Atherosclerosis plus最新文献_第5页

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 : 2025-07-12 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

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 : 2025-07-05 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

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 : 2025-06-28 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。

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引用次数: 0

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 : 2025-06-14 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

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 : 2025-06-08 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

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 : 2025-06-06 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

Fucosterol exerts an anti-atherosclerotic action via NF-κB and p38/Erk MAPK signaling pathways focusterol通过NF-κB和p38/Erk MAPK信号通路发挥抗动脉粥样硬化作用

IF 1.4 Q3 PERIPHERAL VASCULAR DISEASE

Atherosclerosis plus

Pub Date : 2025-05-13 DOI: 10.1016/j.athplu.2025.05.001

Tiancheng Liu , Mengli Zhang , Xian Wu , Zhenxing Liu , Huan Peng , Feng Gui , Wen Xiong , Qijuan Liu , Guojun Du , Bo Liu , Chenchen Zhang , Junfeng Ma , Quan Yuan , Wei Li , Zhen Chen

Background

Fucosterol is a sterol isolated from brown algae and has various biological properties, such anti-inflammatory and antidiabetic effects. In this study, we investigated the anti-atherosclerosis effects of fucosterol in vivo and in vitro.

Methods

ApoE^−/− mice were fed a high fat diet for 12 weeks with or without fucosterol treatment. H&E staining and Oil Red O staining were performed to detect atherosclerotic lesion and lipid content in the aorta of mice. The lipid metabolism indexes in the mouse serum were measured. Macrophage infiltration into the aortic wall was detected using immunohistochemistry of CD68. Human umbilical vein endothelial cells (HUVECs) were treated with 100 μg/mL ox-LDL to establish a cell model of atherosclerosis in vitro. The expression and protein levels of adhesion molecules and inflammatory cytokines in the aorta and HUVECs were measured using RT-qPCR and western blot, respectively. The levels of oxidative stress-related markers in the mouse serum and HUVECs were measured using corresponding detection kits. The effects of fucosterol on the viability and apoptosis of HUVECs were detected using CCK-8 and flow cytometry, respectively. The levels of NF-κB and p38/Erk MAPK pathway-related proteins in HUVECs were assessed by western blot.

Results

Fucosterol reduced atherosclerotic plaques and lipid levels in apoE^−/− mice. Fucosterol alleviated macrophage infiltration, inflammatory response, and oxidative stress in apoE^−/− mice. The ox-LDL-induced inflammatory response, oxidative stress, and apoptosis in HUVECs were attenuated by fucosterol. Additionally, fucosterol reduced the expression of proprotein convertase subtilisin/kexin type 9 (PCSK9) in vivo and in vitro. Moreover, the ox-LDL-induced activation of the NF-κB and p38/Erk MAPK signaling in HUVECs was suppressed by fucosterol.

Conclusion

The current investigation revealed that fucosterol attenuates atherosclerotic plaques in apoE^−/− mice through the inhibition of hyperlipidemia, inflammation, and oxidative stress.

focusterol是一种从褐藻中分离出来的甾醇，具有多种生物学特性，如抗炎和降糖作用。在本研究中，我们研究了focus甾醇在体内和体外的抗动脉粥样硬化作用。方法apoe−/−小鼠分别饲喂高脂饲料12周，加或不加病灶甾醇处理。采用H&；E染色和油红O染色检测小鼠主动脉动脉粥样硬化病变及脂质含量。测定小鼠血清脂质代谢指标。CD68免疫组化检测巨噬细胞浸润主动脉壁。采用100 μg/mL ox-LDL处理人脐静脉内皮细胞（HUVECs），建立体外动脉粥样硬化细胞模型。采用RT-qPCR和western blot分别检测主动脉和HUVECs中粘附分子和炎性细胞因子的表达和蛋白水平。采用相应的检测试剂盒检测小鼠血清和HUVECs中氧化应激相关标志物的水平。采用CCK-8和流式细胞术分别检测focus甾醇对HUVECs细胞活力和凋亡的影响。western blot检测HUVECs中NF-κB和p38/Erk MAPK通路相关蛋白的表达水平。结果：聚脂醇可降低apoE−/−小鼠的动脉粥样硬化斑块和脂质水平。focus甾醇减轻apoE−/−小鼠巨噬细胞浸润、炎症反应和氧化应激。focusterol可减弱ox- ldl诱导的HUVECs炎症反应、氧化应激和细胞凋亡。此外，focus甾醇在体内和体外均可降低枯草素/kexin 9型蛋白转化酶（PCSK9）的表达。此外，ox- ldl诱导的HUVECs中NF-κB和p38/Erk MAPK信号的激活被焦甾醇抑制。结论目前的研究表明，focusterol通过抑制高脂血症、炎症和氧化应激来减轻apoE−/−小鼠的动脉粥样硬化斑块。

