Hypertension and hypertensive left ventricular hypertrophy are associated with ACE2 genetic polymorphism

Fan, Zhimin; Wu, Guihai; Yue, Minghui; Ye, Jianfeng; Chen, Yequn; Xu, Bayi; Shu, Zhouwu; Zhu, Jun; Lu, Nan; Tan, Xuerui

doi:10.1016/j.lfs.2019.03.059

Cited by 61 publications

(54 citation statements)

References 27 publications

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“…Actually, these effects are being investigated in ongoing clinical trials (ClinicalTrials.gov NCT04287686), alongside the use of losartan as first therapy for COVID-19 in hospitalized (NCT04312009) or not hospitalized patients (NCT04311177). A major role in the pathogenesis of (as well as in the clinical response to) COVID-19 could also be played by ACE2 polymorphisms, which are relatively under-investigated if compared to ACE [129,130].…”

Section: Ace2 and Anti-hypertensive Drugs: What Do We Know?mentioning

confidence: 99%

Hypertension, Thrombosis, Kidney Failure, and Diabetes: Is COVID-19 an Endothelial Disease? A Comprehensive Evaluation of Clinical and Basic Evidence

Sardu

Gambardella

Morelli

et al. 2020

JCM

469

436

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The symptoms most commonly reported by patients affected by coronavirus disease (COVID-19) include cough, fever, and shortness of breath. However, other major events usually observed in COVID-19 patients (e.g., high blood pressure, arterial and venous thromboembolism, kidney disease, neurologic disorders, and diabetes mellitus) indicate that the virus is targeting the endothelium, one of the largest organs in the human body. Herein, we report a systematic and comprehensive evaluation of both clinical and preclinical evidence supporting the hypothesis that the endothelium is a key target organ in COVID-19, providing a mechanistic rationale behind its systemic manifestations.

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Section: Ace2 and Anti-hypertensive Drugs: What Do We Know?mentioning

confidence: 99%

Hypertension, Thrombosis, Kidney Failure, and Diabetes: Is COVID-19 an Endothelial Disease? A Comprehensive Evaluation of Clinical and Basic Evidence

Sardu

Gambardella

Morelli

et al. 2020

JCM

469

436

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“…However, in animal models of ageing, pressure overload and chronic ischaemia, ACE2 downregulation has been associated with cardiac hypertrophy, adverse remodelling and fibrosis [28][29][30]. Conversely, ACE2 expression is reduced in hypertension, advanced diabetes mellitus and atherosclerotic plaques and, experimentally, by both angiotensin II (Ang II) and endothelin [28][29][30][31]. Importantly, it has been estimated that heritability accounts for 67% of the variability in ACE2 circulating levels.…”

Section: Angiotensin-converting Enzyme 2 (Ace2)mentioning

confidence: 99%

“…Importantly, it has been estimated that heritability accounts for 67% of the variability in ACE2 circulating levels. Moreover, ACE2 genetic variants have been associated with both essential hypertension and coronary heart disease (CHD), whilst they act as disease modifiers of both hypertrophic and dilated cardiomyopathies [31]. Concerning development, it was shown that ACE2 protein levels and activity are high during gestation and decline postnatally [32].…”

Section: Angiotensin-converting Enzyme 2 (Ace2)mentioning

confidence: 99%

COVID‐19 and renin‐angiotensin system inhibition: role of angiotensin converting enzyme 2 (ACE2) ‐ Is there any scientific evidence for controversy?

et al. 2020

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Renin–angiotensin system (RAS) blockers are extensively used worldwide to treat many cardiovascular disorders, where they are effective in reducing both mortality and morbidity. These drugs are known to induce an increased expression of angiotensin‐converting enzyme 2 (ACE2). ACE2 acts as receptor for the novel SARS coronavirus‐2 (SARS‐CoV‐2) which raising the important issue of possible detrimental effects that RAS blockers could exert on the natural history and pathogenesis of the coronavirus disease‐19 (COVID‐19) and associated excessive inflammation, myocarditis and cardiac arrhythmias. We review the current knowledge on the interaction between SARS‐CoV‐2 infection and RAS blockers and suggest a scientific rationale for continuing RAS blockers therapy in patients with COVID‐19 infection.

