The efficacy of mineral corticoid receptor antagonist, canrenone, in COVID-19 patients

The efficacy of mineral corticoid receptor antagonist, canrenone, in COVID-19 patients | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The efficacy of mineral corticoid receptor antagonist, canrenone, in COVID-19 patients Marco Vicenzi, Massimiliano Ruscica, Simona Iodice, Irene Rota, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-45837/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose: Despite the spread of SARS-CoV-2 global pandemic and the volume of clinical trials launched, no specific therapeutic drug approaches improving outcomes have been so far approved. In COVID-19 patients, aldosterone via ACE2 deregulation may be responsible for systemic and pulmonary vasoconstriction, inflammation and oxidative organ damage. Aim : To verify retrospectively the impact of the mineral corticoid receptor antagonist canrerone i.v. on the need of invasive ventilatory support and/or all-cause in-hospital mortality. Study design : In this retrospective study (CARDIOVID-19, ID-107162), COVID-19 patients hospitalized for severe respiratory failure were taken care by pneumologists or cardiologists and received two different therapeutic approaches according to personal skill of referral medical team on pharmacological management. Group 1 (n=39) were given vasodilator agents or RAAS-inhibitors and group 2 (n=30) were given canrenone i.v. Results : Among 69 consecutive COVID-19 patients, enrolled in COVID-19 NETWORK registry, the group given canrenone (200 mg/q.d. for a median of 14±11) showed a free event rate of 83% with a survival percentage of 90%. In group 1, not receiving canrenone, free event rate was 51% and survival 64%. Kaplan-Meier analysis for composite outcomes showed a Log Rank of 0.0004 and for mortality, Log Rank was 0.005. Conclusions : The novelty of our observation relies on the independent positive impact of the canrenone, a mineral corticoid receptor antagonist, on all-cause mortality and clinical improvement in COVID-19 patients. Preventive Medicine COVID-19 Angiotensin-Converting Enzyme-2 Renin-Angiotensin-Aldosterone System Mineral Corticoid Receptor Antagonist aldosterone Figures Figure 1 Introduction Since early December 2019 when the first pneumonia cases of unknown origin were identified, almost 11.5 millions of people across the globe contracted the infection of Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) [1]. Despite the spread of this global pandemic and the volume of clinical trials launched, no specific therapeutic drug approaches improving outcomes have been so far approved [2, 3]. One of the foremost hypotheses describing the pathway through which SARS-CoV-2 enters the cells is related with the involvement of Angiotensin-Converting Enzyme-2 (ACE2). This enzyme has been described as the receptor for coronaviruses [4]. ACE2 serves a counterbalancing role in Renin-Angiotensin-Aldosterone System (RAAS), i.e. it cleaves away (i) phenylalanine from angiotensin (Ang) II, converting it to Ang-(1-7), and (ii) leucine from Ang I, converting it to Ang-(1-9). SARS-CoV-2 infection appears to downregulate ACE2 possibly making unable the enzyme to exert protective effects in organs. Recent evidence by our group and others showed that progressive activation of the Ang II/AT1R axis along with the final effector aldosterone may be responsible for systemic and pulmonary vasoconstriction, inflammation and oxidative organ damage [5-7]. However, the role of the aldosterone has not been disentangled. To pursue the hypothesis that mineralcorticoid receptor antagonist (MRA) might play a beneficial effect on hypertensive attitude during SARS-CoV-2 infection, the aim has been to verify retrospectively the impact of canrerone i.v. on the need of invasive ventilatory support and/or all-cause in-hospital mortality. Methods Patients In this retrospective study (CARDIOVID-19, ID-107162), between March and April 2020, a series of 69 consecutive COVID-19 patients, enrolled in COVID-19 NETWORK registry, was considered. All patients were hospitalized for severe respiratory failure and they were taken care at Cardiorespiratory Sub-Intensive Unit (Fondazione IRCCS Ca’ Granda Policlinico Hospital of Milan). At admission, patients received standard medical care according to local protocols which were followed by two different therapeutic approaches according to personal skills (pneumologists or cardiologists) of referral medical team on pharmacological management. When arterial hypertension was manifested (systolic pressure ≥ 