Atherosclerosis plus最新文献_第5页

Proposed lipidology and preventive cardiology research priorities in Africa; Results of a Delphi survey 建议的非洲血脂学和预防心脏病学研究重点；德尔菲调查结果

IF 1.4 Q3 PERIPHERAL VASCULAR DISEASE

Atherosclerosis plus

Pub Date : 2025-09-01 Epub Date: 2025-06-14 DOI: 10.1016/j.athplu.2025.05.003

Alexander R.M. Lyons , Frederick J. Raal , Brett S. Mansfield , David Marais , Neusa P.J. Jessen , Lambert T. Appiah , Lilian Mbau , Bernard Samia , Ashraf Reda , Tigist S. Mekonnen , Albertino Damasceno , Chala F. Oljira , Meral Kayikcioglu , Alberto Zambon

Despite a population of over 1.5 billion, lipidology and preventive cardiology research of African origin is lacking in quantity and impact, and accounts for a small percentage of outputs globally due to limited resources to address the full breadth of unexplored research areas. We therefore conducted a Delphi survey on an expert panel of African clinical investigators to ascertain the proposed areas of priority to provide guidance on the future direction of African research in this field. Round one of the survey generated 58 proposed unanswered questions, and subsequent priority ratings of 1–5 of the proposed questions in two further rounds resulted in 42 priority research questions (PRQs) based on a two-thirds majority rating of 3–5 with 5 being the highest rating. Common themes amongst the 42 PRQs included mostly prevalence and distribution studies on hyperlipidaemia and lipid profiles and their risk of cardiovascular disease with emphasis on atherosclerotic cardiovascular disease, aortic stenosis, coronary artery disease, and acute coronary syndrome. The need for a cardiovascular risk score calculator appropriate for the different, diverse African populations was also emphasised. In conclusion, the results of this Delphi survey highlight a number of unanswered PRQs in lipidology and preventive cardiology in Africa that may be helpful to inform the strategic direction of future studies, education and funding in that underrepresented part of the world based on current priorities and may also have relevance globally.

尽管非洲人口超过15亿，但非洲来源的脂质学和预防心脏病学研究在数量和影响方面都缺乏，而且由于资源有限，无法解决所有尚未开发的研究领域，因此在全球产出中所占比例很小。因此，我们对非洲临床研究专家小组进行了德尔菲调查，以确定拟议的优先领域，为非洲在这一领域的未来研究方向提供指导。第一轮调查产生了58个未回答的问题，随后在接下来的两轮中对1-5个问题进行优先级评级，结果产生了42个优先研究问题（PRQs），基于三分之二多数评级（3-5），其中5是最高评级。42个prq的共同主题主要包括高脂血症和脂质谱的患病率和分布研究及其心血管疾病的风险，重点是动脉粥样硬化性心血管疾病、主动脉狭窄、冠状动脉疾病和急性冠状动脉综合征。他们还强调需要一种适合不同、多样化的非洲人口的心血管风险评分计算器。总之，德尔菲调查的结果突出了非洲在脂质学和预防心脏病学方面的一些未解决的prq，这些prq可能有助于根据当前的优先事项为世界上代表性不足的地区的未来研究、教育和资助的战略方向提供信息，也可能具有全球相关性。

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引用次数: 0

Lipidome of high-density lipoprotein is strongly perturbed in hyperalphalipoproteinemia resulting from a rare mutation in endothelial lipase 高密度脂蛋白脂组在由内皮脂肪酶罕见突变引起的高脂蛋白血症中受到强烈干扰

IF 1.4 Q3 PERIPHERAL VASCULAR DISEASE

Atherosclerosis plus

Pub Date : 2025-09-01 Epub Date: 2025-07-05 DOI: 10.1016/j.athplu.2025.07.001

Livia Pisciotta , Marie Lhomme , Chiara Pavanello , Maharajah Ponnaiah , Arianna Strazzella , Alice Ossoli , Wilfried Le Goff , Laura Calabresi , Anatol Kontush

Both low and extremely high concentrations of high-density lipoprotein (HDL)-cholesterol are associated with elevated cardiovascular risk. As extremely high HDL-cholesterol states of hyperalphalipoproteinemia (HALP) are rare, HDL particles in this condition remain poorly characterised. HALP may result from mutations in endothelial lipase (EL), a hydrolytic enzyme present in the circulation. Using targeted LC/MS-MS, we quantified the lipidome of HDL isolated from three female subjects with HALP caused by a heterozygous [c.526 G > T, p.(Gly176Trp)] variant of the LIPG gene and compared them with two healthy female controls. Our findings revealed a strongly perturbed HDL lipidome primarily involving enrichment in several phosphatidylcholine, phosphatidylserine, phosphatidylethanolamine plasmalogen, and lysophosphatidylethanolamine species. Some of these differences were equally observed in whole plasma. These alterations may reflect perturbations of lipoprotein metabolism secondary to defective lipid hydrolysis by EL and may have consequences for atheroprotective HDL functions.

