Pub Date : 2026-02-01Epub Date: 2025-12-29DOI: 10.1016/j.atherosclerosis.2025.120631
Zijie Wang , Xiao Hu , Jianshang Wen , Yanfang Xie , Mengqiu Zhang , Chuanqin Fang , Yanghua Tian , Qi Li
Background and aims
Systemic inflammation plays a significant role in cardiovascular disease (CVD). Monocyte to high-density lipoprotein (HDL) ratio (MHR) has emerged as a surrogate index of residual inflammation risk. We investigated the associations of MHR with incident CVD and mortality, and to explore the additional predictive value of combining MHR with C-reactive protein (CRP).
Methods
We included 366,705 UK Biobank participants without previous coronary heart disease, stroke, or transient ischemic attack. MHR was defined as the monocyte count divided by the HDL value. Quartiles of MHR were assessed as predictors of future CVD (myocardial infarction [MI] and stroke), cardiovascular death, and all-cause mortality after adjusting for sociodemographic, lifestyle, and clinical confounders.
Results
During a median follow-up of 12.7 years (IQR 11.9–13.4), 10,215 (2.8 %) developed MI, 6889 (1.9 %) cases of stroke, and 27,686 (7.5 %) died. Compared with the lowest MHR quartile, the highest MHR quartile (quartile 4) was associated with an increased risk of composite CVD (HR 1.45, 95 % CI 1.37–1.53), MI (1.59, 1.49–1.71), any stroke (1.23, 1.13–1.33); ischemic stroke (1.33, 1.21–1.46); cardiovascular mortality (1.42, 1.22–1.65), and all-cause mortality (1.11, 1.07–1.15) in the fully adjusted model. Risks of future MI, stroke, and mortality were significantly higher in participants with both elevated MHR (≥0.41) and CRP (≥2 mg/L).
Conclusions
MHR is associated with future CVD and mortality irrespective of CRP levels. MHR is an easily accessible marker to detect individuals with high inflammatory risk of CVD and mortality in clinical practice.
背景与目的全身性炎症在心血管疾病（CVD）中起重要作用。单核细胞与高密度脂蛋白（HDL）比率（MHR）已成为残留炎症风险的替代指标。我们研究了MHR与心血管疾病发病率和死亡率的关系，并探讨MHR与c反应蛋白（CRP）联合的额外预测价值。方法：我们纳入了366,705名英国生物银行参与者，他们之前没有冠心病、中风或短暂性脑缺血发作。MHR定义为单核细胞计数除以HDL值。在调整社会人口统计学、生活方式和临床混杂因素后，评估MHR四分位数作为未来CVD（心肌梗死[MI]和卒中）、心血管死亡和全因死亡率的预测因子。结果在中位随访12.7年（IQR 11.9-13.4）期间，10,215例（2.8%）发生心肌梗死，6889例（1.9%）发生脑卒中，27,686例（7.5%）死亡。与最低MHR四分位数相比，最高MHR四分位数（四分位数4）与复合心血管疾病（HR 1.45, 95% CI 1.37-1.53）、心肌梗死（1.59,1.49-1.71）、任何中风（1.23,1.13-1.33）的风险增加相关；缺血性卒中（1.33,1.21-1.46）；在完全调整模型中，心血管死亡率（1.42,1.22-1.65）和全因死亡率（1.11,1.07-1.15）。MHR（≥0.41）和CRP（≥2mg /L）升高的参与者未来发生心肌梗死、卒中和死亡的风险显著增加。结论与CRP水平无关，smhr与未来CVD和死亡率相关。在临床实践中，MHR是检测心血管疾病高炎症风险和死亡率的一种容易获得的标志物。
{"title":"Monocyte to high-density lipoprotein ratio and risk of incident stroke, myocardial infarction, and mortality: A large prospective cohort study","authors":"Zijie Wang , Xiao Hu , Jianshang Wen , Yanfang Xie , Mengqiu Zhang , Chuanqin Fang , Yanghua Tian , Qi Li","doi":"10.1016/j.atherosclerosis.2025.120631","DOIUrl":"10.1016/j.atherosclerosis.2025.120631","url":null,"abstract":"<div><h3>Background and aims</h3><div>Systemic inflammation plays a significant role in cardiovascular disease (CVD). Monocyte to high-density lipoprotein (HDL) ratio (MHR) has emerged as a surrogate index of residual inflammation risk. We investigated the associations of MHR with incident CVD and mortality, and to explore the additional predictive value of combining MHR with C-reactive protein (CRP).</div></div><div><h3>Methods</h3><div>We included 366,705 UK Biobank participants without previous coronary heart disease, stroke, or transient ischemic attack. MHR was defined as the monocyte count divided by the HDL value. Quartiles of MHR were assessed as predictors of future CVD (myocardial infarction [MI] and stroke), cardiovascular death, and all-cause mortality after adjusting for sociodemographic, lifestyle, and clinical confounders.</div></div><div><h3>Results</h3><div>During a median follow-up of 12.7 years (IQR 11.9–13.4), 10,215 (2.8 %) developed MI, 6889 (1.9 %) cases of stroke, and 27,686 (7.5 %) died. Compared with the lowest MHR quartile, the highest MHR quartile (quartile 4) was associated with an increased risk of composite CVD (HR 1.45, 95 % CI 1.37–1.53), MI (1.59, 1.49–1.71), any stroke (1.23, 1.13–1.33); ischemic stroke (1.33, 1.21–1.46); cardiovascular mortality (1.42, 1.22–1.65), and all-cause mortality (1.11, 1.07–1.15) in the fully adjusted model. Risks of future MI, stroke, and mortality were significantly higher in participants with both elevated MHR (≥0.41) and CRP (≥2 mg/L).</div></div><div><h3>Conclusions</h3><div>MHR is associated with future CVD and mortality irrespective of CRP levels. MHR is an easily accessible marker to detect individuals with high inflammatory risk of CVD and mortality in clinical practice.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"413 ","pages":"Article 120631"},"PeriodicalIF":5.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145880918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-12-22DOI: 10.1016/j.atherosclerosis.2025.120627
Robert S. Rosenson , Eliot A. Brinton , Daniel Gaudet , Frederick J. Raal , Carissa Baker-Smith , Patrick M. Moriarty , Susanne Greber-Platzer , Jean Bergeron , Brian W. McCrindle , Alpana Waldron , Shazia Ali , Richard T. George , Robert Pordy , Xue-Qiao Zhao , Albert Wiegman
Background and aims
Children and adolescents with homozygous familial hypercholesterolemia (HoFH) routinely require advanced lipid-lowering therapies (LLTs). We assess the long-term efficacy and safety of evinacumab, a novel LLT, in children and adolescents with HoFH.
