李新立:射血分数保留心力衰竭(HFpEF)合并高血压的治疗策略

2021-01-08 《门诊》杂志 门诊新视野

我国发表的REPRESENT-HF研究表明,目前中国心力衰竭(以下简称心衰)患者中射血分数保留心衰(HFpEF)患者的比例为41%。高血压是HFpEF的主要危险因素之一,

我国发表的REPRESENT-HF研究表明,目前中国心力衰竭(以下简称心衰)患者中射血分数保留心衰(HFpEF)患者的比例为41%。高血压是HFpEF的主要危险因素之一,高血压合并HFpEF的患者临床结局更差,死亡率明显增加。加强针对HFpEF合并高血压患者的血压管理对于有效遏制我国HFpEF患者人数不断增多的趋势具有重要临床意义。

HFpEF概念、流行病学及我国相关患者特征

2016 ESC指南及2018中国心衰指南均定义HFpEF为左心室射血分数(LVEF)≥50%。然而,鉴于心衰为一复杂综合征,2019年42位心衰专家在欧洲心脏杂志发表共识联合呼吁,依据LVEF进行心衰分类及管理的模式具有严重局限性,应打破以单一LVEF为指标的心衰分类方法,在深入认识心衰疾病表型的基础上,建立基于病因/发病机制等的分层方法。

HFpEF通常与患者的不良预后相关。已有调查研究表明,对于LVEF<60%的患者,随着LVEF水平的降低,患者的死亡风险逐渐增加;观察性研究和RCT研究也均已表明,总体上HFpEF患者的死亡率明显高于年龄匹配的普通人群(但低于HFrEF患者)。此外,在众多大型临床研究中,与其它血管试验相比,HFpEF试验中因心衰住院的比例明显更高。

我国HFpEF患者具有多个特征。中国HFpEF患者比HFrEF患者伴有更多的合并症,尤其是高血压。有调查显示,相比于HFrEF患者而言,我国HFpEF患者合并高血压(66.31%)、心房颤动/扑动、糖尿病、血脂异常及慢性阻塞性肺病(COPD)的比例更高;且我国女性HFpEF患者比例更高(50.21%),HFpEF患者年龄普遍较大(71.96岁)。(图1)

图1. 中国HFpEF患者比HFrEF患者伴有更多的合并症

HFpEF发病机制和分类

最新的理论认为,心外膜脂肪在HFpEF的发生和发展过程中发挥了重要作用。在高血压、糖尿病、肥胖和其它慢性系统性炎症患者中,其全身性分泌的炎症细胞因子可引起心外膜脂肪组织累积和炎症反应,心外膜脂肪组织的增加可促进充质干细胞迁移转化和局部分泌炎症细胞因子,进而导致深层次地心肌细胞炎症、心肌僵硬度增加、深层心肌纤维化,最终导致HFpEF。(图2)

图2. 心外膜脂肪在HFpEF中的作用

此外,微循环障碍在HFpEF的发生和发展过程中也起到了重要作用。全身性炎症可导致微血管周围的炎症和内皮激活,引起心肌细胞和细胞外基质出现明显结构和功能改变,包括引起NO和血管舒张肽水平的下降,从而引起血管收缩水平增强,进而引起左心室僵硬和心肌的胶原化,最终导致HFpEF的形成。(图3)

图3. 微循环障碍在HFpEF中的作用

在HFpEF分类上,基于2019年欧洲提出的从病因和机制上对HFpEF进行分类后,2020年葛均波院士团队提出可基于病因学将HFpEF分成5大类,分别为血管疾病相关HFpEF、心肌病相关HFpEF、右心和肺动脉疾病相关HFpEF、瓣膜和心律失常相关HFpEF、心脏外疾病相关HFpEF。该分类对于精准选择治疗策略具有一定实际意义。(表1)