低浓度和极高浓度的高密度脂蛋白(HDL)-胆固醇都与心血管风险升高有关。由于高脂蛋白血症（HALP）的极高HDL-胆固醇状态是罕见的，这种情况下HDL颗粒的特征仍然很差。HALP可能是由内皮脂肪酶（EL）突变引起的，内皮脂肪酶是一种存在于循环中的水解酶。采用靶向LC/MS-MS方法，我们定量了3例女性杂合性HALP患者的HDL脂质组[c.526]G比;T, p.(Gly176Trp)]变异的LIPG基因，并将其与两个健康女性对照进行比较。我们的研究结果显示HDL脂质组受到强烈干扰，主要涉及几种磷脂酰胆碱、磷脂酰丝氨酸、磷脂酰乙醇胺plasmalogen和溶血磷脂酰乙醇胺的富集。其中一些差异在整个血浆中同样观察到。这些改变可能反映了EL对脂质水解缺陷引起的脂蛋白代谢紊乱，并可能对保护动脉粥样硬化的HDL功能产生影响。

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引用次数: 0

Effect of lipid-lowering medications on oxidized phospholipids in individuals with elevated LIPOPROTEIN(a) 降脂药物对脂蛋白升高个体氧化磷脂的影响(a)

IF 2.1 Q3 PERIPHERAL VASCULAR DISEASE

Atherosclerosis plus

Pub Date : 2025-09-01 Epub Date: 2025-09-04 DOI: 10.1016/j.athplu.2025.09.003

Amalia Despoina Koutsogianni , Fotios Barkas , Constantinos Tellis , Alexandros Tselepis , George Liamis , Sotirios Tsimikas , Evangelos Liberopoulos

Background/introduction

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.

氧化磷脂（OxPLs）与载脂蛋白B-100 （OxPL-apoB）和载脂蛋白(a) [OxPL-apo(a)]结合，并自由存在于含载脂蛋白的磷脂壳内。OxPLs与脂蛋白的促炎特性有关(a) [Lp(a)]。携带纤溶酶原（OxPL-PLG）的oxpl可延长纤溶时间。目的探讨降脂药物对Lp(a)浓度升高患者OxPLs水平的影响。方法在本前瞻性研究中，Lp(a)水平≥75 nmol/L的患者（n = 70）根据现行指南分为3个治疗方案：高强度他汀单药治疗（n = 28），在高强度他汀基础上加依泽替米贝（n = 31），在高强度他汀+依泽替米贝基础上加蛋白转化酶subtilisin/ keexin 9型抑制剂（PCSK9i）治疗（n = 11）。随访时间3个月。结果患者平均年龄为51±15岁，40%为男性，39%诊断为家族性高胆固醇血症，16%患有动脉粥样硬化性心血管疾病，36%、33%和15%分别为心血管高危、高危和中度风险。Lp(a)水平在高强度他汀类药物和加用依折替布治疗组无显著变化，但在加用PCSK9i治疗组显著降低。高强度他汀类药物和附加依可替米贝组OxPL-apoB和OxPL-apo(a)均显著升高，OxPL-PLG均显著降低。附加PCSK9i治疗与OxPL-apoB、OxPL-apo(a)和OxPL-PLG水平无显著变化相关。结论在Lp(a)升高的患者中，高强度他汀和加药依泽替米贝均可显著提高OxPL-apoB和OxPL-apo(a)水平，同时显著降低OxPL-PLG水平。添加PCSK9i对OxPLs水平无显著影响。这些发现的临床意义有待进一步探讨。

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引用次数: 0

Comparative 10-year atherosclerotic cardiovascular disease risk in Ethiopian HIV patients on first-line versus second-line combined antiretroviral therapy 埃塞俄比亚艾滋病患者接受一线与二线抗逆转录病毒联合治疗的10年动脉粥样硬化性心血管疾病风险比较

IF 1.4 Q3 PERIPHERAL VASCULAR DISEASE

Atherosclerosis plus

Pub Date : 2025-09-01 Epub Date: 2025-06-28 DOI: 10.1016/j.athplu.2025.06.002

Balew Arega , Gashaw Solela , Tariku Fekadu , Tirhas Tadesse , Bekele Alemayehu , Amanuel Zeleke , Kidat Ayele

Background

Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of morbidity and mortality in HIV patients, but the impact of combined antiretroviral therapy regimens on its risk in Ethiopia is unclear. This study assessed the 10-year ASCVD risk in first-line versus second-line combined antiretroviral therapy and identified predictors of intermediate-to-high risk.

Methods

A comparative cross-sectional study was conducted among HIV patients on first-line and second-line combined antiretroviral therapy, randomly selected from government hospitals in Addis Ababa. A total of 340 patients were initially selected, with 331 included in the final analysis. Data were extracted from combined antiretroviral therapy registers and medical records. The 10-year atherosclerotic cardiovascular disease risk was estimated via pooled cohort risk equations. Logistic regression identified predictors of intermediate-to-high 10-year atherosclerotic cardiovascular disease risk (≥7.5 %).