Methods
Study 17100 (NCT04233918) was a phase 3, single-arm, open-label study enrolling 20 children aged 5–11 years with HoFH. ELIPSE-OLE (NCT03409744) was a phase 3, single-arm study enrolling 14 adolescents aged 12−17 years with HoFH. Participants received intravenous evinacumab 15 mg/kg every 4 weeks; all individuals received stable LLT and most received lipoprotein apheresis (60 % of children aged 5–11 years; 64 % of adolescents aged 12−17 years). Outcomes included change from baseline to weeks 48 and 72 in low-density lipoprotein cholesterol (LDL-C) and other lipid parameters. Safety was assessed as treatment-emergent adverse events (TEAEs).
Results
In children aged 5–11 years, mean (standard deviation [SD]) baseline LDL-C (301.9 [149.1] mg/dL) was lowered by 45 % (131.1 mg/dL) at week 48 and 41 % (115.8 mg/dL) at week 72. In adolescents aged 12–17 years, mean (SD) baseline LDL-C (300.4 [100.5] mg/dL) was lowered by 48 % (156.4 mg/dL) at week 48 and 51 % (165.6 mg/dL) at week 72. TEAEs occurred in 100 % and 86 % of participants aged 5–11 and 12–17 years, respectively. TEAEs were considered treatment related in four individuals aged 5–11 years (20 %); no one aged 12–17 years had treatment-related TEAEs (0 %).
Conclusions
Evinacumab markedly reduced LDL-C in children and adolescents with HoFH, beyond optimized standard LLT and lipoprotein apheresis. LDL-C remains above goal in most pediatric patients with HoFH, and evinacumab should be routinely considered whenever further LDL-C lowering is needed.
{"title":"Evinacumab in patients aged 5–17 years with homozygous familial hypercholesterolemia","authors":"Robert S. Rosenson , Eliot A. Brinton , Daniel Gaudet , Frederick J. Raal , Carissa Baker-Smith , Patrick M. Moriarty , Susanne Greber-Platzer , Jean Bergeron , Brian W. McCrindle , Alpana Waldron , Shazia Ali , Richard T. George , Robert Pordy , Xue-Qiao Zhao , Albert Wiegman","doi":"10.1016/j.atherosclerosis.2025.120627","DOIUrl":"10.1016/j.atherosclerosis.2025.120627","url":null,"abstract":"<div><h3>Background and aims</h3><div>Children and adolescents with homozygous familial hypercholesterolemia (HoFH) routinely require advanced lipid-lowering therapies (LLTs). We assess the long-term efficacy and safety of evinacumab, a novel LLT, in children and adolescents with HoFH.</div></div><div><h3>Methods</h3><div>Study 17100 (NCT04233918) was a phase 3, single-arm, open-label study enrolling 20 children aged 5–11 years with HoFH. ELIPSE-OLE (NCT03409744) was a phase 3, single-arm study enrolling 14 adolescents aged 12−17 years with HoFH. Participants received intravenous evinacumab 15 mg/kg every 4 weeks; all individuals received stable LLT and most received lipoprotein apheresis (60 % of children aged 5–11 years; 64 % of adolescents aged 12−17 years). Outcomes included change from baseline to weeks 48 and 72 in low-density lipoprotein cholesterol (LDL-C) and other lipid parameters. Safety was assessed as treatment-emergent adverse events (TEAEs).</div></div><div><h3>Results</h3><div>In children aged 5–11 years, mean (standard deviation [SD]) baseline LDL-C (301.9 [149.1] mg/dL) was lowered by 45 % (131.1 mg/dL) at week 48 and 41 % (115.8 mg/dL) at week 72. In adolescents aged 12–17 years, mean (SD) baseline LDL-C (300.4 [100.5] mg/dL) was lowered by 48 % (156.4 mg/dL) at week 48 and 51 % (165.6 mg/dL) at week 72. TEAEs occurred in 100 % and 86 % of participants aged 5–11 and 12–17 years, respectively. TEAEs were considered treatment related in four individuals aged 5–11 years (20 %); no one aged 12–17 years had treatment-related TEAEs (0 %).</div></div><div><h3>Conclusions</h3><div>Evinacumab markedly reduced LDL-C in children and adolescents with HoFH, beyond optimized standard LLT and lipoprotein apheresis. LDL-C remains above goal in most pediatric patients with HoFH, and evinacumab should be routinely considered whenever further LDL-C lowering is needed.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"413 ","pages":"Article 120627"},"PeriodicalIF":5.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145931411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-12-18DOI: 10.1016/j.atherosclerosis.2025.120622
Stefano Manzini , Alice Colombo , Elsa Franchi, Giada Poletti, Marco Busnelli , Giulia Chiesa
Background and aims
With the aim of increasing our knowledge on the mutual interplay between miRNAs and lipids, which is still limited, a novel approach integrating miRNomic and lipidomic data gathered from mice with specific lipid traits was explored.
