Rosetta Ragusa, Silvia Rocchiccioli, Serena Del Turco, Antonio Morlando, Giuseppina Basta, Arthur Scholte, Danilo Neglia, Chiara Caselli
{"title":"PCSK9 and coronary atherosclerosis progression beyond LDL-cholesterol in coronary artery disease patients.","authors":"Rosetta Ragusa, Silvia Rocchiccioli, Serena Del Turco, Antonio Morlando, Giuseppina Basta, Arthur Scholte, Danilo Neglia, Chiara Caselli","doi":"10.1111/eci.70083","DOIUrl":"https://doi.org/10.1111/eci.70083","url":null,"abstract":"<p><strong>Background: </strong>This study evaluated whether plasma PCSK9 is associated with coronary plaque progression in patients with coronary artery disease (CAD) and assessed its involvement in molecular processes of atherogenesis.</p><p><strong>Methods: </strong>Plasma PCSK9 was measured in 159 patients with stable CAD submitted to coronary computed tomography angiography (CTA) at baseline and after a follow-up of 6.5 ± 1.1 years. Plaque progression was defined as the annual increase in Total, Fibrous, Fibro-fatty, Necrotic-Core and Dense-Calcium plaque volumes (PV). Pathways linked with PCSK9 were studied by RNA-sequencing of whole blood and in vitro studies using endothelial cells (EC).</p><p><strong>Results: </strong>At multivariable analysis, plasma PCSK9 was associated with an annual increase in Necrotic-Core PV (p = .022) independent of cardiovascular risk factors, molecular markers, and medications, including LDL-C and statins. At RNA-seq analysis, PCSK9 was linked to the expression of genes involved in the innate-immune response. Treating EC with PCSK9 resulted in a significant increase in ICAM-1, VCAM-1, MCP1 and IL6 mRNA expression.</p><p><strong>Conclusions: </strong>In patients with CAD, plasma PCSK9 is associated with progression of Necrotic Core-PV. The link with inflammatory pathways suggested for PCSK9 a potential role for the occurrence of prognostically adverse plaque phenotypes beyond LDL-C regulation.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e70083"},"PeriodicalIF":4.4,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224832","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":"Neuregulin 1β enhances pulmonary vein arrhythmogenesis by modulating electrophysiological characteristics, calcium and sodium homeostasis via the AKT/CaMKII pathway.","authors":"Yao-Chang Chen, Wei-Shiang Lin, Shih-Yu Huang, Yen-Yu Lu, Satoshi Higa, Shih-Ann Chen, Yi-Jen Chen","doi":"10.1111/eci.70084","DOIUrl":"https://doi.org/10.1111/eci.70084","url":null,"abstract":"<p><strong>Background: </strong>Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice and the pulmonary vein (PV) is the most important AF trigger. Neuregulin 1β (NRG1β), which is elevated in patients with paroxysmal AF, may activate signalling pathways that mediate cellular adaptations and subsequent stress in the myocardium. The objectives of this study were to study the effects of NRG1β on the PVs and explore the underlying mechanisms.</p><p><strong>Methods: </strong>A conventional microelectrode, a whole-cell patch clamp, Western blotting and immunofluorescent confocal microscopy were used to investigate electrical activity, calcium (Ca<sup>2+</sup>) regulation, protein expression, ionic currents, reactive oxygen species and cytosolic sodium ([Na<sup>+</sup>]<sub>i</sub>) in isolated rabbit PV tissue and single cardiomyocytes with or without NRG1β (10 nM) incubation for 4 h.</p><p><strong>Results: </strong>NRG1β-treated PVs had faster beating rates and a higher incidence of triggered activity than control PVs. The increased PV spontaneous beating rate induced by NRG1β could be mitigated by ranolazine (a late Na<sup>+</sup> current inhibitor, 10 μM), KN93 (1 μM) and AIP (1 μΜ) (CaMKII inhibitors) and AKTi (AKT-1/2 inhibitor, 10 μM). NRG1β-treated PV cardiomyocytes demonstrated larger late Na<sup>+</sup> and Na<sup>+</sup>-Ca<sup>2+</sup> exchanger current than control PV cardiomyocytes. AIP decreased late Na<sup>+</sup> current in NRG1β-treated PV cardiomyocytes. Furthermore, NRG1β-treated PV cardiomyocytes had smaller intracellular Ca<sup>2+</sup> transients and reduced sarcoplasmic reticulum Ca<sup>2+</sup> contents, but higher levels of [Na<sup>+</sup>]<sub>i</sub>, oxidative stress and RyR-dependent SR Ca<sup>2+</sup> leak than control PV cardiomyocytes. The increased RyR-dependent SR Ca<sup>2+</sup> leak by NRG1β could be alleviated by KN93. Additionally, NRG1β-treated PV cardiomyocytes exhibited upregulated AKT, pAKT, ERK, pERK, CaMKII and pCaMKII, while SERCA2a and PLB were downregulated. AKTi can downregulate oxi-CaMKII and CaMKII in NRG1β-treated PV cardiomyocytes.