Results

The mean age was 53.2 ± 9.1 years, and 55.9 % were male. Among the total patients, 223 (67.5 %) were on first-line combined antiretroviral therapy, and 108 (32.5 %) were on second-line therapy. The proportion of participants with an intermediate-to-high 10-year ASCVD risk was 28.7 % (95 % CI: 25.7–33.8 %), with a significantly higher prevalence observed in the second-line combined antiretroviral therapy group (36.1 %) compared to the first-line group (25.1 %) (p = 0.005). Second-line combined antiretroviral therapy (AOR = 2.3; 95 % CI: 1.23–3.22; p = 0.02), detectable viral load (AOR = 1.73; 95 % CI: 1.04–2.88; p = 0.04), alcohol use (AOR = 2.01; 95 % CI: 1.23–3.49; p = 0.01), and being divorced (AOR = 4.10; 95 % CI: 3.14–9.66; p = 0.001) or widowed (AOR = 6.64; 95 % CI: 3.69–11.59; p = 0.02) were significantly associated with intermediate-to-high 10-year ASCVD risk.

Conclusion

Second-line antiretroviral therapy and modifiable risk factors were associated with significantly higher 10-year ASCVD risk. Routine screening and lipid management should be integrated into HIV care, particularly for patients on second-line therapy.

背景：动脉粥样硬化性心血管疾病（ASCVD）是HIV患者发病和死亡的主要原因，但在埃塞俄比亚，抗逆转录病毒联合治疗方案对其风险的影响尚不清楚。本研究评估了一线与二线抗逆转录病毒联合治疗的10年ASCVD风险，并确定了中高风险的预测因素。方法对在亚的斯亚贝巴政府医院接受一线和二线抗逆转录病毒联合治疗的艾滋病患者进行比较横断面研究。最初共选择340例患者，其中331例纳入最终分析。数据来自抗逆转录病毒联合治疗登记和医疗记录。通过合并队列风险方程估计10年动脉粥样硬化性心血管疾病的风险。Logistic回归确定了中高10年动脉粥样硬化性心血管疾病风险的预测因子（≥7.5%）。结果患者平均年龄53.2±9.1岁，男性占55.9%。在所有患者中，223例（67.5%）接受一线抗逆转录病毒联合治疗，108例（32.5%）接受二线治疗。具有中高10年ASCVD风险的参与者比例为28.7% (95% CI: 25.7 - 33.8%)，二线抗逆转录病毒联合治疗组的患病率（36.1%）明显高于一线组（25.1%）（p = 0.005）。二线抗逆转录病毒联合治疗(AOR = 2.3；95% ci: 1.23-3.22；p = 0.02)，可检测病毒载量(AOR = 1.73；95% ci: 1.04-2.88；p = 0.04)，酒精使用(AOR = 2.01；95% ci: 1.23-3.49；p = 0.01)、离婚(AOR = 4.10；95% ci: 3.14-9.66；p = 0.001)或丧偶(AOR = 6.64；95% ci: 3.69-11.59；p = 0.02)与中高10年ASCVD风险显著相关。结论二线抗逆转录病毒治疗和可改变的危险因素与10年ASCVD风险显著升高相关。常规筛查和血脂管理应纳入艾滋病毒护理，特别是对接受二线治疗的患者。

{"title":"Comparative 10-year atherosclerotic cardiovascular disease risk in Ethiopian HIV patients on first-line versus second-line combined antiretroviral therapy","authors":"Balew Arega , Gashaw Solela , Tariku Fekadu , Tirhas Tadesse , Bekele Alemayehu , Amanuel Zeleke , Kidat Ayele","doi":"10.1016/j.athplu.2025.06.002","DOIUrl":"10.1016/j.athplu.2025.06.002","url":null,"abstract":"<div><h3>Background</h3><div>Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of morbidity and mortality in HIV patients, but the impact of combined antiretroviral therapy regimens on its risk in Ethiopia is unclear. This study assessed the 10-year ASCVD risk in first-line versus second-line combined antiretroviral therapy and identified predictors of intermediate-to-high risk.</div></div><div><h3>Methods</h3><div>A comparative cross-sectional study was conducted among HIV patients on first-line and second-line combined antiretroviral therapy, randomly selected from government hospitals in Addis Ababa. A total of 340 patients were initially selected, with 331 included in the final analysis. Data were extracted from combined antiretroviral therapy registers and medical records. The 10-year atherosclerotic cardiovascular disease risk was estimated via pooled cohort risk equations. Logistic regression identified predictors of intermediate-to-high 10-year atherosclerotic cardiovascular disease risk (≥7.5 %).</div></div><div><h3>Results</h3><div>The mean age was 53.2 ± 9.1 years, and 55.9 % were male. Among the total patients, 223 (67.5 %) were on first-line combined antiretroviral therapy, and 108 (32.5 %) were on second-lin<strong>e</strong> therapy<strong>.</strong> The proportion of participants with an intermediate-to-high 10-year ASCVD risk was 28.7 % (95 % CI: 25.7–33.8 %), with a significantly higher prevalence observed in the second-line combined antiretroviral therapy group (36.1 %) compared to the first-line group (25.1 %) (p = 0.005). Second-line combined antiretroviral therapy (AOR = 2.3; 95 % CI: 1.23–3.22; p = 0.02), detectable viral load (AOR = 1.73; 95 % CI: 1.04–2.88; p = 0.04), alcohol use (AOR = 2.01; 95 % CI: 1.23–3.49; p = 0.01), and being divorced (AOR = 4.10; 95 % CI: 3.14–9.66; p = 0.001) or widowed (AOR = 6.64; 95 % CI: 3.69–11.59; p = 0.02) were significantly associated with intermediate-to-high 10-year ASCVD risk.</div></div><div><h3>Conclusion</h3><div>Second-line antiretroviral therapy and modifiable risk factors were associated with significantly higher 10-year ASCVD risk. Routine screening and lipid management should be integrated into HIV care, particularly for patients on second-line therapy.</div></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"61 ","pages":"Pages 23-28"},"PeriodicalIF":1.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144572883","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}