表1. 基于病因学将HFpEF分成5大类

HFpEF治疗

由于与HFrEF患者不同的是,HFpEF患者通常合并多种疾病,导致截至目前几乎没有任何获得阳性的试验结果,其中包括几个主要的RAAS抑制剂试验结果,如CHARM-Preserved研究、PEP-CHF研究、I-Preserve研究及TOPCAT研究等。(图4)

图4. HFpEF相关研究的阴性结果

血管紧张素受体脑啡肽酶抑制剂(ARNI)的出现为HFpEF患者的治疗带来了一丝曙光,其中的代表性药物为沙库巴曲缬沙坦。PARAGON-HF研究是一项III期、随机、双盲、活性药物对照研究,旨在比较沙库巴曲缬沙坦与缬沙坦在HEpEF患者总心衰住院和心血管死亡方面的差异,研究中95%患者合并高血压。

PARAGON-HF研究结果表明,沙库巴曲缬沙坦较缬沙坦降低总心衰住院和心血管死亡的主要复合终点13%(HR 0.87;95%CI:0.75~1.01),以微小的差距未达到统计学显著性差异(P=0.059);但主要终点的敏感性分析均显著改善,其中包括紧急心衰就诊(RR 0.86;95%CI:0.75~0.99;P=0.040)和研究者报告的主要终点事件(RR 0.84;95%CI:0.74~0.97;P=0.014),且预先设定的两大亚组人群(女性和LVEF≤57%患者)均显著获益。

另外,今年ACC会议上进一步发表了一项PARAGON-HF相关研究,旨在评估该研究中基线SBP对于HFpEF患者治疗结果的影响。该研究结果显示,HFpEF患者的基线SBP水平并不影响沙库巴曲缬沙坦的疗效;且沙库巴曲缬沙坦在女性HFpEF患者中具有更加明显的降压效果。同时,该分析也提示将SBP控制在120~129 mmHg的HFpEF患者预后最佳,且降低SBP可轻度降低HFpEF患者NT-proBNP水平,但与其生活质量的改善无相关性。

在机制上,有研究认为ARNI治疗HFpEF患者可能通过作用于心外膜脂肪与NO-cGMP-PKG双途径改善HFpEF。在心外膜脂肪方面,已有研究表明,RAAS系统和利钠肽系统与脂肪组织炎症相关,ARNI可通过抑制RAAS系统和增强利钠肽系统,减少心外膜脂肪的累积,从而减少炎症因子的释放,进而降低心肌炎症和纤维化,最终带来疾病改善;在NO-cGMP-PKG途径方面,ARNI可通过增加cGMP水平,更好发挥NO-cGMP途径的作用,从而改善心肌细胞的舒张功能,进而抑制心肌重构,改善疾病症状。(图5)

图5. ARNI治疗HFpEF的可能机制

基于上述研究和已有研究结果,2018版中国高血压指南指出:
对于高血压合并HFpEF患者,尽管ACEI/ARB、β受体阻滞剂和盐皮质激素受体拮抗剂(MRA)并不能改善预后,但用于降压治疗仍值得推荐,也是安全的;如仍未能控制高血压,推荐应用不影响心功能的CCB(如氨氯地平、非洛地平);有负性肌力效应的CCB如地尔硫卓和维拉帕米不能用于HFrEF患者,但对于HFpEF患者,仍可能是安全的;不推荐应用α受体阻滞剂、中枢降压药;推荐采用中国高血压防治指南对高血压进行系统的病因鉴别诊断、危险因素及靶器官损害评估。

对于高血压合并HFpEF血压管理目标,该指南指出,既往观察性研究表明,心衰患者的SBP与全因死亡和心衰再入院呈反J型曲线的关系;建议降压目标定为<140/90 mmHg,合并其他高危因素者建议强化降压治疗,SBP<130/80 mmHg,但注意血压值不宜过低;具体血压目标值尚缺少相关RCT来证实,需要更多的循证医学证据进一步探索高血压合并HFpEF血压的最佳靶目标值。

