primary hip arthroplasty rationale and design of the ENABLE-hip trial.","authors":"Philipp Drees, Irene Schmidtmann, Manuel Herbst, Dorothea Becker, Stefano Barco, Frederikus A Klok, Karsten Keller, Lukas Hobohm, Konstantinos C Christodoulou, Christina Abele, Rupert Bauersachs, Walter Ageno, Erik Lerkevang Grove, Henrik Kehlet, Friedhelm Hufen, Thomas Klonschinski, Yama Afghanyar, Lukas Eckhard, Nadine Martin, Susanne Fischer, Stanislav Gorbulev, Dominik Rath, Anna C Mavromanoli, Claude Jabbour, Irene Lang, Francis Couturaud, Christian Heiss, Harald Binder, Stavros Konstantinides","doi":"10.1007/s11239-025-03110-5","DOIUrl":"https://doi.org/10.1007/s11239-025-03110-5","url":null,"abstract":"<p><p>Surgical total hip arthroplasty (THA) is associated with high risk of venous thromboembolism (VTE), but the appropriate duration of postoperative anticoagulation remains controversial. \"Enhanced Recovery and Abbreviated Length of Anticoagulation for Thromboprophylaxis After Primary Hip Arthroplasty\" (ENABLE-Hip) is a multicenter investigator-initiated and academically sponsored randomized double-blind active-control non-inferiority trial. Patients will be mobilized early after surgery, following a standardized enhanced recovery protocol. After an initial open-label prophylactic anticoagulation as per local standard of care until day 2 after surgery, treatment with rivaroxaban (10 mg once daily) will be started on day 3 and continued until day 10. Subsequently, patients will be switched to placebo in the experimental arm, or continue on active drug in the control arm, until a total of 35 days. The primary endpoint is acute symptomatic or fatal VTE within 3 months. A sample size of 2,932 patients will provide ≥ 80% power to reject the null hypothesis that δ ≥ 0.01 (δ = difference between the two arms in symptomatic VTE probability) at a significance level α = 0.05. An interim analysis will be performed after 3-month follow-up of the first 1,760 randomized patients at a significance level α = 0.50, leading to stop for futility if significance is not obtained, or if recalculation yields a sample size of > 3,200 patients. ENABLE-Hip will be the first major randomized trial to test an overall reduction in the duration of post-THA thromboprophylaxis and will inform future guideline recommendations concerning this continuously growing patient population.Trial registration: ClinicalTrials.gov Identifier: NCT06611319.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Clinical outcomes of off-label DOAC underdosing in Japanese patients with atrial fibrillation: a systematic review and meta-analysis.","authors":"Akinori Sairaku, Yuka Kimura, Yukiko Nakano","doi":"10.1007/s11239-025-03107-0","DOIUrl":"https://doi.org/10.1007/s11239-025-03107-0","url":null,"abstract":"<p><p>Japanese patients with atrial fibrillation (AF) often receive underdosed direct oral anticoagulants (DOACs), deviating from standard guidelines. The impact of underdosing compared to standard dosing on thromboembolic and bleeding risks in this population remains unclear. This meta-analysis included 13 studies with 37,633 Japanese AF patients comparing underdose and standard dose groups. Efficacy outcomes included stroke or systemic embolism and ischemic stroke. Safety outcomes were major bleeding, intracranial hemorrhage, gastrointestinal bleeding, all bleeding, and all-cause mortality. Hazard ratios and 95% confidence intervals were pooled using a random-effects model. Sensitivity analyses evaluated robustness by including studies with confounder controls. Underdosing showed similar risks of stroke or systemic embolism (HR 1.03, 95% CI 0.87-1.22) and ischemic stroke (HR 1.05, 95% CI 0.85-1.31) compared to standard dosing. Major bleeding (HR 0.86; 95% CI 0.72-1.04) and all bleeding (HR 0.80; 95% CI 0.63-1.03) showed a non-significant reduction with underdosing. Sensitivity analyses confirmed a significant reduction in major bleeding risk with underdosing (HR 0.77, 95% CI 0.64-0.94). All-cause mortality was significantly higher in the underdose group throughout the primary (HR 1.47, 95% CI 1.13-1.90) and sensitivity analyses. In conclusion, Japanese patients receiving an underdose of DOACs had thromboembolic event rates comparable to those seen with standard dosing, with a reduction in bleeding events confirmed by sensitivity analyses and higher mortality. These findings indicate that ethnic-specific factors may influence DOAC effects, warranting further investigation to validate these observations and inform tailored dosing recommendations for Japanese AF patients.