Methods
miRNomic and lipidomic analyses were previously performed in wild-type, Pcsk9 and Ldlr knockout mice fed normal laboratory diet or Western diet. miRNAs were high-throughput sequenced in liver, aorta, white adipose tissue, duodenum, jejunum, ileum and brain, whereas lipids were quantified by high-throughput mass-spectrometry in liver, aorta and plasma. miRNA expression levels were tested for correlation with each lipid measurement in different samples, and correlations were selected based on strict stringency criteria. In vitro experiments with miRNA mimics or inhibitors in mouse hepatoma cells were performed to validate correlations.
Results
Correlation analyses between miRNA expression levels and lipid concentrations in the different experimental conditions led to the selection of miRNAs potentially playing a major role in the regulation of lipid levels. Correlations mainly clustered in liver. Among selected miRNAs, some were already known to be related to lipid metabolism (miR-33, miR-210 and miR-21a) whereas others, including miR-431–5p, miR-434–3p, miR-434–5p and miR-677–5p had never been associated to lipidome perturbations before. In vitro experiments allowed to highlight a possible role of miR-431–5p andmiR-677–5p in the modulation of cholesterol and triglyceride concentrations.
Conclusions
This study bridged miRNomic and lipidomic data in relevant mouse models, allowing to highlight novel miRNAs potentially playing a role in the modulation of lipid levels.
{"title":"Integrated high-throughput miRNomics and lipidomics in mice with altered lipoprotein metabolism","authors":"Stefano Manzini , Alice Colombo , Elsa Franchi, Giada Poletti, Marco Busnelli , Giulia Chiesa","doi":"10.1016/j.atherosclerosis.2025.120622","DOIUrl":"10.1016/j.atherosclerosis.2025.120622","url":null,"abstract":"<div><h3>Background and aims</h3><div>With the aim of increasing our knowledge on the mutual interplay between miRNAs and lipids, which is still limited, a novel approach integrating miRNomic and lipidomic data gathered from mice with specific lipid traits was explored.</div></div><div><h3>Methods</h3><div>miRNomic and lipidomic analyses were previously performed in wild-type, Pcsk9 and Ldlr knockout mice fed normal laboratory diet or Western diet. miRNAs were high-throughput sequenced in liver, aorta, white adipose tissue, duodenum, jejunum, ileum and brain, whereas lipids were quantified by high-throughput mass-spectrometry in liver, aorta and plasma. miRNA expression levels were tested for correlation with each lipid measurement in different samples, and correlations were selected based on strict stringency criteria. <em>In vitro</em> experiments with miRNA mimics or inhibitors in mouse hepatoma cells were performed to validate correlations.</div></div><div><h3>Results</h3><div>Correlation analyses between miRNA expression levels and lipid concentrations in the different experimental conditions led to the selection of miRNAs potentially playing a major role in the regulation of lipid levels. Correlations mainly clustered in liver. Among selected miRNAs, some were already known to be related to lipid metabolism (miR-33, miR-210 and miR-21a) whereas others, including miR-431–5p, miR-434–3p, miR-434–5p and miR-677–5p had never been associated to lipidome perturbations before. <em>In vitro</em> experiments allowed to highlight a possible role of miR-431–5p andmiR-677–5p in the modulation of cholesterol and triglyceride concentrations.</div></div><div><h3>Conclusions</h3><div>This study bridged miRNomic and lipidomic data in relevant mouse models, allowing to highlight novel miRNAs potentially playing a role in the modulation of lipid levels.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"413 ","pages":"Article 120622"},"PeriodicalIF":5.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146028201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2026-01-08DOI: 10.1016/j.atherosclerosis.2026.120637
Bhawana Singh , Oleg A. Karpov , Manuel Mayr
Background and aims
Commercial high-throughput proteomics platforms, such as Olink and SomaLogic, enable large-scale epidemiological studies with integrated multi-omics measurements. While these proteomics approaches have been widely applied in biobanks, issues of data quality remain underappreciated. In this review, we discuss these limitations and outline a way forward for realizing the clinical translation of proteomics as a comprehensive ‘liquid health check’.