</p><p><strong>Conclusion: </strong>By modulating electrophysiological characteristics, Ca<sup>2+</sup> homeostasis, and enhancing oxidative stress through AKT/CaMKII signalling, NRG1β increased PV arrhythmogenesis with increasing RyR-dependent SR Ca<sup>2+</sup> leak of PV cardiomyocytes.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e70084"},"PeriodicalIF":4.4,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198618","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":"Adverse kidney events with initiation of SGLT2 inhibitors versus DPP4 inhibitors in diabetic people with a history of acute kidney injury.","authors":"Yi-Wei Kao, Tze-Fan Chao, Yu-Wen Cheng, Shao-Wei Chen, Yi-Hsin Chan","doi":"10.1111/eci.70080","DOIUrl":"https://doi.org/10.1111/eci.70080","url":null,"abstract":"<p><strong>Background: </strong>The benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2is) versus dipeptidyl peptidase-4 inhibitors (DPP4is) in type 2 diabetes people with varying acute kidney injury (AKI) intervals or recovery remain unclear.</p><p><strong>Methods: </strong>We retrospectively analysed 3127 paired patients with a prior history of AKI within 60 months before drug initiation, who received either SGLT2i or DPP4i between June 2016 and December 2021, utilizing 1:1 propensity score matching to balance baseline characteristics. AKI was defined as a serum creatinine (sCr) increase of ≥50% or an absolute rise of ≥.3 mg/dL. The AKI recovery was determined by comparing baseline sCr levels before drug initiation with pre-AKI values.</p><p><strong>Results: </strong>Among patients, 17.1% on SGLT2is and 25.6% on DPP4is initiated therapy within 1 month after AKI. AKI near-full recovery (<1.1) was observed in 30.7% of SGLT2i users and 31.4% of DPP4i users before drug initiation. Compared to those with remote AKI (4-5 years prior), the risk of adverse kidney events increased only when SGLT2i therapy began within 3 months after AKI (adjusted HR: 2.15; [95% CI: 1.13-4.10]). However, for DPP4i users, the risk remained elevated for up to a year. A U-shaped association between AKI recovery and kidney outcomes was observed in DPP4i users, with both excessive (<1.0) and impaired (≥1.1) recovery increasing risk. In contrast, impaired recovery did not worsen kidney outcomes in SGLT2i users. The treatment benefits of SGLT2i over DPP4i were consistent across varying AKI intervals and recovery examined as a continuous variable.</p><p><strong>Conclusions: </strong>SGLT2i therapy demonstrated consistent benefits across different AKI intervals and recovery levels, making it a preferable option for patients at risk of AKI.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e70080"},"PeriodicalIF":4.4,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198617","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}
Cheng-Hsuan Tsai, Po-Hsin Kong, Chen-Chan Hsieh, Yen-Chun Huang, Hao-Min Cheng, Chi-Sheng Hung, Chin-Chen Chang, Jeff S Chueh, Anand Vaidya, Vin-Cent Wu, Chen-Chung Liao, Yen-Hung Lin
{"title":"Proteomic signatures to detect unilateral primary aldosteronism in hypertensive patients.","authors":"Cheng-Hsuan Tsai, Po-Hsin Kong, Chen-Chan Hsieh, Yen-Chun Huang, Hao-Min Cheng, Chi-Sheng Hung, Chin-Chen Chang, Jeff S Chueh, Anand Vaidya, Vin-Cent Wu, Chen-Chung Liao, Yen-Hung Lin","doi":"10.1111/eci.70081","DOIUrl":"https://doi.org/10.1111/eci.70081","url":null,"abstract":"<p><strong>Context: </strong>Primary aldosteronism (PA) is a major cause of hypertension and cardiovascular disease; however, diagnosing PA remains challenging.</p><p><strong>Objective: </strong>We investigated whether deep proteomic analyses could be used to diagnose unilateral PA in hypertensive patients.