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The role of maintaining lower LDL-C level during statin treatment for advanced CKD patients 晚期 CKD 患者在他汀类药物治疗期间维持较低 LDL-C 水平的作用。
IF 4.9 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-10-31 DOI: 10.1016/j.atherosclerosis.2024.119042
Chieh-Li Yen , Pei-Chun Fan , Cheng-Chia Lee , Jia-Jin Chen , Chao-Yu Chen , Yi-Ran Tu , Pao-Hsien Chu , Ching-Chung Hsiao , Yung-Chang Chen , Chih-Hsiang Chang

Background and aims

Different from other high cardiovascular (CV) risks populations, the evidence supporting the CV protective effect of LDL-C reduction with statins in chronic kidney disease (CKD) patients is comparatively scarce. This study is aimed to investigate the role of maintaining lower LDL-C level in advanced CKD patients.

Methods

By using Chang Gung Research Database, on the basis of Taiwan's largest healthcare group, a total of 5367 adult patients newly-diagnosed with stage 4 CKD and receiving statin were extracted and further categorized into three groups based on their LDL-C levels: <70 mg/dL, 70–100 mg/dL, and ≥100 mg/dL. The main outcome is major adverse cardiac and cerebrovascular events (MACCEs), a composite of cardiovascular death, myocardial infarction, and stroke. The inverse probability of treatment weighting was performed to achieve balance of baseline characteristics.

Results

At 5-year follow-up, the LDL-C < 70 mg/dL group exhibited significantly lower risks of MACCEs (14.3 % vs. 18.7 %, hazard ratio [HR]: 0.77, 95 % CI: 0.69–0.86), cardiovascular death (7.1 % vs. 9.7 %, subdistribution HR [SHR]: 0.75, 95 % CI: 0.65–0.88), ischemic stroke (4.1 % vs. 5.4 %, [SHR]: 0.65, 95 % CI: 0.54–0.79), and new-onset end-stage renal disease requiring chronic dialysis (25.6 % vs. 29.4 %, SHR: 0.87, 95 % CI: 0.80–0.91) compared to LDL-C > 100 mg/dL group. In contrast, the group with LDL-C levels between 70 and 100 did not significantly differ from the group with LDL-C > 100 mg/dL in study outcomes.

Conclusions

Maintaining LDL-C lower than 70 mg/dL may be beneficial for cardiovascular protection in advanced CKD patients and a lower LDL-C treatment target may be required as CKD progression.
背景和目的:与其他心血管(CV)高风险人群不同,支持慢性肾脏病(CKD)患者使用他汀类药物降低低密度脂蛋白胆固醇(LDL-C)对CV具有保护作用的证据相对较少。本研究旨在探讨维持较低 LDL-C 水平在晚期 CKD 患者中的作用:方法:利用长庚研究数据库,以台湾最大的医疗集团为基础,提取了5367名新诊断为CKD第4阶段并接受他汀类药物治疗的成年患者,并根据他们的LDL-C水平进一步分为三组:结果:在5年的随访中,LDL-C < 70 mg/dL组的澳门巴黎人娱乐官网风险(14.3 % vs. 18.7 %,危险比[HR]:0.77,95 % CI:0.69-0.86)、心血管死亡风险(7.1 % vs. 9.7 %,亚分布HR [SHR]:0.75,95 % CI:0.65-0.88)、缺血性中风(4.1% vs. 5.4%,[SHR]:0.65,95 % CI:0.54-0.79)和需要慢性透析的新发终末期肾病(25.6% vs. 29.4%,SHR:0.87,95 % CI:0.80-0.91)。相比之下,低密度脂蛋白胆固醇水平介于70和100之间的组别与低密度脂蛋白胆固醇>100毫克/分升的组别在研究结果上没有显著差异:结论:维持低密度脂蛋白胆固醇低于 70 毫克/分升可能有利于晚期 CKD 患者的心血管保护,随着 CKD 的进展,可能需要更低的低密度脂蛋白胆固醇治疗目标。
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引用次数: 0
Complement factor B, not the membrane attack complex component C9, promotes neointima formation after arterial wire injury 促进动脉导线损伤后新生内膜形成的是补体因子 B,而非膜攻击复合物成分 C9
IF 4.9 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-10-23 DOI: 10.1016/j.atherosclerosis.2024.118586
Ziyi Guo , Yuze Zhang , Zekun Peng , Haojie Rao , Jianfeng Yang , Zengrong Chen , Wenchao Song , Qing Wan , Hong Chen , Miao Wang

Background and aims

Vascular restenosis due to neointima hyperplasia limits the long-term patency of stented arteries, resulting in angioplasty failure. The complement system has been implicated in restenosis. This study aimed to investigate the role of complement factor B (fB), an essential component of the alternative pathway of complement activation, in neointima formation.

Methods

Angioplasty wire injury was conducted using 12-week-old mice deficient in fB or C9 (the main component of the membrane attacking complex, C5b-9) and littermate controls and neointima formation were assessed. Vascular smooth muscle cell (SMC) and endothelial cell (EC) proliferation and migration were examined in vitro.