引用次数: 0

Inclisiran in a real-world single-center registry of patients with very high atherosclerotic cardiovascular risk 在一个真实世界的单中心注册的患者非常高的动脉粥样硬化性心血管风险

IF 2.1 Q3 PERIPHERAL VASCULAR DISEASE

Atherosclerosis plus

Pub Date : 2025-09-01 Epub Date: 2025-09-04 DOI: 10.1016/j.athplu.2025.09.001

Antonio Centola , Michelangelo Carbonara , Serena De Nuzzo , Andrea Cuculo , Antonio Ruggiero , Giulio Campanale , Massimo Iacoviello , Paola Gargiulo , Pasquale Perrone Filardi , Natale Daniele Brunetti

Background

A mean relative 50 % reduction of LDL cholesterol (LDLc) levels was observed in randomized studies in patients treated with inclisiran, a small-interfering-RNA therapeutic agent that reduces hepatic synthesis of PCSK9. Less is known on real world and every-day practice patients.

Methods

Fifty consecutive patients with or at risk of atherosclerotic cardiovascular disease (ASCVD) or familial hypercholesterolemia (FH) and treated with inclisiran according to Italian indications were enrolled in an observational study. LDLc levels were followed up.

Results

26 patients had an acute coronary syndrome (ACS), 11 FH; 46 % were on high-intensity statin therapy, 68 % on combination therapy statin/ezetimibe.

Mean LDLc level of the study population was 118 ± 12 mg/dl at baseline, 80 ± 18 mg/dl after 3 months, and 70 ± 15 mg/dl after 6 months (ANOVA p < 0.001). The use of inclisiran was associated with significantly reduced LDLc levels of 21 % at 1 month and 44 % at 6 months.

LDLc reduction in patients with ACS was statistically significant and comparable with chronic CS. Patients receiving a background combination therapy (statin/ezetimibe) showed a greater reduction in circulating LDLc levels than patients using inclisiran alone. No significant side effects or treatment drop out were observed during follow up. Rates of subjects with LDLc levels below 70 mg/dl (Italian Drug Agency target) increased from 0 % at baseline to 56 % at 6 months (p < 0.001).

Conclusions

In a real-world population 3–6 months of therapy with inclisiran provide consistent and effective reduction in LDLc levels without significant adverse side-effects.

在随机研究中，接受inclisiran治疗的患者LDL胆固醇（LDLc）水平平均相对降低50%。inclisiran是一种小干扰rna治疗药物，可减少肝脏PCSK9的合成。对现实世界和日常实践患者的了解较少。方法：连续50例动脉粥样硬化性心血管疾病（ASCVD）或家族性高胆固醇血症（FH）患者，并根据意大利适应症接受inclisiran治疗，纳入观察性研究。跟踪ldl水平。结果急性冠脉综合征（ACS） 26例，FH 11例；46%接受高强度他汀类药物治疗，68%接受他汀/依折麦布联合治疗。研究人群的平均ldl水平基线时为118±12 mg/dl， 3个月后为80±18 mg/dl， 6个月后为70±15 mg/dl（方差分析p <； 0.001）。使用inclisiran可显著降低ldl水平，1个月时降低21%，6个月时降低44%。ACS患者ldl降低具有统计学意义，与慢性CS相当。接受背景联合治疗（他汀/依折麦布）的患者比单独使用inclisiran的患者循环ldl水平下降更大。随访期间未观察到明显的副作用或治疗退出。ldl水平低于70 mg/dl（意大利药品管理局目标）的受试者比率从基线时的0%增加到6个月时的56% （p < 0.001）。结论：在现实世界人群中，使用inclisiran治疗3-6个月可以持续有效地降低ldl水平，且没有明显的不良副作用。

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引用次数: 0

Lp(a) in daily clinical routine: risk-factor for both cardiovascular events and heart-failure? A retrospective analysis of the Luebeck Lp(a) heart-failure (HF) registry in patients after myocardial infarction 日常临床常规中的Lp(a)：心血管事件和心力衰竭的危险因素？对心肌梗死后患者Luebeck Lp(A)心力衰竭（HF）登记的回顾性分析

IF 1.4 Q3 PERIPHERAL VASCULAR DISEASE

Atherosclerosis plus

Pub Date : 2025-09-01 Epub Date: 2025-07-12 DOI: 10.1016/j.athplu.2025.07.002

Matthias Mezger , Tilmann Solle , Dominik Jurczyk , Caroline Fatum , Felicitas Lemmer , Ingo Eitel , Christina Paitazoglou