此外,2020国际高血压学会(ISH)发表的国际高血压实践指南指出,建议高血压合并心衰的患者调整生活方式(包括饮食和运动);在药物治疗方面,可采用ARNI替代ACEI或ARB用于高血压合并HFpEF的患者,即使最佳治疗策略目前尚不清楚;高血压的治疗对降低早期心衰和心衰住院的风险有重要影响,如血压≥140/90 mmHg,应进行降压治疗,降压目标为<130/80 mmHg,但>120/70 mmHg。

总 结

我国HFpEF患者合并高血压比例高,重视这部分患者的血压管理尤为重要。在机制上,心外膜脂肪和微循环障碍在HFpEF的发生和发展过程中也起到了重要作用;在治疗方面,几个主要的RAAS抑制剂试验均显示出阴性结果。而以新型ARNI药物沙库巴曲缬沙坦为研究对象的PARAGON-HF研究尽管在主要终点上未显示出显著性差异,但主要终点的敏感性分析均显著改善,且预先设定的两大亚组人群(女性和LVEF≤57%患者)均显著获益;同时,HFpEF患者的基线SBP水平并不影响ARNI的疗效,提示ARNI或许是治疗部分HFpEF患者的有效药物。未来有待研发出更多适合HFpEF患者的治疗药物。

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    2021-07-10 十八线开外美少女

    沙库巴曲缬沙坦 ARNI血管紧张素受体脑啡肽酶抑制剂 治疗射血分数保留心衰

    0

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    2021-03-13 柳叶一刀
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    2021-01-13 kelvinyang

    不明觉厉 谢谢分享

    0

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    2021-01-10 bettycmoon
  6. [GetPortalCommentsPageByObjectIdResponse(id=998290, encodeId=1452998290a5, content=沙库巴曲缬沙坦 ARNI血管紧张素受体脑啡肽酶抑制剂 治疗射血分数保留心衰, beContent=null, objectType=article, channel=null, level=null, likeNumber=65, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220709/a510c1d082a042b5b7d85344c7f8539a/000346081d9f44ca9473cfda715d2eea.jpg, createdBy=5eec5483989, createdName=十八线开外美少女, createdTime=Sat Jul 10 22:06:55 CST 2021, time=2021-07-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1728765, encodeId=feb41e2876545, content=<a href='/topic/show?id=986913980dd' target=_blank style='color:#2F92EE;'>#PE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13980, encryptionId=986913980dd, topicName=PE)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=778d36, createdName=柳叶一刀, createdTime=Sat Mar 13 15:44:42 CST 2021, time=2021-03-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1746315, encodeId=f8781e463150c, content=<a href='/topic/show?id=699a46801f4' target=_blank style='color:#2F92EE;'>#射血分数保留#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=46801, encryptionId=699a46801f4, topicName=射血分数保留)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c84e35706999, createdName=lixiao3338, createdTime=Mon Nov 22 13:44:42 CST 2021, time=2021-11-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=916372, encodeId=86649163e209, content=不明觉厉 谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eq3roWQ6pYFo2weDrJEjaD7MpMqORRs0nurfWdVjEwhsdciaeQJcmLz0xVEMpY1csyB93Pt0p4oiayA/132, createdBy=015e2506437, createdName=kelvinyang, createdTime=Wed Jan 13 22:31:11 CST 2021, time=2021-01-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1313205, encodeId=77ac13132052a, content=<a href='/topic/show?id=028e8e805e' target=_blank style='color:#2F92EE;'>#HFpEF#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8780, encryptionId=028e8e805e, topicName=HFpEF)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ffd5416, createdName=bettycmoon, createdTime=Sun Jan 10 04:44:42 CST 2021, time=2021-01-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=914743, encodeId=12bc914e43aa, content=学习到了 很棒, beContent=null, objectType=article, channel=null, level=null, likeNumber=86, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210108/ba06a2babef54c0f9ce28b3182b0b371/b44e85df0ee6452f89d3bce720d71ef0.jpg, createdBy=71775451257, createdName=ms1000002103771899, createdTime=Fri Jan 08 22:29:31 CST 2021, time=2021-01-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=914646, encodeId=07b8914646c4, content=不错, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=d6025450970, createdName=ms9000000365380320, createdTime=Fri Jan 08 15:05:34 CST 2021, time=2021-01-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=914642, encodeId=ef3091464226, content=非常好, beContent=null, objectType=article, channel=null, level=null, likeNumber=93, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210108/5dfc2866376c424b865e56a1e638c00b/086417caeb184ac0b968d8655dbf5741.jpg, createdBy=6bed5450750, createdName=ms7000000488748710, createdTime=Fri Jan 08 14:58:40 CST 2021, time=2021-01-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=914636, encodeId=2b639146369b, content=这个真有用的 谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eq3roWQ6pYFo2weDrJEjaD7MpMqORRs0nurfWdVjEwhsdciaeQJcmLz0xVEMpY1csyB93Pt0p4oiayA/132, createdBy=015e2506437, createdName=kelvinyang, createdTime=Fri Jan 08 14:45:40 CST 2021, time=2021-01-08, status=1, ipAttribution=)]
    2021-01-08 ms1000002103771899