Methods
We reviewed the recent literature for artificial intelligence (AI) and multi-omics, particularly proteomics in atherosclerotic cardiovascular disease (ASCVD).
Results
AI-driven multi-omics analyses have the potential to advance our understanding of multifactorial causes of ASCVD, including aging. Emerging concepts such as “ageotypes” suggest the potential for personalized intervention to slow aging processes. Commercial proteomics platforms have accelerated biomarker discovery in ASCVD, but challenges remain in clinical translation. Limited correlation between Olink and SomaLogic necessitates orthogonal validation of findings. Platform-specific issues, such as epitope effects and cross-reactivity, can yield divergent protein quantitative trait loci for the same protein, complicating causal inference. While tissue proteomics provides complementary insights to plasma proteomics, reliance on autopsy samples raises concerns about protein degradation and measurement reliability. Increasingly, single-cell and spatial proteomics are being explored to better capture plaque heterogeneity, complementing bulk proteomics in larger cohorts.
Conclusion
Beyond risk prediction, proteomics offers opportunities to elucidate disease mechanisms and enable drug repurposing. To realize the clinical potential of plasma proteomics, absolute or reliably recalibratable relative quantification will be required to guide patient care. Ultimately, the clinical value of proteomics will be determined by the quality rather than the quantity of protein measurements.
{"title":"Clinical proteomics in cardiovascular medicine: Current capabilities, limitations, and future directions","authors":"Bhawana Singh , Oleg A. Karpov , Manuel Mayr","doi":"10.1016/j.atherosclerosis.2026.120637","DOIUrl":"10.1016/j.atherosclerosis.2026.120637","url":null,"abstract":"<div><h3>Background and aims</h3><div>Commercial high-throughput proteomics platforms, such as Olink and SomaLogic, enable large-scale epidemiological studies with integrated multi-omics measurements. While these proteomics approaches have been widely applied in biobanks, issues of data quality remain underappreciated. In this review, we discuss these limitations and outline a way forward for realizing the clinical translation of proteomics as a comprehensive ‘liquid health check’.</div></div><div><h3>Methods</h3><div>We reviewed the recent literature for artificial intelligence (AI) and multi-omics, particularly proteomics in atherosclerotic cardiovascular disease (ASCVD).</div></div><div><h3>Results</h3><div>AI-driven multi-omics analyses have the potential to advance our understanding of multifactorial causes of ASCVD, including aging. Emerging concepts such as “ageotypes” suggest the potential for personalized intervention to slow aging processes. Commercial proteomics platforms have accelerated biomarker discovery in ASCVD, but challenges remain in clinical translation. Limited correlation between Olink and SomaLogic necessitates orthogonal validation of findings. Platform-specific issues, such as epitope effects and cross-reactivity, can yield divergent protein quantitative trait loci for the same protein, complicating causal inference. While tissue proteomics provides complementary insights to plasma proteomics, reliance on autopsy samples raises concerns about protein degradation and measurement reliability. Increasingly, single-cell and spatial proteomics are being explored to better capture plaque heterogeneity, complementing bulk proteomics in larger cohorts.</div></div><div><h3>Conclusion</h3><div>Beyond risk prediction, proteomics offers opportunities to elucidate disease mechanisms and enable drug repurposing. To realize the clinical potential of plasma proteomics, absolute or reliably recalibratable relative quantification will be required to guide patient care. Ultimately, the clinical value of proteomics will be determined by the quality rather than the quantity of protein measurements.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"413 ","pages":"Article 120637"},"PeriodicalIF":5.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145973098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2026-01-05DOI: 10.1016/j.atherosclerosis.2026.120635
Mingqiao Li , Di Tian , Patrice Delafontaine , Sergiy Sukhanov
Background and aims
Rapacz pigs with familial hypercholesterolemia (FH pigs) fed with high-fat diet (HFD) develop early atherosclerotic lesions and complex atheromas in coronaries mimicking human coronary atherosclerotic disease (CAD). FH pigs have proven to be an excellent model for basic and pre-clinical atherosclerosis-focused research. However, unlike human atherosclerosis there has been no established classification system for porcine atherosclerosis.
Methods
We isolated 104 plaque-containing coronary fragments from atherosclerotic FH pigs. A set of indices (features) of vessel and plaque morphology were quantified for each plaque, including intima-media ratio, vessel cross-sectional area, necrotic core area and fibrous cap thickness. The unsupervised K-means clustering multi-featured algorithm was used to distinguish coronary plaque groups. Plaque cellular composition was assessed by immunohistochemistry to quantify relative level of smooth muscle-like, endothelial-like and macrophage-like cells. Plaque neovascularization, collagen levels, cell apoptosis, calcification and features of vulnerable plaque were assessed and used as additional numerical criteria for plaque classification and to establish the similarity of porcine plaque to specific types of human lesions.
Results
The clustering algorithm identified 4 clearly distinguishable plaque groups (A-D). The porcine plaque group A was classified as pre-atheroma and plaque group C-D as advanced atheroma. Our data indicates that porcine plaque group A, B, C and D correspond to human lesions type III (intermediate lesion), type IV (atheroma), type V (fibroatheroma) and type VI (high-risk vulnerable plaque), respectively.
