Leeches and other herbs may improve atherosclerosis symptoms. This study explores Poecilobdella manillensis'effect on AS.
Methods
In vivo used high-fat diet + rabbit carotid balloon injury model, with Poecilobdella manillensis at 0.1, 0.4, 0.8 g/day. In vitro, aortic endothelial cells were treated with ox-LDL to establish AS model, then with animal group sera to assess P.manillensis effects on AS and explore mechanisms.
Results
The in vivo findings indicated that P.manillensis is capable of lowering blood lipid levels and exhibiting anti-thrombotic properties. Additionally, P.manillensis significantly alleviated pathological damage and lipid deposition in the common carotid artery, and reduced apoptosis of the common carotid artery smooth muscle cells. Further assays revealed that P.manillensis markedly decreased the levels of PI3K, p-AKT, NF-κB p65, NLRP3, Caspase-1, eNOS, GSDMD, IL-1β, and IL-18. In vitro results demonstrated that serum containing P.manillensis significantly enhanced cell activity and ATP production while decreasing the apoptosis rate, IL-1β, IL-18, LDH, and ROS, PI3K, p-AKT, NF-κB p65, NLRP3, Caspase-1, GSDMD, and ASC levels.
Conclusion
Both in vivo and in vitro studies have confirmed that P.manillensis ameliorates endothelial damage and inflammatory responses in AS, with involvement of the PI3K/AKT and NF-κB signaling pathways.
{"title":"Poecilobdella manillensis ameliorates atherosclerosis by inhibiting endothelial cell pyroptosis","authors":"Chunxia Guo, Yudong Rao, Hao Zhou, Yiran Feng, Ganyu Deng, Lin Yang, Ying Zhang, Xueya Zhang","doi":"10.1016/j.athplu.2025.12.004","DOIUrl":"10.1016/j.athplu.2025.12.004","url":null,"abstract":"<div><h3>Objective</h3><div>Leeches and other herbs may improve atherosclerosis symptoms. This study explores <em>Poecilobdella manillensis</em>'effect on AS.</div></div><div><h3>Methods</h3><div>In vivo used high-fat diet + rabbit carotid balloon injury model, with <em>Poecilobdella manillensis</em> at 0.1, 0.4, 0.8 g/day. In vitro, aortic endothelial cells were treated with ox-LDL to establish AS model, then with animal group sera to assess P.manillensis effects on AS and explore mechanisms.</div></div><div><h3>Results</h3><div>The in vivo findings indicated that P.manillensis is capable of lowering blood lipid levels and exhibiting anti-thrombotic properties. Additionally, P.manillensis significantly alleviated pathological damage and lipid deposition in the common carotid artery, and reduced apoptosis of the common carotid artery smooth muscle cells. Further assays revealed that P.manillensis markedly decreased the levels of PI3K, p-AKT, NF-κB p65, NLRP3, Caspase-1, eNOS, GSDMD, IL-1β, and IL-18. In vitro results demonstrated that serum containing P.manillensis significantly enhanced cell activity and ATP production while decreasing the apoptosis rate, IL-1β, IL-18, LDH, and ROS, PI3K, p-AKT, NF-κB p65, NLRP3, Caspase-1, GSDMD, and ASC levels.</div></div><div><h3>Conclusion</h3><div>Both in vivo and in vitro studies have confirmed that P.manillensis ameliorates endothelial damage and inflammatory responses in AS, with involvement of the PI3K/AKT and NF-κB signaling pathways.</div></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"63 ","pages":"Pages 1-13"},"PeriodicalIF":2.1,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145754097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.athplu.2025.11.003
Hao Xue , Yu Lin , Youlin Liu , Lin Li , Pengzhen Chen , Mingyang Li , Ling Ji , Yong Xia
Background
Accurate estimation of low-density lipoprotein cholesterol (LDL-C) is crucial for atherosclerotic cardiovascular disease (ASCVD) risk management. Extensive international validation studies have demonstrated that traditional formulas (Friedewald, Martin/Hopkins, Sampson) often yield significant errors under conditions of extreme hypertriglyceridemia. This study aimed to assess the performance of these conventional formulas in Chinese populations and develop a novel neural network–based LDL-C estimation model [LDL-C(NN)].
Methods
In this retrospective study, we analyzed 188,887 lipid profiles—including total cholesterol, triglycerides, high-density lipoprotein cholesterol, and directly measured LDL-C—from Peking University Shenzhen Hospital using Mindray (outpatients, n = 83,731) and Beckman (inpatients, n = 105,156) systems. The test results from the two detection systems are non-overlapping. We used stratified random sampling based on TG levels to select 30,000 profiles from each of the two systems as the training dataset (60,000 profiles in total). Within this training dataset, 70 % of profiles were used for parameter learning, 15 % were used for early-stopping validation, and 15 % were used for post-training testing. The remaining profiles constituted the independent test set for the final performance evaluation (Mindray: n = 53,731; Beckman: n = 75,156). We then compared the performance of LDL-C(NN) with the Friedewald, Martin/Hopkins, and Sampson formulas using correlation coefficient (r), root mean square error (RMSE), Concordance Correlation Coefficient (CCC) and clinical risk stratification accuracy.
Results
Compared with directly measured LDL-C, LDL-C(NN) demonstrated higher correlation and lower RMSE than other traditional LDL-C equations in the Mindray system (r = 0.9778, RMSE = 0.1762 mmol/L; vs Friedewald quation: r = 0.8894, RMSE = 0.4783 mmol/L; vs Martin/Hopkins quation: r = 0.9658, RMSE = 0.2463 mmol/L; vs Sampson quation: r = 0.9548, RMSE = 0.2934 mmol/L, particularly patients with high triglycerides (TG levels, 9.03–13.56 mmol/L, neural network Model: CCC = 0.8750, vs Friedewald quation: CCC = 0.3320; vs Martin/Hopkins quation: CCC = 0.7278; vs Sampson quation: CCC = 0.4176). Beckman database shows the same performance. The clinical classification accuracy for LDL-C(NN) reached 87.5 % (Mindray) and 83.4 % (Beckman), surpassing that of other traditional LDL-C equations (66.6–78.7 %).
Conclusions
By overcoming the linear assumptions of conventional equations, the neural network–based model significantly improves LDL-C estimation in hypertriglyceridemia (especially≥9.03 mmol/L) and complex lipid profiles, thereby expanding the applicability of traditional formulas, while demonstrating robust performance across multiple analytical systems.
