Pub Date : 2026-01-19DOI: 10.1016/j.athplu.2026.01.002
Eduardo Varejão Díaz Placencia , Elisângela Farias-Silva , Melissa Regina Fessel , Maria Claudina de Andrade , Luciana Simão Carmo , Cynthia de Almeida Mendes , Nelson Wolosker , Alexandre Leme Godoy dos Santos , Tulio Diniz Fernandes , Marcel Liberman
This study investigated the mechanistic intersection between aging, diabetes mellitus (DM), and prelamin A accumulation in vascular calcification (VC) progression in patients with peripheral arterial disease (PAD) undergoing lower limb amputation. Arterial segments were collected from amputated PAD patients with (PAD + DM, n = 10) and without DM (PAD, n = 8), as well as from non-vascular amputated patients (CTRL, n = 3). Additional in vivo and in vitro experiments were conducted to investigate early-stages of VC and the impact of insulin resistance on prelamin A accumulation and ZMPSTE24 expression. PAD and PAD + DM patients exhibited greater VC than CTRL patients. Prelamin A accumulation was higher in PAD (6.3 ± 5.0 %) and PAD + DM (10.9 ± 6.4 %) than in CTRL (1.2 ± 1.3 %), while ZMPSTE24 expression was lower in PAD (5.2 ± 2.6 %) and PAD + DM (3.1 ± 3.2 %) than in CTRL (20.0 ± 3.8 %), indicating impaired prelamin A processing. Investigation in a murine VC model, aortae from leptin-deficient ob/ob mice showed increased prelamin A accumulation, independently of calcifying stimulation. Increased prelamin A expression was also observed insulin-resistant ob/ob VSMCs, independently of calcifying stimulation. These findings suggest that aging-related mechanisms, such as prelamin A accumulation, may synergistically contribute to VC progression, particularly in diabetic PAD patients. Targeting prelamin A processing may unveil a potential therapeutic approach to mitigate VC and reduce amputation risk in diabetic PAD patients.
{"title":"Prelamin A accumulation overlaps increased vascular calcification in peripheral artery disease and regulates vascular smooth muscle cells mineralization in diabetes mellitus","authors":"Eduardo Varejão Díaz Placencia , Elisângela Farias-Silva , Melissa Regina Fessel , Maria Claudina de Andrade , Luciana Simão Carmo , Cynthia de Almeida Mendes , Nelson Wolosker , Alexandre Leme Godoy dos Santos , Tulio Diniz Fernandes , Marcel Liberman","doi":"10.1016/j.athplu.2026.01.002","DOIUrl":"10.1016/j.athplu.2026.01.002","url":null,"abstract":"<div><div>This study investigated the mechanistic intersection between aging, diabetes mellitus (DM), and prelamin A accumulation in vascular calcification (VC) progression in patients with peripheral arterial disease (PAD) undergoing lower limb amputation. Arterial segments were collected from amputated PAD patients with (PAD + DM, n = 10) and without DM (PAD, n = 8), as well as from non-vascular amputated patients (CTRL, n = 3). Additional in vivo and <em>in vitro</em> experiments were conducted to investigate early-stages of VC and the impact of insulin resistance on prelamin A accumulation and ZMPSTE24 expression. PAD and PAD + DM patients exhibited greater VC than CTRL patients. Prelamin A accumulation was higher in PAD (6.3 ± 5.0 %) and PAD + DM (10.9 ± 6.4 %) than in CTRL (1.2 ± 1.3 %), while ZMPSTE24 expression was lower in PAD (5.2 ± 2.6 %) and PAD + DM (3.1 ± 3.2 %) than in CTRL (20.0 ± 3.8 %), indicating impaired prelamin A processing. Investigation in a murine VC model, aortae from leptin-deficient ob/ob mice showed increased prelamin A accumulation, independently of calcifying stimulation. Increased prelamin A expression was also observed insulin-resistant ob/ob VSMCs, independently of calcifying stimulation. These findings suggest that aging-related mechanisms, such as prelamin A accumulation, may synergistically contribute to VC progression, particularly in diabetic PAD patients. Targeting prelamin A processing may unveil a potential therapeutic approach to mitigate VC and reduce amputation risk in diabetic PAD patients.</div></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"63 ","pages":"Pages 34-42"},"PeriodicalIF":2.1,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078131","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}
Statins remain to date the primary therapeutic option for dyslipidemia. However, a significant portion of patients with dyslipidemia fail to achieve optimal low-density lipoprotein targets for reasons often related to treating physicians. The aim of STAtin Treatment in Routine clinical Practice (STATRIP) survey was to report and quantify perceptions and common beliefs regarding treatment with statins, among physicians implicated in the primary and secondary care of patients with dyslipidemia.