Background and aims

Atherosclerotic cardiovascular disease (ASCVD) is a major health burden being the leading cause of death in Europe. Lipoprotein (a) (Lp(a)) is an important risk factor for CV events reflected by the 2019 ESC recommendation of a once in a lifetime Lp(a) measurement. Furthermore, heart-failure (HF) is the number one diagnosis for hospital admission in Germany and Europe. HF and ASCVD share common well-known risk factors, e.g. diabetes, obesity and hypertension. So far, there is scarcity of data regarding the relationship between Lp(a) and HF. We hypothesized that Lp(a) might be elevated in a high-risk ASCVD patient collective and that there might also be an association with heart-failure.

Methods

The Luebeck Lp(a) HF registry is a combined retrospective/prospective single-center, all-comers registry which investigates the relationship between Lp(a) and HF. The retrospective analysis reported here, comprises patients who were admitted to our heart-catheterization laboratory in the year 2021 due to ST-segment elevation myocardial infarction (STEMI) or non-ST-segment elevation myocardial infarction (NSTEMI).

Results

We found that Lp(a) was assessed only in a minority of patients presenting with STEMI (33 %) and NSTEMI (14.6 %), p < 0.001. There was no relationship between Lp(a) level and ejection fraction (EF) or NTproBNP as surrogate markers for HF, respectively. Statin pretreatment was more frequent in patients with NSTEMI (31.1 %) compared to STEMI patients (11.3 %), p < 0.001.

Conclusion

Despite ESC recommendation, routine Lp(a) measurement is only rarely performed even in a high-risk patient collective. In patients with MI, we could retrospectively not observe a correlation between Lp(a) levels and heart failure, as assessed by surrogate markers as EF and NTproBNP.

背景和目的动脉粥样硬化性心血管疾病（ASCVD）是欧洲主要的健康负担，是导致死亡的主要原因。脂蛋白(a) （Lp(a)）是心血管事件的重要危险因素，2019年ESC建议一生检测一次Lp(a)。此外，心力衰竭（HF）是德国和欧洲住院的头号诊断。心衰和ASCVD具有众所周知的共同危险因素，如糖尿病、肥胖和高血压。到目前为止，关于Lp(a)与HF之间关系的数据还很缺乏。我们假设Lp(a)可能在高危ASCVD患者集体中升高，并且可能与心力衰竭有关。方法Luebeck Lp(a) HF登记是一项回顾性/前瞻性单中心、全患者联合登记，旨在调查Lp(a)与HF之间的关系。本文报道的回顾性分析包括在2021年因st段抬高型心肌梗死（STEMI）或非st段抬高型心肌梗死（NSTEMI）入住我们心导管实验室的患者。结果我们发现Lp(a)仅在少数STEMI（33%）和NSTEMI（14.6%）患者中被评估。0.001. Lp(a)水平与射血分数（EF）或NTproBNP作为HF的替代指标没有关系。NSTEMI患者（31.1%）比STEMI患者（11.3%）更常使用他汀类药物预处理，p <；0.001.结论：尽管ESC推荐，但即使在高危患者群体中也很少进行常规Lp(a)测量。在心肌梗死患者中，我们不能回顾性地观察到Lp(a)水平与心力衰竭之间的相关性，通过EF和NTproBNP等替代标志物进行评估。

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引用次数: 0

Association of uric acid with all-cause mortality in acute coronary syndrome patients with T2DM 尿酸与急性冠状动脉综合征合并T2DM患者全因死亡率的关系

IF 1.4 Q3 PERIPHERAL VASCULAR DISEASE

Atherosclerosis plus

Pub Date : 2025-09-01 Epub Date: 2025-06-08 DOI: 10.1016/j.athplu.2025.06.001

Bing-Yang Zhou , Jian-Jun Yan , Cui-Ying Zhang , Qi Zhang , Hong-Liang Cong , Le Wang

Background

The specific prognostic value of hyperuricemia for all-cause mortality in patients with concurrent type 2 diabetes mellitus (T2DM) and acute coronary syndrome (ACS) remains unclear, particularly regarding the modifying effect of glycemic control status (HbA1c levels). This study elucidated the uric acid (UA)-mortality association in ACS patients with T2DM and examined this relationship across different HbA1c subgroups.

Methods and results

The study included 2265 ACS patients with T2DM who were assigned to four groups based on UA quartiles. During a median follow-up period of 4.4 years, 203 all-cause deaths occurred. Significant positive associations were found in patients with HbA1c level above 7 (Quartile 1 group: Hazard Ratio (HR): 3.215, 95 % confidence interval (CI): 1.525–6.780, p = 0.002; Quartile 3 group: HR: 2.725, 95 % CI: 1.308–5.678, p = 0.007; Quartile 4 group: HR: 3.369, 95 % CI: 1.644–6.905, p = 0.001). Interaction analysis between UA quartiles and HbA1c subgroups showed no statistical significance (p-interaction = 0.648). Restricted cubic splines revealed a J-shaped relationship between UA and all-cause mortality. Kaplan–Meier analysis demonstrated higher event-free survival rates in the Quartile 2 group (log-rank test: p < 0.001).