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引用次数: 0

Plasma apolipoprotein concentrations and occurrence of cardiovascular events in the general population: an exploratory analysis 普通人群血浆载脂蛋白浓度与心血管事件的发生：一项探索性分析

IF 1.4 Q3 PERIPHERAL VASCULAR DISEASE

Atherosclerosis plus

Pub Date : 2025-05-08 DOI: 10.1016/j.athplu.2025.04.003

Avedis Torossian , Annelise Genoux , Zichun Cai , Nathan Jolivet , Mikaël Croyal , Arsênio Rodrigues Oliveira , Sébastien Dejean , Nathalie Viguerie , Cendrine Cabou , Bertrand Perret , Jean Ferrières , Vanina Bongard , Laurent O. Martinez

Background and aims

The role of many apolipoproteins in cardiovascular disease (CVD) pathophysiology and their predictive potential remains unclear. This study examined the association between plasma concentrations of a broad panel of apolipoproteins and the occurrence of cardiovascular events in a general population.

Methods

A nested case-control study was conducted within a cohort from Southwestern France. Baseline concentrations of apolipoproteins A-I, A-II, A-IV, B100, C-I, C-II, C-III, D, E, H, J, L1 and M were analyzed in 65 cases who experienced a cardiovascular event during the follow-up period, and in 65 controls matched for age and sex (mean age 60.9 ± 10.7 years; 66.9 % men; median follow up 9.3 years for controls, 6.2 years for cases). Baseline correlations were assessed using Spearman's coefficients.

Logistic regression and partial least squares discriminant analysis (PLS-DA) were used to evaluate associations with the occurrence of cardiovascular events.

Results

Concentrations of apolipoproteins A-I, A-IV, C-I, D, H, J and M differed significantly between cases and controls. All expect apoM remained independently associated with cardiovascular events after adjustment for known risk factors. Additionally, PLS-DA revealed that the entire apolipoprotein panel explained 64 % of variance in case-control status with 60 % predictive accuracy, with apolipoproteins D, J, A-IV, H, and C-I contributing the most to group discrimination.

Conclusions

This study identifies a novel panel of apolipoproteins (A-I, A-IV, C-I, D, H, and J) whose levels are associated with occurrence of cardiovascular diseases, independently of traditional risk factors. Further research is needed to confirm these findings and explore underlying mechanisms.

背景与目的载脂蛋白在心血管疾病（CVD）病理生理中的作用及其预测潜力尚不清楚。本研究探讨了一组载脂蛋白的血浆浓度与普通人群心血管事件发生之间的关系。方法采用巢式病例对照研究，对来自法国西南部的一组人群进行研究。我们分析了65例在随访期间发生心血管事件的患者以及65例年龄和性别相匹配的对照组的载脂蛋白a - i、a - ii、a - iv、B100、C-I、C-II、C-III、D、E、H、J、L1和M的基线浓度。男性占66.9%；对照组中位随访9.3年，病例中位随访6.2年)。使用Spearman系数评估基线相关性。使用Logistic回归和偏最小二乘判别分析（PLS-DA）来评估与心血管事件发生的关联。结果载脂蛋白A-I、A-IV、C-I、D、H、J和M的浓度在病例和对照组之间存在显著差异。所有人都认为，在调整了已知的危险因素后，apoM仍然与心血管事件独立相关。此外，PLS-DA显示，整个载脂蛋白组解释了病例对照状态中64%的差异，预测准确率为60%，其中载脂蛋白D、J、A-IV、H和C-I对群体歧视贡献最大。本研究发现了一组新的载脂蛋白（a - i、a - iv、C-I、D、H和J），它们的水平与心血管疾病的发生相关，独立于传统的危险因素。需要进一步的研究来证实这些发现并探索潜在的机制。

