冠狀動脈鈣化成因及治療新進(jìn)展

作者：周玉杰[1]柴萌 -9-1610:14:08冠狀動脈鈣化(Coronaryarterycalcification,CAC)的??現(xiàn)都提示預(yù)后不良?，F(xiàn)在其發(fā)病機(jī)制尚未完全闡明,近年來證明血管鈣化是冠狀動脈鈣化(Coronaryarterycalcification,CAC)可造成血管僵硬度增加，順應(yīng)性減少，心肌灌注受損[1]。臨床研究表明,CAC程度能夠預(yù)測心肌梗死和突CAC的??現(xiàn)都提示預(yù)后不良?，F(xiàn)在其發(fā)病機(jī)制尚未完全闡明,近年來證明血管CACCAC的程度與斑塊負(fù)擔(dān)親密有關(guān)[5]，微鈣化如發(fā)生于覆蓋動脈粥樣硬化斑塊形成,經(jīng)常見于穩(wěn)定心絞痛型和猝死型冠心病患者[7,8]C9p21)和磷酸代謝的罕見突變有關(guān)[9–11]肌細(xì)胞向成骨樣表型轉(zhuǎn)變[12]，也與CAC的進(jìn)展有關(guān)。1CAC是是是是是否是否是否是否否是高否是鈣 磷 慢性腎病患者心血管發(fā)病率和死亡率高很大程度上是由于存在CAC及動脈粥樣硬化。高鈣血癥和高磷血癥均可增進(jìn)CAC。磷酸鹽除了可調(diào)節(jié)磷鈣平衡外,效亢進(jìn)也是CAC的一種危險(xiǎn)因素[14]。另外,腎素-血管緊張素-醛固酮系統(tǒng)可能在中膜鈣化的進(jìn)展中發(fā)揮重要作用,由于在臨床前模型中證明，血管緊張素II-1型受體阻滯劑克制了CAC的進(jìn)展[15]?？赡軙p緩CAC的進(jìn)展（現(xiàn)在這種現(xiàn)象只發(fā)現(xiàn)于1型糖尿病患者）[16]。CAC性[17,18]。這些數(shù)據(jù)表明，CAC增強(qiáng)對CAC傳導(dǎo)通路的研究，可能有助于發(fā)現(xiàn)更有效的治療辦法。CAC近年來多項(xiàng)研究試圖證明有關(guān)藥品治療能夠克制甚至逆轉(zhuǎn)CAC進(jìn)展，但大多得到了陰性成果。早在，St.FrancisHeartStudy1005CAC某些小規(guī)模的隨機(jī)前瞻性研究發(fā)現(xiàn)，鈣通道阻滯劑[20][21],磷酸鹽結(jié)合劑[22]能夠延緩CAC的進(jìn)程，但仍缺少大規(guī)模的前瞻性實(shí)驗(yàn)證據(jù)。BMSDES重建率低。然而，即使DES的植入在一定程度上改善了冠脈鈣化患者的預(yù)后，但CAC患者PCI手術(shù)難度高、成功率低、并發(fā)癥多、預(yù)后差，是介入手術(shù)中最Ⅲ～Ⅳ2mmBittlJA等發(fā)表的一篇Meta分析顯示與普通球囊擴(kuò)張術(shù)相比，切割球囊得到類似的再狹窄率和MACE事件，且心梗和穿孔率更高[23]。而近期Vaquerizo等將切割球囊與旋磨術(shù)進(jìn)行對照，發(fā)現(xiàn)中短期預(yù)后無是PCI術(shù)中解決鈣化病變的重要輔助辦法。冠狀動脈旋磨術(shù)（Rotational00rpm,可將堅(jiān)硬組織研磨成極微小的顆粒(<10mm)[25]。發(fā)表的隨機(jī)對照研究（ROTAXUS研究），將患者RA+DES（120）PCI（120），成果顯示盡管旋磨增加介入手術(shù)的成功率，卻未能減少晚期管腔丟失，更未能在MACE等硬終點(diǎn)上獲益[26]221669PCIRA（不不不大于參考血管直徑的70％為宜），緩慢推動旋磨導(dǎo)管，避免轉(zhuǎn)速下降上個(gè)世紀(jì)90年代，就有人嘗試應(yīng)用激光來攻克介入治療的難題如再狹窄等。源，激光以脈沖方式作用于組織，每次一脈沖的作用時(shí)間僅為135納秒（一百億分之一秒），穿透深度僅為50μm，通過光化學(xué)作用破壞分子鍵，光熱學(xué)作用產(chǎn)3其發(fā)展可能給CAC患者帶來福音。PCI其它PCI有關(guān)器械的選擇也極為重要：（1）強(qiáng)支撐力指導(dǎo)導(dǎo)管（EBU、XB、Amplatz等）；（2）親水涂層（或聚合物涂層）指導(dǎo)導(dǎo)絲；（3）輻射張力強(qiáng)的支架，必要時(shí)可選擇短支架進(jìn)行拼接。，LeeY等的研究證明更薄的藥品支架可明顯改善旋磨術(shù)后患者預(yù)后[29]Cyper支架的鋼梁厚度為140μm，TaxusLiberty為132μmResolute91μm，XienceVPCIPCI冠脈斑塊消融術(shù)給CAC患者提供一種新的選擇，但仍需大規(guī)模隨機(jī)對照實(shí)驗(yàn)證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,C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