    学习到了 很棒

    0

  7. [GetPortalCommentsPageByObjectIdResponse(id=998290, encodeId=1452998290a5, content=沙库巴曲缬沙坦 ARNI血管紧张素受体脑啡肽酶抑制剂 治疗射血分数保留心衰, beContent=null, objectType=article, channel=null, level=null, likeNumber=65, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220709/a510c1d082a042b5b7d85344c7f8539a/000346081d9f44ca9473cfda715d2eea.jpg, createdBy=5eec5483989, createdName=十八线开外美少女, createdTime=Sat Jul 10 22:06:55 CST 2021, time=2021-07-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1728765, encodeId=feb41e2876545, content=<a href='/topic/show?id=986913980dd' target=_blank style='color:#2F92EE;'>#PE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13980, encryptionId=986913980dd, topicName=PE)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=778d36, createdName=柳叶一刀, createdTime=Sat Mar 13 15:44:42 CST 2021, time=2021-03-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1746315, encodeId=f8781e463150c, content=<a href='/topic/show?id=699a46801f4' target=_blank style='color:#2F92EE;'>#射血分数保留#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=46801, encryptionId=699a46801f4, topicName=射血分数保留)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c84e35706999, createdName=lixiao3338, createdTime=Mon Nov 22 13:44:42 CST 2021, time=2021-11-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=916372, encodeId=86649163e209, content=不明觉厉 谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eq3roWQ6pYFo2weDrJEjaD7MpMqORRs0nurfWdVjEwhsdciaeQJcmLz0xVEMpY1csyB93Pt0p4oiayA/132, createdBy=015e2506437, createdName=kelvinyang, createdTime=Wed Jan 13 22:31:11 CST 2021, time=2021-01-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1313205, encodeId=77ac13132052a, content=<a href='/topic/show?id=028e8e805e' target=_blank style='color:#2F92EE;'>#HFpEF#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8780, encryptionId=028e8e805e, topicName=HFpEF)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ffd5416, createdName=bettycmoon, createdTime=Sun Jan 10 04:44:42 CST 2021, time=2021-01-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=914743, encodeId=12bc914e43aa, content=学习到了 很棒, beContent=null, objectType=article, channel=null, level=null, likeNumber=86, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210108/ba06a2babef54c0f9ce28b3182b0b371/b44e85df0ee6452f89d3bce720d71ef0.jpg, createdBy=71775451257, createdName=ms1000002103771899, createdTime=Fri Jan 08 22:29:31 CST 2021, time=2021-01-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=914646, encodeId=07b8914646c4, content=不错, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=d6025450970, createdName=ms9000000365380320, createdTime=Fri Jan 08 15:05:34 CST 2021, time=2021-01-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=914642, encodeId=ef3091464226, content=非常好, beContent=null, objectType=article, channel=null, level=null, likeNumber=93, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210108/5dfc2866376c424b865e56a1e638c00b/086417caeb184ac0b968d8655dbf5741.jpg, createdBy=6bed5450750, createdName=ms7000000488748710, createdTime=Fri Jan 08 14:58:40 CST 2021, time=2021-01-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=914636, encodeId=2b639146369b, content=这个真有用的 谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eq3roWQ6pYFo2weDrJEjaD7MpMqORRs0nurfWdVjEwhsdciaeQJcmLz0xVEMpY1csyB93Pt0p4oiayA/132, createdBy=015e2506437, createdName=kelvinyang, createdTime=Fri Jan 08 14:45:40 CST 2021, time=2021-01-08, status=1, ipAttribution=)]
    2021-01-08 ms9000000365380320