140 mmHg or diastolic pressure ≥90 mmHg), either de novo or exacerbated, two standard care approaches were followed: (i) in group 1 largely managed by pneumologists, the use of RAAS-inhibitors (ACE-inhibitors (ACEi) or angiotensin receptor blockers (ARBs)) and/or vasodilator agents (calcium channel blocker and alpha-1-adrenergic antagonist) and (ii) in group 2 mainly managed by cardiologists only specific active RAAS drugs (canrenone i.v. and ACEi or ARBs). In patients with hypokalemia (≤4 mmol/L), potassium (group 1) or canrenone (group 2) was given. Before treatment and during hospitalization, blood pressure, partial pressure of oxygen to inspiratory fraction of oxygen ratio (PaO 2 /FiO 2 ), alveolar-arterial oxygen gradient (ΔA-aO 2 ), and composite outcomes (invasive ventilatory support and/or all-cause in-hospital mortality) were recorded. Statistical method Data were expressed as mean±standard deviation (normally distributed) or by median (interquartile range). Group 1 and 2 were compared by using Pearson’s chi-square or Fisher’s Exact tests for categorical data, or Welsch’s t-test or Mann-Whitney U-test, for continuous variables. The effect size of MRA treatment was evaluated with Cohen’s d for unequal group size. Independent prognostic value of the two groups on mortality and composite outcomes (invasive ventilatory support and/or all-cause in-hospital mortality), were assessed by Kaplan-Meier survival curves and log-rank tests. Hazard ratios with Cox multivariable regression models were adjusted for age and PaO 2 /FiO 2 . The best model was selected based on the minimization of the Akaike’s information criterion after verifying the presence of the association of each potential covariate in the univariate analysis. The assumption of proportional hazard was checked with the log [log(survival)] plot and by the time-dependent covariate test. Statistical analyses were performed with SAS software. Results As reported in Table 1, baseline features of the group 1 (n= 39) and group 2 (n= 30) did not differ according to general and clinical characteristics, with the exception of median PaO 2 /FiO 2 , i.e. 182 mmHg (group 1) vs 219 mmHg (group 2), p= 0.023. During hospitalization, in group 1, 16 patients experienced hypertension and 15 hypokalemia. In group 2, 17 patients had hypertension and 15 had hypokalemia. The group given canrenone (mean dose 200 mg/q.d. i.v. given for a median of 14±11) showed a free event rate of 83% (25/30) with a survival percentage of 90 (27/30). In the absence of canrenone, free event rate was 51% (21/39) and survival 64% (25/39). Concerning composite outcomes Kaplan-Meier analysis showed a Log Rank of 0.0004 (Figure 1, panel A). Relative to mortality, Log Rank was 0.005 (Figure 1, panel B). MRA treatment was the only effective strategy to reduce event, resulting to be the strongest independent predictor of composite outcome and mortality after adjustment for age and PaO 2 /FiO 2 , HR= 0.097 (95%CI 0.024-0.395, p= 0.001) and HR= 0.158 (95%CI 0.0415-0.601, p=0.007), respectively. Discussion The novelty of our study relies on the independent positive impact of the MRA on all-cause mortality and clinical improvement in COVID-19 patients. As recently demonstrated by our group, these patients are less capable to counteract the progressive activation of the Ang II/AT1R axis [6]. Canrenone, the principal active metabolite of spironolactone, is considered the fourth line therapy for hypertension in patients already treated with multiple medications [8]. When given to COVID-19 patients, suddenly suffered a hypertensive crisis, canrenone improved outcomes, an effect independent of other therapies (ACEi, ARBs, calcium channel blocker, alpha-1-adrenergic antagonist, hydroxychloroquine, lopinavir/ritonavir, anakinra, cortisone). Patients treated with canrenone did not show hyperkalemia ( 5.3 mmol/L). This favorable response may rely on the activity of canrenone that can antagonize the disequilibrium of RAAS pathway. Among the RAAS-inhibiting agents, only canrenone (potassium canreonate), the active metabolite of spironolactone, can be administered intravenously [9]. The positive effects of aldosterone receptor blockers are not confined to the kidney as they are located in other tissues such as endothelium, heart, hippocampus and, in particular, lymphomonocytes [10]. Aldosterone plays an important role in the development of inflammation, fibrosis and endothelial dysfunction. Indeed, these drugs inhibit cardiac and vascular collagen turnover, reduce sympathetic activity, and improve endothelial dysfunction [5]. COVID-19 leads to disproportionate endothelial damage that disrupts pulmonary vasoregulation, promots ventilation-perfusion mismatch, and fosters thrombogenesis [11]. Endothelial dysfunction shifts the vascular equilibrium towards vasoconstriction thus favoring organ ischaemia, tissue oedema, and a pro-coagulant state [12]. Another positive aspect related to the use of canrenone lays on the hypothesis that MRA may reduce directly ACE2 expression on lung-cell surfaces [13]. Relative to the use of ARBs in COVID-19 patients with hypertension, in-patient use of ACEI/ARB was associated with lower risk of all-cause mortality compared with ACEI/ARB non-users [14]. Further evidence supporting the use of RAAS in COVID-19 patients has come from Cannata et al. showing that the in-hospital continuation of ACEi/ARBs medications were associated with lower risk of all-cause mortality [15]. Despite the small population number that could be acknowledged as a limitation, our conclusions are based on the achieved number of events required (at least 15). A sample size of 69 achieved 90% power to test, with a two-sided test, whether the HR is one at a 0.05 significance level and when the HR is 0.20. Based on the recent evidence that describes SARS-CoV-2 to induce an endothelial damage, the present findings open new perspectives supporting the use of MRA in COVID-19 patients. Target specific clinical trials are eagerly awaited to confirm or deny our hypothesis. Declarations Funding. Not applicable Conflict of interest : M. Vicenzi reports personal fees from Janssen-Cilag SpA, personal fees from MSD Italia, outside the submitted work. M. Ruscica, S. Iodice, I. Rota, A. Ratti, R. Di Cosola, V.Bollati have nothing to disclose. A. Corsini received honoraria for speaker activities from MSD, Recordati, Kowa, Amgen, Sanofi, Mylan, Doc and Phizer . S. Aliberti reports grants and personal fees from Bayer Healthcare, grants and personal fees from Aradigm Corporation, grants and personal fees from Grifols, personal fees from Astra Zeneca, personal fees from Basilea, personal fees from Zambon, personal fees from Novartis, personal fees from Raptor, grants and personal fees from Chiesi, personal fees from Actavis UK Ltd, personal fees from Horizon, grants and personal fees from INSMED, outside the submitted work. Dr. Aliberti reports grants and personal fees from Bayer Healthcare, grants and personal fees from Aradigm Corporation, grants and personal fees from Grifols, personal fees from Astra Zeneca, personal fees from Basilea, personal fees from Zambon, personal fees from Novartis, personal fees from Raptor, grants and personal fees from Chiesi, personal fees from Actavis UK Ltd, personal fees from Horizon, grants and personal fees from INSMED, outside the submitted work. F. Blasi reports grants and personal fees from astrazeneca, grants from bayer, grants and personal fees from chiesi, grants and personal fees from gsk, personal fees from guidotti, personal fees from grifols, grants and personal fees from insmed, personal fees from menarini, personal fees from mundipharma, personal fees from novartis, grants and personal fees from pfizer, personal fees from zambon, outside the submitted work. Availability of data and material . Always and at request Authors' contributions. M.V and M.R. wrote and conceive the manuscript. S.I. performed the statistical analyses. I.R., A.R. and R.D. took care of the patients. V.B. critically revised the manuscript. A.C. critically revised the manuscript according to the pharmacological point of view. S.A. and F.B. edited the manuscript and took care of patients. Ethics approval. CARDIOVID-19, ID-107162 STATEMENT OF ETHICS APPROVAL The authors declare that the study titled “The efficacy of mineral corticoid receptor antagonist, canrenone, in COVID-19 patients” submitted to the "Research Square preprint platform” is a publication derived from a sub-clinical registry focused on cardiovascular comorbidities integrating/belonging to the local clinical registry, named COVID-19 NETWORK and approved by local ethic committee, n° of the study 101389. Specifically, the protocol (“CARDIOVID-19: the CARDIOVascular side of COVID-19”) has been preliminary assessed and approved by the local ethic committee of Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano (number of the study 107162). STATEMENT OF PARTICIPANT CONSENT The authors declare that all participants have signed the informed consent to be enrolled in COVID-19 NETWORK. As clinical data we analyzed are included in this registry a specific informed consent has not been requested by our ethic committee. Data have been retrospectively analyzed. References (WHO) WHO. Coronavirus disease (COVID-19). 