Methods and results
This observational cross-sectional study was conducted using an online-distributed questionnaire, which was designed to cover a wide range of physicians’ knowledge and perceptions on treatment with statins. A total of 261 health care providers filled out the survey, mostly general practitioners and internists (93.5 %). Study participants clearly expressed their concerns regarding statin-related side effects, including fears on interactions with other medication, muscle aches and pain, increase in liver enzymes, and gastrointestinal disorders. Myalgias were observed by physicians in as many as 29.2 % of patients receiving rosuvastatin, and in as many as 26.5 % receiving atorvastatin. Combination lipid-lowering therapy with ezetimibe was reported by only 53.6 % of participants as a prevalent strategy for uncontrolled individuals. Only 58.6 % apply non-HDL cholesterol measurements in their clinical practice.
Conclusions
Our study provides a clear perspective of treating physicians regarding statin prescription patterns. Several misconceptions, especially regarding statin-related adverse effects, hold well among treating physicians. Insufficient implementation of dyslipidemia guidelines calls for more targeted educational interventions to achieve optimal management of patients with dyslipidemia.
{"title":"Statin treatment in routine clinical practice: Insights from the STATRIP physician survey","authors":"Panagiota Anyfanti , Christina Antza , Dimitrios Poulis , Konstantinos Konstantaros , Makrina Savvoulidou , Georgios Styliadis , Vasilios Kotsis","doi":"10.1016/j.athplu.2026.01.003","DOIUrl":"10.1016/j.athplu.2026.01.003","url":null,"abstract":"<div><h3>Background</h3><div>Statins remain to date the primary therapeutic option for dyslipidemia. However, a significant portion of patients with dyslipidemia fail to achieve optimal low-density lipoprotein targets for reasons often related to treating physicians. The aim of STAtin Treatment in Routine clinical Practice (STATRIP) survey was to report and quantify perceptions and common beliefs regarding treatment with statins, among physicians implicated in the primary and secondary care of patients with dyslipidemia.</div></div><div><h3>Methods and results</h3><div>This observational cross-sectional study was conducted using an online-distributed questionnaire, which was designed to cover a wide range of physicians’ knowledge and perceptions on treatment with statins. A total of 261 health care providers filled out the survey, mostly general practitioners and internists (93.5 %). Study participants clearly expressed their concerns regarding statin-related side effects, including fears on interactions with other medication, muscle aches and pain, increase in liver enzymes, and gastrointestinal disorders. Myalgias were observed by physicians in as many as 29.2 % of patients receiving rosuvastatin, and in as many as 26.5 % receiving atorvastatin. Combination lipid-lowering therapy with ezetimibe was reported by only 53.6 % of participants as a prevalent strategy for uncontrolled individuals. Only 58.6 % apply non-HDL cholesterol measurements in their clinical practice.</div></div><div><h3>Conclusions</h3><div>Our study provides a clear perspective of treating physicians regarding statin prescription patterns. Several misconceptions, especially regarding statin-related adverse effects, hold well among treating physicians. Insufficient implementation of dyslipidemia guidelines calls for more targeted educational interventions to achieve optimal management of patients with dyslipidemia.</div></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"63 ","pages":"Pages 28-33"},"PeriodicalIF":2.1,"publicationDate":"2026-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146022751","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 : 2026-01-07DOI: 10.1016/j.athplu.2026.01.001
Mitra Nekouei Shahraki , Layal Chaker , Evert van Velsen , Mare van Overbruggen , Chris Heugens , Maryam Kavousi , Bruno H. Stricker , Daniel Bos
Aims
Bisphosphonates may influence arterial calcification through mechanisms shared with bone formation. As treatment often extends over several years, assessing the arterial effects requires long-term follow-up. This population-based cohort estimated the long-term association of bisphosphonates with calcification across multiple key arterial sites.