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引用次数: 0

Association of dietary preferences with cardiovascular disease: a Mendelian randomization study 饮食偏好与心血管疾病的关联：一项孟德尔随机研究

IF 1.4 Q3 PERIPHERAL VASCULAR DISEASE

Atherosclerosis plus

Pub Date : 2025-05-07 DOI: 10.1016/j.athplu.2025.04.002

Mia D. Lee , Benjamin F. Voight

Background and aims

Susceptibility to cardiovascular disease (CVD) is driven by genetic and environmental risk factors. Diet is a modifiable and largely environmental risk factor for CVD. Genetic factors associated with a variety of dietary preferences revealed via recent genome-wide association studies (GWAS) allow further investigate the role of diet in liability to disease that has been limited to observational and epidemiologic studies with mixed findings.

Method

We obtained publicly available genome-wide association data for 38 dietary preference traits and seven common CVDs to investigate causal hypotheses between diet as the exposure to CVD as outcomes using the statistical framework of Mendelian randomization (MR) for hypothesis testing and sensitivity analyses. We also conducted mediation analyses to evaluate the effects of dietary preferences on CVDs to elucidate potential causal graphs and estimate the effects of dietary preferences mediated by potential mediators.

Results

Across all methods, we identified 10 significant causal effects, which included eight dietary preferences across three CVD endpoints (Bonferroni-corrected P < 1.88 × 10⁻⁴). In sensitivity MR and mediation analysis, we observed that obesity - quantified by body mass index (BMI) - was a common mediator that contributed to many of these observed effects. We also found that educational attainment was an exclusive, additional mediator for the effect of preference for muesli with risk to peripheral artery disease (PAD).

Conclusions

Our results provide genetic evidence for a link between diet and CVD that aligns with obesity-mediated risk of CVD in individuals in relation to their specific preferences for food.

背景和目的心血管疾病（CVD）的易感性是由遗传和环境危险因素驱动的。饮食是心血管疾病可改变的主要环境风险因素。最近的全基因组关联研究（GWAS）揭示了与多种饮食偏好相关的遗传因素，从而进一步研究饮食在疾病倾向性中的作用，这些研究仅限于观察性和流行病学研究，结果不一。方法利用公开的38个饮食偏好性状与7种常见心血管疾病的全基因组关联数据，采用孟德尔随机化（Mendelian randomization， MR）的统计框架进行假设检验和敏感性分析，探讨饮食与心血管疾病暴露之间的因果关系。我们还进行了中介分析，评估饮食偏好对心血管疾病的影响，以阐明潜在的因果关系图，并估计饮食偏好在潜在介质中的中介作用。在所有方法中，我们确定了10个显著的因果效应，其中包括3个CVD终点的8种饮食偏好(bonferroni校正P <；1.88 × 10−4)。在敏感性MR和中介分析中，我们观察到肥胖（通过体重指数（BMI）量化）是导致许多观察到的影响的常见中介。我们还发现，受教育程度是外周动脉疾病（PAD）风险偏好muesli影响的唯一额外中介。结论：我们的研究结果为饮食和心血管疾病之间的联系提供了遗传证据，这与肥胖介导的心血管疾病风险与个体特定的食物偏好有关。

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引用次数: 0

Trends of atherosclerosis-related mortality in adults with diabetes: A cross-sectional analysis of U.S. national data 成人糖尿病患者动脉粥样硬化相关死亡率的趋势：美国国家数据的横断面分析