    不错

    0

  8. [GetPortalCommentsPageByObjectIdResponse(id=998290, encodeId=1452998290a5, content=沙库巴曲缬沙坦 ARNI血管紧张素受体脑啡肽酶抑制剂 治疗射血分数保留心衰, beContent=null, objectType=article, channel=null, level=null, likeNumber=65, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220709/a510c1d082a042b5b7d85344c7f8539a/000346081d9f44ca9473cfda715d2eea.jpg, createdBy=5eec5483989, createdName=十八线开外美少女, createdTime=Sat Jul 10 22:06:55 CST 2021, time=2021-07-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1728765, encodeId=feb41e2876545, content=<a href='/topic/show?id=986913980dd' target=_blank style='color:#2F92EE;'>#PE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13980, encryptionId=986913980dd, topicName=PE)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=778d36, createdName=柳叶一刀, createdTime=Sat Mar 13 15:44:42 CST 2021, time=2021-03-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1746315, encodeId=f8781e463150c, content=<a href='/topic/show?id=699a46801f4' target=_blank style='color:#2F92EE;'>#射血分数保留#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=46801, encryptionId=699a46801f4, topicName=射血分数保留)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c84e35706999, createdName=lixiao3338, createdTime=Mon Nov 22 13:44:42 CST 2021, time=2021-11-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=916372, encodeId=86649163e209, content=不明觉厉 谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eq3roWQ6pYFo2weDrJEjaD7MpMqORRs0nurfWdVjEwhsdciaeQJcmLz0xVEMpY1csyB93Pt0p4oiayA/132, createdBy=015e2506437, createdName=kelvinyang, createdTime=Wed Jan 13 22:31:11 CST 2021, time=2021-01-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1313205, encodeId=77ac13132052a, content=<a href='/topic/show?id=028e8e805e' target=_blank style='color:#2F92EE;'>#HFpEF#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8780, encryptionId=028e8e805e, topicName=HFpEF)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ffd5416, createdName=bettycmoon, createdTime=Sun Jan 10 04:44:42 CST 2021, time=2021-01-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=914743, encodeId=12bc914e43aa, content=学习到了 很棒, beContent=null, objectType=article, channel=null, level=null, likeNumber=86, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210108/ba06a2babef54c0f9ce28b3182b0b371/b44e85df0ee6452f89d3bce720d71ef0.jpg, createdBy=71775451257, createdName=ms1000002103771899, createdTime=Fri Jan 08 22:29:31 CST 2021, time=2021-01-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=914646, encodeId=07b8914646c4, content=不错, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=d6025450970, createdName=ms9000000365380320, createdTime=Fri Jan 08 15:05:34 CST 2021, time=2021-01-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=914642, encodeId=ef3091464226, content=非常好, beContent=null, objectType=article, channel=null, level=null, likeNumber=93, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210108/5dfc2866376c424b865e56a1e638c00b/086417caeb184ac0b968d8655dbf5741.jpg, createdBy=6bed5450750, createdName=ms7000000488748710, createdTime=Fri Jan 08 14:58:40 CST 2021, time=2021-01-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=914636, encodeId=2b639146369b, content=这个真有用的 谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eq3roWQ6pYFo2weDrJEjaD7MpMqORRs0nurfWdVjEwhsdciaeQJcmLz0xVEMpY1csyB93Pt0p4oiayA/132, createdBy=015e2506437, createdName=kelvinyang, createdTime=Fri Jan 08 14:45:40 CST 2021, time=2021-01-08, status=1, ipAttribution=)]
    2021-01-08 ms7000000488748710