Methods
We included 2399 Rotterdam Study participants with baseline CT-assessed calcification in the coronary arteries (CAC), aortic arch (AAC), and extra/intracranial carotid arteries (ECAC and ICAC). Among these, 815 participants underwent repeat CT after a mean of 13.6 years. Pharmacy-linked data provided cumulative information on bisphosphonate use from study entry to follow-up. Multivariable linear and mixed-effects regressions evaluated associations between bisphosphonate use, duration, and the dose-response of duration with calcification volume.
Results
Long-term bisphosphonate use (>5 years) was statistically significantly associated with larger baseline CAC compared with both never use (β [95 % CI]: 0.42 [0.10, 0.73]) and short-term use (p-interaction = 0.02). At follow-up, prolonged use (mean duration: 4.9 years) was also significantly associated with increased CAC. Effect estimates increased across quartiles of duration for CAC, AAC, and ECAC (but not ICAC), with a significant linear trend only for CAC (p-trend < 0.0001), suggesting a dose-response relationship. Across arterial sites, CAC showed the largest effect estimates, ICAC the smallest.
Conclusions
Long-term bisphosphonate use is associated with increased arterial calcification, most notably with increased CAC, with a dose-response relationship further strengthening this observation. Large-scale observational studies are encouraged to use advanced causal inference methods to evaluate this long-term association and provide additional evidence to strengthen the causal interpretation.
{"title":"Bisphosphonates use is associated with increased coronary artery calcification in the general population: The Rotterdam study","authors":"Mitra Nekouei Shahraki , Layal Chaker , Evert van Velsen , Mare van Overbruggen , Chris Heugens , Maryam Kavousi , Bruno H. Stricker , Daniel Bos","doi":"10.1016/j.athplu.2026.01.001","DOIUrl":"10.1016/j.athplu.2026.01.001","url":null,"abstract":"<div><h3>Aims</h3><div>Bisphosphonates may influence arterial calcification through mechanisms shared with bone formation. As treatment often extends over several years, assessing the arterial effects requires long-term follow-up. This population-based cohort estimated the long-term association of bisphosphonates with calcification across multiple key arterial sites.</div></div><div><h3>Methods</h3><div>We included 2399 Rotterdam Study participants with baseline CT-assessed calcification in the coronary arteries (CAC), aortic arch (AAC), and extra/intracranial carotid arteries (ECAC and ICAC). Among these, 815 participants underwent repeat CT after a mean of 13.6 years. Pharmacy-linked data provided cumulative information on bisphosphonate use from study entry to follow-up. Multivariable linear and mixed-effects regressions evaluated associations between bisphosphonate use, duration, and the dose-response of duration with calcification volume.</div></div><div><h3>Results</h3><div>Long-term bisphosphonate use (>5 years) was statistically significantly associated with larger baseline CAC compared with both never use (β [95 % CI]: 0.42 [0.10, 0.73]) and short-term use (<em>p-interaction</em> = 0.02). At follow-up, prolonged use (mean duration: 4.9 years) was also significantly associated with increased CAC. Effect estimates increased across quartiles of duration for CAC, AAC, and ECAC (but not ICAC), with a significant linear trend only for CAC (<em>p-trend</em> < 0.0001), suggesting a dose-response relationship. Across arterial sites, CAC showed the largest effect estimates, ICAC the smallest.</div></div><div><h3>Conclusions</h3><div>Long-term bisphosphonate use is associated with increased arterial calcification, most notably with increased CAC, with a dose-response relationship further strengthening this observation. Large-scale observational studies are encouraged to use advanced causal inference methods to evaluate this long-term association and provide additional evidence to strengthen the causal interpretation.</div></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"63 ","pages":"Pages 19-27"},"PeriodicalIF":2.1,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977948","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}
Transferrin receptor 1 (TfR1), an intracellular iron receptor, has multiple biological functions. We have previously reported that aortic TfR1 expression increases in human and murine abdominal aortic aneurysm, but its role in the development of atherosclerosis remains unclear. In the present study, we generated apolipoprotein-E (ApoE) and TfR1 deficient mice and examined the impact of its deletion on the development of atherosclerosis.
