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A collaborative effort across Africa to investigate risk factors and outcomes of premature acute coronary syndrome: Protocol for the EAS Lipid Registry of Africa (LIPRA) 非洲各地共同努力调查过早急性冠状动脉综合征的风险因素和结果:非洲 EAS 血脂登记(LIPRA)议定书
IF 1.4 Q3 PERIPHERAL VASCULAR DISEASE Pub Date : 2024-10-24 DOI: 10.1016/j.athplu.2024.10.002
Ashraf Reda , Alexander R.M. Lyons , Alberto Zambon , Ahmed Bendary , Mutaz Al-Khnifsawi , Habib Gamra , David Marais , Okechukwu S. Ogah , Tigist Seleshi , Ahmed A.A. Suliman , Julius C. Mwita , Albertino Damasceno , Anastase Dzudie , Atef Elbahry , Elsayed Farag , Chala Fekadu , Lilian Mbau , Mohammed Mujahed , Rosemary P. Minja , Bernard Samia , Alexandros Tselepis
Data on acute coronary syndrome (ACS) is lacking in Africa where cases of premature ACS seem to be on the rise. Africa would benefit from an epidemiological assessment of premature ACS to determine its risk factors and management in this demographic to inform guidelines and practice. The European Atherosclerosis Society recognised this urgency and formed a growing network across 11 African countries to create the Lipid Registry of Africa (EAS-LIPRA). This article is based on the EAS-LIPRA protocol and presents the aims, concept and methodological considerations, and the operations and collaborative governance structure of this project. EAS-LIPRA aims to report risk factors and outcomes of premature ACS in Africa to further understand its prevalence and management via collating and pooling multinational prospective data on premature ACS across multiple sites in Africa into a standardised registry. Data will be stratified into subgroups based on country-level income as defined by the World Bank, and within country residence of urban versus rural areas. Valid statistical procedures will be employed to compare and observe trends in the pooled data based on demographics, clinical and laboratory variables, and disparities in its management. Being the first multinational lipid registry in Africa, it is envisaged that the network will expand to other African countries and sites yet to participate, facilitate other epidemiological studies in preventive cardiology, and set a precedent for other developing countries and regions.
非洲缺乏有关急性冠状动脉综合征(ACS)的数据,而过早发生 ACS 的病例似乎正在增加。对过早发生的急性冠状动脉综合征进行流行病学评估,以确定其风险因素和在这一人群中的管理方法,为指南和实践提供参考,将使非洲受益匪浅。欧洲动脉粥样硬化学会认识到了这一紧迫性,并在 11 个非洲国家建立了一个不断发展的网络,创建了非洲血脂登记处(EAS-LIPRA)。本文以 EAS-LIPRA 协议为基础,介绍了该项目的目标、概念、方法、运作和合作管理结构。EAS-LIPRA 旨在报告非洲过早发生 ACS 的风险因素和结果,通过整理和汇集非洲多个地点过早发生 ACS 的多国前瞻性数据并将其纳入标准化登记册,进一步了解其发病率和管理情况。数据将根据世界银行定义的国家级收入以及国内城市与农村居住地进行分层。将采用有效的统计程序,根据人口统计学、临床和实验室变量以及管理方面的差异,比较和观察汇总数据的趋势。作为非洲首个跨国血脂登记处,预计该网络将扩展到其他尚未参与的非洲国家和地区,促进其他预防性心脏病学的流行病学研究,并为其他发展中国家和地区开创先例。
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引用次数: 0
Adherence to the Healthy Nordic Food Index is associated with reduced plasma levels of inflammatory markers in patients with heterozygous familial hypercholesterolemia 遵守北欧健康食品指数与降低杂合子家族性高胆固醇血症患者血浆中的炎症标志物水平有关
IF 1.4 Q3 PERIPHERAL VASCULAR DISEASE Pub Date : 2024-10-24 DOI: 10.1016/j.athplu.2024.10.003
Eirin B. Løvheim , Kjetil Retterstøl , Ingunn Narverud , Martin P. Bogsrud , Bente Halvorsen , Thor Ueland , Pål Aukrust , Kirsten B. Holven

Background and aims

Familial hypercholesterolemia (FH) is an inherited disease associated with hypercholesterolemia, and dietary treatment is part of the treatment. We aimed to assess the dietary pattern in relation to the Healthy Nordic Food Index (HNFI) in adults with and without heterozygous FH (HeFH), and to examine the associations between dietary quality and biomarkers related to cardiovascular disease in adults with HeFH.