{"title":"Neural network model outperforms conventional equations in LDL cholesterol estimation: A comparative study of 188,887 Chinese individuals with focus on hypertriglyceridemia","authors":"Hao Xue , Yu Lin , Youlin Liu , Lin Li , Pengzhen Chen , Mingyang Li , Ling Ji , Yong Xia","doi":"10.1016/j.athplu.2025.11.003","DOIUrl":"10.1016/j.athplu.2025.11.003","url":null,"abstract":"<div><h3>Background</h3><div>Accurate estimation of low-density lipoprotein cholesterol (LDL-C) is crucial for atherosclerotic cardiovascular disease (ASCVD) risk management. Extensive international validation studies have demonstrated that traditional formulas (Friedewald, Martin/Hopkins, Sampson) often yield significant errors under conditions of extreme hypertriglyceridemia. This study aimed to assess the performance of these conventional formulas in Chinese populations and develop a novel neural network–based LDL-C estimation model [LDL-C(NN)].</div></div><div><h3>Methods</h3><div>In this retrospective study, we analyzed 188,887 lipid profiles—including total cholesterol, triglycerides, high-density lipoprotein cholesterol, and directly measured LDL-C—from Peking University Shenzhen Hospital using Mindray (outpatients, n = 83,731) and Beckman (inpatients, n = 105,156) systems. The test results from the two detection systems are non-overlapping. We used stratified random sampling based on TG levels to select 30,000 profiles from each of the two systems as the training dataset (60,000 profiles in total). Within this training dataset, 70 % of profiles were used for parameter learning, 15 % were used for early-stopping validation, and 15 % were used for post-training testing. The remaining profiles constituted the independent test set for the final performance evaluation (Mindray: n = 53,731; Beckman: n = 75,156). We then compared the performance of LDL-C(NN) with the Friedewald, Martin/Hopkins, and Sampson formulas using correlation coefficient (r), root mean square error (RMSE), Concordance Correlation Coefficient (CCC) and clinical risk stratification accuracy.</div></div><div><h3>Results</h3><div>Compared with directly measured LDL-C, LDL-C(NN) demonstrated higher correlation and lower RMSE than other traditional LDL-C equations in the Mindray system (r = 0.9778, RMSE = 0.1762 mmol/L; vs Friedewald quation: r = 0.8894, RMSE = 0.4783 mmol/L; vs Martin/Hopkins quation: r = 0.9658, RMSE = 0.2463 mmol/L; vs Sampson quation: r = 0.9548, RMSE = 0.2934 mmol/L, particularly patients with high triglycerides (TG levels, 9.03–13.56 mmol/L, neural network Model: CCC = 0.8750, vs Friedewald quation: CCC = 0.3320; vs Martin/Hopkins quation: CCC = 0.7278; vs Sampson quation: CCC = 0.4176). Beckman database shows the same performance. The clinical classification accuracy for LDL-C(NN) reached 87.5 % (Mindray) and 83.4 % (Beckman), surpassing that of other traditional LDL-C equations (66.6–78.7 %).</div></div><div><h3>Conclusions</h3><div>By overcoming the linear assumptions of conventional equations, the neural network–based model significantly improves LDL-C estimation in hypertriglyceridemia (especially≥9.03 mmol/L) and complex lipid profiles, thereby expanding the applicability of traditional formulas, while demonstrating robust performance across multiple analytical systems.</div></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"62 ","pages":"Pages 38-46"},"PeriodicalIF":2.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145618037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.athplu.2025.11.002
Takafumi Mito , Daisuke Kinoshita , Yoichiro Otaki , Jun Goto , Seisei Ra , Hiroe Ono , Taku Shikama , Shingo Tachibana , Shigehiko Kato , Tetsu Watanabe , Ik-Kyung Jang , Masafumi Watanabe
Background
Plaque disruption exposes thrombogenic substrates and triggers local thrombosis. When a fresh thrombus forms, endogenous antithrombotic mechanisms activate. The balance between these two pro- and antithrombotic mechanisms determines the outcome of plaque disruption. When thrombogenic stimuli outweigh the antithrombotic mechanisms, an occlusive thrombus forms, leading to acute coronary syndromes. When antithrombotic mechanisms dominate, a non-occlusive thrombus forms, contributing to the rapid progression of atherosclerosis. A layered or healed plaque can be identified using optical coherence tomography (OCT).
Purpose
The study aimed to investigate the association between atherothrombotic biomarkers and layered plaque at culprit lesions.
Methods
We analyzed 119 lesions in patients with chronic coronary syndrome who underwent OCT prior to percutaneous coronary intervention. Four groups of biomarkers were studied: antithrombotic, atherogenic, prothrombotic, and inflammatory. The layer index, defined as the mean layer arc multiplied by the layer length, was assessed using OCT.
Results
Patients were divided into tertiles based on each of the four groups. Among the four groups, only the antithrombotic biomarkers were significantly associated with the layer index (low vs. moderate vs. high: 0 vs. 517 vs. 719, p for trend = 0.037). This positive correlation remained significant after adjusting for confounders. In contrast, no association was found between the layer index and atherogenic, prothrombotic, or inflammatory biomarkers.
Conclusions
The antithrombotic mechanism appears to play a key role in layered plaque formation.
