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Sex Differences in Association Between Anti-Hypertensive Medications and Risk of COVID-19 in Middle-Aged and Older Adults

Ma et al., Drugs & Aging, doi:10.1007/s40266-021-00886-y
Aug 2021  
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Mortality 9% Improvement Relative Risk Hospitalization 2% Symp. case -9% Case -7% Aspirin for COVID-19  Ma et al.  Prophylaxis Is prophylaxis with aspirin beneficial for COVID-19? PSM retrospective 77,221 patients in the United Kingdom No significant difference in outcomes seen c19early.org Ma et al., Drugs & Aging, August 2021 Favorsaspirin Favorscontrol 0 0.5 1 1.5 2+
UK Biobank retrospective 77,271 patients aged 50-86, showing no significant differences with aspirin use. Matching lead to different results for the gender vs. overall analysis, for example the overall result for cases was OR 1.07, however both gender results are lower OR 0.97 and 1.02.
risk of death, 9.0% lower, OR 0.91, p = 0.12, treatment 12,471, control 64,750, RR approximated with OR.
risk of hospitalization, 2.0% lower, OR 0.98, p = 0.47, treatment 12,471, control 64,750, RR approximated with OR.
risk of symptomatic case, 9.0% higher, OR 1.09, p = 0.18, treatment 12,471, control 64,750, RR approximated with OR.
risk of case, 7.0% higher, OR 1.07, p = 0.09, treatment 12,471, control 64,750, RR approximated with OR.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Ma et al., 18 Aug 2021, retrospective, propensity score matching, United Kingdom, peer-reviewed, 9 authors.
This PaperAspirinAll
Sex Differences in Association Between Anti-Hypertensive Medications and Risk of COVID-19 in Middle-Aged and Older Adults
Yue Ma, Yuan Zhang, Shu Li, Hongxi Yang, Huiping Li, Zhi Cao, Fusheng Xu, Li Sun, Yaogang Wang
Drugs & Aging, doi:10.1007/s40266-021-00886-y
Background There is ongoing debate about the associations between drug therapies targeting the renin-angiotensin-aldosterone system (RAAS) and adverse outcomes in coronavirus disease 2019 . Objective This study aims to examine the associations between using medications for the cardiovascular system and the risks associated with COVID-19 in middle-aged and older adults. Methods A total of 77,221 participants (aged 50-86 years) from UK Biobank were tested for SARS-CoV-2 RNA. The medications included angiotensin-converting enzyme inhibitors (ACEI), angiotensin-receptor blockers (ARB), β-blockers, calcium channel blockers (CCB), statins, and aspirin. COVID-19 outcomes comprised a positive test result and severity of COVID-19 (defined as mild, hospitalization or death). We evaluated the risk among total participants and for sub-groups based on sex. Propensity score matching was performed 1:1 and logistic regression models were used. Results Among the middle-and older aged participants, no significant associations between any class of medications and the likelihood of COVID-19 infection were observed. ACEI were associated with a higher mortality risk from COVID-19 (odds ratio [OR] 1.15, 95% confidence interval [CI] 1.01-1.32) and CCB were associated with a lower hospitalization risk for COVID-19 (OR 0.87, 95% CI 0.79-0.96) among the male patients with COVID-19, while a lower mortality risk from COVID-19 (OR 0.67, 95% CI 0.47-0.96) was observed with ARB among the female patients with COVID-19. Conclusions The study suggested sex differences in the risk of death from COVID-19 with the use of ACEI and ARB among middle-aged and older adults. Sex differences in the risk of hospitalization for COVID-19 with the use of CCB was observed as well. It is of clinical importance that clinicians adopt different CVD treatment approaches for female and male patients with COVID-19.
Supplementary Information The online version contains supplementary material available at https:// doi. org/ 10. 1007/ s40266-021-00886-y. Declarations Ethics approval This article does not contain any studies with human participants or animals performed by the authors. Authors' contributions YW directed the study. YW and YM designed the study and analyzed data. YM developed the first manuscript draft. YW, SL, HY and YZ edited the manuscript. All authors critically revised the manuscript, and all authors contributed to the final version.