Results

fB was mainly detected in SMCs of stenotic arteries from humans and mice. Deletion of fB substantially reduced the neointima area and intima-to-media area ratio without affecting the media area at 28 days after injury. At 7 days after injury, fB deficiency decreased SMC proliferation, unaltering neointimal macrophage infiltration and EC reendothelialization. Vascular SMC-expressed fB, not the circulation-sourced fB, played an essential role in SMC proliferation and migration in vitro. fB deficient mice exhibited lower levels of the soluble form of C5b-9, however, deletion of C9 did not alter neointima formation after wire injury, consistent with the null impact of C9 deficiency on SMC proliferation in vitro.

Conclusions

fB promotes neointima formation following wire-induced artery injury independent of forming the membrane-attacking complex. This is attributable to fB-dependent SMC proliferation and migration without affecting EC function. Targeting fB might protect against restenosis after percutaneous coronary intervention.
背景和目的 新内膜增生引起的血管再狭窄限制了支架动脉的长期通畅,导致血管成形术失败。补体系统与血管再狭窄有关。本研究旨在探讨补体激活替代途径的重要组成部分--补体因子 B(fB)在新生内膜形成中的作用。方法使用缺乏 fB 或 C9(膜攻击复合物 C5b-9 的主要成分)的 12 周大小鼠和同窝对照组进行血管成形术线损伤,并评估新生内膜的形成。在体外检测了血管平滑肌细胞(SMC)和内皮细胞(EC)的增殖和迁移。损伤后 28 天,缺失 fB 可显著减少新生内膜面积和内膜与中膜面积比,但不影响中膜面积。损伤后 7 天,缺乏 fB 会减少 SMC 的增殖,但不会改变新生内膜巨噬细胞的浸润和 EC 的再内皮化。血管SMC表达的fB,而非循环来源的fB,在体外SMC增殖和迁移中发挥了重要作用。fB缺乏的小鼠表现出较低水平的可溶性C5b-9,然而,C9的缺失并没有改变钢丝损伤后新内膜的形成,这与C9缺乏对体外SMC增殖的无效影响一致。这归因于 fB 依赖于 SMC 的增殖和迁移,而不影响 EC 的功能。以 fB 为靶点可预防经皮冠状动脉介入治疗后的再狭窄。
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引用次数: 0
Targeting LDL aggregation decreases atherosclerotic lipid burden in a humanized mouse model of familial hypercholesterolemia: Crucial role of ApoB100 conformational stabilization. 在家族性高胆固醇血症人源化小鼠模型中,以低密度脂蛋白聚集为靶点可降低动脉粥样硬化的脂质负担:ApoB100 构象稳定的关键作用。
IF 4.9 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-10-19 DOI: 10.1016/j.atherosclerosis.2024.118630
A Benitez-Amaro, E Garcia, M T La Chica Lhoëst, A Martínez, C Borràs, M Tondo, M V Céspedes, P Caruana, A Pepe, B Bochicchio, A Cenarro, F Civeira, R Prades, J C Escola-Gil, V Llorente-Cortés

Background and aims: Low-density lipoprotein (LDL) aggregation is nowadays considered a therapeutic target in atherosclerosis. DP3, the retro-enantio version of the sequence Gly1127-Cys1140 of LRP1, efficiently inhibits LDL aggregation and foam cell in vitro formation. Here, we investigate whether DP3 modulates atherosclerosis in a humanized ApoB100, LDL receptor (LDLR) knockout mice (Ldlr-/-hApoB100 Tg) and determine the potential LDL-related underlying mechanisms.

Methods: Tg mice were fed an HFD for 21 days to induce atherosclerosis and then randomized into three groups that received a daily subcutaneous administration (10 mg/kg) of i) vehicle, ii) DP3 peptide, or iii) a non-active peptide (IP321). The in vivo biodistribution of a fluorescent-labeled peptide version (TAMRA-DP3), and its colocalization with ApoB100 in the arterial intima, was analyzed by imaging system (IVIS) and confocal microscopy. Heart aortic roots were used for atherosclerosis detection and quantification. LDL functionality was analyzed by biochemical, biophysical, molecular, and cellular studies.

Results: Intimal neutral lipid accumulation in the aortic root was reduced in the DP3-treated group as compared to control groups. ApoB100 in LDLs from the DP3 group exhibited an increased percentage of α-helix secondary structures and decreased immunoreactivity to anti-ApoB100 antibodies. LDL from DP3-treated mice were protected against passive and sphingomyelinase (SMase)-induced aggregation, although they still experienced SMase-induced sphingomyelin phospholysis. In patients with familial hypercholesterolemia (FH), DP3 efficiently inhibited both SMase-induced phospholysis and aggregation.

Conclusions: DP3 peptide administration inhibits atherosclerosis by preserving the α-helix secondary structures of ApoB100 in a humanized ApoB100 murine model that mimicks the hallmark of human hypercholesterolemia.