{"title":"Layered plaque in patients with chronic coronary syndrome","authors":"Takafumi Mito , Daisuke Kinoshita , Yoichiro Otaki , Jun Goto , Seisei Ra , Hiroe Ono , Taku Shikama , Shingo Tachibana , Shigehiko Kato , Tetsu Watanabe , Ik-Kyung Jang , Masafumi Watanabe","doi":"10.1016/j.athplu.2025.11.002","DOIUrl":"10.1016/j.athplu.2025.11.002","url":null,"abstract":"<div><h3>Background</h3><div>Plaque disruption exposes thrombogenic substrates and triggers local thrombosis. When a fresh thrombus forms, endogenous antithrombotic mechanisms activate. The balance between these two pro- and antithrombotic mechanisms determines the outcome of plaque disruption. When thrombogenic stimuli outweigh the antithrombotic mechanisms, an occlusive thrombus forms, leading to acute coronary syndromes. When antithrombotic mechanisms dominate, a non-occlusive thrombus forms, contributing to the rapid progression of atherosclerosis. A layered or healed plaque can be identified using optical coherence tomography (OCT).</div></div><div><h3>Purpose</h3><div>The study aimed to investigate the association between atherothrombotic biomarkers and layered plaque at culprit lesions.</div></div><div><h3>Methods</h3><div>We analyzed 119 lesions in patients with chronic coronary syndrome who underwent OCT prior to percutaneous coronary intervention. Four groups of biomarkers were studied: antithrombotic, atherogenic, prothrombotic, and inflammatory. The layer index, defined as the mean layer arc multiplied by the layer length, was assessed using OCT.</div></div><div><h3>Results</h3><div>Patients were divided into tertiles based on each of the four groups. Among the four groups, only the antithrombotic biomarkers were significantly associated with the layer index (low vs. moderate vs. high: 0 vs. 517 vs. 719, <em>p</em> for trend = 0.037). This positive correlation remained significant after adjusting for confounders. In contrast, no association was found between the layer index and atherogenic, prothrombotic, or inflammatory biomarkers.</div></div><div><h3>Conclusions</h3><div>The antithrombotic mechanism appears to play a key role in layered plaque formation.</div></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"62 ","pages":"Pages 47-52"},"PeriodicalIF":2.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145693799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.athplu.2025.11.004
Harsh Bahrar , Kim Steward , Liesbeth van Emst , Nils Rother , Jeanine E. Roeters van Lennep , Mihai G. Netea , Siroon Bekkering , Niels P. Riksen
Background and aims
Hypercholesterolemia is a major risk factor for atherosclerotic cardiovascular disease. Innate immune cells, including monocytes and neutrophils, play important roles in the pathophysiology of atherosclerosis. We previously reported that monocytes from patients with severely elevated low-density lipoprotein (LDL) cholesterol (LDL-c > 4.9 mmol/l) have a hyperresponsive phenotype, which persists even after three months statin treatment. This long-term hyperresponsive innate immune phenotype is termed trained immunity (innate immune memory), and is mediated by persistent enrichment of activating histone modifications leading to higher chromatin accessibility. In this study we investigated the monocyte and neutrophil phenotype of patients with severe hypercholesterolemia treated for 12 months with statins, compared to normocholesterolemic controls.
Methods
In a multicentric cross-sectional study, treatment-naïve patients with severe hypercholesterolemia (defined as LDL-cholesterol >4.9 mmol/L) requiring statin treatment were included. Blood was drawn after 12 months of lipid lowering therapy with statins (n = 15) and compared to healthy normocholesterolemic controls (LDL-c<3.5 mmol/l; n = 18).
We assessed monocyte phenotype with flow cytometry, cytokine production capacity of PBMCs, and H3K4me3 expression on the TNFA promotor. In addition, we assessed the neutrophil phenotype and function.
Results
Treatment lowered LDL-c from 5.8 to 2.7 mmol/L. PBMC cytokine production capacity, as well as the expression of H3K4me3 histone mark on the TNFA promotor did not differ from the controls (LDL-c 2.6 mmol/L). Although neutrophil CD11b, CD66b, and CD62L expression was the same, production of several granular proteins was lower in patients.
Conclusions
Previous studies reported hyperresponsive monocytes in treatment-naïve patients with LDL-c > 4.9 mmol/l. We now demonstrate that in an independent cohort of patients with LDL-c > 4.9 who are treated for 12 months with lipid-lowering drugs, the monocyte phenotype and function was similar to that of normocholesterolemic controls. In addition, neutrophils phenotype was similar, while the secretion of several granular proteins was lower in the patients.
{"title":"Innate immune cell function in statin-treated patients with severe hypercholesterolemia is comparable to normocholesterolemic individuals: A cross-sectional study","authors":"Harsh Bahrar , Kim Steward , Liesbeth van Emst , Nils Rother , Jeanine E. Roeters van Lennep , Mihai G. Netea , Siroon Bekkering , Niels P. Riksen","doi":"10.1016/j.athplu.2025.11.004","DOIUrl":"10.1016/j.athplu.2025.11.004","url":null,"abstract":"<div><h3>Background and aims</h3><div>Hypercholesterolemia is a major risk factor for atherosclerotic cardiovascular disease. Innate immune cells, including monocytes and neutrophils, play important roles in the pathophysiology of atherosclerosis. We previously reported that monocytes from patients with severely elevated low-density lipoprotein (LDL) cholesterol (LDL-c > 4.9 mmol/l) have a hyperresponsive phenotype, which persists even after three months statin treatment. This long-term hyperresponsive innate immune phenotype is termed trained immunity (innate immune memory), and is mediated by persistent enrichment of activating histone modifications leading to higher chromatin accessibility. In this study we investigated the monocyte and neutrophil phenotype of patients with severe hypercholesterolemia treated for 12 months with statins, compared to normocholesterolemic controls.</div></div><div><h3>Methods</h3><div>In a multicentric cross-sectional study, treatment-naïve patients with severe hypercholesterolemia (defined as LDL-cholesterol >4.9 mmol/L) requiring statin treatment were included. Blood was drawn after 12 months of lipid lowering therapy with statins (n = 15) and compared to healthy normocholesterolemic controls (LDL-c<3.5 mmol/l; n = 18).</div><div>We assessed monocyte phenotype with flow cytometry, cytokine production capacity of PBMCs, and H3K4me3 expression on the <em>TNFA</em> promotor. In addition, we assessed the neutrophil phenotype and function.</div></div><div><h3>Results</h3><div>Treatment lowered LDL-c from 5.8 to 2.7 mmol/L. PBMC cytokine production capacity, as well as the expression of H3K4me3 histone mark on the <em>TNFA</em> promotor did not differ from the controls (LDL-c 2.6 mmol/L). Although neutrophil CD11b, CD66b, and CD62L expression was the same, production of several granular proteins was lower in patients.</div></div><div><h3>Conclusions</h3><div>Previous studies reported hyperresponsive monocytes in treatment-naïve patients with LDL-c > 4.9 mmol/l. We now demonstrate that in an independent cohort of patients with LDL-c > 4.9 who are treated for 12 months with lipid-lowering drugs, the monocyte phenotype and function was similar to that of normocholesterolemic controls. In addition, neutrophils phenotype was similar, while the secretion of several granular proteins was lower in the patients.</div></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"62 ","pages":"Pages 53-61"},"PeriodicalIF":2.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145748238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-18DOI: 10.1016/j.athplu.2025.11.001
Monika Targońska , Anna Janaszak-Jasiecka , Magdalena Chmara , Monika Żuk , Leszek Kalinowski , Krzysztof Waleron , Jacek Jasiecki , Bartosz Wasąg
Background and aims
Familial hypercholesterolemia is a genetic disorder caused by pathogenic or likely pathogenic variants in four key genes: LDLR, APOB, PCSK9, and APOE. It leads to elevated levels of low-density lipoprotein cholesterol in the bloodstream and significantly increases the risk of coronary artery disease. This study aimed to functionally characterize LDLR variants identified in Polish FH patients. Experimental data were used to learn about variants' phenotypes and incorporate them into the ACMG/AMP variant classification framework.
