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HDL and chronic kidney disease 高密度脂蛋白与慢性肾脏疾病
IF 1.6 Pub Date : 2023-06-01 DOI: 10.1016/j.athplu.2023.04.001
Chiara Pavanello, Alice Ossoli

Low HDL-cholesterol (HDL-C) concentrations are a typical trait of the dyslipidemia associated with chronic kidney disease (CKD). In this condition, plasma HDLs are characterized by alterations in structure and function, and these particles can lose their atheroprotective functions, e.g., the ability to promote cholesterol efflux from peripheral cells, anti-oxidant and anti-inflammatory proprieties and they can even become dysfunctional, i.e., exactly damaging. The reduction in plasma HDL-C levels appears to be the only lipid alteration clearly linked to the progression of renal disease in CKD patients. The association between the HDL system and CKD development and progression is also supported by the presence of genetic kidney alterations linked to HDL metabolism, including mutations in the APOA1, APOE, APOL and LCAT genes. Among these, renal disease associated with LCAT deficiency is well characterized and lipid abnormalities detected in LCAT deficiency carriers mirror the ones observed in CKD patients, being present also in acquired LCAT deficiency. This review summarizes the major alterations in HDL structure and function in CKD and how genetic alterations in HDL metabolism can be linked to kidney dysfunction. Finally, the possibility of targeting the HDL system as possible strategy to slow CKD progression is reviewed.

高密度脂蛋白胆固醇(HDL-C)浓度低是与慢性肾脏疾病(CKD)相关的血脂异常的典型特征。在这种情况下,血浆HDL的特征是结构和功能的改变,这些颗粒可能失去其动脉粥样硬化保护功能,例如促进胆固醇从外周细胞流出的能力、抗氧化和抗炎特性,它们甚至可能变得功能失调,即完全具有破坏性。血浆HDL-C水平的降低似乎是唯一与CKD患者肾脏疾病进展明确相关的脂质变化。高密度脂蛋白系统与CKD的发展和进展之间的联系也得到了与高密度脂素代谢相关的遗传性肾脏改变的支持,包括APOA1、APOE、APOL和LCAT基因的突变。其中,与LCAT缺乏相关的肾脏疾病具有很好的特征,在LCAT缺乏携带者中检测到的脂质异常反映了在CKD患者中观察到的异常,在获得性LCAT缺乏中也存在。这篇综述总结了CKD中高密度脂蛋白结构和功能的主要变化,以及高密度脂素代谢的遗传变化如何与肾功能障碍有关。最后,回顾了将HDL系统作为减缓CKD进展的可能策略的可能性。
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引用次数: 1
Low HDL-c levels at admission are associated with greater severity and worse clinical outcomes in patients with COVID-19 disease 入院时低HDL-c水平与COVID-19疾病患者更严重和更差的临床结果相关
IF 1.6 Pub Date : 2023-06-01 DOI: 10.1016/j.athplu.2023.01.002
Sandra Parra , Mireia Saballs , Mark DiNubile , Mireia Feliu , Simona Iftimie , Laia Revuelta , Raul Pavón , Alba Àvila , Susan Levinson , Antoni Castro

Background and aims

HDL particles may act to buffer host cells from excessive inflammatory mediators. The aim of this study is to investigate if the lipid profile provides a prognostic biomarker for COVID-19 outcomes.

Methods

This was a prospective study of the characteristics of 125 adult COVID-19 patients with a lipid profile performed on the day of admission analyzed with regard to clinical outcomes.

Results

Seventy-seven patients (61.2%) were men, with a mean age of 66.3 (15.6) years. 54.1% had bilateral pneumonia. The all-cause mortality rate during hospitalization was 20.8%. We found a direct association between more severe disease assessed by the WHO classification, admission to the ICU and death with more pronounced lymphopenia, higher levels of CRP, ferritin (p < 0.001), D-dímer and lactate dehydrogenase (LDH) all statistically significant. Lower leves of HDL-c and LDL-c were also associated with a worse WHO classification, ICU admission, and death,. HDL-c levels were inversely correlated with inflammatory markers CRP (r = −0.333; p < 0.001), ferritin (r = −0.354; p < 0.001), D-dímer (r = −0.214; p < 0.001), LDH (r = −0.209; p < 0.001. LDL-c levels were significantly associated with CRP (r = −0.320; p < 0.001) and LDH (r = −0.269; p < 0.001). ROC curves showed that HDL [AUC = 0.737(0.586–0.887), p = 0.005] and lymphocytes [AUC = 0.672(0.497–0.847], p < 0.043] had the best prognostic accuracy to predict death. In a multivariate analysis, HDL-c (β = −0.146(0.770–0.971), p = 0.014) and urea (β = 0.029(1.003–1.057), p = 0.027) predicted mortality.

Conclusion

Hypolipidemia including HDL levels at admission identifies patients with a higher risk of death and worse clinical manifestations who may require more intensive care.