背景和目的:低密度脂蛋白(LDL)聚集如今被认为是动脉粥样硬化的治疗靶点。DP3是LRP1的Gly1127-Cys1140序列的逆对映版本,能有效抑制低密度脂蛋白的聚集和体外泡沫细胞的形成。在此,我们研究了DP3是否能调节人源化载脂蛋白B100、低密度脂蛋白受体(LDLR)基因敲除小鼠(Ldlr-/-hApoB100 Tg)的动脉粥样硬化,并确定了潜在的低密度脂蛋白相关潜在机制:给Tg小鼠喂食高密度脂蛋白膳食(HFD)21天以诱发动脉粥样硬化,然后随机分为三组,每组每天皮下注射(10毫克/千克)i)载体、ii)DP3肽或iii)非活性肽(IP321)。通过成像系统(IVIS)和共聚焦显微镜分析了荧光标记肽版本(TAMRA-DP3)的体内生物分布及其与动脉内膜中载脂蛋白B100的共定位。心脏主动脉根部用于动脉粥样硬化的检测和量化。通过生化、生物物理、分子和细胞研究分析了低密度脂蛋白的功能:结果:与对照组相比,DP3 治疗组主动脉根部内膜中性脂质堆积减少。DP3组低密度脂蛋白中载脂蛋白B100的α-螺旋二级结构比例增加,抗载脂蛋白B100抗体的免疫活性降低。经DP3处理的小鼠的低密度脂蛋白对被动和鞘磷脂酶(SMase)诱导的聚集具有保护作用,尽管它们仍经历了SMase诱导的鞘磷脂磷酸化。在家族性高胆固醇血症(FH)患者中,DP3能有效抑制SM酶诱导的磷酸化和聚集:结论:在模拟人类高胆固醇血症特征的人源化载脂蛋白100小鼠模型中,DP3肽通过保留载脂蛋白100的α-螺旋二级结构抑制动脉粥样硬化。
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引用次数: 0
ERICH4 is not involved in the assembly and secretion of intestinal lipoproteins ERICH4不参与肠道脂蛋白的组装和分泌。
IF 4.9 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-10-18 DOI: 10.1016/j.atherosclerosis.2024.118635
Ankia Visser , Willemien van Zwol , Niels Kloosterhuis , Nicolette Huijkman , Marieke Smit , Mirjam Koster , Vincent Bloks , M. Mahmood Hussain , Bart van de Sluis , Jan Albert Kuivenhoven

Background and aims

The small intestine plays a central role in lipid metabolism, most notably the uptake of dietary fats that are packaged into chylomicrons and secreted into the circulation for utilisation by peripheral tissues. While microsomal triglyceride transfer protein (MTP) is known to play a key role in this pathway, the intracellular assembly, trafficking, and secretion of chylomicrons is incompletely understood.

Methods and Results

Using human transcriptome datasets to find genes co-regulated with MTTP, we identified ERICH4 as a top hit. The gene encodes for glutamate-rich protein 4, a protein of unknown function. REACTOME gene-function prediction tools indicated that ERICH4 is involved in intestinal lipid metabolism. In addition, GWAS data point to a strong relationship between ERICH4 and plasma lipids. To validate ERICH4 as a lipid gene, we generated whole-body Erich4 knockout (Erich4−/−) mice. ERICH4 deficiency, however, did not result in changes in body weight and composition, food intake, circulating plasma lipids, energy absorption and excretion, and tissue weights compared to controls. Additionally, there were no morphological abnormalities seen in the small intestine. Challenging mice with a high-fat diet did not give rise to a phenotype either.

