冠状动脉钙化成因及治疗新进展

作者：周玉杰[1]柴萌 -9-1610:14:08冠状动脉钙化(Coronaryarterycalcification,CAC)的🎧现都提示预后不良。现在其发病机制尚未完全阐明,近年来证明血管钙化是冠状动脉钙化(Coronaryarterycalcification,CAC)可造成血管僵硬度增加，顺应性减少，心肌灌注受损[1]。临床研究表明,CAC程度能够预测心肌梗死和突CAC的🎧现都提示预后不良。现在其发病机制尚未完全阐明,近年来证明血管CACCAC的程度与斑块负担亲密有关[5]，微钙化如发生于覆盖动脉粥样硬化斑块形成,经常见于稳定心绞痛型和猝死型冠心病患者[7,8]C9p21)和磷酸代谢的罕见突变有关[9–11]肌细胞向成骨样表型转变[12]，也与CAC的进展有关。1CAC是是是是是否是否是否是否否是高否是钙 磷 慢性肾病患者心血管发病率和死亡率高很大程度上是由于存在CAC及动脉粥样硬化。高钙血症和高磷血症均可增进CAC。磷酸盐除了可调节磷钙平衡外,效亢进也是CAC的一种危险因素[14]。另外,肾素-血管紧张素-醛固酮系统可能在中膜钙化的进展中发挥重要作用,由于在临床前模型中证明，血管紧张素II-1型受体阻滞剂克制了CAC的进展[15]。可能会减缓CAC的进展（现在这种现象只发现于1型糖尿病患者）[16]。CAC性[17,18]。这些数据表明，CAC增强对CAC传导通路的研究，可能有助于发现更有效的治疗办法。CAC近年来多项研究试图证明有关药品治疗能够克制甚至逆转CAC进展，但大多得到了阴性成果。早在，St.FrancisHeartStudy1005CAC某些小规模的随机前瞻性研究发现，钙通道阻滞剂[20][21],磷酸盐结合剂[22]能够延缓CAC的进程，但仍缺少大规模的前瞻性实验证据。BMSDES重建率低。然而，即使DES的植入在一定程度上改善了冠脉钙化患者的预后，但CAC患者PCI手术难度高、成功率低、并发症多、预后差，是介入手术中最Ⅲ～Ⅳ2mmBittlJA等发表的一篇Meta分析显示与普通球囊扩张术相比，切割球囊得到类似的再狭窄率和MACE事件，且心梗和穿孔率更高[23]。而近期Vaquerizo等将切割球囊与旋磨术进行对照，发现中短期预后无是PCI术中解决钙化病变的重要辅助办法。冠状动脉旋磨术（Rotational00rpm,可将坚硬组织研磨成极微小的颗粒(<10mm)[25]。发表的随机对照研究（ROTAXUS研究），将患者RA+DES（120）PCI（120），成果显示尽管旋磨增加介入手术的成功率，却未能减少晚期管腔丢失，更未能在MACE等硬终点上获益[26]221669PCIRA（不不不大于参考血管直径的70％为宜），缓慢推动旋磨导管，避免转速下降上个世纪90年代，就有人尝试应用激光来攻克介入治疗的难题如再狭窄等。源，激光以脉冲方式作用于组织，每次一脉冲的作用时间仅为135纳秒（一百亿分之一秒），穿透深度仅为50µm，通过光化学作用破坏分子键，光热学作用产3其发展可能给CAC患者带来福音。PCI其它PCI有关器械的选择也极为重要：（1）强支撑力指导导管（EBU、XB、Amplatz等）；（2）亲水涂层（或聚合物涂层）指导导丝；（3）辐射张力强的支架，必要时可选择短支架进行拼接。，LeeY等的研究证明更薄的药品支架可明显改善旋磨术后患者预后[29]Cyper支架的钢梁厚度为140µm，TaxusLiberty为132µmResolute91µm，XienceVPCIPCI冠脉斑块消融术给CAC患者提供一种新的选择，但仍需大规模随机对照实验证KalraSS,ShanahanCM.Vascularcalcificationandhypertension:causeandeffect.AnnMed;44Suppl1:S85–92.MurshedM,SchinkeT,McKeeMD,etal.Extracellularmatrixmineralizationisregulatedlocally;differentrolesoftwogla-containingproteins[J].JCellBiol.;165(5):625-630.HoffmannU,MassaroJM,FoxCS,etal.Definingnormaldistributionsofcoronaryarterycalciuminwomenandmen(fromtheFraminghamHeartStudy)[J].AmJCardiol,;102(9):1136-1141.AbedinM,TintutY,DemerLL.Vascularcalcification:mechanismsandclinicalramifications.ArteriosclerThrombVascBiol,;24:1161–70.SangiorgiG,RumbergerJA,SeversonA,etal.Arterialcalcificationandnotlumenstenosisishighlycorrelatedwithatheroscleroticplaqueburdeninhumans:ahistologicstudyof723coronaryarterysegmentsusingnondecalcifyingmethodology.JAmCollCardiol,1998;31:126–33.Kelly-ArnoldA,MaldonadoN,LaudierD,etal.Revisedmicrocalcificationhypothesisforfibrouscapruptureinhumancoronaryarteries.ProcNatlAcadSciUSA,;110:10741–6.VirmaniR,KolodgieFD,BurkeAP,FarbA,SchwartzSM.Lessonsfromsuddencoronarydeath:acomprehensivemorphologicalclassificationschemeforatheroscleroticlesions.ArteriosclerThrombVascBiol,;20:1262–75.BurkeAP,WeberDK,KolodgieFD,etal.Pathophysiologyofcalciumdepositionincoronaryarteries.Herz;