背景和目的高密度脂蛋白颗粒可能起到缓冲宿主细胞免受过度炎症介质影响的作用。本研究的目的是调查脂质概况是否为新冠肺炎结果提供了预后生物标志物。方法对125例成年新冠肺炎患者的特征进行前瞻性研究,并对其入院当天的血脂状况进行临床结果分析。结果77例(61.2%)患者为男性,平均年龄66.3(15.6)岁。54.1%为双侧肺炎。住院期间的全因死亡率为20.8%。我们发现,世界卫生组织分类评估的更严重的疾病、入住重症监护室与更明显的淋巴细胞减少症、更高水平的CRP、铁蛋白(p<0.001)、D-Dímer和乳酸脱氢酶(LDH)死亡之间存在直接关联,所有这些都具有统计学意义。HDL-c和LDL-c水平较低也与更差的世界卫生组织分类、入住ICU和死亡相关,。HDL-c水平与炎症标志物CRP(r=−0.333;p<;0.001)、铁蛋白(r=–0.354;p&llt;0.001。LDL-c水平与CRP(r=-0.320;p<;0.001)和LDH(r=-0.269;p&llt;0.001)显著相关。ROC曲线显示,HDL[AUC=0.737(0.586–0.887),p=0.005]和淋巴细胞[AUC=0.672(0.497–0.847],p<;0.043]具有预测死亡的最佳预后准确性。在多变量分析中,HDL-c(β=−0.146(0.770–0.971),p=0.014)和尿素(β=0.029(1.003-1.057),p=0.027)预测死亡率。结论入院时的低脂血症(包括高密度脂蛋白水平)可识别出死亡风险更高、临床表现更差的患者,这些患者可能需要更多的重症监护。
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引用次数: 3
Young women with familial hypercholesterolemia have higher LDL-cholesterol burden than men: Novel data using repeated measurements during 12-years follow-up 患有家族性高胆固醇血症的年轻女性比男性有更高的ldl -胆固醇负担:在12年随访期间使用重复测量的新数据
IF 1.6 Pub Date : 2023-03-01 DOI: 10.1016/j.athplu.2023.01.001
Anja K. Johansen , Martin P. Bogsrud , Jacob J. Christensen , Amanda Rundblad , Ingunn Narverud , Stine Ulven , Gisle Langslet , Kjetil Retterstøl , Kirsten B. Holven

Background and aims

The concentration and the duration of exposure to low-density lipoprotein cholesterol (LDL-C) (LDL-C burden) is an important determinant of risk for cardiovascular disease and thresholds has recently been estimated. Individuals with familial hypercholesterolemia (FH) have increased risk of premature cardiovascular disease. The overall aim of the present study was to describe differences in LDL-C level and LDL-C burden in females and males with FH visiting an outpatient lipid clinic from a young age, using multiple LDL-C measurements during a follow-up time of 12 years. First, we aimed to study if the LDL-C concentration and the LDL-C burden is different between females and males at ages 0–10, 10–20, 20–30 and >30 years. Second, we aimed to estimate the subject-specific LDL-C burden at age 19 and 30 years, and the proportion of female and male patients that reach suggested LDL-C thresholds indicating high risk of ASCVD.

Methods

Data was retrospectively collected from medical records of 438 subjects (207 girls and 231 boys) with FH, referred to the Lipid Clinic, Oslo University Hospital below the age of 19 years. The LDL-C burden was estimated based on repeated LDL-C measurements over time.

Results

Subjects were followed over a period of mean 12.0 (SD 7.0) years, with median 10 years (7–17; 25–75 percentiles, minimum 2), with median 6 (4–9; 25–75 percentiles, minimum 2) available LDL-C measurements, starting at mean age 11 (SD 3.9) years. There was a difference in both LDL-C and LDL-C burden between sexes at different ages. On average, males had lower LDL-C over time, although this difference was less pronounced with age and males also had lower estimated LDL-C burden over time, and this difference was further exacerbated with age.

Conclusion

Our study shows that young women with FH have a higher LDL-C burden than their male counterparts, potentially explaining the increased excess CVD risk seen among these. It underscores the importance of careful-follow up and early treatment initiation both prior to and after pregnancies in order to limit statin-free periods.

背景和目的低密度脂蛋白胆固醇(LDL-C)的浓度和暴露时间是心血管疾病风险的重要决定因素,最近已经估计了阈值。家族性高胆固醇血症(FH)患者过早患心血管疾病的风险增加。本研究的总体目的是通过在12年的随访时间内进行多次LDL-C测量,描述年轻时到门诊脂质诊所就诊的FH女性和男性的LDL-C水平和LDL-C负荷的差异。首先,我们旨在研究在0-10岁、10-20岁、20-30岁和>;30年。其次,我们旨在估计19岁和30岁时受试者的特定LDL-C负荷,以及达到建议的LDL-C阈值的女性和男性患者的比例,这表明ASCVD.方法回顾性收集438名FH受试者(207名女孩和231名男孩)的医疗记录,这些受试者在19岁以下转诊到奥斯陆大学医院脂质诊所。LDL-C负荷是基于随时间的重复LDL-C测量来估计的。结果受试者平均随访12.0年(SD 7.0),中位随访时间为10年(7-17;25-75个百分点,最小2年),平均年龄11岁(SD 3.9)开始,中位LDL-C测量可用时间为6年(4-9;25-35个百分点,最低2年)。LDL-C和LDL-C负荷在不同年龄的性别之间存在差异。平均而言,随着时间的推移,男性的LDL-C较低,尽管这种差异随着年龄的增长而不那么明显,而且随着时间的增长,男性的估计LDL-C负担也较低,而且这种差异随着时间的增加而进一步加剧。结论我们的研究表明,患有FH的年轻女性比男性具有更高的LDL-C负担,这可能解释了这些女性心血管疾病风险增加的原因。它强调了在怀孕前后仔细随访和早期治疗的重要性,以限制无他汀类药物的时期。
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引用次数: 4
Associations of urinary isoprostanes with measures of subclinical atherosclerosis: The Multi-Ethnic Study of Atherosclerosis (MESA) 尿异前列腺素与亚临床动脉粥样硬化的关系:动脉粥样硬化的多民族研究(MESA)
IF 1.6 Pub Date : 2023-03-01 DOI: 10.1016/j.athplu.2022.12.002
Ryan L. Wallace , Oluseye Ogunmoroti , Di Zhao , Dhananjay Vaidya , Amir Heravi , Eliseo Guallar , Chiadi E. Ndumele , Joao A.C. Lima , Pamela Ouyang , Matthew J. Budoff , Matthew Allison , Isac Thomas , Oluwaseun E. Fashanu , Ron Hoogeveen , Wendy S. Post , Erin D. Michos

Background

Urinary isoprostanes are markers of systemic oxidative stress, which is implicated in the pathogenesis of atherosclerotic cardiovascular disease (ASCVD). Coronary artery calcium (CAC), thoracic aortic calcium (TAC) and carotid plaque are measure subclinical atherosclerosis and prognosticate ASCVD risk. We examined the associations between urinary isoprostane levels and measures of plaque prevalence, burden, incidence and progression across three vascular beds in a cohort from the Multi-Ethnic Study of Atherosclerosis.