Methods
The functional analysis was performed using the HEK293T-ldlrG1 cells with the expression vectors pTetRedLDLR carrying the mutated LDLR gene variants. Receptor expression was evaluated using Western blot and immunofluorescence. The low-density lipoprotein uptake and ligand binding capacity were examined with fluorescent dye-labeled LDL by confocal microscopy. A functional study was performed to analyze the variants under assessment and compare them to known benign and pathogenic control variants.
Results
The experimental study revealed an impaired activity of the c.662A > G p. (Asp221Gly), c.1775G > A p. (Gly592Glu), and c.2483delA p. (Tyr828Phefs∗101) LDLR variants, classifying them as functionally abnormal. In contrast, in vitro activity assessment of the c.91G > A p. (Glu31Lys) LDLR variant showed fully functional low-density lipoprotein binding and uptake activities. These results suggested that c.91G > A p. (Glu31Lys) is unlikely to be a disease-causing variant.
Conclusions
The results provide functional evidence for the activity of selected LDLR variants in a cellular model based on confocal techniques that meets the ACMG/AMP variant classification criteria. These findings highlight the importance of in vitro assays in evaluating the functional impact of LDLR variants and contribute valuable insights for clinical interpretation and genetic counseling.
背景和目的家族性高胆固醇血症是一种由LDLR、APOB、PCSK9和APOE四个关键基因的致病性或可能致病性变异引起的遗传性疾病。它会导致血液中低密度脂蛋白胆固醇水平升高，并显著增加冠状动脉疾病的风险。本研究旨在对波兰FH患者中发现的LDLR变异进行功能表征。利用实验数据了解变异的表型，并将其纳入ACMG/AMP变异分类框架。方法以携带LDLR突变基因变体的pTetRedLDLR表达载体HEK293T-ldlrG1细胞进行功能分析。采用Western blot和免疫荧光法检测受体表达。用荧光染料标记LDL共聚焦显微镜检测低密度脂蛋白摄取和配体结合能力。一项功能研究分析了评估中的变异，并将其与已知的良性和致病对照变异进行了比较。结果实验研究显示c.662A > G . (Asp221Gly), c.1775G > A . （Gly592Glu）和c.2483delA p. (Tyr828Phefs * 101) LDLR变体的活性受损，将其归类为功能异常。相比之下，c.91G > A p. (Glu31Lys) LDLR变体的体外活性评估显示出完全功能的低密度脂蛋白结合和摄取活性。这些结果表明c.91G > A p. （Glu31Lys）不太可能是致病变异。结论该结果为基于共聚焦技术的细胞模型中选定的LDLR变体的活性提供了功能证据，这些变体符合ACMG/AMP变体分类标准。这些发现强调了体外检测在评估LDLR变异的功能影响方面的重要性，并为临床解释和遗传咨询提供了有价值的见解。
{"title":"Characterization of selected LDLR substitutions in patients with familial hypercholesterolemia","authors":"Monika Targońska , Anna Janaszak-Jasiecka , Magdalena Chmara , Monika Żuk , Leszek Kalinowski , Krzysztof Waleron , Jacek Jasiecki , Bartosz Wasąg","doi":"10.1016/j.athplu.2025.11.001","DOIUrl":"10.1016/j.athplu.2025.11.001","url":null,"abstract":"<div><h3>Background and aims</h3><div>Familial hypercholesterolemia is a genetic disorder caused by pathogenic or likely pathogenic variants in four key genes: <em>LDLR</em>, <em>APOB</em>, <em>PCSK9,</em> and <em>APOE</em>. It leads to elevated levels of low-density lipoprotein cholesterol in the bloodstream and significantly increases the risk of coronary artery disease. This study aimed to functionally characterize <em>LDLR</em> variants identified in Polish FH patients. Experimental data were used to learn about variants' phenotypes and incorporate them into the ACMG/AMP variant classification framework.</div></div><div><h3>Methods</h3><div>The functional analysis was performed using the HEK293T-<em>ldlr</em>G1 cells with the expression vectors pTetRedLDLR carrying the mutated <em>LDLR</em> gene variants. Receptor expression was evaluated using Western blot and immunofluorescence. The low-density lipoprotein uptake and ligand binding capacity were examined with fluorescent dye-labeled LDL by confocal microscopy. A functional study was performed to analyze the variants under assessment and compare them to known benign and pathogenic control variants.</div></div><div><h3>Results</h3><div>The experimental study revealed an impaired activity of the c.662A > G p. (Asp221Gly), c.1775G > A p. (Gly592Glu), and c.2483delA p. (Tyr828Phefs∗101) <em>LDLR</em> variants, classifying them as functionally abnormal. In contrast, <em>in vitro</em> activity assessment of the c.91G > A p. (Glu31Lys) <em>LDLR</em> variant showed fully functional low-density lipoprotein binding and uptake activities. These results suggested that c.91G > A p. (Glu31Lys) is unlikely to be a disease-causing variant.</div></div><div><h3>Conclusions</h3><div>The results provide functional evidence for the activity of selected <em>LDLR</em> variants in a cellular model based on confocal techniques that meets the ACMG/AMP variant classification criteria. These findings highlight the importance of <em>in vitro</em> assays in evaluating the functional impact of <em>LDLR</em> variants and contribute valuable insights for clinical interpretation and genetic counseling.</div></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"62 ","pages":"Pages 30-37"},"PeriodicalIF":2.1,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145579088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-30DOI: 10.1016/j.athplu.2025.10.023
Xiaowei Yin , Yajie Zhang , Luyao Shi , Junwen Xue , Zhen Tian , Chicheng Gong , Fen Wang , Yongjun Cao
Aim
Earthworm fibrinolytic enzymes A (EFEa) is the main active component of earthworm fibrinolytic enzymes which possesses anticoagulant, fibrinolytic, and potential anti-atherosclerotic effects. However, the biological function and mechanism of action of EFEa remains unclear. This study aims to investigate the role of EFEa and the fibrin-derived peptide Bβ15-42 (Bβ15-42) in attenuating atherosclerosis by modulating endothelial adhesion and inflammation via the vascular endothelial (VE)-cadherin signaling pathway.