Methods

We included 205 adults (≥18 years) with HeFH who received follow-up at the Lipid Clinic in Oslo and compared them to controls (n = 228). Dietary intake was assessed using a food frequency questionnaire and dietary quality was assessed using the HNFI. Blood samples were analysed for levels of blood lipids, plasma fatty acids (FAs), and markers of inflammation and platelet activation.

Results

The HeFH patients (median 60 years; 50.2 % female; 25.9 % in secondary prevention) had lower intake of total and saturated fat compared to controls (32.6 energy percent (E%) vs. 34.9 E%, and 9.6 E% vs 12.0 E%, respectively; p < 0.001 for both). In the HeFH patients, increasing dietary quality was associated with increased plasma levels of the n-3 polyunsaturated FAs (PUFAs) eicosapentaenoic acid and docosahexaenoic acid, and the n-6 PUFA linoleic acid, and lower plasma levels of the inflammatory cytokines Tumor Necrosis Factor and interleukin-6, and of the platelet-derived inflammatory cytokines Platelet Factor 4 and Neutrophil-Activating Peptide-2.

Conclusion

Norwegian patients with HeFH followed up at a Lipid Clinic eat healthier than controls. Adherence to a healthy dietary pattern is associated with higher plasma levels of n-3 and n-6 PUFA, and lower levels of inflammatory markers, including platelet markers. This may suggest that adherence to an overall healthy dietary pattern might be beneficial for HeFH patients independent of the cholesterol-lowering effect of the diet.
背景和目的家族性高胆固醇血症(FH)是一种与高胆固醇血症相关的遗传性疾病,饮食治疗是治疗方法的一部分。我们的目的是评估患有和未患有杂合子高胆固醇血症(HeFH)的成年人的饮食模式与北欧健康食品指数(HNFI)的关系,并研究患有高胆固醇血症的成年人的饮食质量与心血管疾病相关生物标志物之间的关系。方法我们纳入了在奥斯陆血脂诊所接受随访的 205 名患有高胆固醇血症的成年人(≥18 岁),并将他们与对照组(n = 228)进行了比较。膳食摄入量通过食物频率问卷进行评估,膳食质量通过 HNFI 进行评估。结果与对照组相比,HeFH 患者(中位数为 60 岁;50.2% 为女性;25.9% 为二级预防患者)的总脂肪和饱和脂肪摄入量较低(能量百分比 (E%) 分别为 32.6% 和 34.9%,能量百分比分别为 9.6% 和 12.0%;两者的 p 均为 0.001)。在 HeFH 患者中,饮食质量的提高与血浆中 n-3 多不饱和脂肪酸(PUFAs)二十碳五烯酸和二十二碳六烯酸以及 n-6 多不饱和脂肪酸亚油酸水平的升高有关,与血浆中炎症细胞因子肿瘤坏死因子和白细胞介素-6 以及血小板衍生炎症细胞因子血小板因子 4 和中性粒细胞活化肽-2 水平的降低有关。结论在血脂诊所接受随访的挪威 HeFH 患者的饮食比对照组更健康。坚持健康的饮食模式与血浆中较高水平的 n-3 和 n-6 PUFA 以及较低水平的炎症标志物(包括血小板标志物)有关。这可能表明,坚持整体健康的饮食模式可能对 HeFH 患者有益,而与饮食的降胆固醇作用无关。
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引用次数: 0
Efficacy and safety of lipid-lowering therapies in combination with or without statin to reduce the cardiovascular risk: A systematic review of randomised controlled trials 降脂疗法联合或不联合他汀类药物降低心血管风险的有效性和安全性:随机对照试验的系统回顾
IF 1.4 Q3 PERIPHERAL VASCULAR DISEASE Pub Date : 2024-10-17 DOI: 10.1016/j.athplu.2024.10.001
Gabriella Iannuzzo , Geetank Kamboj , Parinita Barman , Shirish Dongare , Shantanu Jawla