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Edoxaban treatment without initial heparin lead-in for acute venous thromboembolism: insight from the COMMAND VTE registry-2.","authors":"Yuta Tsujisaka, Yugo Yamashita, Takeshi Morimoto, Ryuki Chatani, Kazuhisa Kaneda, Yuji Nishimoto, Nobutaka Ikeda, Yohei Kobayashi, Satoshi Ikeda, Kitae Kim, Moriaki Inoko, Toru Takase, Shuhei Tsuji, Maki Oi, Takuma Takada, Kazunori Otsui, Jiro Sakamoto, Yoshito Ogihara, Takeshi Inoue, Shunsuke Usami, Po-Min Chen, Kiyonori Togi, Norimichi Koitabashi, Seiichi Hiramori, Kosuke Doi, Hiroshi Mabuchi, Yoshiaki Tsuyuki, Koichiro Murata, Kensuke Takabayashi, Hisato Nakai, Daisuke Sueta, Wataru Shioyama, Tomohiro Dohke, Ryusuke Nishikawa, Koh Ono, Takeshi Kimura","doi":"10.1007/s11239-025-03105-2","DOIUrl":"https://doi.org/10.1007/s11239-025-03105-2","url":null,"abstract":"<p><p>The package insert of edoxaban for acute venous thromboembolism (VTE) recommended administration following initial parenteral anticoagulation including heparin. We explored the effectiveness and safety of edoxaban for acute VTE without initial heparin lead-in treatment. The COMMAND VTE Registry-2 is a multicenter registry enrolling 5197 consecutive acute symptomatic VTE patients in Japan between January 2015 and August 2020. The current study population consisted of 1842 patients with acute VTE treated with edoxaban. The baseline characteristics and clinical outcomes were compared between the 2 groups with or without initial heparin lead-in treatment stratified by pulmonary embolism (PE) (848 patients) and deep vein thrombosis (DVT) only (994 patients). Propensity score (PS) matching analysis was performed to balance potential baseline differences. PE and DVT patients without heparin lead-in treatment accounted for 225 (27%) and 750 (75%), respectively. PS matching provided 195 pairs of PE patients and 224 pairs of DVT patients. There was no significant difference between the no heparin and heparin groups in the cumulative 30-day incidence of all-cause death (PE: 2.6% vs. 4.2%, P = 0.40; DVT: 2.7% vs. 3.2%, P = 0.78) and a composite of all-cause death, recurrent VTE, or major bleeding (PE: 5.8% vs. 8.4%, P = 0.32; DVT: 4.6% vs. 6.4%, P = 0.41). In the current real-world VTE registry, a substantial proportion of patients with acute VTE were treated with edoxaban without initial heparin lead-in treatment. There was no obvious signal suggesting worse short-term clinical outcomes with edoxaban treatment without versus with initial heparin lead-in treatment.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Outcomes of patients with in-hospital stroke with and without active cancer.","authors":"Hiroyuki Kawano, Ayumi Sakurai, Yuuki Takizawa, Risa Toyota, Reona Miwa, Hayate Onuki, Ayane Kawatake, Atsushi Yamamichi, Mikito Saito, Kaoru Nakanishi, Eisaku Tsuji, Shinya Tomari, Yuko Honda, Yoshiko Unno, Mayumi Uchida, Teruyuki Hirano","doi":"10.1007/s11239-025-03117-y","DOIUrl":"https://doi.org/10.1007/s11239-025-03117-y","url":null,"abstract":"<p><strong>Background: </strong>Cancer is common in patients with ischemic stroke. The aim was to reveal the differences in acute management and outcomes of patients with in-hospital acute ischemic stroke (IHS) with and without active cancer.</p><p><strong>Methods: </strong>Two hundred IHS patients (58% male, median age 78 years, median NIHSS score 9) from August 2016 to July 2023 at our institution were divided into two groups: 70 with active cancer (IHS-AC 35%) and 130 without AC (IHS-nonAC 65%). Patients' characteristics, time intervals, and clinical outcomes were compared between the groups. A good clinical outcome was defined as modified Rankin Scale score 0-3.</p><p><strong>Results: </strong>IHS was identified most frequently by a nurse (IHS-AC group 67%, IHS-nonAC group 71%). Time from recognition to stroke physician assessment (37 vs. 90 min, p = 0.008) was shorter in the IHS-AC group. Good clinical outcomes at discharge (31% in each group, p = 1.000) and in-hospital mortality (IHS-AC group 29%, IHS-nonAC group 21%, p = 0.225) were similar in the groups. The rates of reperfusion therapy (intravenous rt-PA and/or mechanical thrombectomy) were 16% in the IHS-AC group and 15% in the IHS-nonAC group (p = 1.000). The rates of good clinical outcomes and mortality at discharge in patients with reperfusion therapy were each 36%.</p><p><strong>Discussion and conclusion: </strong>One-third of IHS patients had comorbid active cancer. The rates of reperfusion therapy and good clinical outcomes were similar in groups with and without active cancer. Acute stroke management should not be withheld solely based on cancer.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144159586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Valéria Tavares, Catarina Lopes, Catarina Macedo-Silva, Mónica Farinha, João Costa, Maria Isabel Vilas-Boas, Sofia Pinelas, Joana Assis, Mário Dinis-Ribeiro, Deolinda Pereira, Carina Pereira, Rui Medeiros