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Cell Host ' 'Microbe. 2018;23(6):809–18.', 'journal-title': 'Cell Host Microbe'}, { 'issue': '5', 'key': '886_CR26', 'doi-asserted-by': 'publisher', 'first-page': 'H1895', 'DOI': '10.1152/ajpheart.00469.2008', 'volume': '295', 'author': 'JA Wasserstrom', 'year': '2008', 'unstructured': 'Wasserstrom JA, Kapur S, Jones S, Faruque T, Sharma R, Kelly JE, et al. ' 'Characteristics of intracellular Ca2+ cycling in intact rat heart: a ' 'comparison of sex differences. Am J Physiol Heart Circ Physiol. ' '2008;295(5):H1895–904.', 'journal-title': 'Am J Physiol Heart Circ Physiol'}, { 'issue': '1', 'key': '886_CR27', 'doi-asserted-by': 'publisher', 'first-page': '34', 'DOI': '10.1186/s12964-019-0346-2', 'volume': '17', 'author': 'JO Machuki', 'year': '2019', 'unstructured': 'Machuki JO, Zhang HY, Geng J, Fu L, Adzika GK, Wu L, et al. Estrogen ' 'regulation of cardiac cAMP-L-type Ca2+ channel pathway modulates sex ' 'differences in basal contraction and responses to β2AR-mediated stress ' 'in left ventricular apical myocytes. Cell Commun Signal. 2019;17(1):34.', 'journal-title': 'Cell Commun Signal'}, { 'issue': '1', 'key': '886_CR28', 'doi-asserted-by': 'publisher', 'first-page': 'H296', 'DOI': '10.1152/ajpheart.00755.2020', 'volume': '320', 'author': 'A Viveiros', 'year': '2021', 'unstructured': 'Viveiros A, Rasmuson J, Vu J, Mulvagh SL, Yip CYY, Norris CM, Oudit GY. ' 'Sex differences in COVID-19: candidate pathways, genetics of ACE2, and ' 'sex hormones. Am J Physiol Heart Circ Physiol. 2021;320(1):H296–304.', 'journal-title': 'Am J Physiol Heart Circ Physiol'}, { 'issue': '1', 'key': '886_CR29', 'doi-asserted-by': 'publisher', 'first-page': '1', 'DOI': '10.1152/physrev.00021.2015', 'volume': '97', 'author': 'V Regitz-Zagrosek', 'year': '2017', 'unstructured': 'Regitz-Zagrosek V, Kararigas G. Mechanistic pathways of sex differences ' 'in cardiovascular disease. Physiol Rev. 2017;97(1):1–37.', 'journal-title': 'Physiol Rev'}, { 'issue': '1', 'key': '886_CR30', 'doi-asserted-by': 'publisher', 'first-page': '179', 'DOI': '10.1186/s13054-020-02902-w', 'volume': '24', 'author': 'G Deng', 'year': '2020', 'unstructured': 'Deng G, Yin M, Chen X, Zeng F. Clinical determinants for fatality of ' '44,672 patients with COVID-19. Crit Care. 2020;24(1):179.', 'journal-title': 'Crit Care'}, { 'issue': '22', 'key': '886_CR31', 'doi-asserted-by': 'publisher', 'first-page': '2083', 'DOI': '10.1093/eurheartj/ehaa409', 'volume': '41', 'author': 'S De Rosa', 'year': '2020', 'unstructured': 'De Rosa S, Spaccarotella C, Basso C, Calabrò MP, Curcio A, Filardi PP, ' 'et al. Reduction of hospitalizations for myocardial infarction in Italy ' 'in the COVID-19 era. Eur Heart J. 2020;41(22):2083–8.', 'journal-title': 'Eur Heart J'}, { 'issue': '11', 'key': '886_CR32', 'doi-asserted-by': 'publisher', 'first-page': '1372', 'DOI': '10.1164/rccm.202003-0543OC', 'volume': '201', 'author': 'Y Du', 'year': '2020', 'unstructured': 'Du Y, Tu L, Zhu P, Mu M, Wang R, Yang P, et al. Clinical features of 85 ' 'fatal cases of COVID-19 from Wuhan. A retrospective observational study. ' 'Am J Respir Crit Care Med. 2020;201(11):1372–9.', 'journal-title': 'Am J Respir Crit Care Med'}, { 'issue': '25', 'key': '886_CR33', 'doi-asserted-by': 'publisher', 'first-page': 'e232', 'DOI': '10.3346/jkms.2020.35.e232', 'volume': '35', 'author': 'J Kim', 'year': '2020', 'unstructured': 'Kim J, Kim DW, Kim KI, Kim HB, Kim JH, Lee YG, et al. Compliance of ' 'antihypertensive medication and risk of Coronavirus Disease 2019: a ' 'cohort study using big data from the Korean National Health Insurance ' 'Service. J Korean Med Sci. 2020;35(25):e232.', 'journal-title': 'J Korean Med Sci'}, { 'key': '886_CR34', 'doi-asserted-by': 'publisher', 'first-page': '1185', 'DOI': '10.1002/cpt.2047', 'volume': '108', 'author': 'H Yan', 'year': '2020', 'unstructured': 'Yan H, Valdes AM, Vijay A, Wang S, Liang L, Yang S, et al. Role of drugs ' 'used for chronic disease management on susceptibility and severity of ' 'COVID-19: a large case-control study. Clin Pharmacol Ther. ' '2020;108:1185–94.', 'journal-title': 'Clin Pharmacol Ther'}, { 'issue': '20', 'key': '886_CR35', 'doi-asserted-by': 'publisher', 'first-page': '1648', 'DOI': '10.1161/CIRCULATIONAHA.120.046941', 'volume': '141', 'author': 'KJ Clerkin', 'year': '2020', 'unstructured': 'Clerkin KJ, Fried JA, Raikhelkar J, Sayer G, Griffin JM, Masoumi A, et ' 'al. COVID-19 and cardiovascular disease. Circulation. ' '2020;141(20):1648–55.', 'journal-title': 'Circulation'}, { 'issue': '19', 'key': '886_CR36', 'doi-asserted-by': 'publisher', 'first-page': '1804', 'DOI': '10.1093/eurheartj/ehaa311', 'volume': '41', 'author': 'L Nicin', 'year': '2020', 'unstructured': 'Nicin L, Abplanalp WT, Mellentin H. Cell type-specific expression of the ' 'putative SARS-CoV-2 receptor ACE2 in human hearts. Eur Heart J. ' '2020;41(19):1804–6.', 'journal-title': 'Eur Heart J'}, { 'issue': '3', 'key': '886_CR37', 'doi-asserted-by': 'publisher', 'first-page': '747', 'DOI': '10.3390/cancers12030747', 'volume': '12', 'author': 'SY Lin', 'year': '2020', 'unstructured': 'Lin SY, Lin CL, Lin CC, Hsu WH, Lin CD, Wang IK, et al. Association ' 'between Angiotensin-converting enzyme inhibitors and lung cancer—a ' 'Nationwide, population-based, propensity score-matched cohort study. ' 'Cancers (Basel). 2020;12(3):747.', 'journal-title': 'Cancers (Basel).'}, { 'issue': '17', 'key': '886_CR38', 'doi-asserted-by': 'publisher', 'first-page': '2024', 'DOI': '10.1016/j.jacc.2020.07.069', 'volume': '76', 'author': 'JI Mechanick', 'year': '2020', 'unstructured': 'Mechanick JI, Rosenson RS, Pinney SP, Mancini DM, Narula J, Fuster V. ' 'Coronavirus and cardiometabolic syndrome: JACC focus seminar. J Am Coll ' 'Cardiol. 2020;76(17):2024–35.', 'journal-title': 'J Am Coll Cardiol'}, { 'key': '886_CR39', 'doi-asserted-by': 'publisher', 'first-page': 'm1185', 'DOI': '10.1136/bmj.m1185', 'volume': '368', 'author': 'P Little', 'year': '2020', 'unstructured': 'Little P. Non-steroidal anti-inflammatory drugs and COVID-19. BMJ. ' '2020;368:m1185.', 'journal-title': 'BMJ'}, { 'issue': '25', 'key': '886_CR40', 'doi-asserted-by': 'publisher', 'first-page': '2431', 'DOI': '10.1056/NEJMoa2006923', 'volume': '382', 'author': 'G Mancia', 'year': '2020', 'unstructured': 'Mancia G, Rea F, Ludergnani M, Apolone G, Corrao G. ' 'Renin-Angiotensin-Aldosterone system blockers and the risk of Covid-19. ' 'N Engl J Med. 2020;382(25):2431–40.', 'journal-title': 'N Engl J Med'}, { 'issue': '2', 'key': '886_CR41', 'doi-asserted-by': 'publisher', 'first-page': '366', 'DOI': '10.1161/HYPERTENSIONAHA.120.15324', 'volume': '76', 'author': 'G Iaccarino', 'year': '2020', 'unstructured': 'Iaccarino G, Grassi G, Borghi C, Ferri C, Salvetti M, Volpe M, et al. ' 'Age and multimorbidity predict death among COVID-19 patients: results of ' 'the SARS-RAS study of the Italian Society of hypertension. Hypertension. ' '2020;76(2):366–72.', 'journal-title': 'Hypertension.'}], 'container-title': ['Drugs & Aging'], 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://link.springer.com/content/pdf/10.1007/s40266-021-00886-y.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://link.springer.com/article/10.1007/s40266-021-00886-y/fulltext.html', 'content-type': 'text/html', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://link.springer.com/content/pdf/10.1007/s40266-021-00886-y.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2021, 9, 30]], 'date-time': '2021-09-30T17:41:44Z', 'timestamp': 1633023704000}, 'score': 1, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2021, 8, 18]]}, 'references-count': 41, 'journal-issue': {'issue': '10', 'published-print': {'date-parts': [[2021, 10]]}}, 'alternative-id': ['886'], 'URL': 'http://dx.doi.org/10.1007/s40266-021-00886-y', 'relation': {}, 'ISSN': ['1170-229X', '1179-1969'], 'issn-type': [{'value': '1170-229X', 'type': 'print'}, {'value': '1179-1969', 'type': 'electronic'}], 'subject': ['Pharmacology (medical)', 'Geriatrics and Gerontology'], 'published': {'date-parts': [[2021, 8, 18]]}, 'assertion': [ { 'value': '8 July 2021', 'order': 1, 'name': 'accepted', 'label': 'Accepted', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '18 August 2021', 'order': 2, 'name': 'first_online', 'label': 'First Online', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, {'order': 1, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Declarations'}}, { 'value': 'This study was supported by The National Natural Science Foundation of China ' '(71910107004).', 'order': 2, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Funding'}}, { 'value': 'The authors declare no conflict of interest.', 'order': 3, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Conflicts of interest'}}, { 'value': 'This article does not contain any studies with human participants or animals ' 'performed by the authors.', 'order': 4, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Ethics approval'}}, { 'value': 'The authors can confirm that all relevant data are included in the article ' 'and/or its supplementary information files.', 'order': 5, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Data availability'}}, { 'value': 'YW directed the study. YW and YM designed the study and analyzed data. YM ' 'developed the first manuscript draft. YW, SL, HY and YZ edited the manuscript. ' 'All authors critically revised the manuscript, and all authors contributed to ' 'the final version.', 'order': 6, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': "Authors' contributions"}}, { 'value': 'This content has been made available to all.', 'name': 'free', 'label': 'Free to read'}]}
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