Background and aims

Cardiovascular diseases (CVD) pose a significant global health burden. Lowering low-density lipoprotein-cholesterol is the primary therapeutic aim for preventing primary and secondary CVD events. While statins are the standard treatments, their limitations, such as side effects and intolerance in certain patient groups, necessitate exploration of alternative lipid-lowering therapies (LLTs). We systematically reviewed randomised controlled trials (RCTs) evaluating cardiovascular outcomes associated with non-statin LLTs (bempedoic acid, alirocumab, evolocumab, ezetimibe, and inclisiran) in adults with CVD or high cardiovascular risk.

Methods

EMBASE, Medline, Cochrane Library, and clinical trial registries were systematically searched for eligible studies, from inception until February 08, 2023. Two reviewers independently screened the studies, with discrepancies resolved by a third reviewer. Data extraction and validation were conducted, and the risk of bias was assessed using the Cochrane Risk-of-Bias tool-2 for RCTs.

Results

The search strategy yielded 2104 citations. Post screening for eligibility, nine unique trials/studies (84 publications) were identified. Among these, one trial each was identified for bempedoic acid and alirocumab, three for evolocumab, and four for ezetimibe. No published literature documenting the cardiovascular outcomes of inclisiran was identified. Only one trial (CLEAR Outcomes) included statin-intolerant patients at baseline. Most studies evaluated a 3-component, 4-component, or 5-component major adverse cardiovascular events composite as an outcome along with individual components. The quality of the included trials was found to be fair-to-good.