Conclusions
Our data demonstrates the suitability of using the FH pig as a pre-clinical model of human-like coronary atherosclerosis with great potential to advance emergent research in the field of CAD, especially in study of vulnerable plaque and in discovery research.
{"title":"Coronary atherosclerotic plaque composition and classification in hypercholesterolemic pigs","authors":"Mingqiao Li , Di Tian , Patrice Delafontaine , Sergiy Sukhanov","doi":"10.1016/j.atherosclerosis.2026.120635","DOIUrl":"10.1016/j.atherosclerosis.2026.120635","url":null,"abstract":"<div><h3>Background and aims</h3><div>Rapacz pigs with familial hypercholesterolemia (FH pigs) fed with high-fat diet (HFD) develop early atherosclerotic lesions and complex atheromas in coronaries mimicking human coronary atherosclerotic disease (CAD). FH pigs have proven to be an excellent model for basic and pre-clinical atherosclerosis-focused research. However, unlike human atherosclerosis there has been no established classification system for porcine atherosclerosis.</div></div><div><h3>Methods</h3><div>We isolated 104 plaque-containing coronary fragments from atherosclerotic FH pigs. A set of indices (features) of vessel and plaque morphology were quantified for each plaque, including intima-media ratio, vessel cross-sectional area, necrotic core area and fibrous cap thickness. The unsupervised K-means clustering multi-featured algorithm was used to distinguish coronary plaque groups. Plaque cellular composition was assessed by immunohistochemistry to quantify relative level of smooth muscle-like, endothelial-like and macrophage-like cells. Plaque neovascularization, collagen levels, cell apoptosis, calcification and features of vulnerable plaque were assessed and used as additional numerical criteria for plaque classification and to establish the similarity of porcine plaque to specific types of human lesions.</div></div><div><h3>Results</h3><div>The clustering algorithm identified 4 clearly distinguishable plaque groups (A-D). The porcine plaque group A was classified as pre-atheroma and plaque group C-D as advanced atheroma. Our data indicates that porcine plaque group A, B, C and D correspond to human lesions type III (intermediate lesion), type IV (atheroma), type V (fibroatheroma) and type VI (high-risk vulnerable plaque), respectively.</div></div><div><h3>Conclusions</h3><div>Our data demonstrates the suitability of using the FH pig as a pre-clinical model of human-like coronary atherosclerosis with great potential to advance emergent research in the field of CAD, especially in study of vulnerable plaque and in discovery research.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"413 ","pages":"Article 120635"},"PeriodicalIF":5.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145973097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Despite the frequent co-occurrence of frailty and abdominal aortic aneurysm (AAA), it remains unclear whether frailty is a risk factor for the development of AAA. This study aims to determine the association.
Methods
The study recruited a large-scale cohort from the UK Biobank. The baseline frailty level was assessed through frailty phenotype and frailty index, categorizing participants as non-frail, pre-frail, or frail. The primary outcome was incidence of AAA during follow-up. Cox proportional hazards model was used to explore the association of frailty with AAA risk. The genetic susceptibility was assessed by polygenic risk score.
Results
A total of 410,606 participants were enrolled in this study. Over a median follow-up of 12.56 years, AAA developed in 692(0.3 %), 931(0.5 %), and 180(1.0 %) participants categorized as non-frail, pre-frail, and frail respectively under the frailty phenotype, while the frailty index revealed 626(0.3 %), 873(0.6 %), and 304(1.1 %) cases across corresponding frailty strata. Compared with the non-frail participants, the risk of AAA was significantly elevated in pre-frail participants (frailty phenotype: HR = 1.28, 95 %CI = 1.16–1.42; frailty index: HR = 1.43, 95 %CI = 1.28–1.59) and frail participants (frailty phenotype: HR = 1.82, 95 % CI = 1.52–2.18; frailty index: HR = 2.03, 95 %CI = 1.74–2.37). The association remained robust in further adjustment of genetic susceptibility and subgroup analysis. Using non-frail participants with low genetic susceptibility as the reference group, those frail participants with high genetic susceptibility demonstrated the greatest hazard for incident AAA, underscoring their synergistic effect on AAA.
Conclusions
Frailty was longitudinally associated with a high long-term risk of AAA, suggesting frailty as a new independent risk factor for AAA.