Methods
In this study, we established both a rabbit model of atherosclerosis and an in vitro endothelial cell model. Bβ15-42, EFEa, and rosuvastatin (ROS) were administered to evaluate their effects on atherosclerotic plaque formation and inflammatory responses. Plaque size and intimal thickening were evaluated using Oil Red O and hematoxylin-eosin (HE) staining. Fibrinogen deposition and VE-cadherin expression were analyzed via western blotting and immunohistochemistry. Furthermore, macrophage migration assays and CDH5-positive (CDH5+) human umbilical vein endothelial cell (HUVEC) models were utilized to investigate the effects of these compounds on inflammatory cell migration and VE-cadherin-mediated endothelial barrier function.
Results
Treatment with Bβ15-42, EFEa, and ROS significantly reduced atherosclerotic plaque formation and intimal thickening in the rabbit model of atherosclerosis (P < 0.05). Both Bβ15-42 and EFEa significantly reduced fibrinogen deposition and inflammatory cell infiltration in the aortic tissue of atherosclerotic rabbits (P < 0.05). Western blot and immunohistochemical analyses confirmed that Bβ15-42 and EFEa effectively up-regulated VE-cadherin expression (P < 0.05). In vitro, Bβ15-42 and EFEa significantly inhibited fibrin-induced macrophage transmigration across endothelial cell monolayers, reducing migration by 83.3 % and 56.1 %, respectively (P < 0.05, respectively).
Conclusion
EFEa and Bβ15-42 exert protective effects against atherosclerosis via the VE-cadherin pathway. Our findings lay the groundwork for further research into the anti-atherosclerotic mechanisms of EFEa, as well as its potential for future development and application.
{"title":"Earthworm fibrinolytic enzyme A and fibrin-derived peptide Bβ15-42 attenuate atherosclerosis via the VE-Cadherin signaling pathway","authors":"Xiaowei Yin , Yajie Zhang , Luyao Shi , Junwen Xue , Zhen Tian , Chicheng Gong , Fen Wang , Yongjun Cao","doi":"10.1016/j.athplu.2025.10.023","DOIUrl":"10.1016/j.athplu.2025.10.023","url":null,"abstract":"<div><h3>Aim</h3><div>Earthworm fibrinolytic enzymes A (EFEa) is the main active component of earthworm fibrinolytic enzymes which possesses anticoagulant, fibrinolytic, and potential anti-atherosclerotic effects. However, the biological function and mechanism of action of EFEa remains unclear. This study aims to investigate the role of EFEa and the fibrin-derived peptide Bβ15-42 (Bβ15-42) in attenuating atherosclerosis by modulating endothelial adhesion and inflammation via the vascular endothelial (VE)-cadherin signaling pathway.</div></div><div><h3>Methods</h3><div>In this study, we established both a rabbit model of atherosclerosis and an in vitro endothelial cell model. Bβ15-42, EFEa, and rosuvastatin (ROS) were administered to evaluate their effects on atherosclerotic plaque formation and inflammatory responses. Plaque size and intimal thickening were evaluated using Oil Red O and hematoxylin-eosin (HE) staining. Fibrinogen deposition and VE-cadherin expression were analyzed via western blotting and immunohistochemistry. Furthermore, macrophage migration assays and CDH5-positive (CDH5<sup>+</sup>) human umbilical vein endothelial cell (HUVEC) models were utilized to investigate the effects of these compounds on inflammatory cell migration and VE-cadherin-mediated endothelial barrier function.</div></div><div><h3>Results</h3><div>Treatment with Bβ15-42, EFEa, and ROS significantly reduced atherosclerotic plaque formation and intimal thickening in the rabbit model of atherosclerosis (<em>P</em> < 0.05). Both Bβ15-42 and EFEa significantly reduced fibrinogen deposition and inflammatory cell infiltration in the aortic tissue of atherosclerotic rabbits (<em>P</em> < 0.05). Western blot and immunohistochemical analyses confirmed that Bβ15-42 and EFEa effectively up-regulated VE-cadherin expression (<em>P</em> < 0.05). In vitro, Bβ15-42 and EFEa significantly inhibited fibrin-induced macrophage transmigration across endothelial cell monolayers, reducing migration by 83.3 % and 56.1 %, respectively (<em>P</em> < 0.05, respectively).</div></div><div><h3>Conclusion</h3><div>EFEa and Bβ15-42 exert protective effects against atherosclerosis via the VE-cadherin pathway. Our findings lay the groundwork for further research into the anti-atherosclerotic mechanisms of EFEa, as well as its potential for future development and application.</div></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"62 ","pages":"Pages 21-29"},"PeriodicalIF":2.1,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145474234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-14DOI: 10.1016/j.athplu.2025.10.001
Khaled Abdoun , Justin Swanson , Ian Pollack , Yuefang Chang , Kevin Kip , Oscar L. Lopez , Ann Cohen , Steven Reis , Anum Saeed
Introduction
Systemic inflammation is a well-established risk factor for atherosclerotic cardiovascular disease (ASCVD) and has also been implicated in the progression of neuroinflammation. However, the relationship between inflammation and the combined risk of ASCVD and cognitive decline—particularly during the critical transition from midlife to late life—remains poorly understood. Identifying a shared inflammatory marker that signals vulnerability to both conditions may be an important tool for early intervention. In this study, we examined how baseline inflammatory markers, as well as their changes over one year, relate to long-term risk of ASCVD and cognitive outcomes.
Methods
We analyzed baseline and one-year change (1y-Δ) in an inflammatory biomarker panel [high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), intracellular Adhesion Molecule 1 (ICAM-1) and CD40 ligand (CD40L_)] in the Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) study. Using logistic and linear Cox regression models, the association of inflammatory markers and 1y-Δ, cognitive assessment by MoCA score, coronary artery calcium (CAC), carotid intima-media thickness (CIMT), and major adverse cardiovascular events (MACE) events were assessed longitudinally. All data were adjusted for the pooled cohort equation (PCE) risk factors and area under the receiver operating characteristic curve (AUC) were calculated for incremental risk prediction.
Results
Among 673 participants (mean age 59 ± 6.8 years; 63.9 % female; 31.6 % Black) were followed for 12 years. While both hs-CRP and IL-6 were associated with MACE events at 12 years, only ICAM-1 was linked with long-term MACE (HR 2.34 [1.02–5.37], p < 0.05) as well as lower MoCA scores (β: 0.47 [95 % CI: 0.93 to −0.02], p < 0.05). Compared to the PCE model, inflammatory biomarkers improved risk prediction indices for MACE (0.812, ΔAUC +0.056, p = 0.02) and MoCA (0.664, ΔAUC +0.04, p = 0.048). One-year biomarker changes were not significant for endpoint association.