2020. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports/. Accessed May, 31st 2020. Sanders JM, Monogue ML, Jodlowski TZ, Cutrell JB. Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19): A Review. JAMA. 2020. doi:10.1001/jama.2020.6019. Sarzani R, Giulietti F, Pentima CD, Giordano P, Spannella F. Severe acute respiratory syndrome coronavirus 2 infection, angiotensin-converting enzyme 2 and treatment with angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor blockers. Eur J Prev Cardiol. 2020:2047487320918421. doi:10.1177/2047487320918421. Hoffmann M, Kleine-Weber H, Schroeder S, Kruger N, Herrler T, Erichsen S et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020;181(2):271-80 e8. doi:10.1016/j.cell.2020.02.052. Chen ZW, Tsai CH, Pan CT, Chou CH, Liao CW, Hung CS et al. Endothelial Dysfunction in Primary Aldosteronism. Int J Mol Sci. 2019;20(20). doi:10.3390/ijms20205214. Vicenzi M, Di Cosola R, Ruscica M, Ratti A, Rota I, Rota F et al. The liaison between respiratory failure and high blood pressure: evidence from COVID-19 patients. Eur Respir J. 2020. doi:10.1183/13993003.01157-2020. Ackermann M, Verleden SE, Kuehnel M, Haverich A, Welte T, Laenger F et al. Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19. N Engl J Med. 2020. doi:10.1056/NEJMoa2015432. Batterink J, Stabler SN, Tejani AM, Fowkes CT. Spironolactone for hypertension. Cochrane Database Syst Rev. 2010(8):CD008169. doi:10.1002/14651858.CD008169.pub2. Dabrowski R, Syska P, Maczynska J, Farkowski M, Sawicki S, Kubaszek-Kornatowska A et al. Clinical efficacy of potassium canreonate-canrenone in sinus rhythm restoration among patients with atrial fibrillation - a protocol of a pilot, randomized, double -blind, placebo-controlled study (CANREN-AF trial). Trials. 2020;21(1):397. doi:10.1186/s13063-020-04277-3. Armanini D, Sabbadin C, Dona G, Clari G, Bordin L. Aldosterone receptor blockers spironolactone and canrenone: two multivalent drugs. Expert Opin Pharmacother. 2014;15(7):909-12. doi:10.1517/14656566.2014.896901. Marini JJ, Gattinoni L. Management of COVID-19 Respiratory Distress. JAMA. 2020. doi:10.1001/jama.2020.6825. Bonetti PO, Lerman LO, Lerman A. Endothelial dysfunction: a marker of atherosclerotic risk. Arterioscler Thromb Vasc Biol. 2003;23(2):168-75. doi:10.1161/01.atv.0000051384.43104.fc. Cadegiani FA. Can spironolactone be used to prevent COVID-19-induced acute respiratory distress syndrome in patients with hypertension? Am J Physiol Endocrinol Metab. 2020;318(5):E587-E8. doi:10.1152/ajpendo.00136.2020. Zhang P, Zhu L, Cai J, Lei F, Qin JJ, Xie J et al. Association of Inpatient Use of Angiotensin Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers with Mortality Among Patients With Hypertension Hospitalized With COVID-19. Circ Res. 2020. doi:10.1161/CIRCRESAHA.120.317134. Cannata F, Chiarito M, Reimers B, Azzolini E, Ferrante G, My I et al. Continuation versus discontinuation of ACE inhibitors or angiotensin II receptor blockers in COVID-19: effects on blood pressure control and mortality. Eur Heart J Cardiovasc Pharmacother. 2020. doi:10.1093/ehjcvp/pvaa056. Tables Table 1 : Patients’ general characteristics, clinical parameters at baseline and treatment distribution. Overall population (n=69) Group 1 (n=39/69) Group 2 (n=30/69) Group 1 vs Group 2 d-cohen General characteristics Sex, m (%) 50 (72) 26 (67) 24 (80) 0.219 c Age, years, mean ± SD 61 ±12 60 ±12 62 ±12 0.311 w 0.13 Hypertension, n (%) 31 (45) 18 (46) 13 (43) 0.815 c Dyslipidemia, n (%) 14 (20) 8 (21) 6 (20) 0.958 c Obesity, n (%) 16 (23) 9 (23) 7 (23) 0.980 c Cardiovascular disease, n (%) 8 (12) 5 (13) 3 (10) 1.000 § Clinical assessment at baseline PaO 2 /FiO 2 , mmHg, median (IQR) 190 (99) 182 (110) 214 (116) 0.023 * 0.47 ΔA-aO 2 , mmHg, median (IQR) 219 (102) 234 (151) 197 (86) 0.133 * 0.40 meanBP, mmHg, mean ± SD 97 ±13 97 ±13 96 ±13 0.406 w 0.03 [K + ] plasma , mmol/L, mean ± SD 4.1 ±0.5 4.2 ± 0.6 4.0 ±0.4 0.111 w 0.38 CRP, mg/dL, median (IQR) 12 (10) 11 (10) 13 (10) 0.186 * 0.28 IL-6, pg/mL, median (IQR) 83 (91) 88 (139) 83 (64) 0.757 * 0.16 D-dimer, g/L, median (IQR) 992 (1079) 939 (890) 1057 (1135) 0.215 * 0.33 Ferritin, ng/mL, median (IQR) 1421 (2121) 1262 (2495) 1704 (1866) 0.380 * 0.02 Treatment distribution ACEi or ARBs, n (%) 25 (36) 6 (15) 19 (63) <0.001 c Ca 2+ channel blockers, n (%) 11 (16) 11 (28) 0 (0.0) 0.002 § alpha-1-adrenergic antagonist, n (%) 4 (6) 4 (10) 0 (0.0) 0.127 § Hydroxychloroquine, n (%) 69 (100) 39 (100) 30 (100) - Lopinavir/Ritonavir, n (%) 24 (35) 23 (59) 1 (3) <0.001 * Anakinra, n (%) 20 (29) 9 (23) 11 (37) 0.217 * Cortisone, n (%) 24 (35) 10 (26) 14 (47) 0.069 * SD, standard deviation; PaO 2 /FiO 2 , partial pressure of oxygen to inspiratory fraction of oxygen ratio; IQR, interquartile range; ΔA-aO 2 , alveolar-arterial oxygen gradient (ΔA-aO2); meanBP, mean blood pressure; [K + ] plasma , plasma concentration of potassium; CRP, C-reactive protein; IL-6, interleukin 6; ACEi, inhibitors of angiotensin converting enzyme; ARBs, angiotensin receptor antagonists. c p-value from Pearson’s chi-square test. w p-value from Welch's t-test. § p-value from Fisher’s Exact test. *p-value from Mann-Whitney U-test. Cohen’s d effect size for unequal group size Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-45837","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":915532,"identity":"f2138416-dbb4-46a5-a1d0-b78c915a53e7","order_by":0,"name":"Marco Vicenzi","email":"","orcid":"","institution":"Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Marco","middleName":"","lastName":"Vicenzi","suffix":""},{"id":915533,"identity":"86e999fb-c8fd-4d1f-829b-6ace54ce32f1","order_by":1,"name":"Massimiliano 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Cumulative free-event rate and survival are represented (group 1, stippled line; group 2 continuous line). The respective Log Rank and Chi-square are reported.","description":"","filename":"Schermata20200708alle14.09.46.png","url":"https://assets-eu.researchsquare.com/files/rs-45837/v1/Schermata20200708alle14.09.46.png"},{"id":13555604,"identity":"2ae7925b-7896-4f31-ae51-2296aad58fbb","added_by":"auto","created_at":"2021-09-17 02:45:36","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":369641,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-45837/v1/df880e95-9d96-44af-bb8d-020c96c5a558.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003eThe efficacy of mineral corticoid receptor antagonist, canrenone, in COVID-19 patients\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSince early December 2019 when the first pneumonia cases of unknown origin were identified, almost 11.5 millions of people across the globe contracted the infection of Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) [1]. Despite the spread of this global pandemic and the volume of clinical trials launched, no specific therapeutic drug approaches improving outcomes have been so far approved [2, 3].\u003c/p\u003e\n\u003cp\u003eOne of the foremost hypotheses describing the pathway through which SARS-CoV-2 enters the cells is related with the involvement of Angiotensin-Converting Enzyme-2 (ACE2). This enzyme has been described as the receptor for coronaviruses [4]. ACE2 serves a counterbalancing role in Renin-Angiotensin-Aldosterone System (RAAS), \u003cem\u003ei.e.\u003c/em\u003e it cleaves away (i) phenylalanine from angiotensin (Ang) II, converting it to Ang-(1-7), and (ii) leucine from Ang I, converting it to Ang-(1-9). SARS-CoV-2 infection appears to downregulate ACE2 possibly making unable the enzyme to exert protective effects in organs. Recent evidence by our group and others showed that progressive activation of the Ang II/AT1R axis along with the final effector aldosterone may be responsible for systemic and pulmonary vasoconstriction, inflammation and oxidative organ damage [5-7]. However, the role of the aldosterone has not been disentangled.\u003c/p\u003e\n\u003cp\u003eTo pursue the hypothesis that mineralcorticoid receptor antagonist (MRA) might play a beneficial effect on hypertensive attitude during SARS-CoV-2 infection, the aim has been to verify retrospectively the impact of canrerone \u003cem\u003ei.v.\u003c/em\u003e on the need of invasive ventilatory support and/or all-cause in-hospital mortality.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003ePatients\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn this retrospective study (CARDIOVID-19, ID-107162), between March and April 2020, a series of 69 consecutive COVID-19 patients, enrolled in COVID-19 NETWORK registry, was considered. All patients were hospitalized for severe respiratory failure and they were taken care at Cardiorespiratory Sub-Intensive Unit (Fondazione IRCCS Ca\u0026rsquo; Granda Policlinico Hospital of Milan). At admission, patients received standard medical care according to local protocols which were followed by two different therapeutic approaches according to personal skills (pneumologists or cardiologists) of referral medical team on pharmacological management. When arterial hypertension was manifested (systolic pressure \u0026ge; 140 mmHg or diastolic pressure \u0026ge;90 mmHg), either \u003cem\u003ede novo\u003c/em\u003e or exacerbated, two standard care approaches were followed: (i) in group 1 largely managed by pneumologists, the use of RAAS-inhibitors (ACE-inhibitors (ACEi) or angiotensin receptor blockers (ARBs)) and/or vasodilator agents (calcium channel blocker and alpha-1-adrenergic antagonist) and (ii) in group 2 mainly managed by cardiologists only specific active RAAS drugs (canrenone \u003cem\u003ei.v.