Methods

Urinary levels of 8-isoprostane and 2,3-dinor-8-F2-isoprostane were measured in 1089 participants (mean ± SD 62 ± 8 years, 48% women) at baseline. Participants underwent computed tomography for CAC and TAC, and duplex ultrasound for carotid plaque. TAC and CAC were reassessed at 2.4 and 10 years, respectively. Regression models were adjusted for CVD risk factors.

Results

In adjusted models, there were no significant associations between isoprostane levels with CAC prevalence or progression. Highest versus lowest tertile of 8-isoprostane was associated with 28% lower prevalence of descending TAC at baseline [prevalence ratio (PR) 0.72 95% CI (0.56, 0.94)], while 1-SD higher 2,3-dinor-8-F2-isoprostane was associated with 96% higher incident ascending TAC at follow-up [Relative Risk 1.96 (1.24, 3.09)]. Highest versus lowest tertile of isoprostane measures were associated with 22% higher prevalence of carotid plaque [(PR 1.22 (1.04, 1.45)] and 14% difference [3,26] in greater extent of carotid plaque at baseline.

Conclusions

Higher urinary isoprostanes were inconsistently associated with some measures of subclinical atherosclerosis by imaging. This suggests a limited role of urinary isoprostane levels as a prognostic marker for the development of ASCVD.

Trial registration

The MESA cohort design is registered at clinicaltrials.gov as follows: https://clinicaltrials.gov/ct2/show/NCT00005487.

背景尿异丙肾上腺素是全身氧化应激的标志物,与动脉粥样硬化性心血管疾病(ASCVD)的发病机制有关。冠状动脉钙(CAC)、胸主动脉钙(TAC)和颈动脉斑块是亚临床动脉粥样硬化和预测ASCVD风险的指标。我们在动脉粥样硬化多民族研究的一个队列中,研究了尿异丙肾上腺素水平与三个血管床上斑块患病率、负荷、发病率和进展指标之间的关系。方法在基线时测量1089名参与者(平均值±SD 62±8岁,48%为女性)的尿8-异丙酮和2,3-二Nor-8-F2-异丙酮水平。参与者接受了CAC和TAC的计算机断层扫描,以及颈动脉斑块的双重超声检查。TAC和CAC分别在2.4年和10年时重新评估。对CVD危险因素的回归模型进行了调整。结果在调整后的模型中,异丙肾上腺素水平与CAC患病率或进展之间没有显著相关性。8-异丙肾上腺素的最高和最低三分位数与基线时TAC下降的患病率降低28%相关[患病率(PR)0.72 95%CI(0.56、0.94)],而1-SD较高的2,3-二nor-8-F2-异丙酮与随访时TAC上升事件增加96%有关[相对风险1.96(1.24,3.09)]。异丙酮测量的最高和最低三分位数与颈动脉斑块发生率增加22%有关[(PR 1.22(1.04,1.45)],与基线时颈动脉斑块扩大程度的14%差异[3,26]。结论高尿异丙肾上腺素与某些亚临床动脉粥样硬化的影像学指标不一致。这表明尿异丙肾上腺素水平作为ASCVD发展的预后标志物的作用有限。试验注册MESA队列设计在clinicaltrials.gov上注册如下:https://clinicaltrials.gov/ct2/show/NCT00005487.
{"title":"Associations of urinary isoprostanes with measures of subclinical atherosclerosis: The Multi-Ethnic Study of Atherosclerosis (MESA)","authors":"Ryan L. Wallace ,&nbsp;Oluseye Ogunmoroti ,&nbsp;Di Zhao ,&nbsp;Dhananjay Vaidya ,&nbsp;Amir Heravi ,&nbsp;Eliseo Guallar ,&nbsp;Chiadi E. Ndumele ,&nbsp;Joao A.C. Lima ,&nbsp;Pamela Ouyang ,&nbsp;Matthew J. Budoff ,&nbsp;Matthew Allison ,&nbsp;Isac Thomas ,&nbsp;Oluwaseun E. Fashanu ,&nbsp;Ron Hoogeveen ,&nbsp;Wendy S. Post ,&nbsp;Erin D. Michos","doi":"10.1016/j.athplu.2022.12.002","DOIUrl":"10.1016/j.athplu.2022.12.002","url":null,"abstract":"<div><h3>Background</h3><p>Urinary isoprostanes are markers of systemic oxidative stress, which is implicated in the pathogenesis of atherosclerotic cardiovascular disease (ASCVD). Coronary artery calcium (CAC), thoracic aortic calcium (TAC) and carotid plaque are measure subclinical atherosclerosis and prognosticate ASCVD risk. We examined the associations between urinary isoprostane levels and measures of plaque prevalence, burden, incidence and progression across three vascular beds in a cohort from the Multi-Ethnic Study of Atherosclerosis.</p></div><div><h3>Methods</h3><p>Urinary levels of 8-isoprostane and 2,3-dinor-8-F<sub>2</sub>-isoprostane were measured in 1089 participants (mean ± SD 62 ± 8 years, 48% women) at baseline. Participants underwent computed tomography for CAC and TAC, and duplex ultrasound for carotid plaque. TAC and CAC were reassessed at 2.4 and 10 years, respectively. Regression models were adjusted for CVD risk factors.</p></div><div><h3>Results</h3><p>In adjusted models, there were no significant associations between isoprostane levels with CAC prevalence or progression. Highest versus lowest tertile of 8-isoprostane was associated with 28% lower prevalence of descending TAC at baseline [prevalence ratio (PR) 0.72 95% CI (0.56, 0.94)], while 1-SD higher 2,3-dinor-8-F<sub>2</sub>-isoprostane was associated with 96% higher incident ascending TAC at follow-up [Relative Risk 1.96 (1.24, 3.09)]. Highest versus lowest tertile of isoprostane measures were associated with 22% higher prevalence of carotid plaque [(PR 1.22 (1.04, 1.45)] and 14% difference [3,26] in greater extent of carotid plaque at baseline.</p></div><div><h3>Conclusions</h3><p>Higher urinary isoprostanes were inconsistently associated with some measures of subclinical atherosclerosis by imaging. This suggests a limited role of urinary isoprostane levels as a prognostic marker for the development of ASCVD.</p></div><div><h3>Trial registration</h3><p>The MESA cohort design is registered at <span>clinicaltrials.gov</span><svg><path></path></svg> as follows: <span>https://clinicaltrials.gov/ct2/show/NCT00005487</span><svg><path></path></svg>.</p></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10037087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9561063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Dyslipidemia and the preventive potential in the Greenlandic population 格陵兰人口血脂异常及其预防潜力
IF 1.6 Pub Date : 2023-03-01 DOI: 10.1016/j.athplu.2022.12.003
Johan Skov Bundgaard , Marit E. Jørgensen , Kristine Andersen , Henning Bundgaard , Uka Wilhjelm Geisler , Michael Lynge Pedersen