</p><p><strong>Methods: </strong>We enrolled 52 patients with unilateral PA and 46 with essential hypertension (EH) and divided them into training and validation cohorts. Plasma samples were collected at baseline from all patients and again from PA patients after adrenalectomy. Deep proteomic analysis was performed to identify peptide signatures used to develop a classification model distinguishing PA from EH in the training cohort. The classification model was subsequently tested in the validation cohort and post-adrenalectomy PA patients.</p><p><strong>Results: </strong>After proteomic analysis, six peptide features including HBB, FIBA, Complement CO7, ALBU, C4BPA, and A2AP were selected to generate risk scores and develop a classification model for distinguishing unilateral PA from EH. Risk scores were significantly higher in PA patients compared to those with EH. The classification model had a sensitivity and specificity of 80.5% and 83.3%, respectively, for diagnosing unilateral PA in the training cohort, and 81.8% and 80.0% in the validation cohort. The model demonstrated strong performance with an area under the curve of .92 for distinguishing hypertensive patients with or without PA. Post-unilateral adrenalectomy, the risk scores showed a significant decrease.</p><p><strong>Conclusions: </strong>Proteomic analysis can identify peptide signatures that effectively distinguish unilateral PA from EH. These findings underscore the potential utility of proteomics as an adjunct diagnostic and monitoring tool in the clinical management of PA.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e70081"},"PeriodicalIF":4.4,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173220","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}
Louwana Allawa, Antoine Poirier, Pascale Pignon, Justine Beaumont, Lucie Lebeau, Agnès Barbelivien, Thomas Bochaton, Céline Beauvillain, Daniel Henrion, Yves Delneste, Pascale Jeannin, Fabrice Prunier, Sophie Tamareille
{"title":"Cardioprotective effects of the extracellular chaperone clusterin in acute myocardial infarction.","authors":"Louwana Allawa, Antoine Poirier, Pascale Pignon, Justine Beaumont, Lucie Lebeau, Agnès Barbelivien, Thomas Bochaton, Céline Beauvillain, Daniel Henrion, Yves Delneste, Pascale Jeannin, Fabrice Prunier, Sophie Tamareille","doi":"10.1111/eci.70076","DOIUrl":"https://doi.org/10.1111/eci.70076","url":null,"abstract":"<p><strong>Background: </strong>Acute myocardial infarction (AMI) remains one of the leading causes of mortality worldwide. Recently, a cardioprotective effect of clusterin (CLU), a ubiquitous extracellular chaperone, has been reported. However, the underlying mechanisms remain unresolved. We hypothesized that CLU exerts its protective effect on AMI by neutralizing cytotoxic and proinflammatory properties of extracellular histones, a new class of damage-associated molecular patterns (DAMPs), that are released after massive cell injury.</p><p><strong>Methods and results: </strong>In vitro, we showed that exogenous CLU reduces histone-induced cell death in H9C2 cells after hypoxia-reoxygenation (.78 ± .15 vs. 1.39 ± .20; p = .0059). Moreover, we found increased CLU protein levels in the ischemic zone vs. non-ischemic zone after AMI in mice (p < .05). Correspondingly, CLU-deficient (CLU<sup>-/-</sup>) mice presented significantly increased infarct size vs. wild-type (CLU<sup>+/+</sup>) mice (46.29 ± 5.13% vs. 27.47 ± 1.92%; p = .0176). This cardioprotective effect of CLU is accompanied by an attenuation of the post-AMI proinflammatory response through a decrease in the expression of proinflammatory cytokines interleukin (IL)-6 and IL-1β, a decrease in phosphorylated nuclear factor kappa B (NF-kB) p65, as well as a decrease in the activation of the nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain containing 3 (NLRP3) inflammasome. Also, we found that in patients with acute ST-segment elevation myocardial infarction (STEMI), circulating CLU-histone complexes were significantly increased compared to healthy controls (p < .001).</p><p><strong>Conclusions: </strong>From these results, CLU protects the heart from inflammatory injury in AMI and this cardioprotection is due at least in part to its ability to neutralise extracellular histones released from the damaged tissue.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e70076"},"PeriodicalIF":4.4,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141774","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}