IF 1.4 Q3 PERIPHERAL VASCULAR DISEASE

Atherosclerosis plus

Pub Date : 2025-05-02 DOI: 10.1016/j.athplu.2025.04.001

Yusuf Hasan Ali , Fakhar Latif , Fatimah Hoda , Azeem Hassan , Huda Ahmed , Raheel Ahmed , Vikash Jaiswal

Background

Diabetes mellitus is a rapidly growing global health issue, projected to affect 643 million adults by 2030. Atherosclerosis, a prevalent complication of diabetes, significantly contributes to morbidity and mortality among affected individuals. This study aimed to analyze mortality trends associated with atherosclerosis in diabetic patients aged ≥45 years, with particular focus on variations by sex, race, urban-rural classification, and geographical regions in the US from 1999 to 2020.

Methods

We conducted a study using data from the CDC WONDER database, identifying atherosclerosis-related deaths in diabetic patients. We calculated age-adjusted mortality rates (AAMRs) per 100,000 population and analyzed trends over time using Joinpoint regression to assess annual percentage changes (APC) and average annual percentage changes (AAPC).

Results

A total of 674,582 atherosclerosis-related deaths were recorded in diabetic patients from 1999 to 2020, with a higher prevalence in men (57.40 %). The majority of deaths occurred in NH White individuals (81.70 %). Overall, AAMRs declined from 32.8 in 1999 to 25.8 in 2020. A significant decrease was observed from 1999 to 2014 (APC: −2.61, p < 0.05), followed by stability (2014–2018) and a subsequent rise (APC: 6.97, p < 0.05) till 2020. Sex-stratified analysis indicated persistently higher AAMRs in men, with a significant increase from 2018 to 2020 (APC: 7.33, p < 0.05). Racial disparities were evident, with NH Black individuals demonstrating the highest AAMRs. Geographic analysis revealed higher AAMRs in nonmetropolitan areas, with notable state-level variations. All census regions exhibited an initial decline, followed by a significant rise in AAMRs post-2018 (p < 0.05).

Conclusion

Despite initial declines, recent trends indicate a resurgence in atherosclerosis-related mortality among diabetic patients, particularly in specific racial groups, rural areas, and certain regions. These findings underscore the need for targeted interventions to address disparities and improve cardiovascular outcomes in diabetic populations.

糖尿病是一个快速增长的全球健康问题，预计到2030年将影响6.43亿成年人。动脉粥样硬化是糖尿病的一种常见并发症，是糖尿病患者发病率和死亡率的重要因素。本研究旨在分析1999年至2020年美国年龄≥45岁的糖尿病患者与动脉粥样硬化相关的死亡率趋势，特别关注性别、种族、城乡分类和地理区域的变化。方法：我们使用CDC WONDER数据库的数据进行了一项研究，确定糖尿病患者与动脉粥样硬化相关的死亡。我们计算了每10万人的年龄调整死亡率（AAMRs），并使用Joinpoint回归分析了随时间变化的趋势，以评估年百分比变化（APC）和年平均百分比变化（AAPC）。结果1999 - 2020年糖尿病患者动脉粥样硬化相关死亡674,582例，男性患病率较高（57.40%）。大多数死亡发生在NH白人个体（81.70%）。总体而言，aamr从1999年的32.8下降到2020年的25.8。1999 - 2014年显著下降(APC: - 2.61, p <；0.05)，随后稳定（2014-2018），随后上升(APC: 6.97, p <；0.05)到2020年。性别分层分析显示，男性aamr持续升高，2018年至2020年显著增加(APC: 7.33, p <；0.05)。种族差异很明显，NH黑人表现出最高的aamr。地理分析显示，非大都市地区的aamr较高，且州际差异显著。所有人口普查区都表现出最初的下降，随后在2018年后，aamr显著上升(p <；0.05)。结论：尽管最初有所下降，但最近的趋势表明，糖尿病患者与动脉粥样硬化相关的死亡率再次上升，特别是在特定的种族群体、农村地区和某些地区。这些发现强调需要有针对性的干预措施来解决糖尿病人群的差异和改善心血管预后。

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引用次数: 0