\u003c/em\u003e and ACEi or ARBs). In patients with hypokalemia (\u0026le;4 mmol/L), potassium (group 1) or canrenone (group 2) was given. Before treatment and during hospitalization, blood pressure, partial pressure of oxygen to inspiratory fraction of oxygen ratio (PaO\u003csub\u003e2\u003c/sub\u003e/FiO\u003csub\u003e2\u003c/sub\u003e), alveolar-arterial oxygen gradient (\u0026Delta;A-aO\u003csub\u003e2\u003c/sub\u003e), and composite outcomes (invasive ventilatory support and/or all-cause in-hospital mortality) were recorded.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical method\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData were expressed as mean\u0026plusmn;standard deviation (normally distributed) or by median (interquartile range). Group 1 and 2 were compared by using Pearson\u0026rsquo;s chi-square or Fisher\u0026rsquo;s Exact tests for categorical data, or Welsch\u0026rsquo;s t-test or Mann-Whitney U-test, for continuous variables. The effect size of MRA treatment was evaluated with Cohen\u0026rsquo;s d for unequal group size. Independent prognostic value of the two groups on mortality and composite outcomes (invasive ventilatory support and/or all-cause in-hospital mortality), were assessed by Kaplan-Meier survival curves and log-rank tests. Hazard ratios with Cox multivariable regression models were adjusted for age and PaO\u003csub\u003e2\u003c/sub\u003e/FiO\u003csub\u003e2\u003c/sub\u003e. The best model was selected based on the minimization of the Akaike\u0026rsquo;s information criterion after verifying the presence of the association of each potential covariate in the univariate analysis. The assumption of proportional hazard was checked with the log [log(survival)] plot and by the time-dependent covariate test. Statistical analyses were performed with SAS software.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eAs reported in Table 1, baseline features of the group 1 (n= 39) and group 2 (n= 30) did not differ according to general and clinical characteristics, with the exception of\u0026nbsp; median PaO\u003csub\u003e2\u003c/sub\u003e/FiO\u003csub\u003e2\u003c/sub\u003e, \u003cem\u003ei.e.\u003c/em\u003e 182 mmHg (group 1) \u003cem\u003evs\u003c/em\u003e 219 mmHg (group 2), p= 0.023. During hospitalization, in group 1, 16 patients experienced hypertension and 15 hypokalemia. In group 2, 17 patients had hypertension and 15 had hypokalemia. The group given canrenone (mean dose 200 mg/q.d. i.v. given for a median of 14\u0026plusmn;11) showed a free event rate of 83% (25/30) with a survival percentage of 90 (27/30). In the absence of canrenone, free event rate was 51% (21/39) and survival 64% (25/39). Concerning composite outcomes Kaplan-Meier analysis showed a Log Rank of 0.0004 (Figure 1, panel A). Relative to mortality, Log Rank was 0.005 (Figure 1, panel B). MRA treatment was the only effective strategy to reduce event, resulting to be the strongest independent predictor of composite outcome and mortality after adjustment for age and PaO\u003csub\u003e2\u003c/sub\u003e/FiO\u003csub\u003e2\u003c/sub\u003e, HR= 0.097 (95%CI 0.024-0.395, p= 0.001) and HR= 0.158 (95%CI 0.0415-0.601, p=0.007), respectively.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe novelty of our study relies on the independent positive impact of the MRA on all-cause mortality and clinical improvement in COVID-19 patients. As recently demonstrated by our group, these patients are less capable to counteract the progressive activation of the Ang II/AT1R axis [6]. Canrenone, the principal active metabolite of spironolactone, is considered the fourth line therapy for hypertension in patients already treated with multiple medications [8]. When given to COVID-19 patients, suddenly suffered a hypertensive crisis, canrenone improved outcomes, an effect independent of other therapies (ACEi, ARBs, calcium channel blocker, alpha-1-adrenergic antagonist, hydroxychloroquine, lopinavir/ritonavir, anakinra, cortisone). Patients treated with canrenone did not show hyperkalemia ( 5.3 mmol/L). This favorable response may rely on the activity of canrenone that can antagonize the disequilibrium of RAAS pathway. Among the RAAS-inhibiting agents, only canrenone (potassium canreonate), the active metabolite of spironolactone, can be administered intravenously [9].