Joseph El Roumi, Aldo L Schenone, Paul Cremer, Tom Kai Ming Wang, Allan Klein
{"title":"Recent advances in multimodality imaging-guided therapy in pericarditis.","authors":"Joseph El Roumi, Aldo L Schenone, Paul Cremer, Tom Kai Ming Wang, Allan Klein","doi":"10.1111/eci.70067","DOIUrl":"https://doi.org/10.1111/eci.70067","url":null,"abstract":"<p><strong>Background: </strong>In the era of precision medicine, cardiac multimodality imaging plays a vital role in diagnosing, managing, and monitoring pericarditis. This condition, often marked by inflammation and recurrent episodes, requires precise imaging techniques to guide diagnosis and therapeutic decisions.</p><p><strong>Methods: </strong>We carefully reviewed the medical literature for high-quality data regarding the use of multimodality imaging in pericarditis and the precious value of the novel concept of imaging-guided therapy.</p><p><strong>Results: </strong>While echocardiography remains the cornerstone for detecting pericardial effusion and evaluating hemodynamics, its limited ability to characterize inflammation has driven the use of advanced modalities such as cardiac magnetic resonance imaging (CMR), cardiac computed tomography (CT), and positron emission tomography (PET). CMR offers superior visualization of pericardial inflammation through late gadolinium enhancement, aiding in identifying patients who may benefit from targeted anti-inflammatory therapies. CT imaging, with its high spatial resolution, aids in detecting pericardial calcifications and thickening, particularly in constrictive pericarditis. PET, often combined with CT, is a valuable tool for quantifying metabolic activity, allowing the detection of active inflammation, particularly in complex or refractory cases. Multiple imaging targets have been identified as essential biomarkers to confirm the inflammatory phenotype, assess treatment response, and monitor for complications.</p><p><strong>Conclusion: </strong>Considering the inherent limitations of each imaging modality, the integration of imaging findings with clinical and biomarker data may aid clinicians in tailoring therapy according to different clinical scenarios and better stratification of patients who may benefit from IL-1 blockade. This review explores the valuable role of cardiac multimodality imaging-guided therapy in managing pericarditis.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e70067"},"PeriodicalIF":4.4,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126993","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}
Mehmet Kanbay, Lasin Ozbek, Mustafa Guldan, Zeynep Y Yilmaz, Alberto Ortiz, Francesca Mallamaci, Carmine Zoccali
{"title":"siRNA-based therapeutics for lipoprotein (a) lowering: A path toward precision cardiovascular medicine.","authors":"Mehmet Kanbay, Lasin Ozbek, Mustafa Guldan, Zeynep Y Yilmaz, Alberto Ortiz, Francesca Mallamaci, Carmine Zoccali","doi":"10.1111/eci.70079","DOIUrl":"https://doi.org/10.1111/eci.70079","url":null,"abstract":"<p><p>Elevated Lp(a) is recognized as a significant independent risk factor for atherosclerotic cardiovascular diseases, including coronary artery disease, stroke and aortic valve stenosis. Notably, Lp(a) exhibits unique pro-inflammatory and pro-thrombotic properties contributing to its pathogenic role in cardiovascular disease. Although interventions targeting interleukin-6 (IL-6) and proprotein convertase subtilisin/kexin type 9 (PCSK9) have been shown to reduce Lp(a) levels, the extent to which this reduction contributes to their overall cardiovascular benefits remains uncertain. Recent clinical trials have demonstrated that small interfering RNA (siRNA) therapies are effective in lowering Lp(a) levels, prompting ongoing investigations into their potential to improve cardiovascular outcomes. These developments highlight the clinical significance of targeting Lp(a) as a therapeutic strategy. This paper offers a comprehensive review of the pathophysiological role of Lp(a) as an independent cardiovascular risk factor, followed by an in-depth analysis of siRNA-based therapeutics designed to target Lp(a). It examines their mechanisms of action, clinical efficacy and safety profiles, while also addressing potential risks, limitations and challenges associated with Lp(a)-modulating siRNA treatments. Additionally, the review discusses other RNA-based therapeutic approaches for Lp(a) reduction, along with an overview of ongoing clinical trials. Finally, future perspectives are considered to assess the evolving therapeutic landscape and the potential advancements in Lp(a)-targeting strategies for improving cardiovascular outcomes.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e70079"},"PeriodicalIF":4.4,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126930","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}
