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高血压年会 2020 : 原发性醛固酮增多症——大动脉硬化的帮凶

2020-09-18 《门诊》杂志 门诊新视野

原发性醛固酮增多症(Primary aldosteronism,PA)是由于肾上腺皮质病变导致醛固酮分泌增多,进而导致水钠潴留、肾素-血管紧张素系统活性受抑制所导致的综合征。

原发性醛固酮增多症(Primary aldosteronism,PA)是由于肾上腺皮质病变导致醛固酮分泌增多,进而导致水钠潴留、肾素-血管紧张素系统活性受抑制所导致的综合征。随着医学技术的发展,在高血压人群中原发性醛固酮增多症的检出率也随之增多。2020年9月17日,在2020年中国高血压年会与第22届国际高血压及相关疾病学术研讨会上,新疆维吾尔自治区人民医院的骆秦教授围绕原发性醛固酮增多症进行了详细阐述。

原发性醛固酮增多症的病理生理学

醛固酮与远端肾单位(或醛固酮敏感的远端肾单位)主细胞的受体相互作用引起管腔上皮钠通道(ENaC)增加,从而导致钠的重吸收增加。钠离子重吸收引起的管腔内负电位通过肾髓质外钾通道(ROMKs)排出钾或α-闰细胞排出氢离子中和。最终导致高血压和低血钾,甚至引发心血管疾病和肾脏疾病。研究指出,PA引起的血管内皮功能障碍主要包括四个方面:血管收缩功能损伤,从而使血管张力发生改变;血管与系统的炎症;血管重塑以及早期的动脉粥样硬化。

多项临床研究证实,一些反应血管炎症以及内皮功能的生物标记物,比如细胞间粘附因子(ICAM-1)、氧化修饰型低密度脂蛋白(Ox-LDL)、炎症因子以及包括超敏C反应蛋白(hsCRP)和尿微量白蛋白等临床指标在PA患者中是明显升高的。在反应血管内皮功能的无创检查中,比如FDM,NMD、PWV、增益指数(AI)等,PA患者的指标也是异常的。此外,PA患者的颈动脉内膜增厚增加、主动脉钙化现象增多且心血管疾病发病率和死亡率增高。

PA患者内皮功能障碍治疗和血管钙化的临床研究

研究提示,PA患者经过药物治疗(螺内酯以及依普利酮)与肾上腺切除手术后,反应血管功能的指标有所改善。螺内酯是目前常用的醛固酮拮抗剂,但由于其副作用,临床依从性不佳。新疆维吾尔自治区人民医院高血压诊疗中心纳入了2010-2019年间,确诊为PA且自然进行复诊的145例患者。通过检测患者的尿微量白蛋白观察长期服用螺内酯对于血管内皮功能的影响。该研究将145例患者中停用螺内酯半年以上的纳入非依从组(43例),102例患者纳入依从组。结果显示,螺内酯依从组患者的尿微量白蛋白水平明显低于非依从组。且尿微量白蛋白下降主要发生在服药剂量为40 mg以上的患者中。该研究提示,长期、足量应用螺内酯,对血管内皮具有保护作用。

血管钙化是动脉粥样硬化的热点问题之一。近期一项纳入30项研究的荟萃分析提示,血管钙化患者的心脑血管疾病发生率是非钙化患者的3-4倍。醛固酮和血管钙化的正相关关系是近年来新的研究进展。醛固酮可通过基因组和非基因组的机制影响血管钙化。其中,基因组相关机制主要包括氧化应激、炎症以及细胞凋亡。2018年发布于Hypertension的一项研究首次在PA患者中观察了腹主动脉钙化的情况。结果显示,与年龄、性别和血压水平匹配的原发性高血压患者相比,PA患者腹主动脉钙化发生率显着高于原发性高血压患者。从机制角度而言,PA患者的腹主动脉钙化可能与血清14、15 环氧二十碳三烯酸下调有关。血清14、15环氧二十碳三烯酸可抑制炎症,对血管重塑具有一定保护作用。