Conclusions
In a community cohort of adults, midlife levels of three inflammatory markers (hs-CRP, IL-6, and ICAM-1) were predictive of late life ASCVD; however, only ICAM-1 was identified as a dual marker for ASCVD and cognitive impairment. The role of ICAM-1 as a prognostic marker for adverse cardiovascular and cognitive health should be explored in future studies.
系统性炎症是公认的动脉粥样硬化性心血管疾病（ASCVD）的危险因素，也与神经炎症的进展有关。然而，炎症与ASCVD和认知能力下降的综合风险之间的关系，特别是在从中年到晚年的关键过渡时期，仍然知之甚少。识别一种共同的炎症标志物，表明对这两种疾病的易感性，可能是早期干预的重要工具。在这项研究中，我们研究了基线炎症标志物及其在一年内的变化与ASCVD的长期风险和认知结果的关系。方法：我们分析了心脏策略集中风险评估（Heart SCORE）研究中炎症生物标志物面板[高敏c反应蛋白（hs-CRP）、白细胞介素-6 （IL-6）、细胞内粘附分子1 （ICAM-1）和CD40配体（CD40L_）]的基线和一年变化（1y-Δ）。采用logistic和线性Cox回归模型，纵向评估炎症标志物与1y-Δ、MoCA评分认知评估、冠状动脉钙（CAC）、颈动脉内膜-中膜厚度（CIMT）和主要心血管不良事件（MACE）事件的相关性。对所有数据进行合并队列方程（PCE）危险因素调整，并计算受试者工作特征曲线下面积（AUC），以进行增量风险预测。结果673例患者（平均年龄59±6.8岁，女性63.9%，黑人31.6%）随访12年。虽然hs-CRP和IL-6都与12年时的MACE事件相关，但只有ICAM-1与长期MACE （HR 2.34 [1.02-5.37], p < 0.05）以及较低的MoCA评分相关（β: 0.47 [95% CI: 0.93至- 0.02],p < 0.05）。与PCE模型相比，炎症生物标志物改善了MACE （0.812， ΔAUC +0.056, p = 0.02）和MoCA （0.664， ΔAUC +0.04, p = 0.048）的风险预测指标。一年的生物标志物变化与终点关联不显著。结论：在一个社区成人队列中，三种炎症标志物（hs-CRP、IL-6和ICAM-1）的中年水平可预测晚期ASCVD；然而，只有ICAM-1被确定为ASCVD和认知障碍的双重标志物。ICAM-1作为心血管和认知健康不良的预后标志物的作用应在未来的研究中进一步探讨。
{"title":"Midlife ICAM-1 levels may predict cardiovascular disease and cognitive decline in latelife: Insights from the HeartSCORE study","authors":"Khaled Abdoun , Justin Swanson , Ian Pollack , Yuefang Chang , Kevin Kip , Oscar L. Lopez , Ann Cohen , Steven Reis , Anum Saeed","doi":"10.1016/j.athplu.2025.10.001","DOIUrl":"10.1016/j.athplu.2025.10.001","url":null,"abstract":"<div><h3>Introduction</h3><div>Systemic inflammation is a well-established risk factor for atherosclerotic cardiovascular disease (ASCVD) and has also been implicated in the progression of neuroinflammation. However, the relationship between inflammation and the combined risk of ASCVD and cognitive decline—particularly during the critical transition from midlife to late life—remains poorly understood. Identifying a shared inflammatory marker that signals vulnerability to both conditions may be an important tool for early intervention. In this study, we examined how baseline inflammatory markers, as well as their changes over one year, relate to long-term risk of ASCVD and cognitive outcomes.</div></div><div><h3>Methods</h3><div>We analyzed baseline and one-year change (1y-Δ) in an inflammatory biomarker panel [high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), intracellular Adhesion Molecule 1 (ICAM-1) and CD40 ligand (CD40L_)] in the Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) study. Using logistic and linear Cox regression models, the association of inflammatory markers and 1y-Δ, cognitive assessment by MoCA score, coronary artery calcium (CAC), carotid intima-media thickness (CIMT), and major adverse cardiovascular events (MACE) events were assessed longitudinally. All data were adjusted for the pooled cohort equation (PCE) risk factors and area under the receiver operating characteristic curve (AUC) were calculated for incremental risk prediction.</div></div><div><h3>Results</h3><div>Among 673 participants (mean age 59 ± 6.8 years; 63.9 % female; 31.6 % Black) were followed for 12 years. While both hs-CRP and IL-6 were associated with MACE events at 12 years, only ICAM-1 was linked with long-term MACE (HR 2.34 [1.02–5.37], p < 0.05) as well as lower MoCA scores (β: 0.47 [95 % CI: 0.93 to −0.02], p < 0.05). Compared to the PCE model, inflammatory biomarkers improved risk prediction indices for MACE (0.812, ΔAUC +0.056, p = 0.02) and MoCA (0.664, ΔAUC +0.04, p = 0.048). One-year biomarker changes were not significant for endpoint association.</div></div><div><h3>Conclusions</h3><div>In a community cohort of adults, midlife levels of three inflammatory markers (hs-CRP, IL-6, and ICAM-1) were predictive of late life ASCVD; however, only ICAM-1 was identified as a dual marker for ASCVD and cognitive impairment. The role of ICAM-1 as a prognostic marker for adverse cardiovascular and cognitive health should be explored in future studies.</div></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"62 ","pages":"Pages 15-20"},"PeriodicalIF":2.1,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145364116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-24DOI: 10.1016/j.athplu.2025.09.005
Alessandro Lupi , Martino Baluci , Simone Persampieri , Iacopo Perversi , Davide Presutti , Alberto Somaschini , Giovanni Vincenzo Gaudio , Luigina Guasti , Marc Ferrini , Alberto Corsini , Roberto De Ponti
Background
Elevated low-density lipoprotein cholesterol (LDL-C) after acute coronary syndrome (ACS) significantly increases cardiovascular risk. Timely reduction of LDL-C is crucial, but it takes several weeks to achieve optimal LDL-C levels with standard therapy. Monoclonal antibodies that inhibit PCSK9 have been demonstrated in some small randomised trials to rapidly abate LDL-C levels when used early after hospital admission for ACS. Inclisiran, a PCSK9-inhibiting siRNA, has recently been introduced into clinical practice; however, no information is available about its effectiveness and safety as a fast-track lipid-lowering agent in this clinical context.