背景与目的：尽管虚弱和腹主动脉瘤（AAA）经常共存，但尚不清楚虚弱是否是发生腹主动脉瘤的危险因素，本研究旨在确定两者之间的关系。方法：该研究从英国生物银行招募了一个大规模队列。基线虚弱水平通过虚弱表型和虚弱指数进行评估，将参与者分为非虚弱、虚弱前期和虚弱。主要观察指标为随访期间AAA发生率。采用Cox比例风险模型探讨脆弱性与AAA风险的关系。采用多基因风险评分法评估遗传易感性。结果：本研究共纳入410,606名受试者。在中位12.56年的随访中，在脆弱表型下，AAA分别在692（0.3%）、931（0.5%）和180（1.0%）名参与者中被分类为非虚弱、预虚弱和虚弱，而虚弱指数显示在相应的虚弱层中有626（0.3%）、873（0.6%）和304（1.1%）例。与非体弱组相比，体弱前组（脆弱表型：HR = 1.28, 95% CI = 1.16-1.42；脆弱指数：HR = 1.43, 95% CI = 1.28-1.59）和体弱组（脆弱表型：HR = 1.82, 95% CI = 1.52-2.18；脆弱指数：HR = 2.03, 95% CI = 1.74-2.37）发生AAA的风险显著升高。在进一步的遗传易感性调整和亚群分析中，这种相关性仍然很强。以低遗传易感性、非体弱的受试者为参照组，体弱高遗传易感性的受试者发生AAA的风险最大，强调了它们对AAA的协同作用。结论：体弱与AAA的高长期风险纵向相关，提示体弱是AAA的一个新的独立危险因素。
{"title":"Frailty, genetic susceptibility, and the risk of abdominal aortic aneurysm: Evidence from the UK Biobank cohort study","authors":"Yiyang Tang , Mukamengjiang Juaiti , Xinyi Zhou , Baohua Peng , Zhenzhen Da , Ziwei Ou , Wenchao Lin , Mengqiu Zhang , Zaixin Yu , Lihuang Zha , Benhui Liang","doi":"10.1016/j.atherosclerosis.2025.120623","DOIUrl":"10.1016/j.atherosclerosis.2025.120623","url":null,"abstract":"<div><h3>Background and aims</h3><div>Despite the frequent co-occurrence of frailty and abdominal aortic aneurysm (AAA), it remains unclear whether frailty is a risk factor for the development of AAA. This study aims to determine the association.</div></div><div><h3>Methods</h3><div>The study recruited a large-scale cohort from the UK Biobank. The baseline frailty level was assessed through frailty phenotype and frailty index, categorizing participants as non-frail, pre-frail, or frail. The primary outcome was incidence of AAA during follow-up. Cox proportional hazards model was used to explore the association of frailty with AAA risk. The genetic susceptibility was assessed by polygenic risk score.</div></div><div><h3>Results</h3><div>A total of 410,606 participants were enrolled in this study. Over a median follow-up of 12.56 years, AAA developed in 692(0.3 %), 931(0.5 %), and 180(1.0 %) participants categorized as non-frail, pre-frail, and frail respectively under the frailty phenotype, while the frailty index revealed 626(0.3 %), 873(0.6 %), and 304(1.1 %) cases across corresponding frailty strata. Compared with the non-frail participants, the risk of AAA was significantly elevated in pre-frail participants (frailty phenotype: HR = 1.28, 95 %CI = 1.16–1.42; frailty index: HR = 1.43, 95 %CI = 1.28–1.59) and frail participants (frailty phenotype: HR = 1.82, 95 % CI = 1.52–2.18; frailty index: HR = 2.03, 95 %CI = 1.74–2.37). The association remained robust in further adjustment of genetic susceptibility and subgroup analysis. Using non-frail participants with low genetic susceptibility as the reference group, those frail participants with high genetic susceptibility demonstrated the greatest hazard for incident AAA, underscoring their synergistic effect on AAA.</div></div><div><h3>Conclusions</h3><div>Frailty was longitudinally associated with a high long-term risk of AAA, suggesting frailty as a new independent risk factor for AAA.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"413 ","pages":"Article 120623"},"PeriodicalIF":5.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145861885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2026-01-13DOI: 10.1016/j.atherosclerosis.2025.120515
Alexander Haenel , Ruurt A. Jukema , John K. Khoo , Fionn Coughlan , Philipp Blanke , Aaisha Ferkh , Timothy Fairbairn , Nicholas Ng , Lynne M. Koweek , Pamela Douglas , Mark Rabbat , Gianluca Pontone , Kavitha M. Chinnaiyan , Bernard De Bruyne , Jeroen Bax , Tetsuya Amano , Koen Nieman , Campbell Rogers , Hironori Kitabata , Niels PR. Sand , Georgios Tzimas
Background
Diabetes mellitus, smoking, hypertension, and hyperlipidemia are well-studied cardiovascular risk factors (CVRF) for coronary artery disease (CAD). However, their combined and individual influence on atherosclerotic total plaque volume (TPV) and plaque subtypes as assessed by coronary computed tomographic angiography (CCTA) has not been well evaluated.
Purpose
To evaluate the association between CVRF on TPV and plaque subtypes and to develop quantitative plaque nomograms stratified by sex, age, and CVRF using CCTA findings.
Methods
This analysis included participants from the ADVANCE (Assessing Diagnostic Value of Noninvasive CT-FFR in Coronary Care) registry. Quantitative assessment of TPV and plaque subtypes was performed using an Artificial Intelligence-Enabled Quantitative Coronary Plaque Analysis tool.
