Commentary: What is the relationship between Covid-19 and cardiovascular disease?
Identifieur interne : 000302 ( Pmc/Corpus ); précédent : 000301; suivant : 000303Commentary: What is the relationship between Covid-19 and cardiovascular disease?
Auteurs : R. Ferrari ; G. Di Pasquale ; C. RapezziSource :
- International Journal of Cardiology [ 0167-5273 ] ; 2020.
Url:
DOI: 10.1016/j.ijcard.2020.03.074
PubMed: 32276773
PubMed Central: 7138145
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Commentary: What is the relationship between Covid-19 and cardiovascular disease?</title><author><name sortKey="Ferrari, R" sort="Ferrari, R" uniqKey="Ferrari R" first="R." last="Ferrari">R. Ferrari</name><affiliation><nlm:aff id="af0005">Centro Cardiologico Universitario di Ferrara, University of Ferrara, Italy</nlm:aff></affiliation><affiliation><nlm:aff id="af0010">Maria Cecilia Hospital, GVM Care & Research, Cotignola, RA, Italy</nlm:aff></affiliation></author><author><name sortKey="Di Pasquale, G" sort="Di Pasquale, G" uniqKey="Di Pasquale G" first="G." last="Di Pasquale">G. Di Pasquale</name><affiliation><nlm:aff id="af0015">Division of Cardiology, Maggiore Hospital, Bologna, Italy</nlm:aff></affiliation></author><author><name sortKey="Rapezzi, C" sort="Rapezzi, C" uniqKey="Rapezzi C" first="C." last="Rapezzi">C. Rapezzi</name><affiliation><nlm:aff id="af0005">Centro Cardiologico Universitario di Ferrara, University of Ferrara, Italy</nlm:aff></affiliation><affiliation><nlm:aff id="af0010">Maria Cecilia Hospital, GVM Care & Research, Cotignola, RA, Italy</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">32276773</idno><idno type="pmc">7138145</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138145</idno><idno type="RBID">PMC:7138145</idno><idno type="doi">10.1016/j.ijcard.2020.03.074</idno><date when="2020">2020</date><idno type="wicri:Area/Pmc/Corpus">000302</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000302</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Commentary: What is the relationship between Covid-19 and cardiovascular disease?</title><author><name sortKey="Ferrari, R" sort="Ferrari, R" uniqKey="Ferrari R" first="R." last="Ferrari">R. Ferrari</name><affiliation><nlm:aff id="af0005">Centro Cardiologico Universitario di Ferrara, University of Ferrara, Italy</nlm:aff></affiliation><affiliation><nlm:aff id="af0010">Maria Cecilia Hospital, GVM Care & Research, Cotignola, RA, Italy</nlm:aff></affiliation></author><author><name sortKey="Di Pasquale, G" sort="Di Pasquale, G" uniqKey="Di Pasquale G" first="G." last="Di Pasquale">G. Di Pasquale</name><affiliation><nlm:aff id="af0015">Division of Cardiology, Maggiore Hospital, Bologna, Italy</nlm:aff></affiliation></author><author><name sortKey="Rapezzi, C" sort="Rapezzi, C" uniqKey="Rapezzi C" first="C." last="Rapezzi">C. Rapezzi</name><affiliation><nlm:aff id="af0005">Centro Cardiologico Universitario di Ferrara, University of Ferrara, Italy</nlm:aff></affiliation><affiliation><nlm:aff id="af0010">Maria Cecilia Hospital, GVM Care & Research, Cotignola, RA, Italy</nlm:aff></affiliation></author></analytic><series><title level="j">International Journal of Cardiology</title><idno type="ISSN">0167-5273</idno><idno type="eISSN">1874-1754</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Munster, V J" uniqKey="Munster V">V.J. Munster</name></author><author><name sortKey="Koopmans, M" uniqKey="Koopmans M">M. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Int J Cardiol</journal-id><journal-id journal-id-type="iso-abbrev">Int. J. Cardiol</journal-id><journal-title-group><journal-title>International Journal of Cardiology</journal-title></journal-title-group><issn pub-type="ppub">0167-5273</issn><issn pub-type="epub">1874-1754</issn><publisher><publisher-name>Elsevier B.V.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">32276773</article-id><article-id pub-id-type="pmc">7138145</article-id><article-id pub-id-type="publisher-id">S0167-5273(20)31387-5</article-id><article-id pub-id-type="doi">10.1016/j.ijcard.2020.03.074</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Commentary: What is the relationship between Covid-19 and cardiovascular disease?</article-title></title-group><contrib-group><contrib contrib-type="author" id="au0005"><name><surname>Ferrari</surname><given-names>R.