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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">On December 8&#44; 2019&#44; a case of pneumonia of unknown etiology was detected in Wuhan city&#44; Hubei province&#44; China&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">1</span></a> On December 31&#44; China reported a cluster of cases of pneumonia with unknown etiology to the World Health Organization &#40;WHO&#41;&#44; and seven days later&#44; Chinese scientists identified the pathogen as a novel coronavirus&#44; severe acute respiratory syndrome coronavirus 2 &#40;SARS-CoV-2&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">1</span></a> The WHO declared the outbreak a pandemic on 11 March 2020&#44; due to the increasing number of cases outside China&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">2</span></a> The pandemic is spreading exponentially&#44; with millions of people across the globe at risk of contracting coronavirus disease 2019 &#40;COVID-19&#41;&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Since January 2020 various series of COVID-19 patients have been published from China&#44;<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">3&#8211;6</span></a> Italy<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">7</span></a> and the US&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">8</span></a> Most reports have focused on COVID-19 patients admitted to the hospital&#44; in intensive care or in wards&#46; The series&#44; as expected&#44; differ in terms of demographics&#44; the definition of comorbidities such as chronic cardiovascular disease&#44; and clinical outcomes&#46; Nevertheless&#44; some observations can be made regarding the interaction between cardiovascular comorbidities and COVID-19 infection&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Hypertension&#44; diabetes&#44; and cardiovascular disease were the most frequent comorbidities in infected patients requiring hospitalization&#44; compared to other chronic diseases such as cancer&#44; chronic kidney disease and even chronic obstructive pulmonary disease&#46; In a meta-analysis that included six Chinese studies and 1527 COVID-19 patients&#44; the overall prevalence of hypertension&#44; cardiovascular and cerebrovascular disease&#44; and diabetes were 17&#46;1&#37;&#44; 16&#46;4&#37; and 9&#46;7&#37;&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">9</span></a> More recent studies from Italy<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">7</span></a> and the US<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">8</span></a> which included older patients&#44; the majority of whom were male&#44; report higher proportions of hypertension &#40;over 50&#37;&#41; and diabetes &#40;25&#37;&#41; among COVID-19 patients&#44; which is similar to the last coronavirus pandemic&#44; Middle East respiratory syndrome &#40;MERS&#41;&#44; which mainly affected the Arabian Peninsula&#46; A systematic analysis of 637 MERS cases showed that the prevalence of hypertension and diabetes was over 50&#37; and cardiac diseases were present in 30&#37; of cases&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">10</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Consistently&#44; the severity of the disease and case fatality rates have tended to be higher in COVID-19 patients with cardiovascular comorbidities&#46; Another recent pooled analysis showed that hypertension and a history of cardiovascular disease conferred a 2&#46;4 &#40;95&#37; confidence interval &#91;CI&#93; 1&#46;5-3&#46;8&#41; and 3&#46;4 &#40;95&#37; CI 1&#46;9-6&#46;2&#41; times higher risk of severe COVID-19 disease&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">11</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The exact mechanisms underlying the worse prognosis of hypertensive COVID-19 patients remain unknown&#46; One current hypothesis is that the excessive activation of the renin-angiotensin system &#40;RAS&#41; typical of the hypertensive patient may contribute to the progression of COVID-19 lung injury by promoting an inflammatory response &#40;cytokine storm&#41;&#44; smooth muscle cell contraction and vasoconstriction&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">12</span></a> Moreover&#44; some authors speculate that the use of angiotensin-converting enzyme inhibitors &#40;ACEIs&#41; and angiotensin receptor blockers &#40;ARBs&#41;&#44; commonly used to treat patients with cardiovascular disease&#44; could explain their worse outcomes&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">13</span></a> In animal studies&#44; ACEIs&#47;ARBs increase the expression of angiotensin-converting enzyme 2 &#40;ACE2&#41;&#44; the receptor which SARS-CoV-2 uses for viral entry and propagation in host cells&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">14</span></a> On the other hand&#44; the upregulation of ACE2 expression by ACEIs&#47;ARBs may mitigate the deleterious ACE2 downregulation associated with COVID-19 infection&#44; conferring pulmonary &#40;and cardiac&#41; protection&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">15</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">At the beginning of the pandemic&#44; all published guidelines recommended continuing ACEIs&#47;ARBs in patients with COVID-19&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">14</span></a> In a recently published retrospective analysis of 1128 adult patients with hypertension diagnosed with COVID-19 from Hubei province&#44; the use of ACEIs or ARBs was associated with a lower risk of both non-adjusted and adjusted all-cause mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">16</span></a> Two randomized phase II clinical trials in outpatient &#40;ClinicalTrials&#46;gov identifier&#58; NCT04311177&#41; and inpatient &#40;ClinicalTrials&#46;gov identifier&#58; NCT04312009&#41; settings are currently being planned to study the effect of losartan in the context of COVID-19 infection&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">14</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">At the end of March 2020&#44; the Centers for Disease Control and Prevention &#40;CDC&#41; reported data