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Lipid-lowering therapy and renin-angiotensin-aldosterone system inhibitors in the era of the COVID-19 pandemic.
Archives of Medical Science ( IF 3.8 ) Pub Date : 2020-04-14 , DOI: 10.5114/aoms.2020.94503 Niki Katsiki 1 , Maciej Banach 2, 3 , Dimitri P Mikhailidis 4
Archives of Medical Science ( IF 3.8 ) Pub Date : 2020-04-14 , DOI: 10.5114/aoms.2020.94503 Niki Katsiki 1 , Maciej Banach 2, 3 , Dimitri P Mikhailidis 4
Affiliation
The novel coronavirus (severe acute respiratory syndrome coronavirus 2 â SARS-Cov-2) disease 2019 (COVID-19) pandemic has been associated with severe respiratory disease incidence and increased mortality [1]. Angiotensin converting enzyme (ACE) 2 is a homologue of ACE, but also a receptor for the coronaviruses [2]. ACE2 is highly expressed in the lungs, heart, gastrointestinal (GI) tract and kidney, thus affecting the cardiovascular system (CV) and the immune system [3]. The overexpression of ACE2 was reported to enhance viral entry and replication intracellularly [4]. COVID-19, also called SARS-CoV-2, may also use ACE2 as a receptor to initiate infection, leading to severe complications from the heart (acute coronary syndrome (ACS) and fulminant myocarditis), lungs (pneumonia and acute respiratory distress syndrome (ARDS)) and GI tract (diarrhoea syndrome) [5].
ACE2 gene expression is affected by several factors, including gender (ACE2 gene is X-linked), ACE2 gene polymorphisms, comorbidities (increased in the presence of CVD, hypertension, diabetes), and drug therapy [6]. With regard to drugs, angiotensin II receptor blockers (ARBs) and mineralocorticoid receptor antagonists (MRA) have been reported to raise ACE2 activity in human and animal studies [7]. There are only a few animal studies available showing that statins may also increase ACE2 activity [8, 9]. In the era of the COVID-19 pandemic, such a drug effect may be considered as potentially worrying [10]. In this context, it was recently even suggested that ARBs could be replaced with ACE inhibitors and that statin treatment may be discontinued during the pandemic, particularly in primary prevention settings [11].
However, before implementing such strategies, we should consider several issues. Firstly, as the COVID-19 infection progresses, ACE2 is downregulated, thus potentially generating an inflammatory response leading to impaired cardiac contractility and acute lung injury [5, 7, 12]. Therefore, reduced ACE2 expression is linked to worse outcomes. On the other hand, ACE2 overexpression has been associated with several beneficial effects, i.e. prevention of adverse cardiac remodelling and fibrosis, improvement of vascular endothelial dysfunction, reduction of blood pressure, and protection from ARDS [7, 12]. Both statins and ARBs were reported to exert these benefits.
Secondly, a combination of statins/ARBs were used during the 2014 Ebola virus disease epidemic in Sierra...
中文翻译：
COVID-19大流行时代的降脂治疗和肾素-血管紧张素-醛固酮系统抑制剂。
新型冠状病毒（严重急性呼吸系统综合症冠状病毒2 ?? SARS-Cov-2）疾病2019（COVID-19）大流行与严重的呼吸系统疾病发生率和死亡率增加相关[1]。血管紧张素转换酶（ACE）2是ACE的同源物，也是冠状病毒的受体[2]。ACE2在肺，心脏，胃肠道和肾脏中高度表达，从而影响心血管系统（CV）和免疫系统[3]。据报道，ACE2的过表达可增强病毒进入细胞并在细胞内复制[4]。COVID-19（也称为SARS-CoV-2）也可以使用ACE2作为受体来引发感染，从而导致心脏严重并发症（急性冠状动脉综合征（ACS）和暴发性心肌炎），
ACE2基因表达受多种因素影响，包括性别（ACE2基因X连锁），ACE2基因多态性，合并症（在CVD，高血压，糖尿病的情况下增加）和药物治疗[6]。关于药物，在人类和动物研究中，据报道血管紧张素II受体阻滞剂（ARB）和盐皮质激素受体拮抗剂（MRA）可以提高ACE2的活性[7]。只有少数动物研究表明他汀类药物也可能增加ACE2的活性[8，9]。在COVID-19大流行的时代，这种药物作用可能被认为令人担忧[10]。在这种情况下，最近甚至有人提出可以用ACE抑制剂代替ARB，并且在大流行期间，尤其是在一级预防环境中，可以停止他汀类药物的治疗[11]。
但是，在实施此类策略之前，我们应该考虑几个问题。首先，随着COVID-19感染的进展，ACE2被下调，从而可能产生炎症反应，从而导致心脏收缩力下降和急性肺损伤[5，7，12]。因此，减少的ACE2表达与较差的结果有关。另一方面，ACE2的过表达与几种有益的作用有关，例如，预防不良的心脏重塑和纤维化，改善血管内皮功能障碍，降低血压以及保护ARDS [7，12]。据报道，他汀类药物和ARB均可发挥这些作用。
其次，在2014年塞拉利昂埃博拉病毒病流行期间使用了他汀类药物/ ARBs的组合...