Conclusions

Despite prediction tools indicating ERICH4 as a strong candidate gene in intestinal lipid metabolism, we here show that ERICH4 does not play a role in intestinal lipid metabolism in mice. It remains to be established whether ERICH4 plays a role in human lipid metabolism.
背景和目的:小肠在脂质代谢中起着核心作用,其中最主要的是吸收饮食中的脂肪,这些脂肪被包装成乳糜微粒并分泌到血液循环中供外周组织利用。众所周知,微粒体甘油三酯转移蛋白(MTP)在这一途径中发挥着关键作用,但人们对乳糜微粒的细胞内组装、贩运和分泌却知之甚少:利用人类转录组数据集寻找与MTTP共调的基因,我们发现ERICH4是最热门的基因。该基因编码富谷氨酸蛋白 4,这是一种功能未知的蛋白质。REACTOME 基因功能预测工具表明,ERICH4 参与了肠道脂质代谢。此外,GWAS 数据表明 ERICH4 与血浆脂质之间存在密切关系。为了验证ERICH4是一个脂质基因,我们产生了全身Erich4基因敲除(Erich4-/-)小鼠。然而,与对照组相比,ERICH4 基因缺失不会导致体重和组成、食物摄入量、循环血浆脂质、能量吸收和排泄以及组织重量发生变化。此外,小肠也未出现形态异常。用高脂肪饮食挑战小鼠也没有产生表型:结论:尽管预测工具显示ERICH4是肠道脂质代谢的一个强有力的候选基因,但我们在这里发现ERICH4在小鼠肠道脂质代谢中并没有发挥作用。ERICH4是否在人类脂质代谢中发挥作用,还有待进一步证实。
{"title":"ERICH4 is not involved in the assembly and secretion of intestinal lipoproteins","authors":"Ankia Visser ,&nbsp;Willemien van Zwol ,&nbsp;Niels Kloosterhuis ,&nbsp;Nicolette Huijkman ,&nbsp;Marieke Smit ,&nbsp;Mirjam Koster ,&nbsp;Vincent Bloks ,&nbsp;M. Mahmood Hussain ,&nbsp;Bart van de Sluis ,&nbsp;Jan Albert Kuivenhoven","doi":"10.1016/j.atherosclerosis.2024.118635","DOIUrl":"10.1016/j.atherosclerosis.2024.118635","url":null,"abstract":"<div><h3>Background and aims</h3><div>The small intestine plays a central role in lipid metabolism, most notably the uptake of dietary fats that are packaged into chylomicrons and secreted into the circulation for utilisation by peripheral tissues. While microsomal triglyceride transfer protein (MTP) is known to play a key role in this pathway, the intracellular assembly, trafficking, and secretion of chylomicrons is incompletely understood.</div></div><div><h3>Methods and Results</h3><div>Using human transcriptome datasets to find genes co-regulated with <em>MTTP</em>, we identified <em>ERICH4</em> as a top hit. The gene encodes for glutamate-rich protein 4, a protein of unknown function. REACTOME gene-function prediction tools indicated that ERICH4 is involved in intestinal lipid metabolism. In addition, GWAS data point to a strong relationship between <em>ERICH4</em> and plasma lipids. To validate <em>ERICH4</em> as a lipid gene, we generated whole-body <em>Erich4</em> knockout (<em>Erich4</em><sup><em>−/−</em></sup>) mice. ERICH4 deficiency<em>,</em> however, did not result in changes in body weight and composition, food intake, circulating plasma lipids, energy absorption and excretion, and tissue weights compared to controls. Additionally, there were no morphological abnormalities seen in the small intestine. Challenging mice with a high-fat diet did not give rise to a phenotype either.</div></div><div><h3>Conclusions</h3><div>Despite prediction tools indicating <em>ERICH4</em> as a strong candidate gene in intestinal lipid metabolism, we here show that ERICH4 does not play a role in intestinal lipid metabolism in mice. It remains to be established whether ERICH4 plays a role in human lipid metabolism.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"399 ","pages":"Article 118635"},"PeriodicalIF":4.9,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Publication bias in pharmacogenetics of statin-associated muscle symptoms: A meta-epidemiological study. 他汀类药物相关肌肉症状药物遗传学的发表偏差:一项荟萃流行病学研究。
IF 4.9 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-10-18 DOI: 10.1016/j.atherosclerosis.2024.118624
A Gougeon, I Aribi, S Guernouche, J C Lega, J M Wright, C Verstuyft, A Lajoinie, F Gueyffier, G Grenet

Background and aims: Statin-associated muscle symptoms (SAMS) are a major cause of treatment discontinuation. Clinical Pharmacogenetics Implementation Consortium (CPIC) recommend dose adjustment for statin treatment according to known SLCO1B1 genotype to reduce SAMS. We hypothesized that the association between SLCO1B1 genotype and SAMS is misestimated because of publication bias.

Methods: We searched published systematic reviews on the association between SLCO1B1 genotype and SAMS. To assessed publication bias, we used funnel plot visual inspection, Egger's test, and the Bayes Factor (BFPublication-bias) from Robust Bayesian Meta-Analysis (RoBMA). We compared the odds ratios (ORUncorrected) from meta-analyses before and after correcting for publication bias using trim-and-fill (ORTrim&Fill) and RoBMA (ORRoBMA) methods.

Results: We included 8 cohort and 11 case-control studies, totaling 62 OR of three SLCO1B1 genotypes and six statin drugs. In the primary analysis, the funnel plot was suggestive of publication bias, confirmed by Egger's test (p=0.001) and RoBMA (BFPublication-bias = 18). Correcting the estimate for publication bias resulted in loss of the association, from a significant ORUncorrected (1.31 95%CI [1.13-1.53]) to corrected ORs suggesting no difference: ORTrim&Fill (1.07 95%CI [0.89-1.30]) and ORRoBMA (1.02 95%CI [1.00-1.33]). This suggested that publication bias overestimated the association by 18 % and 23 %, respectively. Similar results were found for genotype rs4149056, simvastatin and atorvastatin.

Conclusions: The effect of the SLCO1B1 genotype on the risk of developing SAMS is overestimated in the published literature, especially rs4149056. This could lead prescribers to incorrectly decreasing statin doses or even avoiding statin use, leading to a loss of the potential cardiovascular benefit of statins.