Methods
We conducted a prospective, real-world study evaluating a fast-track lipid-lowering approach starting inclisiran on top of standard therapy in 16 consecutive ACS patients admitted to our cardiac intensive care unit with a high baseline LDL-C level (147.2 ± 35.7 mg/dL). Patients started inclisiran as add-on therapy as soon as baseline LDL-C levels were available. We assessed LDL-C levels and the mean change of LDL-C at baseline, discharge, 15-day and 30-day follow-up.
Results
Inclisiran, added to standard therapy, reduced LDL-C levels to 30.3 ± 13.0 mg/dL at 30-day follow-up. The guideline-recommended LDL-C levels (≤55 mg/dL, ≥50 % reduction) were achieved in 73.3 % of patients at 15 days and in 100 % of patients at 30 days, with no adverse effects.
Conclusion
This pilot study shows promise for inclisiran as a novel therapeutic option to improve cardiovascular outcomes in patients with ACS by contributing to achieving an early and sustained reduction in LDL-C levels.
{"title":"Inclisiran for fast-track lipid-lowering treatment early after an acute coronary syndrome: a pilot study","authors":"Alessandro Lupi , Martino Baluci , Simone Persampieri , Iacopo Perversi , Davide Presutti , Alberto Somaschini , Giovanni Vincenzo Gaudio , Luigina Guasti , Marc Ferrini , Alberto Corsini , Roberto De Ponti","doi":"10.1016/j.athplu.2025.09.005","DOIUrl":"10.1016/j.athplu.2025.09.005","url":null,"abstract":"<div><h3>Background</h3><div>Elevated low-density lipoprotein cholesterol (LDL-C) after acute coronary syndrome (ACS) significantly increases cardiovascular risk. Timely reduction of LDL-C is crucial, but it takes several weeks to achieve optimal LDL-C levels with standard therapy. Monoclonal antibodies that inhibit PCSK9 have been demonstrated in some small randomised trials to rapidly abate LDL-C levels when used early after hospital admission for ACS. Inclisiran, a PCSK9-inhibiting siRNA, has recently been introduced into clinical practice; however, no information is available about its effectiveness and safety as a fast-track lipid-lowering agent in this clinical context.</div></div><div><h3>Methods</h3><div>We conducted a prospective, real-world study evaluating a fast-track lipid-lowering approach starting inclisiran on top of standard therapy in 16 consecutive ACS patients admitted to our cardiac intensive care unit with a high baseline LDL-C level (147.2 ± 35.7 mg/dL). Patients started inclisiran as add-on therapy as soon as baseline LDL-C levels were available. We assessed LDL-C levels and the mean change of LDL-C at baseline, discharge, 15-day and 30-day follow-up.</div></div><div><h3>Results</h3><div>Inclisiran, added to standard therapy, reduced LDL-C levels to 30.3 ± 13.0 mg/dL at 30-day follow-up. The guideline-recommended LDL-C levels (≤55 mg/dL, ≥50 % reduction) were achieved in 73.3 % of patients at 15 days and in 100 % of patients at 30 days, with no adverse effects.</div></div><div><h3>Conclusion</h3><div>This pilot study shows promise for inclisiran as a novel therapeutic option to improve cardiovascular outcomes in patients with ACS by contributing to achieving an early and sustained reduction in LDL-C levels.</div></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"62 ","pages":"Pages 9-14"},"PeriodicalIF":2.1,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145159687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-20DOI: 10.1016/j.athplu.2025.09.004
Farah Yasmin , Abdul Moeed , Muhammad Ahmed Ali Fahim , Gaurav Kumar , Maryam Shaharyar , Muhammad Sohaib Asghar
Objectives
National estimates of deaths related to cardiovascular disease (CVD) and liver cirrhosis remain ambiguous. The purpose of this study was to observe the contemporary trends in CVD and liver cirrhosis-related mortality in the United States.
Methods
We evaluated the trends using the CDC WONDER database to identify adults with CVD and liver cirrhosis associated death between 1999 and 2019. Age-adjusted mortality rates (AAMRs) per 100,000 population and associated average annual percent changes (AAPCs) with 95 % confidence intervals (CIs) were assessed using Joinpoint regression.
Results
Between 1999 and 2019, a total of 374,090 deaths occurred due to CVD and liver cirrhosis. In the overall population, the AAMR increased from 7.54 (95 % CI 7.41–7.67) in 1999 to 10.55 (95 % CI 10.43–10.68) with an AAPC of 1.68 (95 % CI 1.59–1.77). The highest AAMRs were seen in males, Native Americans, and those living in West. A substantial increase in AAMRs was observed in all age groups with the highest seen in 70–84 year group. Moreover, non-metropolitan cities had a much higher increase in AAMRs compared to large metropolitan cities. The highest AAMRs were observed in California whereas the lowest in Utah.
Conclusion
There is a rising trend of CVD and liver cirrhosis-associated mortality in all groups. However, disparities continue to exist in association with gender, race, age, and geographical region. Future trials should address alleviating CVD and liver cirrhosis-related deaths in all population groups equitably.