{"title":"Genetic markers of thrombophilia as predictors of outcome in colorectal cancer.","authors":"Valéria Tavares, Catarina Lopes, Catarina Macedo-Silva, Mónica Farinha, João Costa, Maria Isabel Vilas-Boas, Sofia Pinelas, Joana Assis, Mário Dinis-Ribeiro, Deolinda Pereira, Carina Pereira, Rui Medeiros","doi":"10.1007/s11239-025-03106-1","DOIUrl":"https://doi.org/10.1007/s11239-025-03106-1","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is the second leading cause of malignancy-related death worldwide, representing a significant health concern. Understanding the disease pathogenesis and identifying potential prognostic biomarkers is critical for improving patients' clinical outcomes. Haemostatic components implicated in cancer-associated thrombosis (CAT) seem to favour CRC progression. As such, genetic markers of thrombophilia might be potential prognostic biomarkers among patients with this malignant disease. To offer perspectives, a retrospective cohort study with 204 CRC patients was conducted to investigate the impact of seven germline haemostatic gene determinants on patient prognosis. A sex-stratified analysis was performed as the variants seem to have a distinct influence depending on the patient's sex. Genomic DNA was extracted from FFPE samples enriched in tumour cells. While the polymorphisms CNTN6 rs6764623 (CC/CA vs. AA; adjusted hazard ratio (aHR) = 0.44; 95% confidence interval (CI), 0.20-0.96; P = 0.040), PTGS2 rs20417 (GG vs. CC/CG; aHR = 2.88; 95%CI, 1.10-7.51; P = 0.031) and RGS7 rs2502448 (TT vs. CT/CC; aHR = 2.35; 95%CI, 1.20-4.61; P = 0.013) were associated with the five-year risk of cancer recurrence, ITGB3 rs5918 was a predictor of the risk of death due to all causes, particularly among male patients (TT vs. CT/CC; aHR = 2.05; 95% confidence interval (CI), 1.13-3.72; P = 0.019). While a sex-specific impact of the SNPs was observed, further investigation in larger cohorts, particularly with an increased representation of female patients, is required to confirm these associations. Collectively, these markers could help improve the prognosis assessment of CRC patients towards a more personalised intervention.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144159582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mon4 as a novel monocyte subset with distinct profile and predictor of poor outcomes in individuals with myocardial infarction.","authors":"Maxime Boidin, Gregory Y H Lip, Eduard Shantsila","doi":"10.1007/s11239-025-03111-4","DOIUrl":"https://doi.org/10.1007/s11239-025-03111-4","url":null,"abstract":"<p><p>Recently, a new monocyte subset known as Mon4, characterized by distinct gene expressions, has been identified but remains poorly characterized. In this study, our objective was to comprehensively characterise Mon4 in healthy individuals and explore its correlation with major adverse cardiovascular events (MACE) in patients with ST-elevation myocardial infarction (STEMI). Our study enrolled 20 healthy individuals and 245 STEMI patients who underwent primary percutaneous coronary intervention (PCI). We analysed monocyte subsets using flow cytometry and collected bone marrow samples from 11 healthy individuals. Cardiac function assessments were performed in STEMI patients through echocardiography within 3 days post-PCI. Mon4 displayed significant differences compared to Mon1, Mon2, and Mon3 in various parameters among healthy individuals, underscoring its distinct profile. In STEMI patients, above-median Mon4 counts were associated with a increased risk of MACE (hazard ratio [HR] 3.11, 95% confidence interval [CI] 1.55-6.24, p = 0.01) and heart failure (HR 3.25, 95% CI 1.14-9.24, p = 0.03) after adjusting for other predictive factors. This study highlights the unique characteristics of Mon4 and its clinical significance. The distinctive gene signature of Mon4, coupled with its association with MACE and heart failure, suggests its potential utility as a biomarker for risk assessment in MI patients. Further investigations are warranted to explore the therapeutic potential of targeting Mon4 in reducing cardiovascular complications following MACE.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Madeline K Mahowald, Luis Ortega-Paz, Claudio Laudani, Dominick J Angiolillo