Background

Low-density lipoprotein cholesterol (LDL-C) is a well-established risk factor for development of cardiovascular diseases. Based on available clinical data, we aimed to investigate the plasma lipid profile in the Greenlandic population, the proportion on cholesterol-lowering treatment and the adherence to local indications for cholesterol-lowering therapy.

Methods

This is an observational cross-sectional study of the adult (≥21 years) Greenlandic population with focus on clinically determined lipid levels from 2017 to early 2022. We investigated levels of dyslipidemia and assessed cholesterol-lowering medication usage in individuals with an indication according to current Greenlandic guidelines, which include a) LDL-C >5 mmol/l, b) diabetes, c) diagnosed atherosclerotic disease and 4) a SCORE2 >7.5%.

Results

In the adult Greenlandic population of 40,565 individuals a lipid profile was available in 13,895 with a mean LDL-C of 3.0 mmol/L and 976 (7%) had a LDL-C >5 mmol/l. One or more indications for cholesterol-lowering medication was present in 3988 individuals and a total of 5464 adult Greenlanders either fulfilled local criteria for statin therapy or received a statin (some without current indication) and among these, 2232 (41%) individuals received no statin.

Conclusion

These findings indicate that clinically significant dyslipidemia is common in the adult Greenlandic population and that the cardiovascular preventive potential of cholesterol-lowering therapy is currently underutilized.

背景低密度脂蛋白胆固醇(LDL-C)是心血管疾病发展的一个公认的危险因素。根据现有的临床数据,我们旨在研究格陵兰人群的血脂状况、胆固醇降低治疗的比例以及对胆固醇降低治疗局部适应症的依从性。方法这是一项针对成年(≥21岁)格陵兰人群的观察性横断面研究,重点关注2017年至2022年初临床测定的脂质水平。我们调查了根据当前格陵兰指南(包括a)LDL-C>;5mmol/l,b)糖尿病,c)诊断为动脉粥样硬化性疾病和4)SCORE2>;结果在40565人的成年格陵兰人群中,13895人的平均LDL-C为3.0mmol/L,976人(7%)的LDL-C>;5毫摩尔/升。3988名患者出现了一种或多种降胆固醇药物的适应症,共有5464名成年格陵兰人符合当地他汀类药物治疗标准或接受了他汀类药物(有些患者目前没有适应症),其中2232人(41%)未接受他汀类药物。结论这些发现表明,临床上显著的血脂异常在成年格陵兰人中很常见,而降胆固醇治疗的心血管预防潜力目前尚未得到充分利用。
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引用次数: 1
Lp(a) does not affect intima media thickness in hypercholesterolemic children –a retrospective cross sectional study Lp(a)不影响高胆固醇血症儿童的内膜中膜厚度——一项回顾性横断面研究
IF 1.6 Pub Date : 2023-03-01 DOI: 10.1016/j.athplu.2022.11.001
Oliver Helk , Andreas Böck , Claudia Stefanutti , Kurt Widhalm

Purpose

Combined hyperlipidaemia results in premature atherosclerosis and a high burden of cardiovascular morbidity and mortality. Early identification of highly affected subjects within this population is of utmost importance to enable informed treatment decisions. The measurement of intima media thickness (IMT) is a readily available, non-invasive method to investigate evidence of early atherosclerosis. To assess the usefulness of this method in pediatric subjects with hypercholesterolemia, we here examined a possible interaction of LDL-C and Lp(a) on IMT.

Methods

Blood lipids (Lp(a), LDL-cholesterol, total cholesterol, triglycerides, high density lipoprotein (HDL) -cholesterol, apolipoprotein A1, apolipoprotein B), anthropometric parameters (age, height, weight, body mass index (BMI)) and possibly existing early evidence of atherosclerotic lesions measured by intima media thickness (IMT zscore).as a surrogate parameter was examined retrospectively in 113 children and adolescents (aged 1–18 years) with elevated Lp(a) and/or LDL-cholesterol (Lp(a) > 30 mg/dL, LDL>130 mg/dL). Furthermore, we compared hsCRP levels between groups.

Results

There were no significant differences in IMT Zscore or hsCRP between groups. Regression analysis did not reveal a statistically significant interaction between Lp(a) and LDL-C.