目的：国家对心血管疾病（CVD）和肝硬化相关死亡的估计仍不明确。本研究的目的是观察美国心血管疾病和肝硬化相关死亡率的当代趋势。方法：我们使用CDC WONDER数据库评估1999年至2019年期间心血管疾病和肝硬化相关死亡的趋势。使用Joinpoint回归评估每10万人的年龄调整死亡率（AAMRs）和相关的年平均百分比变化（AAPCs）， 95%置信区间（ci）。结果1999年至2019年，共有374090人死于心血管疾病和肝硬化。在总体人群中，AAMR从1999年的7.54 （95% CI 7.41 ~ 7.67）增加到10.55 (95% CI 10.43 ~ 10.68)， AAPC为1.68 （95% CI 1.59 ~ 1.77）。男性、美洲原住民和居住在西部的人的aamr最高。在所有年龄组中均观察到AAMRs的显著增加，其中70-84岁组最高。此外，与大城市相比，非大城市的aamr增幅要高得多。aamr最高的是加利福尼亚州，最低的是犹他州。结论各年龄组CVD及肝硬化相关死亡率均有上升趋势。然而，与性别、种族、年龄和地理区域相关的差异仍然存在。未来的试验应在所有人群中公平地减轻心血管疾病和肝硬化相关死亡。
{"title":"Demographic and regional trends of mortality in patients with cardiovascular disease and liver cirrhosis in the United States between 1999 and 2019","authors":"Farah Yasmin , Abdul Moeed , Muhammad Ahmed Ali Fahim , Gaurav Kumar , Maryam Shaharyar , Muhammad Sohaib Asghar","doi":"10.1016/j.athplu.2025.09.004","DOIUrl":"10.1016/j.athplu.2025.09.004","url":null,"abstract":"<div><h3>Objectives</h3><div>National estimates of deaths related to cardiovascular disease (CVD) and liver cirrhosis remain ambiguous. The purpose of this study was to observe the contemporary trends in CVD and liver cirrhosis-related mortality in the United States.</div></div><div><h3>Methods</h3><div>We evaluated the trends using the CDC WONDER database to identify adults with CVD and liver cirrhosis associated death between 1999 and 2019. Age-adjusted mortality rates (AAMRs) per 100,000 population and associated average annual percent changes (AAPCs) with 95 % confidence intervals (CIs) were assessed using Joinpoint regression.</div></div><div><h3>Results</h3><div>Between 1999 and 2019, a total of 374,090 deaths occurred due to CVD and liver cirrhosis. In the overall population, the AAMR increased from 7.54 (95 % CI 7.41–7.67) in 1999 to 10.55 (95 % CI 10.43–10.68) with an AAPC of 1.68 (95 % CI 1.59–1.77). The highest AAMRs were seen in males, Native Americans, and those living in West. A substantial increase in AAMRs was observed in all age groups with the highest seen in 70–84 year group. Moreover, non-metropolitan cities had a much higher increase in AAMRs compared to large metropolitan cities. The highest AAMRs were observed in California whereas the lowest in Utah.</div></div><div><h3>Conclusion</h3><div>There is a rising trend of CVD and liver cirrhosis-associated mortality in all groups. However, disparities continue to exist in association with gender, race, age, and geographical region. Future trials should address alleviating CVD and liver cirrhosis-related deaths in all population groups equitably.</div></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"62 ","pages":"Pages 1-8"},"PeriodicalIF":2.1,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145121166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Oxidized phospholipids (OxPLs) are bound to apolipoprotein B-100 (OxPL-apoB) and apolipoprotein(a) [OxPL-apo(a)] and are present freely within the phospholipid shell of apoB-containing lipoproteins. OxPLs have been linked with the pro-inflammatory properties of lipoprotein(a) [Lp(a)]. OxPLs carried on plasminogen (OxPL-PLG) may extend the time to fibrinolysis.
Purpose
To evaluate the effect of lipid-lowering medications on OxPLs levels in individuals with elevated Lp(a) concentrations.
Methods
In this prospective study, patients (n = 70) with Lp(a) levels ≥75 nmol/L were assigned to 3 treatment regimens according to current guidelines: high-intensity statin monotherapy (n = 28), ezetimibe added to high-intensity statin (n = 31) and proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) added to high-intensity statin plus ezetimibe (n = 11). Follow-up duration was 3 months.
Results
Patients had a mean age of 51 ± 15 years, 40 % were male, 39 % were diagnosed with familial hypercholesterolemia, 16 % had atherosclerotic cardiovascular disease, and 36 %, 33 % and 15 % were at very high, high, and moderate cardiovascular risk, respectively. Lp(a) levels did not change significantly with high-intensity statin and add-on ezetimibe but significantly decreased with add-on PCSK9i treatment. OxPL-apoB and OxPL-apo(a) significantly increased, while OxPL-PLG significantly decreased with both high-intensity statin and add-on ezetimibe. Add-on PCSK9i treatment was associated with no significant changes in OxPL-apoB, OxPL-apo(a) and OxPL-PLG levels.
Conclusions
Among patients with elevated Lp(a), both high-intensity statin and add-on ezetimibe significantly increased OxPL-apoB and OxPL-apo(a) levels, while significantly decreased OxPL-PLG levels. Add-on PCSK9i had no significant effect on OxPLs levels. The clinical implications of these findings should be further explored.
{"title":"Effect of lipid-lowering medications on oxidized phospholipids in individuals with elevated LIPOPROTEIN(a)","authors":"Amalia Despoina Koutsogianni , Fotios Barkas , Constantinos Tellis , Alexandros Tselepis , George Liamis , Sotirios Tsimikas , Evangelos Liberopoulos","doi":"10.1016/j.athplu.2025.09.003","DOIUrl":"10.1016/j.athplu.2025.09.003","url":null,"abstract":"<div><h3>Background/introduction</h3><div>Oxidized phospholipids (OxPLs) are bound to apolipoprotein B-100 (OxPL-apoB) and apolipoprotein(a) [OxPL-apo(a)] and are present freely within the phospholipid shell of apoB-containing lipoproteins. OxPLs have been linked with the pro-inflammatory properties of lipoprotein(a) [Lp(a)]. OxPLs carried on plasminogen (OxPL-PLG) may extend the time to fibrinolysis.</div></div><div><h3>Purpose</h3><div>To evaluate the effect of lipid-lowering medications on OxPLs levels in individuals with elevated Lp(a) concentrations.</div></div><div><h3>Methods</h3><div>In this prospective study, patients (n = 70) with Lp(a) levels ≥75 nmol/L were assigned to 3 treatment regimens according to current guidelines: high-intensity statin monotherapy (n = 28), ezetimibe added to high-intensity statin (n = 31) and proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) added to high-intensity statin plus ezetimibe (n = 11). Follow-up duration was 3 months.</div></div><div><h3>Results</h3><div>Patients had a mean age of 51 ± 15 years, 40 % were male, 39 % were diagnosed with familial hypercholesterolemia, 16 % had atherosclerotic cardiovascular disease, and 36 %, 33 % and 15 % were at very high, high, and moderate cardiovascular risk, respectively. Lp(a) levels did not change significantly with high-intensity statin and add-on ezetimibe but significantly decreased with add-on PCSK9i treatment. OxPL-apoB and OxPL-apo(a) significantly increased, while OxPL-PLG significantly decreased with both high-intensity statin and add-on ezetimibe. Add-on PCSK9i treatment was associated with no significant changes in OxPL-apoB, OxPL-apo(a) and OxPL-PLG levels.</div></div><div><h3>Conclusions</h3><div>Among patients with elevated Lp(a), both high-intensity statin and add-on ezetimibe significantly increased OxPL-apoB and OxPL-apo(a) levels, while significantly decreased OxPL-PLG levels. Add-on PCSK9i had no significant effect on OxPLs levels. The clinical implications of these findings should be further explored.</div></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"61 ","pages":"Pages 58-66"},"PeriodicalIF":2.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145026415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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