Sebastien Elvinger, Stephanie G Kuehne, Andrea Patrignani, Maximilian Tscharre, Matthias Freynhofer, Leor Perl, Ran Kornowski, Francesca Cesari, Rossella Marcucci, Laura Novelli, Isabell Bernlochner, Philip W Raake, Mauro Chiarito, Dario Bongiovanni
{"title":"Sex-specific predictive value of reticulated platelets in coronary artery disease: A systematic review and meta-analysis.","authors":"Sebastien Elvinger, Stephanie G Kuehne, Andrea Patrignani, Maximilian Tscharre, Matthias Freynhofer, Leor Perl, Ran Kornowski, Francesca Cesari, Rossella Marcucci, Laura Novelli, Isabell Bernlochner, Philip W Raake, Mauro Chiarito, Dario Bongiovanni","doi":"10.1111/eci.70078","DOIUrl":"https://doi.org/10.1111/eci.70078","url":null,"abstract":"<p><strong>Background: </strong>Platelets play a crucial role in immune responses and haemostasis. Among them, reticulated platelets (RPs) have gathered attention for their association with prothrombotic states and as a potential biomarker for cardiovascular events. However, the sex-specific prognostic value of RPs remains underexplored.</p><p><strong>Objective: </strong>This study aimed to systematically review and analyse sex-specific differences in the prognostic role of RPs in cardiovascular disease.</p><p><strong>Methods: </strong>We conducted a comprehensive search on studies that reported patient outcomes related to RPs. Study authors were contacted to provide sex-specific patient-level data. Two studies were excluded due to data unavailability. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE). Secondary endpoints included cardiovascular death, myocardial infarction, stroke, urgent revascularization, and bleeding incidents. All outcomes were stratified by sex.</p><p><strong>Results: </strong>The analysis included 5 studies, reporting outcomes in 1835 patients (527 females and 1308 males). RPs are a significant predictor of MACCE independently of sex males (OR 1.99 [95% CI 1.3, 3.05; I<sup>2</sup> = 29%]), females (2.29 [95% CI 1.31, 3.99; I<sup>2</sup> = 10%]). For cardiovascular death RPs were predictive in females (OR 3.29 [95% CI 1.69, 6.40] I<sup>2</sup> = .83%) and showed a trend toward significance in males (OR 2.19 95% CI [.98, 4.9] I<sup>2</sup> = 42.72%). No sex-specific differences were observed in all other secondary endpoints.</p><p><strong>Conclusion: </strong>RPs significantly predict MACCE in cardiovascular disease independently from sex and may have a stronger association with cardiovascular death in females. Further research is needed to explore the sex-specific mechanisms of RPs' prognostic value.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e70078"},"PeriodicalIF":4.4,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093245","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}
Vera Ciornolutchii, Abdulrahman Ismaiel, Jennifer Bogdan, Stefan-Lucian Popa, Teodora Surdea-Blaga, Dan L Dumitrascu
{"title":"From liver to limb: Exploring the association between fatty liver disease and peripheral artery disease-A systematic review.","authors":"Vera Ciornolutchii, Abdulrahman Ismaiel, Jennifer Bogdan, Stefan-Lucian Popa, Teodora Surdea-Blaga, Dan L Dumitrascu","doi":"10.1111/eci.70075","DOIUrl":"https://doi.org/10.1111/eci.70075","url":null,"abstract":"<p><strong>Introduction: </strong>Fatty liver disease, encompassing nonalcoholic fatty liver disease (NAFLD), metabolic dysfunction-associated fatty liver disease (MAFLD), and the recently redefined metabolic dysfunction-associated steatotic liver disease (MASLD), is a growing global health concern with significant cardiovascular implications. Peripheral artery disease (PAD), a common manifestation of systemic atherosclerosis, shares key pathophysiological mechanisms with fatty liver disease, including insulin resistance, systemic inflammation and endothelial dysfunction. Although emerging evidence suggests a link between fatty liver disease and PAD, the nature and extent of this association remain unclear. This systematic review synthesizes current research evaluating the relationship between fatty liver disease and PAD.