</given-names></name><email>fri@unife.it</email><xref rid="af0005" ref-type="aff">a</xref><xref rid="af0010" ref-type="aff">b</xref><xref rid="cr0005" ref-type="corresp">⁎</xref></contrib><contrib contrib-type="author" id="au0010"><name><surname>Di Pasquale</surname><given-names>G.</given-names></name><xref rid="af0015" ref-type="aff">c</xref></contrib><contrib contrib-type="author" id="au0015"><name><surname>Rapezzi</surname><given-names>C.</given-names></name><xref rid="af0005" ref-type="aff">a</xref><xref rid="af0010" ref-type="aff">b</xref></contrib></contrib-group><aff id="af0005"><label>a</label>Centro Cardiologico Universitario di Ferrara, University of Ferrara, Italy</aff><aff id="af0010"><label>b</label>Maria Cecilia Hospital, GVM Care & Research, Cotignola, RA, Italy</aff><aff id="af0015"><label>c</label>Division of Cardiology, Maggiore Hospital, Bologna, Italy</aff><author-notes><corresp id="cr0005"><label>⁎</label>Corresponding author at: Azienda Ospedaliero-Universitaria di Ferrara, Ospedale di Cona, Via Aldo Moro 8, 44124 Cona, Ferrara, Italy. <email>fri@unife.it</email></corresp></author-notes><pub-date pub-type="pmc-release"><day>31</day><month>3</month><year>2020</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on .</pmc-comment>
<pub-date pub-type="epub"><day>31</day><month>3</month><year>2020</year></pub-date><elocation-id></elocation-id><history><date date-type="received"><day>30</day><month>3</month><year>2020</year></date><date date-type="accepted"><day>30</day><month>3</month><year>2020</year></date></history><permissions><copyright-statement>© 2020 Elsevier B.V. All rights reserved.</copyright-statement><copyright-year>2020</copyright-year><copyright-holder>Elsevier B.V.</copyright-holder><license><license-p>Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.</license-p></license></permissions><kwd-group id="ks0005"><title>Keywords</title><kwd>Covid-19</kwd><kwd>Cardiovascular disease</kwd><kwd>Infections</kwd></kwd-group></article-meta></front><body><p id="p0005">Compared to other sections of medicine, cardiology only has a marginal role in the fight against Covid-19. Nevertheless, cardiologists are potentially involved in this story in at least three ways:<list list-type="simple" id="l0005"><list-item id="li0005"><label>1)</label><p id="p0010"><bold>A number of cardiovascular diseases may increase mortality among affected patients</bold>.</p></list-item></list></p><p id="p0015">Covid-19 appears less pathogenic than previous viruses such as SARS-COV or MERS-COV. But, deaths in the Wuhan Province where the Covid-19 epidemic started were between 0.5% to 2.5% [<xref rid="bb0005" ref-type="bibr">1</xref>]. In Europe, where the virus has recently migrated, the rate may be higher from 4% to 6%. However, the death rate depends on the number of infected people which is, at present, still unknown. Hypertension or coronary heart disease is present in 38% and diabetes in 19% of COVID-19 patients [<xref rid="bb0010" ref-type="bibr">2</xref>]. A report on 136 Covid-19 patients shows that 26% of them required cardiovascular intensive care. They had a higher rate of death and a higher prevalence of diabetes and cardiovascular disease than those not requiring intensive care [<xref rid="bb0015" ref-type="bibr">3</xref>]. A recent report on 72.314 cases from the Chinese centre of the disease control shows a mean death rate of 2.3% which increases to 5% in patients with cardiovascular disease and to 7.3% in those with diabetes [<xref rid="bb0020" ref-type="bibr">4</xref>,<xref rid="bb0025" ref-type="bibr">5</xref>]. Although the vulnerability of the patients with heart diseases to Covid-19 is quite evident in these reports, the single study using multivariable regression analysis shows that only older age, higher Sequential Organ Failure Assessment Score and high values of d-dimer on admission are independent predictive values of mortality [<xref rid="bb0010" ref-type="bibr">2</xref>].<list list-type="simple" id="l0010"><list-item id="li0010"><label>2)</label><p id="p0020"><bold>Viral infection could be the cause or a contributory cause of a new heart disease</bold>.