更新日期：2020-04-14
ACE2 gene expression is affected by several factors, including gender (ACE2 gene is X-linked), ACE2 gene polymorphisms, comorbidities (increased in the presence of CVD, hypertension, diabetes), and drug therapy [6]. With regard to drugs, angiotensin II receptor blockers (ARBs) and mineralocorticoid receptor antagonists (MRA) have been reported to raise ACE2 activity in human and animal studies [7]. There are only a few animal studies available showing that statins may also increase ACE2 activity [8, 9]. In the era of the COVID-19 pandemic, such a drug effect may be considered as potentially worrying [10]. In this context, it was recently even suggested that ARBs could be replaced with ACE inhibitors and that statin treatment may be discontinued during the pandemic, particularly in primary prevention settings [11].
However, before implementing such strategies, we should consider several issues. Firstly, as the COVID-19 infection progresses, ACE2 is downregulated, thus potentially generating an inflammatory response leading to impaired cardiac contractility and acute lung injury [5, 7, 12]. Therefore, reduced ACE2 expression is linked to worse outcomes. On the other hand, ACE2 overexpression has been associated with several beneficial effects, i.e. prevention of adverse cardiac remodelling and fibrosis, improvement of vascular endothelial dysfunction, reduction of blood pressure, and protection from ARDS [7, 12]. Both statins and ARBs were reported to exert these benefits.
Secondly, a combination of statins/ARBs were used during the 2014 Ebola virus disease epidemic in Sierra...
中文翻译：
COVID-19大流行时代的降脂治疗和肾素-血管紧张素-醛固酮系统抑制剂。
新型冠状病毒（严重急性呼吸系统综合症冠状病毒2 ?? SARS-Cov-2）疾病2019（COVID-19）大流行与严重的呼吸系统疾病发生率和死亡率增加相关[1]。血管紧张素转换酶（ACE）2是ACE的同源物，也是冠状病毒的受体[2]。ACE2在肺，心脏，胃肠道和肾脏中高度表达，从而影响心血管系统（CV）和免疫系统[3]。据报道，ACE2的过表达可增强病毒进入细胞并在细胞内复制[4]。COVID-19（也称为SARS-CoV-2）也可以使用ACE2作为受体来引发感染，从而导致心脏严重并发症（急性冠状动脉综合征（ACS）和暴发性心肌炎），
ACE2基因表达受多种因素影响，包括性别（ACE2基因X连锁），ACE2基因多态性，合并症（在CVD，高血压，糖尿病的情况下增加）和药物治疗[6]。关于药物，在人类和动物研究中，据报道血管紧张素II受体阻滞剂（ARB）和盐皮质激素受体拮抗剂（MRA）可以提高ACE2的活性[7]。只有少数动物研究表明他汀类药物也可能增加ACE2的活性[8，9]。在COVID-19大流行的时代，这种药物作用可能被认为令人担忧[10]。在这种情况下，最近甚至有人提出可以用ACE抑制剂代替ARB，并且在大流行期间，尤其是在一级预防环境中，可以停止他汀类药物的治疗[11]。
但是，在实施此类策略之前，我们应该考虑几个问题。首先，随着COVID-19感染的进展，ACE2被下调，从而可能产生炎症反应，从而导致心脏收缩力下降和急性肺损伤[5，7，12]。因此，减少的ACE2表达与较差的结果有关。另一方面，ACE2的过表达与几种有益的作用有关，例如，预防不良的心脏重塑和纤维化，改善血管内皮功能障碍，降低血压以及保护ARDS [7，12]。据报道，他汀类药物和ARB均可发挥这些作用。
其次，在2014年塞拉利昂埃博拉病毒病流行期间使用了他汀类药物/ ARBs的组合...
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