</p><p><strong>Methods: </strong>A systematic search of PubMed, Embase and Scopus was conducted up to December 19, 2024, following PRISMA 2020 guidelines. Eligible observational studies assessing PAD in MASLD, MAFLD or NAFLD patients were included. Quality assessment was performed independently by two reviewers using the Newcastle-Ottawa Scale (NOS).</p><p><strong>Results: </strong>Eleven observational studies, including approximately 848,027 participants, were analysed. Most studies reported a significant association between NAFLD or MAFLD and increased PAD risk, particularly in individuals with type 2 diabetes and metabolic syndrome. Studies using MAFLD criteria demonstrated a stronger association with PAD than those using NAFLD definitions. The presence of hepatic fibrosis was linked to a higher PAD risk in some studies. However, not all studies found a consistent relationship, and a few reported no independent association between fatty liver disease and PAD, highlighting the need for further research. Notably, none of the included studies used MASLD criteria.</p><p><strong>Conclusions: </strong>Patients with NAFLD or MAFLD, particularly those with metabolic comorbidities, may have an elevated risk of PAD. The severity of liver disease, including fibrosis, appears to contribute to this risk. Future studies should incorporate MASLD definitions and advanced diagnostic methods to clarify this relationship and guide clinical strategies for integrated cardiovascular and liver disease management.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e70075"},"PeriodicalIF":4.4,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093244","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":"Aging in focus: A comprehensive view to enhance healthspan","authors":"","doi":"10.1111/eci.70057","DOIUrl":"https://doi.org/10.1111/eci.70057","url":null,"abstract":"<p>With great pleasure, we welcome you to the 59th annual scientific meeting of the European Society for Clinical Investigation, in Genoa, Italy, on May 21–23, 2025.</p><p>Gaining awareness on aging as an unavoidable process isn't a defeat but rather a catalyst for contemporary scientific research. While the medical field takes the lead in this endeavour, it's increasingly intertwined with ever-broader areas of science.</p><p>These are the principles we aim to imprint and upon which we work to build an exciting scientific program. We are planning several parallel symposia covering different aspects of aging in human health and disease. Keynote lectures, abstract presentations and pre-meeting courses will compose a consolidated recipe for a successful ESCI meeting.</p><p>Not by chance, Liguria, with Genoa as its capital, has been certified by the European Community as the oldest region in Europe. Long-time aware of this—and a paradigm of the abovementioned concepts—the local government and healthcare system had to rethink the economic activities, environmental management, connectivity and housing to maintain resident well-being.</p><p>Why do people live longer in Liguria? We invite you to discover it! Amazing landscapes, where the mountains meet the sea face to face, a thousand-year history and a cuisine waiting to be discovered. These are some of our secrets that provide an ideal backdrop for 3 days of science, networking and why not, a bit of fun!</p><p>We are happy and proud to have you here as our guests in Genoa!</p><p>\u0000 <b>Luca Liberale</b>\u0000 </p><p>\u0000 <b>Federico Carbone</b>\u0000 </p><p>Department of Internal Medicine, University of Genoa IRCCS Ospedale Policlinico San Martino, Genoa, Italy</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 S2","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.70057","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144091312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}