Results
A total of 4430 patients were included in the analysis, with a median age of 67.0 [59.0–73.0] years, and 1512 (34.1 %) were women. The median TPV was 390 mm3 (IQR: 163–760 mm3) and it was significantly higher in male participants (460 mm3; IQR 197–855 mm3) compared to female participants (280.5 mm3; IQR: 118–583 mm3) (P < 0.0001). Independent of sex, participants with CVRF had higher median TPVs (404.5 mm3; IQR: 175–788.5 mm3) than those without CVRF (187 mm3; IQR: 74–431 mm3) (P < 0.0001). On ROC analysis, age emerged as the strongest predictor of TPV >250 mm3 (AUC 0.62; CI: 0.60–0.64), with only modest improvements in the model after adding male sex (0.67; CI: 0.65–0.69) and CVRF (0.69; CI: 0.68–0.71).
Conclusions
Our data indicate that TPV is significantly higher in participants with CVRF compared to those without. Age demonstrated the strongest association with plaque volume, while the addition of CVRF only modestly increased the AUC. Altogether, age and CVRF were only modestly associated with plaque volume, highlighting the need for further research to fully understand the potential and limitations of plaque imaging assessing the extent and severity of CAD, in patients with and without CVRF.
{"title":"The association of risk factors on coronary computed tomography angiography derived atherosclerotic plaque volume - Lessons from the ADVANCE registry","authors":"Alexander Haenel , Ruurt A. Jukema , John K. Khoo , Fionn Coughlan , Philipp Blanke , Aaisha Ferkh , Timothy Fairbairn , Nicholas Ng , Lynne M. Koweek , Pamela Douglas , Mark Rabbat , Gianluca Pontone , Kavitha M. Chinnaiyan , Bernard De Bruyne , Jeroen Bax , Tetsuya Amano , Koen Nieman , Campbell Rogers , Hironori Kitabata , Niels PR. Sand , Georgios Tzimas","doi":"10.1016/j.atherosclerosis.2025.120515","DOIUrl":"10.1016/j.atherosclerosis.2025.120515","url":null,"abstract":"<div><h3>Background</h3><div>Diabetes mellitus, smoking, hypertension, and hyperlipidemia are well-studied cardiovascular risk factors (CVRF) for coronary artery disease (CAD). However, their combined and individual influence on atherosclerotic total plaque volume (TPV) and plaque subtypes as assessed by coronary computed tomographic angiography (CCTA) has not been well evaluated.</div></div><div><h3>Purpose</h3><div>To evaluate the association between CVRF on TPV and plaque subtypes and to develop quantitative plaque nomograms stratified by sex, age, and CVRF using CCTA findings.</div></div><div><h3>Methods</h3><div>This analysis included participants from the ADVANCE (Assessing Diagnostic Value of Noninvasive CT-FFR in Coronary Care) registry. Quantitative assessment of TPV and plaque subtypes was performed using an Artificial Intelligence-Enabled Quantitative Coronary Plaque Analysis tool.</div></div><div><h3>Results</h3><div>A total of 4430 patients were included in the analysis, with a median age of 67.0 [59.0–73.0] years, and 1512 (34.1 %) were women. The median TPV was 390 mm<sup>3</sup> (IQR: 163–760 mm<sup>3</sup>) and it was significantly higher in male participants (460 mm<sup>3</sup>; IQR 197–855 mm<sup>3</sup>) compared to female participants (280.5 mm<sup>3</sup>; IQR: 118–583 mm<sup>3</sup>) (P < 0.0001). Independent of sex, participants with CVRF had higher median TPVs (404.5 mm<sup>3</sup>; IQR: 175–788.5 mm<sup>3</sup>) than those without CVRF (187 mm<sup>3</sup>; IQR: 74–431 mm<sup>3</sup>) (P < 0.0001). On ROC analysis, age emerged as the strongest predictor of TPV >250 mm<sup>3</sup> (AUC 0.62; CI: 0.60–0.64), with only modest improvements in the model after adding male sex (0.67; CI: 0.65–0.69) and CVRF (0.69; CI: 0.68–0.71).</div></div><div><h3>Conclusions</h3><div>Our data indicate that TPV is significantly higher in participants with CVRF compared to those without. Age demonstrated the strongest association with plaque volume, while the addition of CVRF only modestly increased the AUC. Altogether, age and CVRF were only modestly associated with plaque volume, highlighting the need for further research to fully understand the potential and limitations of plaque imaging assessing the extent and severity of CAD, in patients with and without CVRF.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"413 ","pages":"Article 120515"},"PeriodicalIF":5.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2026-02-04DOI: 10.1016/j.atherosclerosis.2025.120630
Rajib Mondal , Yuichiro Yano
{"title":"Reply to: “Considerations on statistical analysis of NHANES data in oral microbiome diversity and mortality study”","authors":"Rajib Mondal , Yuichiro Yano","doi":"10.1016/j.atherosclerosis.2025.120630","DOIUrl":"10.1016/j.atherosclerosis.2025.120630","url":null,"abstract":"","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"413 ","pages":"Article 120630"},"PeriodicalIF":5.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-12-23DOI: 10.1016/j.atherosclerosis.2025.120624
Yanjun Zhang, Yu Huang, Xiaoqin Gan, Ziliang Ye, Yuanyuan Zhang, Sisi Yang, Hao Xiang, Yiwei Zhang, Yiting Wu, Xianhui Qin
Background and aims
Abdominal aortic aneurysm (AAA) lacks reliable circulating biomarkers and effective pharmacological therapies. This study aimed to investigate the observational and causal associations between plasma proteins and AAA to enhance understanding of its biological mechanisms, improve disease prediction, and identify potential therapeutic targets.