Conclusions

A J-shaped curve characterizes the association between UA levels and all-cause mortality in patients with T2DM and ACS. Patients with an appropriate UA level exhibited better prognosis. Post-hoc analyses revealed stronger point estimates for the prognostic effect of UA in patients with suboptimal glycemic control, although interaction testing did not achieve statistical significance. Further studies with larger subgroup samples are warranted.

背景：高尿酸血症对并发2型糖尿病（T2DM）和急性冠脉综合征（ACS）患者全因死亡率的具体预后价值尚不清楚，特别是关于血糖控制状态（HbA1c水平）的调节作用。本研究阐明了ACS合并T2DM患者尿酸（UA）与死亡率的关系，并在不同的HbA1c亚组中检验了这种关系。方法和结果本研究纳入2265例ACS合并T2DM患者，根据UA四分位数分为四组。在平均4.4年的随访期间，发生203例全因死亡。HbA1c水平高于7的患者存在显著正相关(四分位数1组：风险比（HR）： 3.215, 95%可信区间（CI）： 1.525 ~ 6.780, p = 0.002；四分位数3组：HR: 2.725, 95% CI: 1.308-5.678, p = 0.007；四分位数4组：HR: 3.369, 95% CI: 1.644-6.905, p = 0.001)。UA四分位数与HbA1c亚组的交互作用分析无统计学意义（p-interaction = 0.648）。受限三次样条显示UA与全因死亡率呈j型关系。Kaplan-Meier分析显示，四分位2组的无事件生存率更高(log-rank检验：p <；0.001)。结论UA水平与T2DM合并ACS患者全因死亡率呈j型曲线关系。适当UA水平的患者预后较好。事后分析显示，在血糖控制欠佳的患者中，UA对预后的影响有更强的点估计，尽管相互作用测试没有达到统计学意义。进一步研究更大的亚组样本是必要的。

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引用次数: 0

Monocytes from people with Familial Hypercholesterolaemia are inflammatory, despite statin-treatment 尽管他汀类药物治疗，家族性高胆固醇血症患者的单核细胞仍具有炎症性

IF 2.1 Q3 PERIPHERAL VASCULAR DISEASE

Atherosclerosis plus

Pub Date : 2025-09-01 Epub Date: 2025-09-10 DOI: 10.1016/j.athplu.2025.09.002

Helen Williams , Habib Francis , Jasmin Huang , Rekha Marimuthu , Rana Baraz , Heather Medbury , Stephen Li

Background and aims

Familial Hypercholesterolaemia (FH) is characterised by high cholesterol and premature cardiovascular disease. While hypercholesterolaemia and inflammation are both key drivers in the formation of atherosclerotic plaques, inflammation remains understudied in FH. Inflammatory (M1) macrophages contribute to plaque destabilisation and macrophage precursors, monocytes, can be skewed towards an inflammatory state. Aims: Determine; whether monocytes of FH individuals are inflammatory, if they readily form inflammatory macrophages, and whether this remains so in statin-treated individuals.

Methods

Blood samples were collected from people with FH (statin-treated and untreated) and healthy controls. Lipid profile was obtained and monocyte inflammatory marker expression was determined by whole blood flow cytometry. Monocytes were cultured with autologous serum and resultant macrophage profile determined by flow cytometry.

Results

Total cholesterol and low-density lipoprotein cholesterol (LDL-C) were higher in the Untreated-FH group compared to the Treated-FH group and controls. In both Treated-FH and Untreated-FH groups, monocytes were inflammatory with high CD86 (M1). The ratio of inflammatory/anti-inflammatory markers (CD86/CD163) significantly correlated with LDL-C and ApoB/ApoA1 ratio across the cohort, indicating the high LDL-C of FH may promote an inflammatory monocyte profile. Monocyte-derived-macrophages from (Treated) FH individuals also had a more inflammatory profile (CD86 and CD86/CD163).

Conclusions

Overall, monocytes show inflammatory skewing in FH individuals, even those with moderately-reduced cholesterol levels. These monocytes readily become inflammatory macrophages. This, along with subsequent inflammatory macrophage formation, could contribute to plaque destabilisation and downstream clinical events. This supports inflammatory monocyte targeting as a potential approach to reduce residual risk in FH individuals.