</p></list-item></list></p><p id="p0025">The National Health Commission of China reported that often the first contact of patients with doctors is with reported palpitations or chest pain rather than respiratory symptoms. Only later are they diagnosed as positive for Covid-19 [<xref rid="bb0030" ref-type="bibr">6</xref>]. Some Covid-19 patients have high sensitivity cardiac troponin 1 levels, suggesting myocardial injury [<xref rid="bb0030" ref-type="bibr">6</xref>]. 26% of patients hospitalised at Zhongnan University Hospital of Wuhan required cardiovascular intensive care. Of these, 16.7% developed arrhythmias and 7.2% and acute coronary syndrome [<xref rid="bb0015" ref-type="bibr">3</xref>].</p><p id="p0030">It is unclear whether these cardiac conditions are provoked by Covid-19 or are just comorbidities or non-specific complications of infection. Studies during the flu epidemic in the USA and clinical practice show that inflammation due to flu may destabilise coronary plaque and cause myocardial infarction (MI) [<xref rid="bb0030" ref-type="bibr">6</xref>] This, in turn, is due to multiple mechanisms such as tachycardia, hypoxia, increased wall stress and inflammatory cytokines as well as thrombophilia [<xref rid="bb0035" ref-type="bibr">7</xref>]. Similar links with MI were shown for more recent epidemics of SARS and Covid-19 [<xref rid="bb0040" ref-type="bibr">8</xref>]. Only future studies will establish a possible relationship between Covid-19 and coronary artery disease. Only the awareness of such a link will encourage the cardiovascular community to search for it and to set appropriate studies to clarify this issue.<list list-type="simple" id="l0015"><list-item id="li0015"><label>3)</label><p id="p0035"><bold>Drugs for patients with cardiovascular disease could interfere with the pathophysiology of Covid-19</bold>.</p></list-item></list></p><p id="p0040">As was the case for the SARS-COV infection, the receptor for the new 2019 Covid-19 is human angiotensin-converting enzyme 2 (ACE2), a homologue of ACE1 [<xref rid="bb0030" ref-type="bibr">6</xref>]. The virus spike protein binds to ACE2 which allows the penetration of the virus into the epithelial cells of the lungs. ACE2 is found primarily in the lower respiratory tract, rather than in the upper airway [<xref rid="bb0045" ref-type="bibr">9</xref>]. This distribution can explain the few upper respiratory tract symptoms typical of flu and why Covid-19 is not just a common cold [<xref rid="bb0045" ref-type="bibr">9</xref>]. Contrary to ACE1 which converts angiotensin 1 to angiotensin 2 and is a therapeutic target for hypertension and heart failure, the biology of ACE2 and its therapeutic potential is unclear [<xref rid="bb0030" ref-type="bibr">6</xref>]. It is believed that ACE2 plays an antagonist part to the effects of ACE1, converting angiotensin 2 back to angiotensin 1. In view of the role of ACE2 in the penetration of 2019-nCov, drugs such as angiotensin 2 receptor blockers (ARBs) that increase angiotensin 2 plasma levels could activate ACE2 and an adverse Covid-19 pandemic [<xref rid="bb0050" ref-type="bibr">10</xref>]. ARBs are mainly prescribed for hypertension and it has been suggested that alternative drugs to ARBs should be used to treat hypertension during the Covid-19 pandemic [<xref rid="bb0050" ref-type="bibr">10</xref>]. The caveats here are a) there is no evidence of increased ACE2 expression with ARBs in the lung b) ACE2 expression is reduced in hypertension models c) hypertension and its treatment with ARBs did not affect previous coronavirus infections.</p><p id="p0045">The same considerations apply to heart failure.</p><p id="p0050">Although this hypothesis should be considered and further investigated, at present the discontinuation of ARBs in hypertensive and heart failure patients is not supported by any evidence.</p><p id="p0055">Finally, although the cardiovascular side effects of the current drugs empirically used for the Covid-19 infection and now tested in experimental protocols (such as anti-viral–remdisivir or lopinavir+ritonavir– or anti-leukin 6 –tocilizumab– or other antinflammatory –chloroquine–) are rare and not serious, an active surveillance is mandatory.</p><p id="p0060">In conclusion, besides the possible impact of Covid-19 on cardiology, the pandemic has created a perfect storm for the health organisations across the globe. 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