Conclusions

At the age of 6–18 years, we found no significant differences in early markers of atherosclerosis between subjects with high Lp(a)- and/or high LDL-cholesterol with no detectable synergistic effects between the two lipoproteins.

目的合并高脂血症可导致早期动脉粥样硬化和心血管疾病的高发病率和死亡率。早期识别该人群中受影响严重的受试者对于做出知情的治疗决定至关重要。内膜-中膜厚度(IMT)的测量是一种容易获得的、非侵入性的方法,用于研究早期动脉粥样硬化的证据。为了评估这种方法在患有高胆固醇血症的儿童受试者中的有用性,我们在这里检查了LDL-C和Lp(a)对IMT的可能相互作用,人体测量参数(年龄、身高、体重、体重指数(BMI))以及通过内膜-中膜厚度(IMT-zscore)测量的动脉粥样硬化病变的可能存在的早期证据。作为替代参数,在113名Lp(a)和/或LDL胆固醇升高的儿童和青少年(1-18岁)中进行了回顾性检查;30mg/dL、LDL>;130mg/dL)。此外,我们比较了各组之间的hsCRP水平。结果各组间IMT-Zscore和hsCRP无显著性差异。回归分析没有显示Lp(a)和LDL-C之间存在统计学上显著的相互作用。结论在6-18岁时,我们发现高Lp(a)和/或高LDL胆固醇受试者之间动脉粥样硬化的早期标志物没有显著差异,两种脂蛋白之间没有可检测的协同作用。
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引用次数: 0
Dendritic cell marker Clec4a4 deficiency limits atherosclerosis progression 树突状细胞标志物Clec4a4缺乏限制动脉粥样硬化进展
IF 1.6 Pub Date : 2023-03-01 DOI: 10.1016/j.athplu.2022.12.001
Rossella Bellini , Annalisa Moregola , Jasmine Nour , Yoann Rombouts , Olivier Neyrolles , Patrizia Uboldi , Fabrizia Bonacina , Giuseppe Danilo Norata

Background and aims

Atherogenesis results from altered lipid metabolism and impaired immune response. Emerging evidence has suggested that dendritic cells (DCs) participate to atherosclerosis-related immune response, but their impact is scarcely characterized. Clec4a4 or DCIR2 (Dendritic cell immunoreceptor 2) is a C-type lectin receptor, mainly expressed by CD8α DCs, able to modulate T cell immunity. However, whether this DC subset could play a role in the atherogenesis is still poorly understood. Thus, the aim of this study is to investigate whether the absence of Clec4a4 could affect atherosclerosis-related immune response and atherosclerosis itself.

Methods

Dcir2−/− Ldlr−/− and Ldlr−/− mice were fed a standard diet or cholesterol-enriched diet for 12 weeks. Subsequently, the profile of circulating and lymph nodes-resident immune cells was investigated together with the analysis of plasma lipid levels and atherosclerotic plaque extension in the aorta.

Results

Here, we show that Clec4a4 expression is downregulated under hypercholesterolemia and its deficiency in Ldlr−/− mice results in the reduction of atherosclerotic plaque formation, together with altered lipid metabolism and impaired myeloid immune cell distribution.

Conclusions

Our findings suggest a pro-atherosclerotic role of Clec4a4 in experimental atherosclerosis.

背景和目的动脉粥样硬化是由脂质代谢改变和免疫反应受损引起的。新出现的证据表明,树突状细胞(DC)参与动脉粥样硬化相关的免疫反应,但其影响几乎没有特征。Clec4a4或DCIR2(树突状细胞免疫受体2)是一种C型凝集素受体,主要由CD8α−DCs表达,能够调节T细胞免疫。然而,这一DC亚群是否在动脉粥样硬化形成中发挥作用仍知之甚少。因此,本研究的目的是研究Clec4a4的缺失是否会影响动脉粥样硬化相关的免疫反应和动脉粥样硬化本身。方法给Dcir2−/−Ldlr−/−和Ldlr–/−小鼠喂食标准饮食或高胆固醇饮食12周。随后,对循环和淋巴结固有免疫细胞的分布进行了研究,同时对血浆脂质水平和主动脉中动脉粥样硬化斑块的扩展进行了分析。结果在这里,我们发现Clec4a4的表达在高胆固醇血症下下调,其在Ldlr−/−小鼠中的缺乏导致动脉粥样硬化斑块形成减少,同时脂质代谢改变和骨髓免疫细胞分布受损。结论我们的研究结果表明Clec4a4在实验性动脉粥样硬化中具有促动脉粥样硬化作用。
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引用次数: 2
Clinical characteristics and cardiovascular outcomes among young patients with acute myocardial infarction in Kerala, India: A secondary analysis of ACS QUIK trial 印度喀拉拉邦年轻急性心肌梗死患者的临床特征和心血管结局:ACS QUIK试验的二次分析
IF 1.6 Pub Date : 2022-12-01 DOI: 10.1016/j.athplu.2022.08.003
Haitham Khraishah , Lina Karout , Sun Young Jeong , Barrak Alahmad , Abdelrahman AlAshqar , Matthew J. Belanger , Francine K. Welty , Erin D. Michos , Mazen Albaghdadi

Background

Limited data exist on the risk profile and outcomes among young patients with acute myocardial infarction(AMI) in low-and middle-income countries(LMICs). This study explored differences in the clinical characteristics, medical care, and outcomes of AMI in young adults in India with a subanalysis focusing on sex disparities amongst the young.

Methods

Using the Acute Coronary Syndrome Quality Improvement in Kerala trial database, we compared baseline characteristics, management, and outcomes amongst the young patients(≤50 years) and their older counterparts. The primary outcomes were the rates of in-hospital and 30-day composite of in-hospital major adverse cardiovascular events(MACE).