Conclusions

The systematic review findings emphasise the significance of considering non-statin LLTs as viable treatment options for individuals with CVD or high cardiovascular risk who cannot tolerate or achieve optimal lipid control with statin therapy alone.
背景和目的心血管疾病(CVD)给全球健康造成了巨大负担。降低低密度脂蛋白胆固醇是预防原发性和继发性心血管疾病的主要治疗目标。虽然他汀类药物是标准疗法,但由于其副作用和某些患者群体的不耐受性等局限性,有必要探索其他降脂疗法(LLTs)。我们系统地回顾了评估非白金类 LLTs(贝美多酸、阿利曲库单抗、依维莫单抗、依泽替米贝和 inclisiran)对患有心血管疾病或心血管风险较高的成人的心血管预后的随机对照试验(RCT)。两名审稿人独立筛选研究,不一致之处由第三名审稿人解决。进行了数据提取和验证,并使用针对 RCT 的 Cochrane Risk-of-Bias 工具-2 评估了偏倚风险。经过资格筛选,确定了 9 项独特的试验/研究(84 篇出版物)。其中,贝美多克酸和阿利曲库单抗各确定了一项试验,依维莫司确定了三项试验,依泽替米贝确定了四项试验。未发现记录 inclisiran 心血管疗效的已发表文献。只有一项试验(CLEAR Outcomes)纳入了基线时不耐受他汀类药物的患者。大多数研究评估了由 3 个部分、4 个部分或 5 个部分组成的主要心血管不良事件复合结果以及单个部分。结论系统综述结果强调,对于不能耐受或不能通过他汀治疗达到最佳血脂控制效果的心血管疾病患者或高心血管风险患者,考虑将非他汀类 LLTs 作为可行的治疗方案具有重要意义。
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引用次数: 0
Lipoprotein(a) and the atherosclerotic burden – Should we wait for clinical trial evidence before taking action? 脂蛋白(a)与动脉粥样硬化负担--我们是否应等待临床试验证据后再采取行动?
IF 1.4 Q3 PERIPHERAL VASCULAR DISEASE Pub Date : 2024-09-26 DOI: 10.1016/j.athplu.2024.09.004
Isabella Fichtner , Chiara Macchi , Alessandra Stefania Rizzuto , Stefano Carugo , Alberto Corsini , Massimiliano Ruscica
The fact that lipoprotein(a) levels should be regarded as a causal residual risk factor in the atherosclerotic cardiovascular diseases (ASCVD) is now a no-brainer. This review article aims to summarize the latest evidence supporting the causal role of lipoprotein(a) in ASCVD and the potential strategies to reduce the lipoprotein(a) burden until clinical trial results are available. Epidemiological and genetic data demonstrate the causal link between lipoprotein(a) and increased ASCVD risk. That being said, a specific question comes to mind: “must we wait for outcome trials in order to take action?”. Given that lipoprotein(a) levels predict incident ASCVD in both primary and secondary prevention contexts, with a linear risk gradient across its distribution, measuring lipoprotein(a) can unequivocally help identify patients who may later benefit from specific lipoprotein(a)-lowering therapies. This understanding has led various National Societies to recommend dosing lipoprotein(a) in high-risk individuals and to support the recommendation of measuring lipoprotein(a) levels at least once in every adult for risk stratification.
脂蛋白(a)水平应被视为动脉粥样硬化性心血管疾病(ASCVD)的一个因果残余危险因素,这一点现在已毋庸置疑。这篇综述文章旨在总结支持脂蛋白(a)在 ASCVD 中的因果作用的最新证据,以及在临床试验结果出来之前减轻脂蛋白(a)负担的潜在策略。流行病学和遗传学数据证明了脂蛋白(a)与 ASCVD 风险增加之间的因果关系。尽管如此,我还是想到了一个具体的问题:"我们是否必须等到临床试验结果出来后才能采取行动?鉴于脂蛋白(a)水平在一级和二级预防中都能预测急性心血管疾病的发生,且其分布呈线性风险梯度,因此测量脂蛋白(a)能明确帮助识别日后可能从特定的降低脂蛋白(a)疗法中获益的患者。基于这一认识,多个国家学会建议对高危人群使用脂蛋白(a)剂量,并支持对每个成年人至少测量一次脂蛋白(a)水平以进行风险分层的建议。
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引用次数: 0
Coronary artery calcification score and 19 biomarkers on cardiovascular events; a 10-year follow-up DanRisk substudy 冠状动脉钙化评分和 19 种生物标志物对心血管事件的影响;DanRisk 子研究的 10 年跟踪调查
IF 1.4 Q3 PERIPHERAL VASCULAR DISEASE Pub Date : 2024-09-24 DOI: 10.1016/j.athplu.2024.09.003
Mie Schæffer , Jeppe Holm Rasmussen , Maise Høigaard Fredgart , Selma Hasific , Frederikke Nørregaard Jakobsen , Flemming Hald Steffensen , Jess Lambrechtsen , Niels Peter Rønnow Sand , Lars Melholt Rasmussen , Axel CP. Diederichsen

Aim

The SCORE2 algorithm is recommended to estimate risk of cardiovascular disease (CVD). Coronary artery calcification (CAC) score is expensive but improves the risk prediction. This study aims to determine and compare the additive value of CAC-score and 19 biomarkers in risk prediction.

Methods

Traditional cardiovascular (CV) risk factors, CAC-score, and a wide range of biomarkers (including lipids, calcium-phosphate metabolism, troponin, inflammation, kidney function and ankle brachial index (ABI)) were collected from 1211 randomly selected middle-aged men and women in this multicenter prospective cohort in 2009–2010. 10-year follow-up data on CV-events were obtained via the Danish Health Registries. CV-event was defined as stroke, myocardial infarction, hospitalization for heart failure, coronary artery revascularization or death from CVD. The association between SCORE2, CAC-score, biomarkers, and CV-events was assessed using cox proportional hazard rates (HR) and compared using AUC-calculation of ROC-curves. Finally, net reclassification improvement (NRI) was calculated.