背景和目的:他汀类药物相关肌肉症状(SAMS)是导致治疗中断的主要原因。临床药物遗传学实施联合会(CPIC)建议根据已知的 SLCO1B1 基因型调整他汀类药物治疗剂量,以减少 SAMS。我们假设,由于发表偏倚,SLCO1B1 基因型与 SAMS 之间的关联被错误估计:我们检索了已发表的有关 SLCO1B1 基因型与 SAMS 之间关系的系统综述。为了评估发表偏倚,我们使用了漏斗图目测、Egger 检验和稳健贝叶斯荟萃分析(Robust Bayesian Meta-Analysis,RoBMA)中的贝叶斯因子(BFPublication-bias)。我们比较了使用修剪与填充(ORTrim&Fill)和RoBMA(ORRoBMA)方法纠正发表偏倚前后荟萃分析的几率比(ORUncorrected):我们纳入了 8 项队列研究和 11 项病例对照研究,共计 62 个 OR,涉及 3 种 SLCO1B1 基因型和 6 种他汀类药物。在主要分析中,漏斗图提示存在发表偏倚,Egger 检验(P=0.001)和 RoBMA(BFP 发表偏倚 = 18)证实了这一点。对发表偏倚的估计值进行校正后,相关性消失,从显著的未校正 OR(1.31 95%CI [1.13-1.53])变为校正 OR,表明没有差异:ORTrim&Fill(1.07 95%CI [0.89-1.30])和 ORRoBMA(1.02 95%CI [1.00-1.33])。这表明,发表偏倚分别高估了 18% 和 23% 的相关性。基因型 rs4149056、辛伐他汀和阿托伐他汀也发现了类似的结果:结论:在已发表的文献中,SLCO1B1 基因型对罹患 SAMS 风险的影响被高估了,尤其是 rs4149056。这可能会导致处方者错误地减少他汀类药物的剂量,甚至避免使用他汀类药物,从而失去他汀类药物对心血管的潜在益处。
{"title":"Publication bias in pharmacogenetics of statin-associated muscle symptoms: A meta-epidemiological study.","authors":"A Gougeon, I Aribi, S Guernouche, J C Lega, J M Wright, C Verstuyft, A Lajoinie, F Gueyffier, G Grenet","doi":"10.1016/j.atherosclerosis.2024.118624","DOIUrl":"https://doi.org/10.1016/j.atherosclerosis.2024.118624","url":null,"abstract":"<p><strong>Background and aims: </strong>Statin-associated muscle symptoms (SAMS) are a major cause of treatment discontinuation. Clinical Pharmacogenetics Implementation Consortium (CPIC) recommend dose adjustment for statin treatment according to known SLCO1B1 genotype to reduce SAMS. We hypothesized that the association between SLCO1B1 genotype and SAMS is misestimated because of publication bias.</p><p><strong>Methods: </strong>We searched published systematic reviews on the association between SLCO1B1 genotype and SAMS. To assessed publication bias, we used funnel plot visual inspection, Egger's test, and the Bayes Factor (BF<sub>Publication-bias</sub>) from Robust Bayesian Meta-Analysis (RoBMA). We compared the odds ratios (OR<sub>Uncorrected</sub>) from meta-analyses before and after correcting for publication bias using trim-and-fill (OR<sub>Trim&Fill</sub>) and RoBMA (OR<sub>RoBMA</sub>) methods.</p><p><strong>Results: </strong>We included 8 cohort and 11 case-control studies, totaling 62 OR of three SLCO1B1 genotypes and six statin drugs. In the primary analysis, the funnel plot was suggestive of publication bias, confirmed by Egger's test (p=0.001) and RoBMA (BF<sub>Publication-bias</sub> = 18). Correcting the estimate for publication bias resulted in loss of the association, from a significant OR<sub>Uncorrected</sub> (1.31 95%CI [1.13-1.53]) to corrected ORs suggesting no difference: OR<sub>Trim&Fill</sub> (1.07 95%CI [0.89-1.30]) and OR<sub>RoBMA</sub> (1.02 95%CI [1.00-1.33]). This suggested that publication bias overestimated the association by 18 % and 23 %, respectively. Similar results were found for genotype rs4149056, simvastatin and atorvastatin.</p><p><strong>Conclusions: </strong>The effect of the SLCO1B1 genotype on the risk of developing SAMS is overestimated in the published literature, especially rs4149056. This could lead prescribers to incorrectly decreasing statin doses or even avoiding statin use, leading to a loss of the potential cardiovascular benefit of statins.</p>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":" ","pages":"118624"},"PeriodicalIF":4.9,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142563490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
VascuFit: Aerobic exercise improves endothelial function independent of cardiovascular risk: A randomized-controlled trial VascuFit:有氧运动可改善内皮功能,与心血管风险无关:随机对照试验
IF 4.9 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-10-16 DOI: 10.1016/j.atherosclerosis.2024.118631
Daniel Goeder , Julia Maria Kröpfl , Thomas Angst , Henner Hanssen , Christoph Hauser , Denis Infanger , Debbie Maurer , Renate Oberhoffer-Fritz , Arno Schmidt-Trucksäss , Karsten Königstein

Background and aims

Endothelial dysfunction predicts elevated cardiovascular (CV) risk in healthy individuals. Aerobic exercise reduces endothelial dysfunction in part by improving CV risk factors. Yet, this explains less than 50 % of the effect and a direct influence of exercise training on the endothelium is discussed as possible contributor. The VascuFit study applied non-linear periodized aerobic exercise (NLPE) training to assess its multilevel effects on endothelial function including potential epigenetic endothelial modifications by circulating micro-ribonucleic acids (endomiRs).