Results

Of the 21,374 adults enrolled, 4762(22%) were young, of which 614 (12.9%) were females. Young patients with AMI were more likely to be smokers(41.9% vs. 27.8%;P < 0.001) and undergo coronary angiography (66.3%vs.57.3%;P < 0.001) and percutaneous coronary intervention (PCI)(57.5% vs. 47.0%;P < 0.001), compared to older patients. After adjustment for potential confounders, younger patients had a lower likelihood of in-hospital (RR = 0.49; 95%CI 0.40–0.61;P < 0.001) and 30-day MACE (RR = 0.54; 95%CI 0.46–0.64;P < 0.001). Subgroup analysis comparing young males and females revealed worse cardiovascular risk profile among young women except for smoking. In-hospital MACE(RR = 1.60; 95%CI, 1.0–2.45;P = 0.048) were higher for young women compared to men.

Conclusion

Young AMI patients had higher prevalence of modifiable risk factors, were more likely to receive reperfusion therapy, and had better short and intermediate outcomes, compared to older patients. Compared to young men with AMI, young women had worse cardiovascular risk profile, were less likely to be treated with diagnostic angiography or PCI and experienced higher in-hospital death and MACE.

背景:关于中低收入国家(LMICs)年轻急性心肌梗死(AMI)患者的风险概况和结局的数据有限。本研究探讨了印度年轻人急性心肌梗死的临床特征、医疗护理和结果的差异,并对年轻人的性别差异进行了亚分析。方法使用喀拉拉邦急性冠状动脉综合征质量改善试验数据库,我们比较了年轻患者(≤50岁)和老年患者的基线特征、管理和结局。主要结局是住院和30天住院主要心血管不良事件(MACE)的发生率。结果在21374名成人中,4762名(22%)为年轻人,其中614名(12.9%)为女性。年轻AMI患者吸烟的可能性更大(41.9% vs. 27.8%;P <0.001)并行冠状动脉造影(66.3%vs.57.3%;P <0.001)和经皮冠状动脉介入治疗(PCI)(57.5% vs. 47.0%;P <0.001),与老年患者相比。调整潜在混杂因素后,年轻患者住院的可能性较低(RR = 0.49;95%CI 0.40-0.61;P <0.001)和30天MACE (RR = 0.54;95%CI 0.46-0.64;P <0.001)。比较年轻男性和女性的亚组分析显示,除了吸烟外,年轻女性的心血管风险状况更差。院内MACE(RR = 1.60;95%CI, 1.0-2.45;P = 0.048),年轻女性的死亡率高于男性。结论与老年AMI患者相比,年轻AMI患者可改变的危险因素患病率更高,接受再灌注治疗的可能性更大,中短期预后更好。与患有AMI的年轻男性相比,年轻女性的心血管风险状况更差,接受诊断性血管造影或PCI治疗的可能性更小,住院死亡率和MACE更高。
{"title":"Clinical characteristics and cardiovascular outcomes among young patients with acute myocardial infarction in Kerala, India: A secondary analysis of ACS QUIK trial","authors":"Haitham Khraishah ,&nbsp;Lina Karout ,&nbsp;Sun Young Jeong ,&nbsp;Barrak Alahmad ,&nbsp;Abdelrahman AlAshqar ,&nbsp;Matthew J. Belanger ,&nbsp;Francine K. Welty ,&nbsp;Erin D. Michos ,&nbsp;Mazen Albaghdadi","doi":"10.1016/j.athplu.2022.08.003","DOIUrl":"10.1016/j.athplu.2022.08.003","url":null,"abstract":"<div><h3>Background</h3><p>Limited data exist on the risk profile and outcomes among young patients with acute myocardial infarction(AMI) in low-and middle-income countries(LMICs). This study explored differences in the clinical characteristics, medical care, and outcomes of AMI in young adults in India with a subanalysis focusing on sex disparities amongst the young.</p></div><div><h3>Methods</h3><p>Using the Acute Coronary Syndrome Quality Improvement in Kerala trial database, we compared baseline characteristics, management, and outcomes amongst the young patients(≤50 years) and their older counterparts. The primary outcomes were the rates of in-hospital and 30-day composite of in-hospital major adverse cardiovascular events(MACE).</p></div><div><h3>Results</h3><p>Of the 21,374 adults enrolled, 4762(22%) were young, of which 614 (12.9%) were females. Young patients with AMI were more likely to be smokers(41.9% vs. 27.8%;<em>P</em> &lt; 0.001) and undergo coronary angiography (66.3%vs.57.3%;<em>P</em> &lt; 0.001) and percutaneous coronary intervention (PCI)(57.5% vs. 47.0%;<em>P</em> &lt; 0.001), compared to older patients. After adjustment for potential confounders, younger patients had a lower likelihood of in-hospital (RR = 0.49; 95%CI 0.40–0.61;<em>P</em> &lt; 0.001) and 30-day MACE (RR = 0.54; 95%CI 0.46–0.64;<em>P</em> &lt; 0.001). Subgroup analysis comparing young males and females revealed worse cardiovascular risk profile among young women except for smoking. In-hospital MACE(RR = 1.60; 95%CI, 1.0–2.45;<em>P</em> = 0.048) were higher for young women compared to men.</p></div><div><h3>Conclusion</h3><p>Young AMI patients had higher prevalence of modifiable risk factors, were more likely to receive reperfusion therapy, and had better short and intermediate outcomes, compared to older patients. Compared to young men with AMI, young women had worse cardiovascular risk profile, were less likely to be treated with diagnostic angiography or PCI and experienced higher in-hospital death and MACE.</p></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/eb/c4/main.PMC9833239.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10540452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
TACE/ADAM17 substrates associate with ACS (Ep-CAM, HB-EGF) and follow-up MACE (TNFR1 and TNFR2) TACE/ADAM17底物与ACS (Ep-CAM, HB-EGF)和后续MACE (TNFR1和TNFR2)相关
IF 1.6 Pub Date : 2022-12-01 DOI: 10.1016/j.athplu.2022.09.001
Melody Chemaly , Roisin McAllister , Aaron Peace , Anthony John Bjourson , Steve Watterson , Andrew Parton , Matthias Clauss , Victoria McGilligan

Background and aims

TACE/ADAM17 is a membrane bound metalloprotease, which cleaves substrates involved in immune and inflammatory responses and plays a role in coronary artery disease (CAD). We measured TACE and its substrates in CAD patients to identify potential biomarkers within this molecular pathway with potential for acute coronary syndrome (ACS) and major adverse cardiovascular events (MACE) prediction.