Results

92 participants had CV-events. Adjusted for risk factors, CAC-score was significantly associated with events (adjusted HR 1.9 (95%CI:1.1; 3.3), 3.6 (95%CI:1.9; 6.8), and 5. (95%CI:2.6; 10.3) for CAC-score 1–99, CAC-score 100–399 and CAC-score ≥400, respectively. HR for the highest quartile of CRP was 2.3 (95%CI:1.2; 4.5), while none of the remaining biomarkers improved HR. Adjusted for SCORE2, the CAC-score improved AUC (AUCCAC: 0.72, AUCSCORE2: 0.67, p<0.01). A combination of selected biomarkers (total cholesterol, low-density lipoprotein, phosphate, troponin, CRP, and creatinine) borderline improved AUC (AUCBiomarkers + SCORE2: 0.71, AUCSCORE2: 0.67, p=0.06). NRI for CAC score was 63 % (p<0.0001).

Conclusion

CAC-score improved prediction of CV-events, however the selected biomarkers did not.
建议采用 SCORE2 算法来估计心血管疾病(CVD)的风险。冠状动脉钙化(CAC)评分价格昂贵,但能改善风险预测。本研究旨在确定并比较 CAC 评分和 19 种生物标志物在风险预测中的附加值。方法在 2009-2010 年的多中心前瞻性队列中,从随机挑选的 1211 名中年男性和女性中收集了传统心血管(CV)风险因素、CAC 评分和多种生物标志物(包括血脂、钙磷代谢、肌钙蛋白、炎症、肾功能和踝肱指数(ABI))。有关心血管事件的 10 年随访数据通过丹麦健康登记处获得。心血管事件被定义为中风、心肌梗塞、心力衰竭住院、冠状动脉血运重建或心血管疾病导致的死亡。SCORE2、CAC-分数、生物标志物和心血管事件之间的关联采用cox比例危险率(HR)进行评估,并通过ROC曲线的AUC计算进行比较。最后,计算了净再分类改善率(NRI)。经风险因素调整后,CAC-分数与事件显著相关(调整后 HR 分别为 1.9 (95%CI:1.1; 3.3)、3.6 (95%CI:1.9; 6.8) 和 5. (95%CI:2.6; 10.3),CAC-分数为 1-99、CAC-分数为 100-399 和 CAC-分数≥400。CRP最高四分位数的HR为2.3(95%CI:1.2;4.5),而其余生物标志物均未改善HR。对 SCORE2 进行调整后,CAC-评分提高了 AUC(AUCCAC:0.72,AUCSCORE2:0.67,p<0.01)。所选生物标志物(总胆固醇、低密度脂蛋白、磷酸盐、肌钙蛋白、CRP 和肌酐)的组合可在一定程度上改善 AUC(AUCBiomarkers + SCORE2:0.71,AUCSCORE2:0.67,p=0.06)。CAC评分的NRI为63%(p<0.0001)。
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引用次数: 0
Eligibility for marine omega-3 fatty acid supplementation after acute coronary syndromes 急性冠状动脉综合征后补充海洋欧米伽-3 脂肪酸的资格
IF 1.4 Q3 PERIPHERAL VASCULAR DISEASE Pub Date : 2024-09-15 DOI: 10.1016/j.athplu.2024.09.002
Cédric Follonier , Gabriel Rabassa , Mattia Branca , David Carballo , Konstantinos Koskinas , Dik Heg , David Nanchen , Lorenz Räber , Roland Klingenberg , Moa Lina Haller , Sebastian Carballo , Stephan Windecker , Christian M. Matter , Nicolas Rodondi , François Mach , Baris Gencer

Background and aims

The 2019 European Society of Cardiology guidelines for the management of dyslipidemia consider the use of high-dose marine omega-3 fatty acid (FA) eicosapentaenoic acid (EPA) supplementation (icosapent ethyl 2 × 2g/day) to lower residual cardiovascular risk in high-risk patients with hypertriglyceridemia. This study aimed to assess the eligibility for omega-3 FA-EPA supplementation in patients with acute coronary syndromes (ACS).

Methods

In a prospective Swiss cohort of patients hospitalized for ACS, eligibility for marine omega-3 FA-EPA, defined as plasma triglyceride levels ranging from 1.5 to 5.6 mmol/l, was assessed at baseline and one-year follow-up and compared across subgroups. Lipid-lowering therapy intensification with statin and ezetimibe was modelled to simulate a hypothetical systematic treatment and its effect on omega-3 FA-EPA supplementation eligibility.