26:239–44.vanSettenJ,IsgumI,SmolonskaJ,etal.Genome-wideassociationstudyofcoronaryandaorticcalcificationimplicatesrisklociforcoronaryarterydiseaseandmyocardialinfarction.Atherosclerosis;228:400–5.HofmannBowmanMA,McNallyEM.Geneticpathwaysofvascularcalcification.TrendsCardiovascMed;22:93–8.O’DonnellCJ,KavousiM,SmithAV,etal.Genome-wideassociationstudyforcoronaryarterycalcificationwithfollow-upinmyocardialinfarction.Circulation;124:2855–64.GoettschC,HutchesonJD,AikawaE.MicroRNAincardiovascularcalcification:focusontargetsandextracellularvesicledeliverymechanisms.CircRes;112:1073–84.SpeerMY,LiX,HiremathPG,GiachelliCM.Runx2/Cbfa1,butnotlossofmyocardin,isrequiredforsmoothmusclecelllineagereprogrammingtowardosteochondrogenesis.JCellBiochem,;110:935–47.DemerLL,TintutY.Vascularcalcification:pathobiologyofamultifaceteddisease.Circulation;117:2938–48.ArmstrongZB,BoughnerDR,DrangovaM,RogersKA.AngiotensinIItype1receptorblockerinhibitsarterialcalcificationinapreclinicalmodel.CardiovascRes;90:165–70.ClearyPA,OrchardTJ,GenuthS,etal.Theeffectofintensiveglycemictreatmentoncoronaryarterycalcificationintype1diabeticparticipantsoftheDiabetesControlandComplicationsTrial/EpidemiologyofDiabetesInterventionsandComplications(DCCT/EDIC)Study.Diabetes;55:SamelsonEJ,BoothSL,FoxCS,etal.Calciumintakeisnotassociatedwithincreasedcoronaryarterycalcification:theFraminghamStudy.AmJClinNutr;96:1274–80.WangL,MansonJE,SessoHD.Calciumintakeandriskofcardiovasculardisease:areviewofprospectivestudiesandrandomizedclinicaltrials.AmJCardiovascDrugs;12:105–16AradY,SpadaroLA,RothM,etal.Treatmentofasymptomaticadultswithelevatedcoronarycalciumscoreswithatorvastatin,vitaminC,andvitaminE:theSt.FrancisHeartStudyrandomizedclinicaltrial.JAmCollCardiol,;46:166–72MotroM,ShemeshJ.Calciumchannelblockernifedipineslowsdownprogressionofcoronarycalcificationinhypertensivepatientscomparedwithdiuretics.Hypertension;37:1410–3.MansonJE,AllisonMA,RossouwJE,etal.Estrogentherapyandcoronary-arterycalcification.NEnglJMed;356:2591–602.QunibiW,MoustafaM,MuenzLR,etal.A1-yearrandomizedtrialofcalciumacetateversussevelameronprogressionofcoronaryarterycalcificationinhemodialysispatientswithcomparablelipidcontrol:theCalciumAcetateRenagelEvaluation-2(CARE-2)study.AmJKidneyDis;51:952–65.BittlJA,ChewDP,TopolEJ,etal.Meta-analysisofrandomizedtrialsfpercutaneoustransluminalcoronaryangioplastyversusatherectomy,gballoonatherotomy,orlaserangioplasty.JAmCollCardiol;43:936–42.deRibamarCostaJJr.,MintzGS,CarlierSG,etal.Nonrandomizedcomparisonofcoronarystentingunderintravascularultrasoundguidanceofdirectstentingwithoutpredilationversusconventionalpredilationwithasemi-compliantballoonversuspredilationwithanewscor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