Methods

Blood samples were obtained from consecutive patients (n = 229) with coronary angiographic evidence of CAD admitted with ACS or electively. MACE were recorded after a median 3-year follow-up. Controls (n = 115) had a <10% CAD risk as per the HeartSCORE. TACE and TIMP3 protein and mRNA levels were measured by ELISA and RT-qPCR respectively. TACE substrates were measured using a multiplex proximity extension assay.

Results

TACE mRNA and cell protein levels (p < 0.01) and TACE substrates LDLR (p = 0.006), TRANCE (p = 0.045), LAG-3 (p < 0.001) and ACE2 (p < 0.001) plasma levels were significantly higher in CAD patients versus controls. TACE inhibitor TIMP3 mRNA levels were significantly lower in CAD patients and tended to be lower in the ACS population (p < 0.05). TACE substrates TNFR1 (OR:3.237,CI:1.514–6.923,p = 0.002), HB-EGF (OR:0.484,CI:0.288–0.813,p = 0.006) and Ep-CAM (OR:0.555,CI:0.327–0.829,p = 0.004) accurately classified ACS patients with HB-EGF and Ep-CAM levels being lower compared to electively admitted patients. TNFR1 (OR:2.317,CI:1.377–3.898,p = 0.002) and TNFR2 (OR:1.902,CI:1.072–3.373,p = 0.028) were significantly higher on admission in those patients who developed MACE within 3 years.

Conclusions

We demonstrate a possible role of TACE substrates LAG-3, HB-EGF and Ep-CAM in atherosclerotic plaque development and stability. We also underline the importance of measuring TNFR1 and TNFR2 earlier than previously appreciated for MACE prediction. We report an important role of TIMP3 in regulating TACE levels.

背景和aimsTACE/ADAM17是一种膜结合的金属蛋白酶,它可以切割参与免疫和炎症反应的底物,并在冠状动脉疾病(CAD)中发挥作用。我们测量了CAD患者的TACE及其底物,以确定该分子途径中具有预测急性冠脉综合征(ACS)和主要不良心血管事件(MACE)潜力的潜在生物标志物。方法采集连续229例冠心病冠脉造影证实合并ACS或选择性冠脉造影证实的患者的血样。中位随访3年后记录MACE。根据HeartSCORE,对照组(n = 115)患冠心病的风险为10%。ELISA和RT-qPCR分别检测各组TACE和TIMP3蛋白及mRNA水平。TACE底物采用多重接近延伸法测定。结果stace mRNA和细胞蛋白水平(p <0.01)和TACE底物LDLR (p = 0.006)、TRANCE (p = 0.045)、LAG-3 (p <0.001)和ACE2 (p <0.001),冠心病患者血浆水平明显高于对照组。TACE抑制剂TIMP3 mRNA水平在CAD患者中显著降低,在ACS人群中趋于降低(p <0.05)。TACE底物TNFR1 (OR:3.237,CI: 1.514-6.923,p = 0.002)、HB-EGF (OR:0.484,CI: 0.288-0.813,p = 0.006)和Ep-CAM (OR:0.555,CI: 0.327-0.829,p = 0.004)准确分类了与选择性住院患者相比HB-EGF和Ep-CAM水平较低的ACS患者。3年内发生MACE的患者入院时TNFR1 (OR:2.317,CI: 1.377-3.898,p = 0.002)和TNFR2 (OR:1.902,CI: 1.072-3.373,p = 0.028)显著升高。结论:我们证明了TACE底物LAG-3、HB-EGF和Ep-CAM可能在动脉粥样硬化斑块的发展和稳定中起作用。我们还强调了比以前更早测量TNFR1和TNFR2对MACE预测的重要性。我们报道了TIMP3在调节TACE水平中的重要作用。
{"title":"TACE/ADAM17 substrates associate with ACS (Ep-CAM, HB-EGF) and follow-up MACE (TNFR1 and TNFR2)","authors":"Melody Chemaly ,&nbsp;Roisin McAllister ,&nbsp;Aaron Peace ,&nbsp;Anthony John Bjourson ,&nbsp;Steve Watterson ,&nbsp;Andrew Parton ,&nbsp;Matthias Clauss ,&nbsp;Victoria McGilligan","doi":"10.1016/j.athplu.2022.09.001","DOIUrl":"10.1016/j.athplu.2022.09.001","url":null,"abstract":"<div><h3>Background and aims</h3><p>TACE/ADAM17 is a membrane bound metalloprotease, which cleaves substrates involved in immune and inflammatory responses and plays a role in coronary artery disease (CAD). We measured TACE and its substrates in CAD patients to identify potential biomarkers within this molecular pathway with potential for acute coronary syndrome (ACS) and major adverse cardiovascular events (MACE) prediction.</p></div><div><h3>Methods</h3><p>Blood samples were obtained from consecutive patients (n = 229) with coronary angiographic evidence of CAD admitted with ACS or electively. MACE were recorded after a median 3-year follow-up. Controls (n = 115) had a &lt;10% CAD risk as per the HeartSCORE. TACE and TIMP3 protein and mRNA levels were measured by ELISA and RT-qPCR respectively. TACE substrates were measured using a multiplex proximity extension assay.</p></div><div><h3>Results</h3><p><em>TACE</em> mRNA and cell protein levels (<em>p &lt; 0.01</em>) and TACE substrates LDLR (<em>p = 0.006</em>), TRANCE (<em>p = 0.045</em>), LAG-3 (<em>p &lt; 0.001</em>) and ACE2 (<em>p &lt; 0.001</em>) plasma levels were significantly higher in CAD patients versus controls. TACE inhibitor TIMP3 mRNA levels were significantly lower in CAD patients and tended to be lower in the ACS population (<em>p &lt; 0.05</em>). TACE substrates TNFR1 (OR:3.237,CI:1.514–6.923,<em>p = 0.002</em>), HB-EGF (OR:0.484,CI:0.288–0.813,<em>p = 0.006</em>) and Ep-CAM (OR:0.555,CI:0.327–0.829,<em>p = 0.004</em>) accurately classified ACS patients with HB-EGF and Ep-CAM levels being lower compared to electively admitted patients. TNFR1 (OR:2.317,CI:1.377–3.898,<em>p = 0.002</em>) and TNFR2 (OR:1.902,CI:1.072–3.373,<em>p = 0.028</em>) were significantly higher on admission in those patients who developed MACE within 3 years.</p></div><div><h3>Conclusions</h3><p>We demonstrate a possible role of TACE substrates LAG-3, HB-EGF and Ep-CAM in atherosclerotic plaque development and stability. We also underline the importance of measuring TNFR1 and TNFR2 earlier than previously appreciated for MACE prediction. We report an important role of TIMP3 in regulating TACE levels.</p></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7c/7e/main.PMC9833260.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10540450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Periostin contributes to the adventitial remodeling of atherosclerosis by activating adventitial fibroblasts 骨膜蛋白通过激活外膜成纤维细胞参与动脉粥样硬化的外膜重塑
IF 1.6 Pub Date : 2022-12-01 DOI: 10.1016/j.athplu.2022.10.001
Zhonghua Wang , Guoliang Li , Mingpeng Li , Lu Hu , Zichen Hao , Qian Li , Chaofeng Sun