Methods

Sedentary adults with elevated CV risk between 40 and 60 years were randomized 2:1 and engaged in an eight-week ergometer-based NLPE training (n = 30) or received standard exercise recommendations (n = 14). Macro-, microvascular, cellular and molecular adaptations were assessed via brachial-arterial flow-mediated dilation (baFMD), static retinal vessel analysis (SVA), flow cytometry, and endomiRs regulating key pathways of endothelial function. Statistics included ANCOVA, Principal Component Analysis (PCA), and regression analyses.

Results

baFMD improved by 2.38 % (CI:0.70–4.06, p = 0.007) independent of CV risk, whereas SVA parameters and circulating endothelial (progenitor) cells did not significantly change in the NLPE group. The mean distance between baseline and follow-up PCA loadings of the endomiR dataset explaining 44.2 % of dataset variability was higher in the NLPE-group compared to the control group (2.71 ± 2.02 vs. 1.65 ± 0.93). However, regression analyses showed no evidence of endomiRs explaining the improvement of baFMD.

Conclusions

The improvement of macrovascular endothelial function by aerobic exercise training was independent from CV risk factors. Increased heterogeneity among endomiRs did not explain this effect, but suggests an adaptive response to the exercise stimulus on the epigenetic level.
背景和目的:内皮功能障碍预示着健康人的心血管(CV)风险升高。有氧运动可通过改善心血管疾病风险因素来减轻内皮功能障碍。然而,这只能解释不到 50% 的效果,运动训练对内皮的直接影响被认为是可能的原因。VascuFit 研究采用非线性周期性有氧运动(NLPE)训练来评估其对内皮功能的多层次影响,包括循环微核糖核酸(endomiRs)对内皮的潜在表观遗传修饰:方法:将年龄在 40 至 60 岁之间、心血管疾病风险较高的久坐成年人按 2:1 随机分组,参加为期八周、以测力计为基础的 NLPE 训练(30 人)或接受标准运动建议(14 人)。通过肱动脉血流介导的扩张(baFMD)、静态视网膜血管分析(SVA)、流式细胞术和调节内皮功能关键通路的内切酶Rs评估宏观、微观血管、细胞和分子适应性。统计包括方差分析、主成分分析(PCA)和回归分析。结果:baFMD改善了2.38%(CI:0.70-4.06,P = 0.007),与CV风险无关,而SVA参数和循环内皮(祖细胞)细胞在NLPE组中没有显著变化。与对照组相比,NLPE 组基线与随访内皮细胞数据集 PCA 负载之间的平均距离更高(2.71 ± 2.02 vs. 1.65 ± 0.93),而 PCA 负载可解释数据集变异性的 44.2%。然而,回归分析表明,没有证据表明内皮生长因子能解释 baFMD 的改善:结论:有氧运动训练对大血管内皮功能的改善与冠心病风险因素无关。结论:有氧运动训练对大血管内皮功能的改善与冠状动脉风险因素无关。内皮生长因子之间的异质性增加并不能解释这种效果,但表明在表观遗传学水平上对运动刺激的适应性反应。
{"title":"VascuFit: Aerobic exercise improves endothelial function independent of cardiovascular risk: A randomized-controlled trial","authors":"Daniel Goeder ,&nbsp;Julia Maria Kröpfl ,&nbsp;Thomas Angst ,&nbsp;Henner Hanssen ,&nbsp;Christoph Hauser ,&nbsp;Denis Infanger ,&nbsp;Debbie Maurer ,&nbsp;Renate Oberhoffer-Fritz ,&nbsp;Arno Schmidt-Trucksäss ,&nbsp;Karsten Königstein","doi":"10.1016/j.atherosclerosis.2024.118631","DOIUrl":"10.1016/j.atherosclerosis.2024.118631","url":null,"abstract":"<div><h3>Background and aims</h3><div>Endothelial dysfunction predicts elevated cardiovascular (CV) risk in healthy individuals. Aerobic exercise reduces endothelial dysfunction in part by improving CV risk factors. Yet, this explains less than 50 % of the effect and a direct influence of exercise training on the endothelium is discussed as possible contributor. The VascuFit study applied non-linear periodized aerobic exercise (NLPE) training to assess its multilevel effects on endothelial function including potential epigenetic endothelial modifications by circulating micro-ribonucleic acids (endomiRs).</div></div><div><h3>Methods</h3><div>Sedentary adults with elevated CV risk between 40 and 60 years were randomized 2:1 and engaged in an eight-week ergometer-based NLPE training (n = 30) or received standard exercise recommendations (n = 14). Macro-, microvascular, cellular and molecular adaptations were assessed via brachial-arterial flow-mediated dilation (baFMD), static retinal vessel analysis (SVA), flow cytometry, and endomiRs regulating key pathways of endothelial function. Statistics included ANCOVA, Principal Component Analysis (PCA), and regression analyses.</div></div><div><h3>Results</h3><div>baFMD improved by 2.38 % (CI:0.70–4.06, <em>p</em> = 0.007) independent of CV risk, whereas SVA parameters and circulating endothelial (progenitor) cells did not significantly change in the NLPE group. The mean distance between baseline and follow-up PCA loadings of the endomiR dataset explaining 44.2 % of dataset variability was higher in the NLPE-group compared to the control group (2.71 ± 2.02 <em>vs.</em> 1.65 ± 0.93). However, regression analyses showed no evidence of endomiRs explaining the improvement of baFMD.</div></div><div><h3>Conclusions</h3><div>The improvement of macrovascular endothelial function by aerobic exercise training was independent from CV risk factors. Increased heterogeneity among endomiRs did not explain this effect, but suggests an adaptive response to the exercise stimulus on the epigenetic level.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"399 ","pages":"Article 118631"},"PeriodicalIF":4.9,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Unraveling the complex interplay of PPARα and age in cardiac metabolism: Implications for managing age-related cardiac dysfunctions. 揭示 PPARα 和年龄在心脏新陈代谢中的复杂相互作用:对控制与年龄相关的心脏功能障碍的启示。
IF 4.9 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-10-11 DOI: 10.1016/j.atherosclerosis.2024.118627
Sina Rashedi, Mohammad Keykhaei
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引用次数: 0
Single bolus PCSK9 Inhibition: A new approach to plaque stabilisation. 单次注射 PCSK9 抑制剂:稳定斑块的新方法。
IF 4.9 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-10-11 DOI: 10.1016/j.atherosclerosis.2024.118628
Stephen J Nicholls, Gavin Pr Manmathan
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引用次数: 0
Comparison of pooled cohort equation and PREVENT™ risk calculator for statin treatment allocation 用于他汀类药物治疗分配的汇集队列方程与 PREVENT™ 风险计算器的比较。
IF 4.9 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-10-10 DOI: 10.1016/j.atherosclerosis.2024.118626
Joseph Heaton , Abbas Alshami , Steven Imburgio , Vandan Upadhyaya , Matthew Saybolt , Renato Apolito , Riple Hansalia , Jeffrey Selan , Jesus Almendral , Brett Sealove

Background and aims

Effective hypercholesterolemia management is linked to lower all-cause and cardiovascular mortality. The 2018 AHA/ACC guidelines recommended using the Pooled Cohort Equations (PCE) for lipid management, but these may overestimate risk and be less accurate for certain racial groups. The AHA's new PREVENT equation, which omits race and includes cardiometabolic factors, aims to provide a more accurate risk assessment for a diverse population. However, it has not yet been applied to a nationally representative US population, and implementation guidelines are still lacking. Our study aimed to evaluate potential changes in hypercholesterolemia management for primary prevention by using the PREVENT equation instead of the PCE.

Methods

Analyzing pre-pandemic NHANES 2017–2020 data, participants aged 40–75 without prior lipid-lowering treatment or other compelling indication were identified for elevated risk (≥7.5 %) using the PCE and PREVENT equations. We assessed risk shifts and indications for statin therapy, comparing the two risk equations. NHANES guidelines with weighting were followed to obtain US nationally representative estimates.

Results

Out of 77, 647, 807 (unweighted = 2494) participants, 81.0 % had no change in risk. The PCE flagged 18.8 % (n = 14,614,094) of participants at elevated risk not identified by PREVENT, while 0.20 % (n = 107,813) were flagged only by PREVENT. Participants identified solely by the PCE were older, with higher systolic blood pressure and increased estimated glomerular filtration rates.
Indications for statin therapy were largely unchanged (81.0 %). PREVENT newly identified (0.20 %) for moderate-intensity therapy and none for high-intensity therapy. Participants qualifying for moderate intensity therapy by the PCE were reclassified to no therapy in 74.59 % of cases, while 25.41 % remained unchanged. Participants qualifying for high-intensity therapy by the PCE were reclassified to moderate therapy in 93.97 % of cases, and 6.03 % were reclassified to no therapy.

Conclusions

The PREVENT equation notably differs in identifying hypercholesterolemia candidates compared to the PCE. Its adoption would influence cardiovascular risk reduction therapy recommendations, emphasizing the need for comprehensive studies to understand its long-term impact and reevaluate the threshold of treatment strategies for improved patient outcomes.
背景和目的:有效的高胆固醇血症管理与降低全因死亡率和心血管死亡率有关。2018 年 AHA/ACC 指南建议使用集合队列方程 (PCE) 进行血脂管理,但这些方程可能会高估风险,对某些种族群体的准确性较低。美国心脏病学会的新 PREVENT 方程省略了种族因素并包含了心脏代谢因素,旨在为不同人群提供更准确的风险评估。然而,该方程尚未应用于具有全国代表性的美国人群,也缺乏实施指南。我们的研究旨在评估使用 PREVENT 方程而非 PCE 进行一级预防时高胆固醇血症管理的潜在变化:通过分析大流行前的 NHANES 2017-2020 年数据,使用 PCE 和 PREVENT 方程确定了年龄在 40-75 岁、既往未接受过降脂治疗或无其他强制指征的参与者的高风险(≥7.5%)。我们对两种风险方程进行了比较,评估了他汀类药物治疗的风险转移和适应症。为了获得具有美国全国代表性的估计值,我们遵循了 NHANES 的加权指南:在 77 647 807(未加权 = 2494)名参与者中,81.0% 的风险没有变化。PCE标记了18.8%(n=14,614,094)未被PREVENT识别的高风险参与者,而0.20%(n=107,813)仅被PREVENT标记。仅通过 PCE 确定的参与者年龄较大,收缩压较高,估计肾小球滤过率较高。他汀类药物治疗的适应症基本未变(81.0%)。PREVENT 新发现(0.20%)可接受中等强度治疗的患者,没有发现可接受高强度治疗的患者。有 74.59% 符合 PCE 中度治疗条件的参与者被重新分类为无需治疗,25.41% 保持不变。93.97%的病例被重新分类为中度治疗,6.03%的病例被重新分类为无治疗:与 PCE 相比,PREVENT 方程在确定高胆固醇血症候选者方面存在显著差异。结论:与 PCE 相比,PREVENT 方程在确定高胆固醇血症候选者方面存在显著差异,它的采用将影响降低心血管风险疗法的建议,因此需要进行全面研究以了解其长期影响,并重新评估治疗策略的阈值,以改善患者的预后。
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引用次数: 0
Statin use is associated with less ST-elevation versus non-ST-elevation myocardial infarction in a nationwide study 在一项全国性研究中,使用他汀类药物可减少ST段抬高与非ST段抬高心肌梗死的发生率。
IF 4.9 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-10-09 DOI: 10.1016/j.atherosclerosis.2024.118625
Sofie B. Simony , Anne Langsted , Martin B. Mortensen , Børge G. Nordestgaard , Shoaib Afzal

Background and aims

Statin therapy reduces myocardial infarction rate but whether it is associated with a shift of ST-elevation myocardial infarction (STEMI) towards non-ST-elevation myocardial infarction (non-STEMI) remains unknown. Thus, we tested the hypothesis that statin use is associated with less STEMI relative to non-STEMI in first-time myocardial infarction.

Methods

In a nationwide study, including 66,896 patients with first-time myocardial infarction between 2010 and 2021, we obtained multivariable risk estimates for STEMI versus non-STEMI according to any statin use, cumulated statin use, and daily statin dose. Furthermore, we obtained hazard ratios for 60-day mortality (5545 deaths) following myocardial infarction according to type of infarction.

Results

Odds ratios for STEMI versus non-STEMI were 0.81 (95 % CI:0.77–0.85) and 1.07 (1.01–1.13) in current and previous statin users compared to never statin users. Cumulated statin exposure yielded odds ratios of 0.96 (0.87–1.07) for <2 statin-years, 0.87 (0.79–0.95) for 2–4.9 statin-years, 0.80 (0.74–0.87) for 5–10 statin-years, and 0.75 (0.70–0.80) for >10 statin-years compared to never users. Corresponding odds ratios for statin dose intensity were 0.89 (0.84–0.95) for low-intensity, 0.77 (0.73–0.82) for moderate-intensity, and 0.70 (0.63–0.77) for high-intensity. Results were similar in multiple sensitivity analyses and using a cohort design. The hazard ratio for 60-day mortality after first-time STEMI versus non-STEMI was 2.24 (2.13–2.37).

Conclusions

In this nationwide study, prior statin use is associated with less STEMI relative to non-STEMI in a dose dependent manner. This indicates that statin therapy, in addition to reducing myocardial infarction event rates, also result in a less severe presentation of myocardial infarctions.
背景和目的:他汀类药物治疗可降低心肌梗死发生率,但它是否与ST段抬高型心肌梗死(STEMI)向非ST段抬高型心肌梗死(非STEMI)的转变有关仍是未知数。因此,我们对他汀类药物的使用与首次心肌梗死中STEMI相对于非STEMI的减少有关这一假设进行了检验:在一项全国性研究(包括 2010 年至 2021 年间的 66,896 例首次心肌梗死患者)中,我们根据是否使用过他汀类药物、累计使用他汀类药物的情况以及他汀类药物的日剂量,得出了 STEMI 与非 STEMI 的多变量风险估计值。此外,我们还根据心肌梗死类型得出了心肌梗死后 60 天死亡率(5545 例死亡)的危险比:与从未使用过他汀类药物的患者相比,目前和曾经使用过他汀类药物的患者STEMI与非STEMI的危险比分别为0.81(95 % CI:0.77-0.85)和1.07(1.01-1.13)。与从未使用过他汀类药物者相比,累积他汀类药物暴露 10 年的几率比为 0.96(0.87-1.07)。他汀类药物剂量强度的相应几率比分别为:低强度 0.89(0.84-0.95),中强度 0.77(0.73-0.82),高强度 0.70(0.63-0.77)。多重敏感性分析和队列设计的结果相似。首次 STEMI 后 60 天死亡率与非 STEMI 后 60 天死亡率的危险比为 2.24(2.13-2.37):在这项全国性研究中,他汀类药物的使用剂量与STEMI的发生率相关,而非STEMI的发生率较低。这表明他汀类药物治疗除了能降低心肌梗死的发生率外,还能减少心肌梗死的严重程度。
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引用次数: 0
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Atherosclerosis
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