甲状旁腺激素在PA中的作用

目前,肾上腺静脉取血(AVS)是对PA患者进行分型的“金标准”。PA主要分为单侧型和双侧型。单侧型PA多见于醛固酮腺瘤(APA),双侧型PA多见于原发性肾上腺增生(IHA)。单侧型PA与双侧型相比,患者往往表现为更高的血压水平、更低的血钾水平和更高的醛固酮分泌,CT往往可以观察到更典型的肾上腺肿瘤。2012年发布的一项针对甲状旁腺亢进的研究发现在单侧型PA患者中,甲状旁腺激素(PTH)水平明显升高。该研究提示,PTH升高对分辨单侧型PA具有一定的诊断价值。另一项来自德国的研究结果显示,在PA患者中,PTH水平明显升高,尤其是单侧型PA患者。原发性甲状旁腺机能亢进发生率较低,为1.6%。而继发性甲状旁腺机能亢进发生率高达56.0%,尤其在单侧型PA患者中发生率更高。经手术治疗或药物治疗后,患者PTH值水平明显下降。在CKD患者中,已有多项研究证实PTH水平升高与冠状动脉钙化相关。近年来,我国学者在无肾衰的患者中也发现PTH可以影响冠状动脉钙化进程。

既往证据表明PTH与醛固酮互相影响,二者相互作用将进一步加重对血管和心脏的损害。新疆维吾尔自治区人民医院高血压诊疗中心纳入了2017-2018一年间,经过严格筛查和诊断后确诊为PA的患者156例。通过AVS分型,76例为单侧型,80例为双侧型。研究结果显示,在PA患者中,醛固酮水平和PTH水平均高于原发性高血压患者。同时,PA患者的腹主动脉钙化发生率和腹主动脉钙化指数都明显高于原发性高血压患者。此外,单侧PA患者的醛固酮水平、PTH水平以及腹主动脉钙化发生率和指数均高于双侧型患者。多因素分析提示,在单侧型PA患者中,腹主动脉钙化情况加重主要与醛固酮和PTH水平增高相关。

总 结

最后,骆秦教授总结道,醛固酮增多是造成PA患者血管损伤的核心机制。同时,PTH水平也与PA患者的动脉血管钙化具有相关性,尤其是单侧型PA。因此,PA是大动脉血管硬化的“帮凶”。需要强调的是及早发现PA并及时进行干预是必要的,包括基于准确分型基础上的手术治疗和药物治疗。

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    2021-12-04 ms2000001432825724

    醛固酮PA增多,如何检查诊断?

    0

  3. 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encryptionId=ef1d898002a, topicName=血管钙化), TopicDto(id=33293, encryptionId=98773329350, topicName=动脉粥样硬化)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=lovetcm, createdTime=Fri Sep 18 22:08:05 CST 2020, time=2020-09-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1670516, encodeId=851716e05165e, content=<a href='/topic/show?id=ece0436250d' target=_blank style='color:#2F92EE;'>#大动脉硬化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=94, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=43625, encryptionId=ece0436250d, topicName=大动脉硬化)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=520426715614, createdName=wmr120, createdTime=Thu Mar 18 06:14:16 CST 2021, time=2021-03-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2080080, encodeId=544c208008072, content=<a href='/topic/show?id=5efa956449d' target=_blank style='color:#2F92EE;'>#醛固酮增多症#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=78, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=95644, encryptionId=5efa956449d, topicName=醛固酮增多症)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a7b6284, createdName=FukaiBao, createdTime=Wed Jun 02 20:14:16 CST 2021, time=2021-06-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=888233, encodeId=c50f88823356, content=醛固酮增多是造成PA患者血管损伤的核心机制。, beContent=null, objectType=article, channel=null, level=null, likeNumber=110, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b58d5402080, createdName=咻凡, createdTime=Fri Sep 25 11:38:29 CST 2020, time=2020-09-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=887946, encodeId=246a88e946a2, content=需要强调的是及早发现PA并及时进行干预是必要的,包括基于准确分型基础上的手术治疗和药物治疗。, beContent=null, objectType=article, channel=null, level=null, likeNumber=117, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ae205385871, createdName=Lexi, createdTime=Thu Sep 24 14:13:24 CST 2020, time=2020-09-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1379257, encodeId=db9b13e9257af, content=<a href='/topic/show?id=ac549564240' target=_blank style='color:#2F92EE;'>#醛固酮#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=103, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=95642, encryptionId=ac549564240, topicName=醛固酮)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=aad0444, createdName=cmsvly, createdTime=Sun Sep 20 12:14:16 CST 2020, time=2020-09-20, status=1, 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  4. 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encryptionId=ef1d898002a, topicName=血管钙化), TopicDto(id=33293, encryptionId=98773329350, topicName=动脉粥样硬化)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=lovetcm, createdTime=Fri Sep 18 22:08:05 CST 2020, time=2020-09-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1670516, encodeId=851716e05165e, content=<a href='/topic/show?id=ece0436250d' target=_blank style='color:#2F92EE;'>#大动脉硬化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=94, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=43625, encryptionId=ece0436250d, topicName=大动脉硬化)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=520426715614, createdName=wmr120, createdTime=Thu Mar 18 06:14:16 CST 2021, time=2021-03-18, status=1, ipAttribution=), 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ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=886475, encodeId=b17d8864e5a9, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=122, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/1IAgiaWNJ5zFKEL0BJP1eUeP64r1N39eQeSrqjiaMqNccGbpLia00lKuN1NWjV40oQgfw01I0WBj34BrFl5ARgDPw/132, createdBy=d7205268185, createdName=太空旅客, createdTime=Fri Sep 18 21:38:18 CST 2020, time=2020-09-18, status=1, ipAttribution=)]
    2020-09-18 lovetcm

