{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T07:25:46Z","timestamp":1768548346514,"version":"3.49.0"},"posted":{"date-parts":[[2020,6,1]]},"group-title":"Cardiovascular Medicine","reference-count":30,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2020,6,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The novel coronavirus SARS-Cov2 uses the angiotensin-converting enzyme 2 (ACE2) receptor as an entry point to the cell. Cardiovascular disease (CVD) is a risk factor for the novel coronavirus disease (Covid-19) with poor outcomes. We hypothesized that the rate of ACE inhibitor (ACEI) and angiotensin receptor blocker (ARB) use is associated with the rate of Covid-19 confirmed cases and deaths.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We conducted a geospatial study using publicly available county-level data. The Medicare ACEI and ARB prescription rate was exposure. The Covid-19 confirmed case and death rates were outcomes. Spatial autoregression models were adjusted for the percentage of Black residents, children, residents with at least some college degree, median household income, air quality index, CVD hospitalization rate in Medicare beneficiaries, and CVD death rate in a total county population.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Findings<\/jats:title>\n                  <jats:p>After adjustment for confounders, the ACEI use rate did not associate with Covid-19 confirmed case rate (direct county-own effect +0.11 %; 95%CI -0.31 to 0.53; P=0.600, and indirect spillover effect -0.53 %; 95%CI -3.89 to 2.84; P=0.760). The ARB use rate was associated with increased Covid-19 confirmed case rate (direct county-owned effect +0.12 %; 95%CI 0.05-0.19; P=0.002, and indirect spillover effect -0.33 %; 95%CI -2.11 to 1.44; P=0.714). Sensitivity analysis indicated an absence of significant reverse causality bias for analyses with Covid-19 confirmed case rate, but not death rate outcome.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Interpretation<\/jats:title>\n                  <jats:p>Our results highlight the safety of ACEI use for patients with clinical indications for ACEI use. However, an increase in ARB use by 1% was associated with a 0.12 % increase in Covid-19 confirmed cases. The use of ARB, due to known ACE2 upregulation, may facilitate SARS-CoV-2 entry into target cells and increase infectivity. Cluster-randomized controlled trial is warranted to answer the question of whether the replacement of ARB by ACEI may reduce the Covid-19 confirmed case rate.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Funding<\/jats:title>\n                  <jats:p>LGT was supported in part by the National Institute of Health (HL118277).<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2020.05.31.20118802","type":"posted-content","created":{"date-parts":[[2020,6,1]],"date-time":"2020-06-01T17:21:55Z","timestamp":1591032115000},"source":"Crossref","is-referenced-by-count":5,"title":["The Association Between the Rate of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers Use and the Number of Covid-19 Confirmed Cases and Deaths in the United States: Geospatial Study"],"prefix":"10.64898","author":[{"given":"Kyle","family":"Johnson","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maedeh","family":"Khayyat-Kholghi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Blake","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6976-1313","authenticated-orcid":false,"given":"Larisa G.","family":"Tereshchenko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2021010523501342000_2020.05.31.20118802v2.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2012-7"},{"key":"2021010523501342000_2020.05.31.20118802v2.2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1267"},{"key":"2021010523501342000_2020.05.31.20118802v2.3","doi-asserted-by":"publisher","DOI":"10.1056\/nejmsr2005760"},{"key":"2021010523501342000_2020.05.31.20118802v2.4","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30566-3"},{"key":"2021010523501342000_2020.05.31.20118802v2.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2004.05.114"},{"key":"2021010523501342000_2020.05.31.20118802v2.6","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000124667.34652.1a"},{"key":"2021010523501342000_2020.05.31.20118802v2.7","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.90488.2008"},{"issue":"8","key":"2021010523501342000_2020.05.31.20118802v2.8","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.7150\/ijbs.7.1077","article-title":"Cardioprotective effects of telmisartan against heart failure in rats induced by experimental autoimmune myocarditis through the modulation of angiotensin-converting enzyme-2\/angiotensin 1-7\/mas receptor axis","volume":"7","year":"2011","journal-title":"Int J Biol Sci"},{"key":"2021010523501342000_2020.05.31.20118802v2.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2011.07.041"},{"key":"2021010523501342000_2020.05.31.20118802v2.10","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00068.2005"},{"key":"2021010523501342000_2020.05.31.20118802v2.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.regpep.2010.09.005"},{"key":"2021010523501342000_2020.05.31.20118802v2.12","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.bcp.2017.07.022","article-title":"Azilsartan ameliorates diabetic cardiomyopathy in young db\/db mice through the modulation of ACE-2\/ANG 1-7\/Mas receptor cascade","volume":"144","year":"2017","journal-title":"Biochemical pharmacology"},{"key":"2021010523501342000_2020.05.31.20118802v2.13","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.104.510461"},{"key":"2021010523501342000_2020.05.31.20118802v2.14","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehi114"},{"key":"2021010523501342000_2020.05.31.20118802v2.15","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.2007.041855"},{"key":"2021010523501342000_2020.05.31.20118802v2.16","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20040634"},{"key":"2021010523501342000_2020.05.31.20118802v2.17","unstructured":"United States Census Bureau. 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