Background and aims

Adventitial remodeling is an important pathological process of atherosclerosis, but cues implicated in adventitial remodeling are far from fully understood. Periostin (POSTN), a matricellular protein, has been demonstrated to have multiple roles in cardiovascular diseases. The aim of the study was to explore the function of POSTN in adventitial remodeling during atherosclerosis.

Methods

An atherosclerosis model was constructed based on ApoE-/- mice fed a high-fat and high-cholesterol diet. The expression of POSTN in the adventitia of mouse atherosclerotic vascular specimens was detected by immunohistochemical staining. The roles of POSTN in regulating adventitial fibroblast activation were assessed by cell contractility and activation marker α-smooth muscle actin (α-SMA) expression evaluation in adventitial fibroblasts overexpressing POSTN. In addition, we performed quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting to examine the expression of the proinflammatory chemokines transforming growth factor-β1 (TGF-β1) and monocyte chemotactic protein 1 (MCP1), as well as some extracellular matrix (ECM)-related proteins, in POSTN-overexpressing adventitial fibroblasts. Finally, the integrin-related signaling pathway was detected upon POSTN overexpression in adventitial fibroblasts.

Results

POSTN was highly expressed in the adventitia of atherosclerotic aortae in the mouse atherosclerosis model and promoted the activation and contraction of adventitial fibroblasts. Meanwhile, POSTN also induced adventitial fibroblasts to express TGF-β1, monocyte chemotactic protein-1 (MCP1), and ECM-related proteins and activated the phosphorylation of focal adhesion kinase (FAK) and Src.

Conclusions

Our results revealed that POSTN is elevated in adventitia during atherosclerosis and contributes to the adventitial remodeling of atherosclerosis by activating adventitial fibroblasts.

背景和目的外膜重构是动脉粥样硬化的一个重要病理过程,但与外膜重构相关的线索还远未完全了解。骨膜蛋白(POSTN)是一种基质细胞蛋白,已被证明在心血管疾病中具有多种作用。本研究的目的是探讨POSTN在动脉粥样硬化期间内皮重塑中的功能。方法采用ApoE-/-小鼠高脂高胆固醇饮食,建立小鼠动脉粥样硬化模型。采用免疫组化染色法检测小鼠动脉粥样硬化血管标本外膜中POSTN的表达。通过细胞收缩性和活化标志物α-平滑肌肌动蛋白(α-SMA)在过表达POSTN的外层成纤维细胞中的表达评估,评估POSTN在调节外层成纤维细胞活化中的作用。此外,我们采用定量实时聚合酶链反应(qRT-PCR)和Western blotting检测促炎趋化因子转化生长因子-β1 (TGF-β1)和单核细胞趋化蛋白1 (MCP1)以及一些细胞外基质(ECM)相关蛋白在过表达postn的上皮成纤维细胞中的表达。最后,我们在外层成纤维细胞中检测到POSTN过表达的整合素相关信号通路。结果在小鼠动脉粥样硬化模型中,spostn在动脉粥样硬化主动脉外膜中高表达,促进外膜成纤维细胞的活化和收缩。同时,POSTN还诱导外膜成纤维细胞表达TGF-β1、单核细胞趋化蛋白-1 (MCP1)和ecm相关蛋白,激活局灶黏附激酶(FAK)和Src的磷酸化。结论动脉粥样硬化过程中,动脉粥样硬化外膜中POSTN升高,并通过激活外膜成纤维细胞参与动脉粥样硬化外膜重构。
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引用次数: 1
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Atherosclerosis plus
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