背景和目的家族性高胆固醇血症（FH）以高胆固醇和早发心血管疾病为特征。虽然高胆固醇血症和炎症都是动脉粥样硬化斑块形成的关键驱动因素，但炎症在FH中的研究仍然不足。炎性（M1）巨噬细胞有助于斑块不稳定和巨噬细胞前体，单核细胞，可以偏向炎症状态。目的:确定;FH个体的单核细胞是否具有炎性，它们是否容易形成炎性巨噬细胞，以及在他汀类药物治疗的个体中是否仍然如此。方法采集FH患者（他汀治疗组和未治疗组）和健康对照者的血液样本。通过全血流式细胞术检测脂质谱和单核细胞炎症标志物的表达。用自体血清培养单核细胞，用流式细胞术测定巨噬细胞谱。结果fh治疗组总胆固醇和低密度脂蛋白胆固醇（LDL-C）高于fh治疗组和对照组。fh治疗组和未治疗组单核细胞均呈炎性，CD86 （M1）升高。在整个队列中，炎症/抗炎标志物（CD86/CD163）的比值与LDL-C和ApoB/ApoA1比值显著相关，表明FH的高LDL-C可能促进炎症单核细胞谱。来自（治疗）FH个体的单核细胞衍生巨噬细胞也具有更多的炎症谱（CD86和CD86/CD163）。总体而言，FH个体的单核细胞表现出炎症偏态，即使是胆固醇水平适度降低的个体。这些单核细胞很容易变成炎性巨噬细胞。这与随后的炎性巨噬细胞形成一起，可能导致斑块不稳定和下游临床事件。这支持炎症单核细胞靶向作为减少FH个体残留风险的潜在方法。

{"title":"Monocytes from people with Familial Hypercholesterolaemia are inflammatory, despite statin-treatment","authors":"Helen Williams , Habib Francis , Jasmin Huang , Rekha Marimuthu , Rana Baraz , Heather Medbury , Stephen Li","doi":"10.1016/j.athplu.2025.09.002","DOIUrl":"10.1016/j.athplu.2025.09.002","url":null,"abstract":"<div><h3>Background and aims</h3><div>Familial Hypercholesterolaemia (FH) is characterised by high cholesterol and premature cardiovascular disease. While hypercholesterolaemia and inflammation are both key drivers in the formation of atherosclerotic plaques, inflammation remains understudied in FH. Inflammatory (M1) macrophages contribute to plaque destabilisation and macrophage precursors, monocytes, can be skewed towards an inflammatory state. Aims: Determine; whether monocytes of FH individuals are inflammatory, if they readily form inflammatory macrophages, and whether this remains so in statin-treated individuals.</div></div><div><h3>Methods</h3><div>Blood samples were collected from people with FH (statin-treated and untreated) and healthy controls. Lipid profile was obtained and monocyte inflammatory marker expression was determined by whole blood flow cytometry. Monocytes were cultured with autologous serum and resultant macrophage profile determined by flow cytometry.</div></div><div><h3>Results</h3><div>Total cholesterol and low-density lipoprotein cholesterol (LDL-C) were higher in the Untreated-FH group compared to the Treated-FH group and controls. In both Treated-FH and Untreated-FH groups, monocytes were inflammatory with high CD86 (M1). The ratio of inflammatory/anti-inflammatory markers (CD86/CD163) significantly correlated with LDL-C and ApoB/ApoA1 ratio across the cohort, indicating the high LDL-C of FH may promote an inflammatory monocyte profile. Monocyte-derived-macrophages from (Treated) FH individuals also had a more inflammatory profile (CD86 and CD86/CD163).</div></div><div><h3>Conclusions</h3><div>Overall, monocytes show inflammatory skewing in FH individuals, even those with moderately-reduced cholesterol levels. These monocytes readily become inflammatory macrophages. This, along with subsequent inflammatory macrophage formation, could contribute to plaque destabilisation and downstream clinical events. This supports inflammatory monocyte targeting as a potential approach to reduce residual risk in FH individuals.</div></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"61 ","pages":"Pages 73-81"},"PeriodicalIF":2.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145048796","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}

引用次数: 0

The role and mechanism of PGC-1α in oxLDL-induced ferroptosis of vascular endothelial cells PGC-1α在氧化低密度脂蛋白诱导的血管内皮细胞铁下垂中的作用及机制

IF 1.4 Q3 PERIPHERAL VASCULAR DISEASE

Atherosclerosis plus

Pub Date : 2025-09-01 Epub Date: 2025-06-06 DOI: 10.1016/j.athplu.2025.05.002

Jiao Li , Pingping He , Yu Zhang , Ranzun Zhao, Changyin Shen, Chaofu Li, Weiwei Liu, Zhijiang Liu, Xianping Long, Yan Wang, Bei Shi

Ferroptosis is a regulated form of cell death that is dependent on reactive oxygen species (ROS) and iron metabolism. Ferroptosis can participate in the formation and rupture of atherosclerotic plaque by regulating apoptosis. However, the mechanism of vascular endothelial cells (VECs) ferroptosis in the occurrence and development of atherosclerosis (AS) requires further exploration. Previous studies have shown that peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) can improve mitochondrial dysfunction and apoptosis induced by oxidized low-density lipoprotein (oxLDL), but its specific role in VECs ferroptosis remains unclear. In this study, we found that oxLDL can induce VECs ferroptosis, and mitochondria are key to oxLDL-induced VECs ferroptosis. As a key regulator of mitochondrial function, the protein expression of PGC-1α was lower in oxLDL-treated VECs. Moreover, overexpression of PGC-1α inhibited oxLDL-induced VECs ferroptosis, whereas the role of PGC-1α was affected by its upstream regulatory molecule AMPK in this process. This study explores the new idea of oxLDL-induced VECs ferroptosis mediated by AMPK/PGC-1α to better understand the pathogenesis of vascular lesions caused by high lipid levels and provides a theoretical basis for the early prevention of AS.