    非常好

    0

  9. [GetPortalCommentsPageByObjectIdResponse(id=998290, encodeId=1452998290a5, content=沙库巴曲缬沙坦 ARNI血管紧张素受体脑啡肽酶抑制剂 治疗射血分数保留心衰, beContent=null, objectType=article, channel=null, level=null, likeNumber=65, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220709/a510c1d082a042b5b7d85344c7f8539a/000346081d9f44ca9473cfda715d2eea.jpg, createdBy=5eec5483989, createdName=十八线开外美少女, createdTime=Sat Jul 10 22:06:55 CST 2021, time=2021-07-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1728765, encodeId=feb41e2876545, content=<a href='/topic/show?id=986913980dd' target=_blank style='color:#2F92EE;'>#PE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13980, encryptionId=986913980dd, topicName=PE)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=778d36, createdName=柳叶一刀, createdTime=Sat Mar 13 15:44:42 CST 2021, time=2021-03-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1746315, encodeId=f8781e463150c, content=<a href='/topic/show?id=699a46801f4' target=_blank style='color:#2F92EE;'>#射血分数保留#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=46801, encryptionId=699a46801f4, topicName=射血分数保留)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c84e35706999, createdName=lixiao3338, createdTime=Mon Nov 22 13:44:42 CST 2021, time=2021-11-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=916372, encodeId=86649163e209, content=不明觉厉 谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eq3roWQ6pYFo2weDrJEjaD7MpMqORRs0nurfWdVjEwhsdciaeQJcmLz0xVEMpY1csyB93Pt0p4oiayA/132, createdBy=015e2506437, createdName=kelvinyang, createdTime=Wed Jan 13 22:31:11 CST 2021, time=2021-01-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1313205, encodeId=77ac13132052a, content=<a href='/topic/show?id=028e8e805e' target=_blank style='color:#2F92EE;'>#HFpEF#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8780, encryptionId=028e8e805e, topicName=HFpEF)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ffd5416, createdName=bettycmoon, createdTime=Sun Jan 10 04:44:42 CST 2021, time=2021-01-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=914743, encodeId=12bc914e43aa, content=学习到了 很棒, beContent=null, objectType=article, channel=null, level=null, likeNumber=86, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210108/ba06a2babef54c0f9ce28b3182b0b371/b44e85df0ee6452f89d3bce720d71ef0.jpg, createdBy=71775451257, createdName=ms1000002103771899, createdTime=Fri Jan 08 22:29:31 CST 2021, time=2021-01-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=914646, encodeId=07b8914646c4, content=不错, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=d6025450970, createdName=ms9000000365380320, createdTime=Fri Jan 08 15:05:34 CST 2021, time=2021-01-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=914642, encodeId=ef3091464226, content=非常好, beContent=null, objectType=article, channel=null, level=null, likeNumber=93, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210108/5dfc2866376c424b865e56a1e638c00b/086417caeb184ac0b968d8655dbf5741.jpg, createdBy=6bed5450750, createdName=ms7000000488748710, createdTime=Fri Jan 08 14:58:40 CST 2021, time=2021-01-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=914636, encodeId=2b639146369b, content=这个真有用的 谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eq3roWQ6pYFo2weDrJEjaD7MpMqORRs0nurfWdVjEwhsdciaeQJcmLz0xVEMpY1csyB93Pt0p4oiayA/132, createdBy=015e2506437, createdName=kelvinyang, createdTime=Fri Jan 08 14:45:40 CST 2021, time=2021-01-08, status=1, ipAttribution=)]
    2021-01-08 kelvinyang

    这个真有用的 谢谢分享

    0

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