Methods and results
Homozygous ApoE deficient (ApoE−/−) mice were crossbred to heterozygous TfR1 deficient (TfR1+/−) mice to generate ApoE and TfR1 deficient (ApoE−/−/TfR1+/−) mice. ApoE−/− and ApoE−/−/TfR1+/− mice presented a similar phenotype including body weight and lipid values. Of note, after a high-fat feeding for 16 weeks, ApoE−/−/TfR1+/− mice exhibited a reduction of the atherosclerotic areas in the aortic sinus and aorta compared with ApoE−/− mice despite similar lipid values. In addition, ApoE−/−/TfR1+/− mice showed decreases in oxidative stress and macrophage accumulation in the aortic sinus and aorta compared with ApoE−/− mice.
Conclusions
These results indicate that TfR1 deletion attenuates the development of atherosclerotic lesion formation in ApoE−/− mice.
{"title":"Heterozygous transferrin receptor 1 deletion reduces atherosclerotic lesion formation in apolipoprotein E-deficient mice","authors":"Yoshiro Naito, Tetsuo Horimatsu, Masanori Asakura, Masaharu Ishihara","doi":"10.1016/j.athplu.2025.12.003","DOIUrl":"10.1016/j.athplu.2025.12.003","url":null,"abstract":"<div><h3>Background</h3><div>Transferrin receptor 1 (TfR1), an intracellular iron receptor, has multiple biological functions. We have previously reported that aortic TfR1 expression increases in human and murine abdominal aortic aneurysm, but its role in the development of atherosclerosis remains unclear. In the present study, we generated apolipoprotein-E (ApoE) and TfR1 deficient mice and examined the impact of its deletion on the development of atherosclerosis.</div></div><div><h3>Methods and results</h3><div>Homozygous ApoE deficient (<em>ApoE</em><sup><em>−/−</em></sup>) mice were crossbred to heterozygous TfR1 deficient (<em>TfR1</em><sup><em>+/−</em></sup>) mice to generate ApoE and TfR1 deficient (<em>ApoE</em><sup><em>−/−</em></sup><em>/TfR1</em><sup><em>+/−</em></sup>) mice. <em>ApoE</em><sup><em>−/−</em></sup> and <em>ApoE</em><sup><em>−/−</em></sup><em>/TfR1</em><sup><em>+/−</em></sup> mice presented a similar phenotype including body weight and lipid values. Of note, after a high-fat feeding for 16 weeks, <em>ApoE</em><sup><em>−/−</em></sup><em>/TfR1</em><sup><em>+/−</em></sup> mice exhibited a reduction of the atherosclerotic areas in the aortic sinus and aorta compared with <em>ApoE</em><sup><em>−/−</em></sup> mice despite similar lipid values. In addition, <em>ApoE</em><sup><em>−/−</em></sup><em>/TfR1</em><sup><em>+/−</em></sup> mice showed decreases in oxidative stress and macrophage accumulation in the aortic sinus and aorta compared with <em>ApoE</em><sup><em>−/−</em></sup> mice.</div></div><div><h3>Conclusions</h3><div>These results indicate that TfR1 deletion attenuates the development of atherosclerotic lesion formation in <em>ApoE</em><sup><em>−/−</em></sup> mice.</div></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"63 ","pages":"Pages 14-18"},"PeriodicalIF":2.1,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145884880","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}
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.2025.10.004
M. Futema , T. Ingegneri , M. Sharifi , F. Drenos , S.E. Humphries
{"title":"Polygenic predisposition to increased LDL-cholesterol concentration and Carotid Artery Intima Media Thickness in childhood and early adulthood","authors":"M. Futema , T. Ingegneri , M. Sharifi , F. Drenos , S.E. Humphries","doi":"10.1016/j.athplu.2025.10.004","DOIUrl":"10.1016/j.athplu.2025.10.004","url":null,"abstract":"","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"62 ","pages":"Page 3"},"PeriodicalIF":2.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145808510","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.2025.10.015
P. Chua, L. Barton, C. Neuwirth, J. Cegla, A. David, S. Walji
{"title":"Paediatric Familial Hypercholesterolaemia database at a single tertiary centre: a review of patients managed under the paediatric lipid clinic at Hammersmith Hospital","authors":"P. Chua, L. Barton, C. Neuwirth, J. Cegla, A. David, S. Walji","doi":"10.1016/j.athplu.2025.10.015","DOIUrl":"10.1016/j.athplu.2025.10.015","url":null,"abstract":"","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"62 ","pages":"Page 8"},"PeriodicalIF":2.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145808441","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}