Results

Of 2643 patients, 98 % were prescribed statin therapy at discharge, including 62 % at a high-intensity regimen; 93 % maintained it after one year, including 53 % at a high-intensity regimen. The use of ezetimibe was 3 % at discharge and 7 % at one year. Eligibility was observed in 32 % (32 % men, 29 % women) one year post-ACS. After modelling systematic treatment with statins, ezetimibe, and both, eligibility decreased to 31 %, 25 % and 24 %, respectively. Eligibility was higher in individuals aged <70 (34 vs 25 %), smokers (38 vs 28 %), diabetics (46 vs 29 %), hypertensive (35 vs 29 %), and obese patients (46 vs 22 % for normal weight), all with p-values <0.001.

Conclusion

In a contemporary Swiss cohort of patients with ACS, up to 32 % would be eligible for omega-3 FA-EPA supplementation one year after ACS, highlighting an opportunity to mitigate residual cardiovascular risk in patients with ACS and hypertriglyceridemia.

背景和目的2019年欧洲心脏病学会血脂异常管理指南考虑使用高剂量海洋ω-3脂肪酸(FA)二十碳五烯酸(EPA)补充剂(icosapent ethyl 2 × 2g/天)来降低高甘油三酯血症高危患者的残余心血管风险。本研究旨在评估急性冠状动脉综合征(ACS)患者补充欧米伽-3 FA-EPA 的资格。方法在瑞士的前瞻性 ACS 住院患者队列中,对血浆甘油三酯水平介于 1.5 至 5.6 mmol/l 之间的患者补充海洋欧米伽-3 FA-EPA 的资格进行基线评估和一年随访,并在不同亚组之间进行比较。对使用他汀和依折麦布加强降脂治疗的情况进行了模拟,以模拟假设的系统治疗及其对ω-3 FA-EPA补充资格的影响。出院时使用依折麦布的比例为 3%,一年后为 7%。32% 的患者(男性 32%,女性 29%)在 ACS 一年后符合条件。在对他汀类药物、依折麦布和两者进行系统治疗建模后,合格率分别降至 31%、25% 和 24%。年龄为 70 岁(34% 对 25%)、吸烟者(38% 对 28%)、糖尿病患者(46% 对 29%)、高血压患者(35% 对 29%)和肥胖患者(46% 对 22% 正常体重)的合格率较高,P 值均为 0.001。结论 在当代瑞士的 ACS 患者队列中,多达 32% 的患者在 ACS 一年后符合补充欧米伽-3 FA-EPA 的条件,这为降低 ACS 和高甘油三酯血症患者的残余心血管风险提供了机会。
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引用次数: 0
Clinical Service Quality and Unmet Needs in Homozygous Familial Hypercholesterolaemia Patients: Insights from UK Tertiary Centres 同型家族性高胆固醇血症患者的临床服务质量和未满足的需求:来自英国三级医疗中心的启示
IF 1.4 Q3 PERIPHERAL VASCULAR DISEASE Pub Date : 2024-09-01 DOI: 10.1016/j.athplu.2024.08.022
Heleen A. Hussein , Haya Haso , Bilal Bashir , Raabya Pasha , Anoushka Kamath , Maryam Ferdousi , Handrean Soran , Mariamma Baptist , Kirsty Nicholson
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引用次数: 0
Total Circulating PCSK9 Positively Correlates with Age and Free Circulating PCSK9 Positively Correlated with Body Mass Index in Healthy Volunteers 健康志愿者的总循环 PCSK9 与年龄呈正相关,游离循环 PCSK9 与体重指数呈正相关
IF 1.4 Q3 PERIPHERAL VASCULAR DISEASE Pub Date : 2024-09-01 DOI: 10.1016/j.athplu.2024.08.006
Anoushka Kamath , Maryam Ferdousi , Bilal Bashir , Raabya Pasha , Handrean Soran
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引用次数: 0
The pro-atherogenic enzyme PAPP-A is active in eluates from human carotid and femoral atherosclerotic plaques 促动脉粥样硬化酶 PAPP-A 在人体颈动脉和股动脉粥样硬化斑块的洗脱液中具有活性
IF 1.4 Q3 PERIPHERAL VASCULAR DISEASE Pub Date : 2024-09-01 DOI: 10.1016/j.athplu.2024.09.001
Mette Faurholdt Gude , Rikke Hjortebjerg , Mette Bjerre , Anne Kathrine Nissen Pedersen , Claus Oxvig , Lars Melholt Rasmussen , Jan Frystyk , Lasse Steffensen