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“…On the other hand, it has been shown in a, Chinese population that rs12692386 G promotor polymorphism was associated with higher ADMA17 expression 32 .Moreover, several ACE2 polymorphisms have been reported in different populations including the Chinese. These polymorphisms have been shown to be associated with HTN, DM and CVD as well as with ACE2 activity, and serum ACE2 and angiotensin-(1-7) peptide levels 33 .It remains to be determined whether increased circulating ACE2 levels are due to increased shedding or due to both increased shedding and expression. Notwithstanding, these differences in regulatory processes of ACE2 may modify membrane ACE2 density and theoretically, could influence susceptibility to SARS-CoV-2 infection.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers and The Risk of SARS-CoV-2 Infection: A Systematic Review and Meta-analysis 

Tleyjeh

Abdulhak

Tlayjeh

et al. 2020

Preprint

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Importance:SARS-CoV-2 virus gains access and infects target cells via angiotensin converting enzyme 2 (ACE2) receptor. Because angiotensin converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) could increase the expression of ACE2, there are growing concerns that their use could increase the risk of SARS-CoV-2 infection. Cardiac societies have called for epidemiological research about this emerging controversy. Objective:We sought to systematically review the literature and perform a meta-analysis about prior use of ACEI/ARBs and risk of SARS-CoV-2 infection.Data source:We searched multiple data sources including PubMed , ClinicalTrial.org , and medrxiv.org from November 2019 through May 16, 2020. Study selection:Any study that reported on the adjusted association of prior use of ACEIs / ARBs and risk of acquiring SARS-CoV-2 infection was eligible. Two authors independently reviewed eligible studies and extracted data into a prespecified data collection form. Data synthesis:An inverse variance meta-analytic approach was used to pool adjusted odds ratios using a random effect model meta-analysis. I2 test was used to assess in-between studies heterogeneity. The Newcastle–Ottawa quality assessment scale (NOS) was used to assess the quality of included studies. Main outcome and Measures:The association between the prior use of ACEIs or ARBs and risk of SARS-CoV-2 infection was assessed using pooled OR and 95% confidence interval. Results:Six case control studies that enrolled a total of 5657 patients (2536 patients in ACEIs arm and 3121 patients in ARBs arm ) and 721,859 controls were included in our meta-analysis. Two of the included studies were from the USA, one from Italy, one from China, one from Spain, and one from South Korea. All included studies scored high based on NOS scale. Prior use of ACEIs was not significantly associated with an increased risk of SARS-CoV-2 infection, OR 0.93, CI (0.85,1.02), I2=20%. Similarly, prior use of ARBs was not significantly associated with an increased risk of SARS-CoV-2 infection, OR 0.86, CI (0.67,1.10), I2=93%. Sensitivity analysis was performed by removing a study that could have been affected by residual confounding; OR for ARB 1.04, CI (0.96,1.12), I2=32%.Conclusion:Findings from this systematic review and meta-analysis suggest that prior use of ACEIs or ARBs is not associated with a higher risk of COVID-19. Our results are in support of the recent recommendations of cardiac societies and provide a reassurance to the public not to discontinue prescribed ACEIs/ARBs due to fear of COVID-19.

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Hypertension and hypertensive left ventricular hypertrophy are associated with ACE2 genetic polymorphism

Cited by 61 publications

References 27 publications

Hypertension, Thrombosis, Kidney Failure, and Diabetes: Is COVID-19 an Endothelial Disease? A Comprehensive Evaluation of Clinical and Basic Evidence

Hypertension, Thrombosis, Kidney Failure, and Diabetes: Is COVID-19 an Endothelial Disease? A Comprehensive Evaluation of Clinical and Basic Evidence

COVID‐19 and renin‐angiotensin system inhibition: role of angiotensin converting enzyme 2 (ACE2) ‐ Is there any scientific evidence for controversy?

Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers and The Risk of SARS-CoV-2 Infection: A Systematic Review and Meta-analysis

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Hypertension and hypertensive left ventricular hypertrophy are associated with ACE2 genetic polymorphism

Cited by 61 publications

References 27 publications

Hypertension, Thrombosis, Kidney Failure, and Diabetes: Is COVID-19 an Endothelial Disease? A Comprehensive Evaluation of Clinical and Basic Evidence

Hypertension, Thrombosis, Kidney Failure, and Diabetes: Is COVID-19 an Endothelial Disease? A Comprehensive Evaluation of Clinical and Basic Evidence

COVID‐19 and renin‐angiotensin system inhibition: role of angiotensin converting enzyme 2 (ACE2) ‐ Is there any scientific evidence for controversy?

Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers and The Risk of SARS-CoV-2 Infection: A Systematic Review and Meta-analysis&nbsp;

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Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers and The Risk of SARS-CoV-2 Infection: A Systematic Review and Meta-analysis