    #原发性醛固酮增多症##血管钙化##动脉粥样硬化#等皆密切相关,它可能是始动因素之一

    1

    展开1条回复
  5. [GetPortalCommentsPageByObjectIdResponse(id=1191381, encodeId=7b4e119138186, content=实用, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f0b32432573, createdName=123bc59dm18暂无昵称, createdTime=Wed Feb 09 11:14:37 CST 2022, time=2022-02-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1076925, encodeId=69d710e6925fb, content=醛固酮PA增多,如何检查诊断?, beContent=null, objectType=article, channel=null, level=null, likeNumber=94, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c8d85638607, createdName=ms2000001432825724, createdTime=Sat Dec 04 20:07:43 CST 2021, time=2021-12-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1846930, encodeId=45c21846930c7, content=<a href='/topic/show?id=d3a33e0306d' target=_blank style='color:#2F92EE;'>#原发性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=82, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=37030, encryptionId=d3a33e0306d, topicName=原发性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8e4c53, createdName=jiyangfei, createdTime=Mon Nov 23 07:14:16 CST 2020, time=2020-11-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=886505, encodeId=d703886505bd, content=<a href='/topic/show?id=e01f3e12825' target=_blank style='color:#2F92EE;'>#原发性醛固酮增多症#</a>与<a href='/topic/show?id=ef1d898002a' target=_blank style='color:#2F92EE;'>#血管钙化#</a>,<a href='/topic/show?id=98773329350' target=_blank style='color:#2F92EE;'>#动脉粥样硬化#</a>等皆密切相关,它可能是始动因素之一, beContent=null, objectType=article, channel=null, level=null, likeNumber=285, replyNumber=1, topicName=null, topicId=null, topicList=[TopicDto(id=37128, encryptionId=e01f3e12825, topicName=原发性醛固酮增多症), TopicDto(id=89800, encryptionId=ef1d898002a, topicName=血管钙化), TopicDto(id=33293, encryptionId=98773329350, topicName=动脉粥样硬化)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=lovetcm, createdTime=Fri Sep 18 22:08:05 CST 2020, time=2020-09-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1670516, encodeId=851716e05165e, content=<a href='/topic/show?id=ece0436250d' target=_blank style='color:#2F92EE;'>#大动脉硬化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=94, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=43625, encryptionId=ece0436250d, topicName=大动脉硬化)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=520426715614, createdName=wmr120, createdTime=Thu Mar 18 06:14:16 CST 2021, time=2021-03-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2080080, encodeId=544c208008072, content=<a href='/topic/show?id=5efa956449d' target=_blank style='color:#2F92EE;'>#醛固酮增多症#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=78, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=95644, encryptionId=5efa956449d, topicName=醛固酮增多症)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a7b6284, createdName=FukaiBao, createdTime=Wed Jun 02 20:14:16 CST 2021, time=2021-06-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=888233, encodeId=c50f88823356, content=醛固酮增多是造成PA患者血管损伤的核心机制。, beContent=null, objectType=article, channel=null, level=null, likeNumber=110, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b58d5402080, createdName=咻凡, createdTime=Fri Sep 25 11:38:29 CST 2020, time=2020-09-25, status=1, ipAttribution=), 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ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=886475, encodeId=b17d8864e5a9, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=122, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/1IAgiaWNJ5zFKEL0BJP1eUeP64r1N39eQeSrqjiaMqNccGbpLia00lKuN1NWjV40oQgfw01I0WBj34BrFl5ARgDPw/132, createdBy=d7205268185, createdName=太空旅客, createdTime=Fri Sep 18 21:38:18 CST 2020, time=2020-09-18, status=1, ipAttribution=)]