Background

Pregnancy-associated plasma protein-A (PAPP-A) regulates bioavailability of insulin-like growth factor 1 (IGF1) in various tissues by proteolytic cleavage of a subset of IGF-binding proteins (IGFBPs). Pre-clinical studies have established a role of PAPP-A in atherosclerosis and proposed that targeting the proteolytic activity of PAPP-A has therapeutic value.

This study aimed to investigate whether human atherosclerotic plaques contain proteolytically active PAPP-A, a prerequisite for further considering PAPP-A as a therapeutic target in patients.

Methods

We obtained carotid (n = 9) and femoral (n = 11) atherosclerotic plaques from patients undergoing vascular surgery and incubated freshly harvested plaque tissue in culture media for 24 h. Subsequently, conditioned media were assayed for PAPP-A, STC2, IGFBP4, and IGF1 using immunoassays. Enzymatic activity of PAPP-A was assessed by its ability to process recombinant IGFBP4-IGF1 complexes - a specific substrate of PAPP-A - by Western blotting.

Results

PAPP-A and STC2 were detectable in conditioned media from both carotid and femoral plaques, with higher STC2 concentrations in eluates from carotid plaque incubations (p = 0.02). IGFBP4 and IGF1 were undetectable. Conditioned media from all 20 plaques exhibited PAPP-A proteolytic activity. However, no correlation between PAPP-A concentration and its proteolytic activity was observed, whereas the PAPP-A: STC2 molar ratio correlated with PAPP-A activity (R2 = 0.25, p = 0.03).

Conclusion

This study provides evidence for the presence of enzymatically active PAPP-A in atherosclerotic plaques and underscores the need for further investigating potential beneficial effects associated with targeting PAPP-A in atherosclerotic cardiovascular disease.

背景妊娠相关血浆蛋白-A(PAPP-A)通过蛋白水解IGF结合蛋白(IGFBPs)子集,调节胰岛素样生长因子1(IGF1)在各种组织中的生物利用率。临床前研究已经确定了 PAPP-A 在动脉粥样硬化中的作用,并提出针对 PAPP-A 的蛋白水解活性具有治疗价值。本研究旨在调查人类动脉粥样硬化斑块是否含有蛋白水解活性 PAPP-A,这是进一步考虑将 PAPP-A 作为患者治疗靶点的前提条件。方法我们从接受血管手术的患者身上获取了颈动脉(n = 9)和股动脉(n = 11)动脉粥样硬化斑块,并将新鲜获取的斑块组织在培养基中培养 24 小时,然后用免疫测定法测定条件培养基中的 PAPP-A、STC2、IGFBP4 和 IGF1。结果在颈动脉斑块和股动脉斑块的条件培养基中都能检测到 PAPP-A 和 STC2,其中颈动脉斑块培养液中的 STC2 浓度更高(p = 0.02)。IGFBP4和IGF1检测不到。所有 20 个斑块的条件培养基都显示出 PAPP-A 蛋白溶解活性。结论这项研究为动脉粥样硬化斑块中存在具有酶活性的 PAPP-A 提供了证据,并强调有必要进一步研究针对动脉粥样硬化心血管疾病的 PAPP-A 的潜在有益作用。
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引用次数: 0
Ketogenic diet and extreme hypercholesterolaemia: A case of polygenic hypercholesteroalemia 生酮饮食与极端高胆固醇血症:一个多基因高胆固醇血症病例
IF 1.4 Q3 PERIPHERAL VASCULAR DISEASE Pub Date : 2024-09-01 DOI: 10.1016/j.athplu.2024.08.007
T. Mazaheri , A. David , B. Jones , J.Cegla
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引用次数: 0
期刊
Atherosclerosis plus
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