{"title":"Antiplatelet therapy following conservatively managed spontaneous coronary artery dissection.","authors":"Madeline K Mahowald, Luis Ortega-Paz, Claudio Laudani, Dominick J Angiolillo","doi":"10.1007/s11239-025-03114-1","DOIUrl":"https://doi.org/10.1007/s11239-025-03114-1","url":null,"abstract":"<p><p>Spontaneous coronary artery dissection (SCAD) is a relatively uncommon but increasingly recognized etiology of acute coronary syndrome (ACS). Conservative management is generally recommended, but optimal medical therapy is unknown. The majority of patients are discharged on dual antiplatelet therapy consisting of aspirin and a P2Y12 inhibitor based on trials and guidelines developed for ACS caused by plaque rupture and subsequent platelet activation and aggregation. Observational trials have shown conflicting results on the effects of antiplatelet therapy on major adverse cardiac events after SCAD. This manuscript provides a review of the available data, including a meta- analysis, and offers recommendations for antiplatelet therapy after conservatively managed SCAD in clinical practice.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhang Lingyu, Zhong Wanting, Guo Ying, Jin Qianqian, Wang Chunfang
{"title":"Association of lipid-lowering drugs with venous thromboembolism outcomes: a phenome-wide association study and a drug-target Mendelian randomization study.","authors":"Zhang Lingyu, Zhong Wanting, Guo Ying, Jin Qianqian, Wang Chunfang","doi":"10.1007/s11239-025-03108-z","DOIUrl":"https://doi.org/10.1007/s11239-025-03108-z","url":null,"abstract":"<p><p>Common anticoagulants can lead to potentially fatal internal bleeding, which restricts their extensive use in the prevention of Venous thromboembolism (VTE). We aimed to use a PheWAS and MR analysis to find novel therapeutic targets for VTE events(containing pulmonary embolism (PE) and deep vein thrombosis (DVT)) and offer new opportunities to develop safer and more effective preventative medications. The present study utilized a PheWAS analysis to examine 2005 health-related phenotypes from the MRC-IEU consortium on VTE risk genetic variants to pinpoint possible treatment targets. Subsequently, through Summary-data-based MR (SMR) and inverse-variance-weighted MR (IVW-MR) analysis, we assessed the associations between lipid-lowering drug targets (including HMGCR inhibitor, PCSK9 inhibitor, and NPC1L1 inhibitor) and VTE events. We utilized two types of genetic instruments to represent the exposure to lipid-lowering drugs: eQTLs of drug target genes and genetic variants within or near drug target genes associated with LDL cholesterol from genome-wide association studies. PheWAS analysis identified 13 cholesterol-related traits significantly associated with VTE risk, indicating lipid-lowering drugs might be targets of VTE outcomes. SMR analysis showed that higher NPC1L1 gene expression in the blood was a risk factor for PE (OR = 1.107, 95%CI = 1.026-1.195; p = 0.009). Additionally, an IVW-MR association was found between LDL mediated by NPC1L1 and blood clot in the lung (OR = 4.091, 95% CI = 1.375-12.173; p = 0.011). This study suggested a potential causal relationship between NPC1L1 inhibition and the reduced risk of PE.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Decreased circulating microRNA-22 expression as a potential biomarker for predicting a higher risk of recurrent ischemic stroke related to inner carotid artery stenosis: a multicenter study.","authors":"Li-Yang Wen, Na Qi, Shi-Yan Li","doi":"10.1007/s11239-025-03112-3","DOIUrl":"https://doi.org/10.1007/s11239-025-03112-3","url":null,"abstract":"<p><p>Carotid endarterectomy has proved to be beneficial in the prevention of stroke in patients with carotid artery stenosis ≥ 70%, while the benefit in symptomatic patients with moderate stenosis (50-69%) was undetermined, and some of them may be at higher risk of recurrent ipsilateral stroke (RIS). To date, it's hard to define vulnerable populations and novel biomarkers should be exploited. Thus, we aim to explore the predictive role of miR-22 in the presence of RIS and the prognosis of symptomatic patients with moderate stenosis. 400 patients were prospectively recruited, and miR-22 levels were assessed. The incidence of RIS and major adverse cardiovascular and cerebrovascular events (MACCE)-free survival were presented and the risk factors for RIS and MACCE-free survival were investigated. The area under the curve (AUC) was also investigated for RIS. The degree of carotid artery stenosis was negatively associated with miR-22 level (P < 0.001). The median value of miR-22 was 4.16 in the overall distribution, patients with miR-22 levels ≥ 4.16 had a significantly improved MACCE-free survival (P = 0.012) and lower incidence of RIS (P = 0.020) compared with miR-22 levels < 4.16. The multivariable cox regression analysis demonstrated that patients with lower miR-22 levels were prone to the presence of RIS (P < 0.001). The AUC of miR-22 in predicting RIS was 0.662 (95% CI, 0.550-0.774). This study implies that lower miR-22 levels may play a predictive role in the higher incidence of RIS in patients with moderate stenosis. Moreover, lower miR-22 levels can also prognosticate a higher risk for MACCE in these patients.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}