Methods
We included 51,381 participants from the UK Biobank(43,317 in the training set and 8064 in the test set) without aortic aneurysm or dissection. Observational associations between 2911 plasma proteins and incident AAA were assessed, and causal associations were evaluated using two-sample cis-Mendelian randomization (MR) analyses.
Results
Over a median follow-up of 13.1 years, 329 incident AAA cases were identified. 113 plasma proteins were significantly associated with AAA, enriched in collagen-containing extracellular matrix and pathways related to immune response, death receptor activity, cytokine-cytokine receptor interaction, and apoptosis. A simple predictive model incorporating MMP12(macrophage metalloelastase-12), CXCL17(CXC motif chemokine-17), IL6(interleukin-6), and WFDC2(WAP four-disulfide core domain protein-2)—alone or in combination—along with age and sex, demonstrated comparable predictive performance(C-index: 0.826–0.864) to the clinical risk factors model(C-index: 0.852). In cis-MR analyses, MMP12 (OR: 1.14; 95 %CI: 1.09–1.20), WFDC2 (OR:1.32; 95 %CI: 1.13–1.55), and NCR3LG1 (natural cytotoxicity triggering receptor 3 ligand 1; OR: 1.15; 95 %CI: 1.09–1.22) were causally associated with AAA. Notably, MMP12 is already a drug target for aortic aneurysm and other diseases.
Conclusions
MMP12, CXCL17, IL6, and WFDC2 are effective circulating biomarkers for AAA prediction, while MMP12, WFDC2, and NCR3LG1 represent promising therapeutic targets for AAA. These findings provide valuable insights into AAA pathogenesis and highlight potential avenues for drug development.
{"title":"Identifying plasma proteomic biomarkers for risk prediction and therapeutic targets of abdominal aortic aneurysm: Prospective cohort and Mendelian randomization analyses","authors":"Yanjun Zhang, Yu Huang, Xiaoqin Gan, Ziliang Ye, Yuanyuan Zhang, Sisi Yang, Hao Xiang, Yiwei Zhang, Yiting Wu, Xianhui Qin","doi":"10.1016/j.atherosclerosis.2025.120624","DOIUrl":"10.1016/j.atherosclerosis.2025.120624","url":null,"abstract":"<div><h3>Background and aims</h3><div>Abdominal aortic aneurysm (AAA) lacks reliable circulating biomarkers and effective pharmacological therapies. This study aimed to investigate the observational and causal associations between plasma proteins and AAA to enhance understanding of its biological mechanisms, improve disease prediction, and identify potential therapeutic targets.</div></div><div><h3>Methods</h3><div>We included 51,381 participants from the UK Biobank(43,317 in the training set and 8064 in the test set) without aortic aneurysm or dissection. Observational associations between 2911 plasma proteins and incident AAA were assessed, and causal associations were evaluated using two-sample cis-Mendelian randomization (MR) analyses.</div></div><div><h3>Results</h3><div>Over a median follow-up of 13.1 years, 329 incident AAA cases were identified. 113 plasma proteins were significantly associated with AAA, enriched in collagen-containing extracellular matrix and pathways related to immune response, death receptor activity, cytokine-cytokine receptor interaction, and apoptosis. A simple predictive model incorporating MMP12(macrophage metalloelastase-12), CXCL17(CXC motif chemokine-17), IL6(interleukin-6), and WFDC2(WAP four-disulfide core domain protein-2)—alone or in combination—along with age and sex, demonstrated comparable predictive performance(C-index: 0.826–0.864) to the clinical risk factors model(C-index: 0.852). In <em>cis</em>-MR analyses, MMP12 (OR: 1.14; 95 %CI: 1.09–1.20), WFDC2 (OR:1.32; 95 %CI: 1.13–1.55), and NCR3LG1 (natural cytotoxicity triggering receptor 3 ligand 1; OR: 1.15; 95 %CI: 1.09–1.22) were causally associated with AAA. Notably, MMP12 is already a drug target for aortic aneurysm and other diseases.</div></div><div><h3>Conclusions</h3><div>MMP12, CXCL17, IL6, and WFDC2 are effective circulating biomarkers for AAA prediction, while MMP12, WFDC2, and NCR3LG1 represent promising therapeutic targets for AAA. These findings provide valuable insights into AAA pathogenesis and highlight potential avenues for drug development.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"413 ","pages":"Article 120624"},"PeriodicalIF":5.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145880880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-12-03DOI: 10.1016/j.atherosclerosis.2025.120607
Ahmed Ibrahim Ahmed MD MPH , Mouaz H. Al-Mallah MD MSc
{"title":"Refining risk in the power of zero era: The added value of cardiorespiratory fitness","authors":"Ahmed Ibrahim Ahmed MD MPH , Mouaz H. Al-Mallah MD MSc","doi":"10.1016/j.atherosclerosis.2025.120607","DOIUrl":"10.1016/j.atherosclerosis.2025.120607","url":null,"abstract":"","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"413 ","pages":"Article 120607"},"PeriodicalIF":5.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145751419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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