on underlying health conditions in COVID 19 patients in the US&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">17</span></a> Among 122 653 US COVID-19 cases&#44; 7162 &#40;5&#46;8&#37;&#41; patients had data available on underlying health conditions and other potential risk factors for severe outcomes from respiratory infections&#44; and similarly to other series&#44; a higher proportion of patients with comorbidities were admitted to the hospital and to intensive care&#46; On the other hand&#44; the prevalence of common clinical conditions in the US is similar to that described in this CDC report&#46; For example&#44; in 2018 the prevalence of diabetes among US adults was 10&#46;1&#37;&#44; similar to the COVID 19 patients &#40;10&#46;9&#37;&#41;&#46; Regarding all types of heart disease &#40;excluding hypertension&#41;&#44; the US prevalence in 2017 was 10&#46;6&#37;&#44; comparable to that observed in the CDC data&#44; and the findings are similar regarding chronic obstructive pulmonary disease and asthma&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">17</span></a> Moreover&#44; data from China are also in agreement&#58; according to the Summary of the 2018 Report on Cardiovascular Diseases in China&#44; the prevalence of hypertension and diabetes was 23&#46;2&#37; and 10&#46;9&#37;&#44; respectively&#44; which is in line with the above-mentioned pooled prevalence&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">18</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">In summary&#44; a higher prevalence of hypertension&#44; diabetes&#44; and chronic heart disease compared to other chronic conditions has been reported among COVID-19 patients&#46; The prevalence of these comorbidities may nevertheless be similar to that in the general population&#44; and these patients may not be more susceptible to COVID-19 infection&#46; Hypertension can function as a proxy for older age and cardiovascular and non-cardiovascular comorbidities&#44; and hence for the association in these patients with more aggressive COVID-19 disease&#46; There is no evidence to support the idea that ACEIs or ARBs could be harmful by increasing SARS-CoV-2 infectivity&#46; It is as yet unknown whether the severity or level of control of underlying health conditions affects the risk for severe disease in COVID-19&#46; Nonetheless&#44; given the limited data and potential hazard to individual and public health&#44; a precautionary approach should be followed by carefully protecting from infection and more closely monitoring patients with multiple comorbidities&#44; in particular those with hypertension and cardiovascular disease&#46;</p></span>"
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Editorial note
COVID-19 and cardiovascular comorbidities: An update
COVID-19 e comorbilidades cardiovasculares: uma atualização
Rogério Teixeiraa,b,
Corresponding author
rogeriopteixeira@gmail.com

Corresponding author.
, Mário Santosc,d, Victor Gile,f
a Serviço de Cardiologia, Hospital Geral, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
b Faculdade de Medicina da Universidade de Coimbra, Coimbra, Portugal
c Serviço de Cardiologia, Hospital Santo António, Centro Hospitalar Universitário do Porto, Porto, Portugal
d Faculdade de Medicina da Universidade do Porto, Porto, Portugal
e Centro Cardiovascular, Hospital dos Lusíadas, Lisboa, Portugal
f Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">On December 8&#44; 2019&#44; a case of pneumonia of unknown etiology was detected in Wuhan city&#44; Hubei province&#44; China&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">1</span></a> On December 31&#44; China reported a cluster of cases of pneumonia with unknown etiology to the World Health Organization &#40;WHO&#41;&#44; and seven days later&#44; Chinese scientists identified the pathogen as a novel coronavirus&#44; severe acute respiratory syndrome coronavirus 2 &#40;SARS-CoV-2&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">1</span></a> The WHO declared the outbreak a pandemic on 11 March 2020&#44; due to the increasing number of cases outside China&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">2</span></a> The pandemic is spreading exponentially&#44; with millions of people across the globe at risk of contracting coronavirus disease 2019 &#40;COVID-19&#41;&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Since January 2020 various series of COVID-19 patients have been published from China&#44;<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">3&#8211;6</span></a> Italy<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">7</span></a> and the US&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">8</span></a> Most reports have focused on COVID-19 patients admitted to the hospital&#44; in intensive care or in wards&#46; The series&#44; as expected&#44; differ in terms of demographics&#44; the definition of comorbidities such as chronic cardiovascular disease&#44; and clinical outcomes&#46; Nevertheless&#44; some observations can be made regarding the interaction between cardiovascular comorbidities and COVID-19 infection&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Hypertension&#44; diabetes&#44; and cardiovascular disease were the most frequent comorbidities in infected patients requiring hospitalization&#44; compared to other chronic diseases such as cancer&#44; chronic kidney disease and even chronic obstructive pulmonary disease&#46; In a meta-analysis that included six Chinese studies and 1527 COVID-19 patients&#44; the overall prevalence of hypertension&#44; cardiovascular and cerebrovascular disease&#44; and diabetes were 17&#46;1&#37;&#44; 16&#46;4&#37; and 9&#46;7&#37;&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">9</span></a> More recent studies from Italy<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">7</span></a> and the US<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">8</span></a> which included older patients&#44; the majority of whom were male&#44; report higher proportions of hypertension &#40;over 50&#37;&#41; and diabetes &#40;25&#37;&#41; among COVID-19 patients&#44; which is similar to the last coronavirus pandemic&#44; Middle East respiratory syndrome &#40;MERS&#41;&#44; which mainly affected the Arabian Peninsula&#46; A systematic analysis of 637 MERS cases showed that the prevalence of hypertension and diabetes was over 50&#37; and cardiac diseases were present in 30&#37; of cases&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">10</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Consistently&#44; the severity of the disease and case fatality rates have tended to be higher in COVID-19 patients with cardiovascular comorbidities&#46; Another recent pooled analysis showed that hypertension and a history of cardiovascular disease conferred a 2&#46;4 &#40;95&#37; confidence interval &#91;CI&#93; 1&#46;5-3&#46;8&#41; and 3&#46;4 &#40;95&#37; CI 1&#46;9-6&#46;2&#41; times higher risk of severe COVID-19 disease&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">11</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The exact mechanisms underlying the worse prognosis of hypertensive COVID-19 patients remain unknown&#46; One current hypothesis is that the excessive activation of the renin-angiotensin system &#40;RAS&#41; typical of the hypertensive patient may contribute to the progression of COVID-19 lung injury by promoting an inflammatory response &#40;cytokine storm&#41;&#44; smooth muscle cell contraction and vasoconstriction&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">12</span></a> Moreover&#44; some authors speculate that the use of angiotensin-converting enzyme inhibitors &#40;ACEIs&#41; and angiotensin receptor blockers &#40;ARBs&#41;&#44; commonly used to treat patients with cardiovascular disease&#44; could explain their worse outcomes&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">13</span></a> In animal studies&#44; ACEIs&#47;ARBs increase the expression of angiotensin-converting enzyme 2 &#40;ACE2&#41;&#44; the receptor which SARS-CoV-2 uses for viral entry and propagation in host cells&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">14</span></a> On the other hand&#44; the upregulation of ACE2 expression by ACEIs&#47;ARBs may mitigate the deleterious ACE2 downregulation associated with COVID-19 infection&#44; conferring pulmonary &#40;and cardiac&#41; protection&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">15</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">At the beginning of the pandemic&#44; all published guidelines recommended continuing ACEIs&#47;ARBs in patients with COVID-19&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">14</span></a> In a recently published retrospective analysis of 1128 adult patients with hypertension diagnosed with COVID-19 from Hubei province&#44; the use of ACEIs or ARBs was associated with a lower risk of both non-adjusted and adjusted all-cause mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">16</span></a> Two randomized phase II clinical trials in outpatient &#40;ClinicalTrials&#46;gov identifier&#58; NCT04311177&#41; and inpatient &#40;ClinicalTrials&#46;gov identifier&#58; NCT04312009&#41; settings are currently being planned to study the effect of losartan in the context of COVID-19 infection&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">14</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">At the end of March 2020&#44; the Centers for Disease Control and Prevention &#40;CDC&#41; reported data on underlying health conditions in COVID 19 patients in the US&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">17</span></a> Among 122 653 US COVID-19 cases&#44; 7162 &#40;5&#46;8&#37;&#41; patients had data available on underlying health conditions and other potential risk factors for severe outcomes from respiratory infections&#44; and similarly to other series&#44; a higher proportion of patients with comorbidities were admitted to the hospital and to intensive care&#46; On the other hand&#44; the prevalence of common clinical conditions in the US is similar to that described in this CDC report&#46; For example&#44; in 2018 the prevalence of diabetes among US adults was 10&#46;1&#37;&#44; similar to the COVID 19 patients &#40;10&#46;9&#37;&#41;&#46; Regarding all types of heart disease &#40;excluding hypertension&#41;&#44; the US prevalence in 2017 was 10&#46;6&#37;&#44; comparable to that observed in the CDC data&#44; and the findings are similar regarding chronic obstructive pulmonary disease and asthma&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">17</span></a> Moreover&#44; data from China are also in agreement&#58; according to the Summary of the 2018 Report on Cardiovascular Diseases in China&#44; the prevalence of hypertension and diabetes was 23&#46;2&#37; and 10&#46;9&#37;&#44; respectively&#44; which is in line with the above-mentioned pooled prevalence&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">18</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">In summary&#44; a higher prevalence of hypertension&#44; diabetes&#44; and chronic heart disease compared to other chronic conditions has been reported among COVID-19 patients&#46; The prevalence of these comorbidities may nevertheless be similar to that in the general population&#44; and these patients may not be more susceptible to COVID-19 infection&#46; Hypertension can function as a proxy for older age and cardiovascular and non-cardiovascular comorbidities&#44; and hence for the association in these patients with more aggressive COVID-19 disease&#46; There is no evidence to support the idea that ACEIs or ARBs could be harmful by increasing SARS-CoV-2 infectivity&#46; It is as yet unknown whether the severity or level of control of underlying health conditions affects the risk for severe disease in COVID-19&#46; Nonetheless&#44; given the limited data and potential hazard to individual and public health&#44; a precautionary approach should be followed by carefully protecting from infection and more closely monitoring patients with multiple comorbidities&#44; in particular those with hypertension and cardiovascular disease&#46;</p></span>"
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ISSN: 21742049
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Revista Portuguesa de Cardiologia (English edition)
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