铁下垂是一种受调控的细胞死亡形式，依赖于活性氧（ROS）和铁代谢。铁下垂可通过调节细胞凋亡参与动脉粥样硬化斑块的形成和破裂。然而，血管内皮细胞（VECs）铁下垂在动脉粥样硬化（AS）发生发展中的机制有待进一步探讨。既往研究表明，过氧化物酶体增殖体激活受体γ辅助激活因子1α (PGC-1α)可改善氧化低密度脂蛋白（oxLDL）诱导的线粒体功能障碍和细胞凋亡，但其在VECs铁凋亡中的具体作用尚不清楚。在本研究中，我们发现oxLDL可以诱导VECs铁凋亡，线粒体是oxLDL诱导VECs铁凋亡的关键。作为线粒体功能的关键调节因子，PGC-1α在氧化ldl处理的VECs中表达较低。此外，过表达PGC-1α可抑制氧化ldl诱导的vec铁下垂，而PGC-1α在此过程中的作用受其上游调控分子AMPK的影响。本研究探索由AMPK/PGC-1α介导的氧化低密度脂蛋白诱导vec铁下沉的新思路，以更好地了解高脂血症引起血管病变的发病机制，为AS的早期预防提供理论依据。

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引用次数: 0

ApoE [−/−] CA1-overexpressing knock-in mice aggravated atherosclerosis by increasing M1 macrophages ApoE[−/−]ca1过表达敲入小鼠通过增加M1巨噬细胞加重动脉粥样硬化

IF 1.4 Q3 PERIPHERAL VASCULAR DISEASE

Atherosclerosis plus

Pub Date : 2025-06-01 Epub Date: 2025-03-27 DOI: 10.1016/j.athplu.2025.03.003

Jinbao Zong , Changyuan Wang , Hongji Zhou , Yu Song , Kehua Fang , Xiaotian Chang

Background

Carbonic anhydrase I (CA1) has been reported to be a diagnostic and therapeutic target for atherosclerosis (AS). This study aimed to verify the essential role of CA1 in AS progression in CA1-overexpressing mice.

Methods

A ApoE [−/−] CA1-overexpressing knock-in mouse model was constructed via CRISPR/Cas9-mediated genome engineering. AS was then induced in these transgenic mice via the administration of a high-fat diet, and a second group simultaneously received treatment with methazolamide (MTZ), a carbonic anhydrase inhibitor.

Results

Compared with ApoE [−/−] mice without CA1 overexpression, CA1-overexpressing mice had a greater average body weight, regardless of whether their treatment with MTZ or their AS induction status. Sudan IV, hematoxylin and eosin and Oil Red O staining revealed more plaques and fat deposits in the cardiac aortas of CA1-overexpressing mice than in those of ordinary ApoE−/− mice when AS was induced. Moreover, the atherogenic index; low-density lipoprotein, total cholesterol and triglyceride levels were significantly elevated, and high-density lipoprotein levels were declined in the peripheral blood of CA1-overexpressing mice than in that of ordinary ApoE [−/−] mice, regardless of whether these animals were induced to AS. Immunohistochemistry, Von Kossa staining and fluorescence immunohistochemistry revealed increases in CA1 expression, calcium deposition and M1 macrophages in the aortic tissues of CA1-overexpressing mice with AS. MTZ treatment significantly suppressed AS pathologies in the above experiments.

Conclusion

These findings revealed aggravated AS in ApoE [−/−] CA1-overexpressing mice and suggest that CA1 aggravates AS by increasing M1-type macrophages, a proinflammatory macrophage subtype.

碳酸酐酶I （CA1）已被报道为动脉粥样硬化（AS）的诊断和治疗靶点。本研究旨在验证CA1在CA1过表达小鼠AS进展中的重要作用。方法采用CRISPR/ cas9介导的基因组工程技术，构建过表达ApoE[−/−]ca1的敲入小鼠模型。然后通过高脂肪饮食在这些转基因小鼠中诱导AS，第二组同时接受甲基唑胺（MTZ）治疗，一种碳酸酐酶抑制剂。结果与没有CA1过表达的ApoE[−/−]小鼠相比，CA1过表达小鼠的平均体重更大，无论是MTZ治疗还是AS诱导状态。苏丹红、苏木精、伊红和油红O染色显示，AS诱导时，ca1过表达小鼠的心主动脉斑块和脂肪沉积比普通ApoE−/−小鼠多。此外，动脉粥样硬化指数；ca1过表达小鼠的外周血低密度脂蛋白、总胆固醇和甘油三酯水平显著升高，高密度脂蛋白水平低于普通ApoE[−/−]小鼠，无论这些动物是否被诱导为AS。免疫组织化学、Von Kossa染色和荧光免疫组织化学显示，过表达CA1的AS小鼠主动脉组织中CA1表达、钙沉积和M1巨噬细胞增加。在上述实验中，MTZ治疗明显抑制AS病理。结论ApoE[−/−]CA1过表达小鼠的AS加重，提示CA1通过增加促炎巨噬细胞亚型m1型加重AS。

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引用次数: 0