\u003c/p\u003e\n\u003cp\u003eThe positive effects of aldosterone receptor blockers are not confined to the kidney as they are located in other tissues such as endothelium, heart, hippocampus and, in particular, lymphomonocytes [10]. Aldosterone plays an important role in the development of inflammation, fibrosis and endothelial dysfunction. Indeed, these drugs inhibit cardiac and vascular collagen turnover, reduce sympathetic activity, and improve endothelial dysfunction [5]. COVID-19 leads to disproportionate endothelial damage that disrupts pulmonary vasoregulation, promots ventilation-perfusion mismatch, and fosters thrombogenesis [11]. Endothelial dysfunction shifts the vascular equilibrium towards vasoconstriction thus favoring organ ischaemia, tissue oedema, and a pro-coagulant state [12].\u003c/p\u003e\n\u003cp\u003eAnother positive aspect related to the use of canrenone lays on the hypothesis that MRA may reduce directly ACE2 expression on lung-cell surfaces [13]. Relative to the use of ARBs in COVID-19 patients with hypertension, in-patient use of ACEI/ARB was associated with lower risk of all-cause mortality compared with ACEI/ARB non-users [14]. Further evidence supporting the use of RAAS in COVID-19 patients has come from Cannata et al. showing that the in-hospital continuation of ACEi/ARBs medications were associated with lower risk of all-cause mortality [15].\u003c/p\u003e\n\u003cp\u003eDespite the small population number that could be acknowledged as a limitation, our conclusions are based on the achieved number of events required (at least 15). A sample size of 69 achieved 90% power to test, with a two-sided test, whether the HR is one at a 0.05 significance level and when the HR is 0.20.\u003c/p\u003e\n\u003cp\u003eBased on the recent evidence that describes SARS-CoV-2 to induce an endothelial damage, the present findings open new perspectives supporting the use of MRA in COVID-19 patients. Target specific clinical trials are eagerly awaited to confirm or deny our hypothesis.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding. \u003c/strong\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e: M. Vicenzi reports personal fees from Janssen-Cilag SpA, personal fees from MSD Italia, outside the submitted work. M. Ruscica, S. Iodice, I. Rota, A. Ratti, R. Di Cosola, V.Bollati have nothing to disclose. A. Corsini received honoraria for speaker activities from MSD, Recordati, Kowa, Amgen, Sanofi, Mylan, Doc and Phizer\u003cstrong\u003e. \u003c/strong\u003eS. Aliberti reports grants and personal fees from Bayer Healthcare, grants and personal fees from Aradigm Corporation, grants and personal fees from Grifols, personal fees from Astra Zeneca, personal fees from Basilea, personal fees from Zambon, personal fees from Novartis, personal fees from Raptor, grants and personal fees from Chiesi, personal fees from Actavis UK Ltd, personal fees from Horizon, grants and personal fees from INSMED, outside the submitted work. Dr. Aliberti reports grants and personal fees from Bayer Healthcare, grants and personal fees from Aradigm Corporation, grants and personal fees from Grifols, personal fees from Astra Zeneca, personal fees from Basilea, personal fees from Zambon, personal fees from Novartis, personal fees from Raptor, grants and personal fees from Chiesi, personal fees from Actavis UK Ltd, personal fees from Horizon, grants and personal fees from INSMED, outside the submitted work. F. Blasi reports grants and personal fees from astrazeneca, grants from bayer, grants and personal fees from chiesi, grants and personal fees from gsk, personal fees from guidotti, personal fees from grifols, grants and personal fees from insmed, personal fees from menarini, personal fees from mundipharma, personal fees from novartis, grants and personal fees from pfizer, personal fees from zambon, outside the submitted work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material\u003c/strong\u003e. Always and at request\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions. \u003c/strong\u003eM.V and M.R. wrote and conceive the manuscript. S.I. performed the statistical analyses. I.R., A.R. and R.D. took care of the patients. V.B. critically revised the manuscript. A.C. critically revised the manuscript according to the pharmacological point of view. S.A. and F.B. edited the manuscript and took care of patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval. \u003c/strong\u003eCARDIOVID-19, ID-107162\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSTATEMENT OF ETHICS APPROVAL\u003c/strong\u003e The authors declare that the study titled \u0026ldquo;The efficacy of mineral corticoid receptor antagonist, canrenone, in COVID-19 patients\u0026rdquo; submitted to the \"Research Square preprint platform\u0026rdquo; is a publication derived from a sub-clinical registry focused on cardiovascular comorbidities integrating/belonging to the local clinical registry, named COVID-19 NETWORK and approved by local ethic committee, n\u0026deg; of the study 101389. Specifically, the protocol (\u0026ldquo;CARDIOVID-19: the CARDIOVascular side of COVID-19\u0026rdquo;) has been preliminary assessed and approved by the local ethic committee of Fondazione IRCCS Ca\u0026rsquo; Granda Ospedale Maggiore Policlinico di Milano (number of the study 107162).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSTATEMENT OF PARTICIPANT CONSENT\u003c/strong\u003e The authors declare that all participants have signed the informed consent to be enrolled in COVID-19 NETWORK. As clinical data we analyzed are included in this registry a specific informed consent has not been requested by our ethic committee. Data have been retrospectively analyzed.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003e(WHO) WHO. Coronavirus disease (COVID-19). 2020. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports/. Accessed May, 31st 2020.\u003c/li\u003e\n\u003cli\u003eSanders JM, Monogue ML, Jodlowski TZ, Cutrell JB. Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19): A Review. JAMA. 2020. doi:10.1001/jama.2020.6019.\u003c/li\u003e\n\u003cli\u003eSarzani R, Giulietti F, Pentima CD, Giordano P, Spannella F. Severe acute respiratory syndrome coronavirus 2 infection, angiotensin-converting enzyme 2 and treatment with angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor blockers. Eur J Prev Cardiol. 2020:2047487320918421. doi:10.1177/2047487320918421.\u003c/li\u003e\n\u003cli\u003eHoffmann M, Kleine-Weber H, Schroeder S, Kruger N, Herrler T, Erichsen S et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020;181(2):271-80 e8. doi:10.1016/j.cell.2020.02.052.\u003c/li\u003e\n\u003cli\u003eChen ZW, Tsai CH, Pan CT, Chou CH, Liao CW, Hung CS et al. Endothelial Dysfunction in Primary Aldosteronism. Int J Mol Sci. 2019;20(20). doi:10.3390/ijms20205214.\u003c/li\u003e\n\u003cli\u003eVicenzi M, Di Cosola R, Ruscica M, Ratti A, Rota I, Rota F et al. The liaison between respiratory failure and high blood pressure: evidence from COVID-19 patients. Eur Respir J. 2020. doi:10.1183/13993003.01157-2020.\u003c/li\u003e\n\u003cli\u003eAckermann M, Verleden SE, Kuehnel M, Haverich A, Welte T, Laenger F et al. Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19. N Engl J Med. 2020. doi:10.1056/NEJMoa2015432.\u003c/li\u003e\n\u003cli\u003eBatterink J, Stabler SN, Tejani AM, Fowkes CT. Spironolactone for hypertension. Cochrane Database Syst Rev. 2010(8):CD008169. doi:10.1002/14651858.CD008169.pub2.\u003c/li\u003e\n\u003cli\u003eDabrowski R, Syska P, Maczynska J, Farkowski M, Sawicki S, Kubaszek-Kornatowska A et al. Clinical efficacy of potassium canreonate-canrenone in sinus rhythm restoration among patients with atrial fibrillation - a protocol of a pilot, randomized, double -blind, placebo-controlled study (CANREN-AF trial). Trials. 2020;21(1):397. doi:10.1186/s13063-020-04277-3.\u003c/li\u003e\n\u003cli\u003eArmanini D, Sabbadin C, Dona G, Clari G, Bordin L. Aldosterone receptor blockers spironolactone and canrenone: two multivalent drugs. Expert Opin Pharmacother. 2014;15(7):909-12. doi:10.1517/14656566.2014.896901.\u003c/li\u003e\n\u003cli\u003eMarini JJ, Gattinoni L. Management of COVID-19 Respiratory Distress. JAMA. 2020. doi:10.1001/jama.2020.6825.\u003c/li\u003e\n\u003cli\u003eBonetti PO, Lerman LO, Lerman A. Endothelial dysfunction: a marker of atherosclerotic risk. Arterioscler Thromb Vasc Biol. 2003;23(2):168-75. doi:10.1161/01.atv.0000051384.43104.fc.\u003c/li\u003e\n\u003cli\u003eCadegiani FA. Can spironolactone be used to prevent COVID-19-induced acute respiratory distress syndrome in patients with hypertension? Am J Physiol Endocrinol Metab. 2020;318(5):E587-E8. doi:10.1152/ajpendo.00136.2020.\u003c/li\u003e\n\u003cli\u003eZhang P, Zhu L, Cai J, Lei F, Qin JJ, Xie J et al. Association of Inpatient Use of Angiotensin Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers with