Normal cardiac tissue glucose homeostasis is essential for the physiological function of the heart and the prevention of diabetic cardiomyopathies. The onset of diabetes mellitus has been reported to precede cardiovascular complications including cardiomyopathy, aortic stenosis, cardiac hypertrophy and hypertension. In addition to metabolic derangements, chronic medications such as HIV-antiretrovirals have also been associated with the risk factors of CVDs such as insulin resistance, dyslipidaemia, inflammation and oxidative stress and impaired glucose tolerance. Previous ART regimens have been associated with systemic insulin resistance and ectopic fat accumulation, leading to impaired glucose tolerance. The underlying molecular mechanisms behind the development of diabetic cardiomyopathies in persons chronically taking HIV-antiretrovirals remains unclear. Prediabetes is a condition of impaired glucose tolerance that is associated with low-grade inflammation and oxidative stress, which are precursors of CVDs. The link between chronic HIV-antiretroviral medication and prediabetes remains elusive. However, the increase in dispensation of HIV-antiretroviral medications has been associated with an increase in cases of prediabetes and diabetes, which could contribute to the development of CVDs. Hence, this review aims to provide insight into how the use of ARVs interacts with glucose metabolism and cardiovascular disease risk factors in patients on chronic HIV antiretrovirals.
{"title":"HIV-pharmacotherapy and pathogenesis of diabetes-induced cardiovascular complications: An updated narrative review.","authors":"Khanyisa Maswanganyi,Andile Khathi,Mlindeli Gamede","doi":"10.1093/cvr/cvag036","DOIUrl":"https://doi.org/10.1093/cvr/cvag036","url":null,"abstract":"Normal cardiac tissue glucose homeostasis is essential for the physiological function of the heart and the prevention of diabetic cardiomyopathies. The onset of diabetes mellitus has been reported to precede cardiovascular complications including cardiomyopathy, aortic stenosis, cardiac hypertrophy and hypertension. In addition to metabolic derangements, chronic medications such as HIV-antiretrovirals have also been associated with the risk factors of CVDs such as insulin resistance, dyslipidaemia, inflammation and oxidative stress and impaired glucose tolerance. Previous ART regimens have been associated with systemic insulin resistance and ectopic fat accumulation, leading to impaired glucose tolerance. The underlying molecular mechanisms behind the development of diabetic cardiomyopathies in persons chronically taking HIV-antiretrovirals remains unclear. Prediabetes is a condition of impaired glucose tolerance that is associated with low-grade inflammation and oxidative stress, which are precursors of CVDs. The link between chronic HIV-antiretroviral medication and prediabetes remains elusive. However, the increase in dispensation of HIV-antiretroviral medications has been associated with an increase in cases of prediabetes and diabetes, which could contribute to the development of CVDs. Hence, this review aims to provide insight into how the use of ARVs interacts with glucose metabolism and cardiovascular disease risk factors in patients on chronic HIV antiretrovirals.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"40 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146088914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Architects of decay: How fibroblast-like mesenchymal cells shape the necrotic core.","authors":"Yusuke Adachi,Alyssa Grogan,Aloke V Finn","doi":"10.1093/cvr/cvag025","DOIUrl":"https://doi.org/10.1093/cvr/cvag025","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"64 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146056774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to: Cardioprotection induced by a brief exposure to acetaldehyde: role of aldehyde dehydrogenase 2.","authors":"","doi":"10.1093/cvr/cvaf277","DOIUrl":"https://doi.org/10.1093/cvr/cvaf277","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"42 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146056845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Laura Pala,María Torres-López,Stuart T Caldwell,Joyce Valadares,Emily M Smith,Katherine L Hammond,Olga Sauchanka,Jiro Abe,Thomas Krieg,Richard C Hartley,Michael P Murphy,Hiran A Prag
BACKGROUNDSuccinate accumulates significantly during myocardial ischemia, and its rapid oxidation upon reperfusion is a critical driver of ischemia/reperfusion (I/R) injury. The transport of succinate across the mitochondrial inner membrane, particularly by the dicarboxylate carrier (DIC; SLC25A10), is hypothesized to play a crucial role in mediating these pathological succinate dynamics. However, tools to test this hypothesis by modulating mitochondrial succinate transport in biological systems are lacking.METHODS AND RESULTSC57BL/6J mice, isolated Wistar Rat heart mitochondria, bovine heart mitochondrial membranes, C2C12 mouse myoblasts and primary adult cardiomyocytes were used as in vitro and in vivo models. Butylmalonate prodrugs were synthesized and tested. Isolated mitochondria were used to assess succinate-dependent respiration and reactive oxygen species (ROS) production. Cells were treated with succinate dehydrogenase (SDH) inhibitors or exposed to anoxia and butylmalonate esters. Mouse hearts were subjected to in vivo left anterior descending coronary artery ligation. Succinate and butylmalonate levels were measured by targeted liquid chromatography-tandem mass spectrometry, and infarct size by TTC (2,3,5-triphenyl-2H-tetrazolium chloride) staining.Knockdown of DIC, but not of the oxoglutarate carrier OGC, in C2C12 cells prevented succinate accumulation by SDH inhibition and anoxia. The only extant DIC inhibitor butylmalonate, is limited by poor cell permeability. We synthesized diacetoxymethyl butylmalonate (DAB), which efficiently delivers butylmalonate intramitochondrially in isolated heart mitochondria and cells. DAB inhibited succinate-dependent respiration and ROS production. DAB prevented succinate accumulation in cells treated with SDH inhibitors. DAB delivered butylmalonate to cardiac mitochondria when administered to mice in vivo and reduced infarct size by perturbing mitochondrial succinate transport.CONCLUSIONSThe DIC is a key node in the cellular distribution of succinate, controlling its transport between mitochondria and the cytosol. These findings highlight the potential of DIC as a promising therapeutic target for conditions where succinate elevation contributes to pathogenesis, such as cardiac I/R injury.
{"title":"Mitochondrial succinate transport is required for cardiac ischemia/reperfusion injury.","authors":"Laura Pala,María Torres-López,Stuart T Caldwell,Joyce Valadares,Emily M Smith,Katherine L Hammond,Olga Sauchanka,Jiro Abe,Thomas Krieg,Richard C Hartley,Michael P Murphy,Hiran A Prag","doi":"10.1093/cvr/cvag031","DOIUrl":"https://doi.org/10.1093/cvr/cvag031","url":null,"abstract":"BACKGROUNDSuccinate accumulates significantly during myocardial ischemia, and its rapid oxidation upon reperfusion is a critical driver of ischemia/reperfusion (I/R) injury. The transport of succinate across the mitochondrial inner membrane, particularly by the dicarboxylate carrier (DIC; SLC25A10), is hypothesized to play a crucial role in mediating these pathological succinate dynamics. However, tools to test this hypothesis by modulating mitochondrial succinate transport in biological systems are lacking.METHODS AND RESULTSC57BL/6J mice, isolated Wistar Rat heart mitochondria, bovine heart mitochondrial membranes, C2C12 mouse myoblasts and primary adult cardiomyocytes were used as in vitro and in vivo models. Butylmalonate prodrugs were synthesized and tested. Isolated mitochondria were used to assess succinate-dependent respiration and reactive oxygen species (ROS) production. Cells were treated with succinate dehydrogenase (SDH) inhibitors or exposed to anoxia and butylmalonate esters. Mouse hearts were subjected to in vivo left anterior descending coronary artery ligation. Succinate and butylmalonate levels were measured by targeted liquid chromatography-tandem mass spectrometry, and infarct size by TTC (2,3,5-triphenyl-2H-tetrazolium chloride) staining.Knockdown of DIC, but not of the oxoglutarate carrier OGC, in C2C12 cells prevented succinate accumulation by SDH inhibition and anoxia. The only extant DIC inhibitor butylmalonate, is limited by poor cell permeability. We synthesized diacetoxymethyl butylmalonate (DAB), which efficiently delivers butylmalonate intramitochondrially in isolated heart mitochondria and cells. DAB inhibited succinate-dependent respiration and ROS production. DAB prevented succinate accumulation in cells treated with SDH inhibitors. DAB delivered butylmalonate to cardiac mitochondria when administered to mice in vivo and reduced infarct size by perturbing mitochondrial succinate transport.CONCLUSIONSThe DIC is a key node in the cellular distribution of succinate, controlling its transport between mitochondria and the cytosol. These findings highlight the potential of DIC as a promising therapeutic target for conditions where succinate elevation contributes to pathogenesis, such as cardiac I/R injury.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"42 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146056849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Retesh Bajaj,Xingru Huang,Natasha Alves-Kotzev,Jill J Weyers,Molly Levine,Mohil Garg,Mohamed Mohamed,Soe Maung,Ramya Parasa,Murat Çap,Ryo Torii,Rob Krams,Jagdish Butany,Flavio Giuseppe Biccirè,Hector Garcia-Garcia,Lorenz Raber,Anthony Mathur,Andreas Baumbach,Qianni Zhang,Brian K Courtney,Christos V Bourantas
AIMSHybrid intravascular ultrasound-optical coherence tomography (IVUS-OCT) can enable more accurate plaque characterization than single-modality intravascular imaging, enhancing treatment planning and vulnerable plaque detection. However, image interpretation in IVUS-OCT is challenging and time-consuming. To overcome this limitation, we introduce a novel histology-trained deep learning (DL)-classifier for plaque component classification in IVUS-OCT images and compare its performance against single-modality DL and expert analysts.METHODS AND RESULTSIVUS-OCT frames and matched histological sections from 10 cadaveric human hearts were included in this analysis. The histological data were used to define fibrotic, calcific, and necrotic core tissue regions of interest (ROIs) in IVUS-OCT and used to train three DL-classifiers for IVUS, OCT, or hybrid IVUS-OCT image analysis (992 frames) and test their performance (264 frames). The test set was additionally annotated by experts from three different core labs, and their estimations and those of the DL-classifiers were compared with histology.The IVUS-OCT DL-classifier had a superior performance to the IVUS-DL, OCT-DL, and the expert analysts in detecting plaque phenotypes (Kappa 0.60 vs. 0.19, 0.35, and 0.53, respectively) and accurately classified 68% of histologically defined fibroatheromas. The hybrid IVUS-OCT DL-classifier also had a better performance than single-modality DL-classifiers and the experts in assessing tissue types in ROIs annotated by histology (overall accuracy 86.7% compared with 73.2% for IVUS-DL, 66.6% for OCT-DL, and 70.6% for the experts).CONCLUSIONPlaque characterization using a histology-trained hybrid IVUS-OCT DL-classifier is feasible and enables more accurate detection of plaque components and phenotype classification than single-modality DL-classifiers and expert analysts.
{"title":"Deep learning-based plaque characterization in hybrid IVUS-OCT images is superior to single-modality deep learning analysis and human experts: head-to-head comparison against histology.","authors":"Retesh Bajaj,Xingru Huang,Natasha Alves-Kotzev,Jill J Weyers,Molly Levine,Mohil Garg,Mohamed Mohamed,Soe Maung,Ramya Parasa,Murat Çap,Ryo Torii,Rob Krams,Jagdish Butany,Flavio Giuseppe Biccirè,Hector Garcia-Garcia,Lorenz Raber,Anthony Mathur,Andreas Baumbach,Qianni Zhang,Brian K Courtney,Christos V Bourantas","doi":"10.1093/cvr/cvaf281","DOIUrl":"https://doi.org/10.1093/cvr/cvaf281","url":null,"abstract":"AIMSHybrid intravascular ultrasound-optical coherence tomography (IVUS-OCT) can enable more accurate plaque characterization than single-modality intravascular imaging, enhancing treatment planning and vulnerable plaque detection. However, image interpretation in IVUS-OCT is challenging and time-consuming. To overcome this limitation, we introduce a novel histology-trained deep learning (DL)-classifier for plaque component classification in IVUS-OCT images and compare its performance against single-modality DL and expert analysts.METHODS AND RESULTSIVUS-OCT frames and matched histological sections from 10 cadaveric human hearts were included in this analysis. The histological data were used to define fibrotic, calcific, and necrotic core tissue regions of interest (ROIs) in IVUS-OCT and used to train three DL-classifiers for IVUS, OCT, or hybrid IVUS-OCT image analysis (992 frames) and test their performance (264 frames). The test set was additionally annotated by experts from three different core labs, and their estimations and those of the DL-classifiers were compared with histology.The IVUS-OCT DL-classifier had a superior performance to the IVUS-DL, OCT-DL, and the expert analysts in detecting plaque phenotypes (Kappa 0.60 vs. 0.19, 0.35, and 0.53, respectively) and accurately classified 68% of histologically defined fibroatheromas. The hybrid IVUS-OCT DL-classifier also had a better performance than single-modality DL-classifiers and the experts in assessing tissue types in ROIs annotated by histology (overall accuracy 86.7% compared with 73.2% for IVUS-DL, 66.6% for OCT-DL, and 70.6% for the experts).CONCLUSIONPlaque characterization using a histology-trained hybrid IVUS-OCT DL-classifier is feasible and enables more accurate detection of plaque components and phenotype classification than single-modality DL-classifiers and expert analysts.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"105 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146056846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Akinkunmi Paul Okekunle,Osahon Jeffery Asowata,Ifeoluwa Jesuloluwa Owoseni,Adekunle Fakunle,Benedict Calys-Tagoe,Reginald O Obiako,Paul Olowoyo,Oladotun Olalusi,Philip Ibinaye,Oyedunni Sola Arulogun,Morenikeji Komolafe,Adeniyi Sunday,Ayomide Owolabi,Ijezie Chukwuonye,Oladimeji Adebayo,Joshua Odun Akinyemi,Wisdom Oguike,Lisa Micklesfield,Godfrey Agongo,Romuald Palwendé Boua,Daniel Lackland,Hemant K Tiwari,Bruce Ovbiagele,Onoja Matthew Akpa,Michele Ramsay,Mayowa Owolabi
AIMThe burden of dyslipidaemia is increasing, and the association of dietary exposure, especially vegetable consumption, with dyslipidaemia among Africans is poorly characterized. This study evaluated the relationship between vegetable consumption and dyslipidaemia among continental Africans.METHODS AND RESULTSThe frequency of vegetable consumption (servings/week) was assessed in this study involving 13,172 participants, including 6,586 pairs of dyslipidaemia cases and non-cases (matched for age within ±5 years, sex, and country), in a matched case-control design. Multivariable-adjusted conditional logistic regression models were applied to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of dyslipidaemia across quartiles of frequency of vegetable consumption at a two-sided P < 0.05. The mean age was 52.18±10.15 years, and 6,898 (52.4%) were females. The median (IQR) vegetable consumption intake was 7.0 (2.0, 14.0) servings per week and the prevalence of dyslipidaemia by the distribution of vegetable consumption was 1776 (52.0%) for low (first quartile), 1530 (49.9%) for moderate (second quartile), 1720 (49.2%) for sufficient (third quartile); and 1560 (48.9%) for high (fourth quartile) frequency of vegetable consumption. The multivariable-adjusted OR (95%CI) of dyslipidaemia by the distribution of vegetable consumption were 1.00 for low, 0.89 (0.80, 0.99) for moderate, 0.84 (0.75, 0.93) for sufficient and 0.81 (0.72, 0.92) for high; p for trend = 0.005, with a OR (95%CI) of 0.97 (0.94, 0.99) per +7 servings/week change after adjusting for age, family history of cardiovascular diseases, education, ever smoked, currently consume alcohol, physical inactivity, body mass index, diabetes mellitus status, and hypertension. A similar trend was observed for low high-density lipoprotein (<40 mg/dL): 1.00 for low, 0.90 (0.78, 1.04) for moderate, 0.93 (0.81, 1.06) for medium, and 0.80 (0.68, 0.94) for high; P for trend = 0.01, adjusting for similar covariates.CONCLUSIONSIn continental Africans, higher vegetable consumption was associated with lower odds of dyslipidemia after accounting for multiple covariates.
{"title":"Dose-response association between vegetable consumption and dyslipidemia among continental Africans in five countries: Evidence from the SIREN and AWI-Gen studies.","authors":"Akinkunmi Paul Okekunle,Osahon Jeffery Asowata,Ifeoluwa Jesuloluwa Owoseni,Adekunle Fakunle,Benedict Calys-Tagoe,Reginald O Obiako,Paul Olowoyo,Oladotun Olalusi,Philip Ibinaye,Oyedunni Sola Arulogun,Morenikeji Komolafe,Adeniyi Sunday,Ayomide Owolabi,Ijezie Chukwuonye,Oladimeji Adebayo,Joshua Odun Akinyemi,Wisdom Oguike,Lisa Micklesfield,Godfrey Agongo,Romuald Palwendé Boua,Daniel Lackland,Hemant K Tiwari,Bruce Ovbiagele,Onoja Matthew Akpa,Michele Ramsay,Mayowa Owolabi","doi":"10.1093/cvr/cvag032","DOIUrl":"https://doi.org/10.1093/cvr/cvag032","url":null,"abstract":"AIMThe burden of dyslipidaemia is increasing, and the association of dietary exposure, especially vegetable consumption, with dyslipidaemia among Africans is poorly characterized. This study evaluated the relationship between vegetable consumption and dyslipidaemia among continental Africans.METHODS AND RESULTSThe frequency of vegetable consumption (servings/week) was assessed in this study involving 13,172 participants, including 6,586 pairs of dyslipidaemia cases and non-cases (matched for age within ±5 years, sex, and country), in a matched case-control design. Multivariable-adjusted conditional logistic regression models were applied to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of dyslipidaemia across quartiles of frequency of vegetable consumption at a two-sided P < 0.05. The mean age was 52.18±10.15 years, and 6,898 (52.4%) were females. The median (IQR) vegetable consumption intake was 7.0 (2.0, 14.0) servings per week and the prevalence of dyslipidaemia by the distribution of vegetable consumption was 1776 (52.0%) for low (first quartile), 1530 (49.9%) for moderate (second quartile), 1720 (49.2%) for sufficient (third quartile); and 1560 (48.9%) for high (fourth quartile) frequency of vegetable consumption. The multivariable-adjusted OR (95%CI) of dyslipidaemia by the distribution of vegetable consumption were 1.00 for low, 0.89 (0.80, 0.99) for moderate, 0.84 (0.75, 0.93) for sufficient and 0.81 (0.72, 0.92) for high; p for trend = 0.005, with a OR (95%CI) of 0.97 (0.94, 0.99) per +7 servings/week change after adjusting for age, family history of cardiovascular diseases, education, ever smoked, currently consume alcohol, physical inactivity, body mass index, diabetes mellitus status, and hypertension. A similar trend was observed for low high-density lipoprotein (<40 mg/dL): 1.00 for low, 0.90 (0.78, 1.04) for moderate, 0.93 (0.81, 1.06) for medium, and 0.80 (0.68, 0.94) for high; P for trend = 0.01, adjusting for similar covariates.CONCLUSIONSIn continental Africans, higher vegetable consumption was associated with lower odds of dyslipidemia after accounting for multiple covariates.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"86 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146069831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J Kjaergaard, L E Bang, E Sonne-Holm, S Wiberg, L Holmvang, J F Lassen, R Sørensen, D E Høfsten, P S Ulriksen, S Jawad, P Palm, C Søe, M K Ersbøll, S Boesgaard, J E Møller, J J Thune, C Hassager, H-H Tilsted, J Lønborg, M Egstrup, O P Kristiansen, E Seven, M G Lindholm, K Eskesen, S Fanø, J Carlsen
Aims Intermediate high-risk pulmonary embolism is associated with increased risk of hemodynamic deterioration and death, but balancing risk of thrombolytics or catheter-based treatment and efficacy has been challenging. This trial compared the additional efficacy of catheter-based ultrasound low-dose thrombolysis (USAT) over intravenous low-dose thrombolysis or heparin alone. Methods and results In an investigator-initiated randomized clinical multi-center trial we randomized 210 adult patients with acute, intermediate high-risk pulmonary embolism admitted to emergency departments in two regions of Denmark. Patients were allocated 1:1:1 to one of three treatment strata: low-dose thrombolysis (20 mg alteplase administered over 6 hours) by USAT, by intravenous administration or heparin alone. The efficacy of the interventions was assessed by comparing the refined Modified Miller Score, rmMS, (0-40 points, higher score indicating higher thrombus burden) from CT angiographies performed at baseline and 48-96 h post randomization. Two comparisons were investigated: the reduction of rmMS with low-dose thrombolysis (USAT or intravenously) compared to heparin alone, and the reduction of rmMS with low-dose thrombolysis administered by USAT compared to intravenous route. Safety endpoint included risk of bleeding. We included 210 patients with acute pulmonary embolism, 49% were female, mean age was 70 (IQR 62-76) and mean body mass index 30 (26-34). Compared to heparin alone, low-dose thrombolysis reduced the rmMS by 3.6 points, (95% CI 2.2-5.0, p < 0.001), but the reduction in rmMS was not different in the ultrasound assisted thrombolysis vs. intravenous route, mean difference -0.1, (95% CI: -1.9–1.7), p = 0.88. Bleeding complications were numerically more frequent with low-dose thrombolysis, albeit not statically significant. No differences in other outcomes were observed. Conclusions Low-dose thrombolysis reduced thrombus burden more than heparin alone in patients with acute intermediate high-risk pulmonary embolism. However, ultrasound assisted thrombolysis did not show greater thrombus reduction than thrombolysis administrated intravenously. The rate of death and risk of bleeding complications was increased with low-dose thrombolysis. Trial Registration clinicaltrials.gov, NCT04088292
目的：中高危肺栓塞与血流动力学恶化和死亡风险增加相关，但平衡溶栓或导管治疗的风险和疗效一直具有挑战性。该试验比较了基于导管的超声低剂量溶栓（USAT）与静脉低剂量溶栓或单独使用肝素的额外疗效。方法和结果在一项由研究者发起的随机临床多中心试验中，我们在丹麦两个地区的急诊科随机收治了210名急性、中高危肺栓塞的成年患者。患者按1:1:1的比例分配到三个治疗层之一：USAT低剂量溶栓（20mg阿替普酶超过6小时给药），静脉给药或单独使用肝素。通过比较基线和随机分组后48-96小时CT血管造影的改良Miller评分（rmMS）（0-40分，评分越高表明血栓负担越重）来评估干预措施的有效性。研究了两项比较：与单独使用肝素相比，低剂量溶栓（USAT或静脉注射）降低rmMS；与静脉注射相比，USAT低剂量溶栓降低rmMS。安全终点包括出血风险。我们纳入了210例急性肺栓塞患者，49%为女性，平均年龄70岁（IQR 62-76），平均体重指数30（26-34）。与单独使用肝素相比，低剂量溶栓使rmMS降低了3.6点（95% CI 2.2-5.0, p < 0.001），但超声辅助溶栓与静脉溶栓的rmMS降低无差异，平均差为-0.1,(95% CI: -1.9-1.7), p = 0.88。低剂量溶栓的出血并发症在数字上更常见，尽管没有统计学意义。其他结果未见差异。结论低剂量溶栓比单独使用肝素更能减轻急性中高危肺栓塞患者的血栓负担。然而，超声辅助溶栓并没有显示出比静脉溶栓更大的血栓减少。低剂量溶栓增加了死亡率和出血并发症的风险。临床试验注册网站clinicaltrials.gov, NCT04088292
{"title":"Randomized trial of low-dose -, ultrasound assisted thrombolysis or heparin for pulmonary embolism","authors":"J Kjaergaard, L E Bang, E Sonne-Holm, S Wiberg, L Holmvang, J F Lassen, R Sørensen, D E Høfsten, P S Ulriksen, S Jawad, P Palm, C Søe, M K Ersbøll, S Boesgaard, J E Møller, J J Thune, C Hassager, H-H Tilsted, J Lønborg, M Egstrup, O P Kristiansen, E Seven, M G Lindholm, K Eskesen, S Fanø, J Carlsen","doi":"10.1093/cvr/cvag038","DOIUrl":"https://doi.org/10.1093/cvr/cvag038","url":null,"abstract":"Aims Intermediate high-risk pulmonary embolism is associated with increased risk of hemodynamic deterioration and death, but balancing risk of thrombolytics or catheter-based treatment and efficacy has been challenging. This trial compared the additional efficacy of catheter-based ultrasound low-dose thrombolysis (USAT) over intravenous low-dose thrombolysis or heparin alone. Methods and results In an investigator-initiated randomized clinical multi-center trial we randomized 210 adult patients with acute, intermediate high-risk pulmonary embolism admitted to emergency departments in two regions of Denmark. Patients were allocated 1:1:1 to one of three treatment strata: low-dose thrombolysis (20 mg alteplase administered over 6 hours) by USAT, by intravenous administration or heparin alone. The efficacy of the interventions was assessed by comparing the refined Modified Miller Score, rmMS, (0-40 points, higher score indicating higher thrombus burden) from CT angiographies performed at baseline and 48-96 h post randomization. Two comparisons were investigated: the reduction of rmMS with low-dose thrombolysis (USAT or intravenously) compared to heparin alone, and the reduction of rmMS with low-dose thrombolysis administered by USAT compared to intravenous route. Safety endpoint included risk of bleeding. We included 210 patients with acute pulmonary embolism, 49% were female, mean age was 70 (IQR 62-76) and mean body mass index 30 (26-34). Compared to heparin alone, low-dose thrombolysis reduced the rmMS by 3.6 points, (95% CI 2.2-5.0, p &lt; 0.001), but the reduction in rmMS was not different in the ultrasound assisted thrombolysis vs. intravenous route, mean difference -0.1, (95% CI: -1.9–1.7), p = 0.88. Bleeding complications were numerically more frequent with low-dose thrombolysis, albeit not statically significant. No differences in other outcomes were observed. Conclusions Low-dose thrombolysis reduced thrombus burden more than heparin alone in patients with acute intermediate high-risk pulmonary embolism. However, ultrasound assisted thrombolysis did not show greater thrombus reduction than thrombolysis administrated intravenously. The rate of death and risk of bleeding complications was increased with low-dose thrombolysis. Trial Registration clinicaltrials.gov, NCT04088292","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"4 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146071505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AIMSAgeing leads to a progressive loss in structural integrity and a functional decline of human organs, alongside telomere attrition and alterations in DNA methylation patterns. Their relationships in the human kidney in the context of ageing remain elusive.METHODS AND RESULTSWe analysed 200 participants from the Human Kidney Tissue Resource (HKTR) with matching information on kidney histology, renal function, blood leukocyte and kidney telomere length, as well as kidney genome-wide DNA methylation profiles. Additional 71 HKTR individuals without telomere data were used in validation analyses. Kidney telomere length showed a significant inverse association with age (β = -0.029, confidence interval = -0.043 to -0.016, P = 0.00003). Shorter kidney telomeres were strongly associated with both renal structure and function, independent of demographic and clinical confounders. Nephrosclerosis score showed a gradual increase with age categories, while kidney telomere length dropped simultaneously. Leukocyte telomere length was not related to the extent of age-related changes in kidney function or structure. Kidney DNA methylation analysis revealed that kidney CpGs, genes, pathways and chromatin patterns associated with kidney telomere length are partly independent of these associated with chronological age. Consisted of 57 CpGs, epigenetic clock of kidney telomere length showed a predictive potential for nephrosclerosis, independent of clinical cofounders, chronological and epigenetic age.CONCLUSIONOur study revealed that gradual age-related structural involution of human kidney and a decline in its filtration capacity are accompanied by shortening of telomeres in renal cells and that changes in the kidney epigenome (i.e., DNA methylation) may contribute to nephrosclerosis (at least in part) independently of chronological age.
{"title":"Shorter kidney telomeres are associated with nephrosclerosis by an epigenetic signature.","authors":"Olutope Arinola Akinnibosun,Xiaoguang Xu,Amber Emmett,Huy Nguyen,Shadi Hames-Fathi,Maciej Drzal,James Eales,David Scannali,Priscilla R Prestes,Matthew Denniff,Pawel Bogdanski,Joanna Zywiec,Wojciech Wystrychowski,Ewa Zukowska-Szczechowska,Tomasz J Guzik,Nilesh J Samani,John Dormer,Maciej Tomaszewski,Fadi J Charchar","doi":"10.1093/cvr/cvag034","DOIUrl":"https://doi.org/10.1093/cvr/cvag034","url":null,"abstract":"AIMSAgeing leads to a progressive loss in structural integrity and a functional decline of human organs, alongside telomere attrition and alterations in DNA methylation patterns. Their relationships in the human kidney in the context of ageing remain elusive.METHODS AND RESULTSWe analysed 200 participants from the Human Kidney Tissue Resource (HKTR) with matching information on kidney histology, renal function, blood leukocyte and kidney telomere length, as well as kidney genome-wide DNA methylation profiles. Additional 71 HKTR individuals without telomere data were used in validation analyses. Kidney telomere length showed a significant inverse association with age (β = -0.029, confidence interval = -0.043 to -0.016, P = 0.00003). Shorter kidney telomeres were strongly associated with both renal structure and function, independent of demographic and clinical confounders. Nephrosclerosis score showed a gradual increase with age categories, while kidney telomere length dropped simultaneously. Leukocyte telomere length was not related to the extent of age-related changes in kidney function or structure. Kidney DNA methylation analysis revealed that kidney CpGs, genes, pathways and chromatin patterns associated with kidney telomere length are partly independent of these associated with chronological age. Consisted of 57 CpGs, epigenetic clock of kidney telomere length showed a predictive potential for nephrosclerosis, independent of clinical cofounders, chronological and epigenetic age.CONCLUSIONOur study revealed that gradual age-related structural involution of human kidney and a decline in its filtration capacity are accompanied by shortening of telomeres in renal cells and that changes in the kidney epigenome (i.e., DNA methylation) may contribute to nephrosclerosis (at least in part) independently of chronological age.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"28 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146069874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：