  6. [GetPortalCommentsPageByObjectIdResponse(id=1191381, encodeId=7b4e119138186, content=实用, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f0b32432573, createdName=123bc59dm18暂无昵称, createdTime=Wed Feb 09 11:14:37 CST 2022, time=2022-02-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1076925, encodeId=69d710e6925fb, content=醛固酮PA增多,如何检查诊断?, beContent=null, objectType=article, channel=null, level=null, likeNumber=94, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c8d85638607, createdName=ms2000001432825724, createdTime=Sat Dec 04 20:07:43 CST 2021, time=2021-12-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1846930, encodeId=45c21846930c7, content=<a href='/topic/show?id=d3a33e0306d' target=_blank style='color:#2F92EE;'>#原发性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=82, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=37030, encryptionId=d3a33e0306d, topicName=原发性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8e4c53, createdName=jiyangfei, createdTime=Mon Nov 23 07:14:16 CST 2020, time=2020-11-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=886505, encodeId=d703886505bd, content=<a href='/topic/show?id=e01f3e12825' target=_blank style='color:#2F92EE;'>#原发性醛固酮增多症#</a>与<a href='/topic/show?id=ef1d898002a' target=_blank style='color:#2F92EE;'>#血管钙化#</a>,<a href='/topic/show?id=98773329350' target=_blank style='color:#2F92EE;'>#动脉粥样硬化#</a>等皆密切相关,它可能是始动因素之一, beContent=null, objectType=article, channel=null, level=null, likeNumber=285, replyNumber=1, topicName=null, topicId=null, topicList=[TopicDto(id=37128, encryptionId=e01f3e12825, topicName=原发性醛固酮增多症), TopicDto(id=89800, 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ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=886475, encodeId=b17d8864e5a9, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=122, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/1IAgiaWNJ5zFKEL0BJP1eUeP64r1N39eQeSrqjiaMqNccGbpLia00lKuN1NWjV40oQgfw01I0WBj34BrFl5ARgDPw/132, createdBy=d7205268185, createdName=太空旅客, createdTime=Fri Sep 18 21:38:18 CST 2020, time=2020-09-18, status=1, ipAttribution=)]
  7. 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ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=886475, encodeId=b17d8864e5a9, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=122, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/1IAgiaWNJ5zFKEL0BJP1eUeP64r1N39eQeSrqjiaMqNccGbpLia00lKuN1NWjV40oQgfw01I0WBj34BrFl5ARgDPw/132, createdBy=d7205268185, createdName=太空旅客, createdTime=Fri Sep 18 21:38:18 CST 2020, time=2020-09-18, status=1, ipAttribution=)]
    2020-09-25 咻凡

    醛固酮增多是造成PA患者血管损伤的核心机制。

    0

  8. 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ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=886475, encodeId=b17d8864e5a9, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=122, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/1IAgiaWNJ5zFKEL0BJP1eUeP64r1N39eQeSrqjiaMqNccGbpLia00lKuN1NWjV40oQgfw01I0WBj34BrFl5ARgDPw/132, createdBy=d7205268185, createdName=太空旅客, createdTime=Fri Sep 18 21:38:18 CST 2020, time=2020-09-18, status=1, ipAttribution=)]
    2020-09-24 Lexi

    需要强调的是及早发现PA并及时进行干预是必要的,包括基于准确分型基础上的手术治疗和药物治疗。

    0

  9. 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ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=886475, encodeId=b17d8864e5a9, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=122, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/1IAgiaWNJ5zFKEL0BJP1eUeP64r1N39eQeSrqjiaMqNccGbpLia00lKuN1NWjV40oQgfw01I0WBj34BrFl5ARgDPw/132, createdBy=d7205268185, createdName=太空旅客, createdTime=Fri Sep 18 21:38:18 CST 2020, time=2020-09-18, status=1, ipAttribution=)]
    2020-09-20 cmsvly
  10. 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    2020-09-18 太空旅客

    学习了

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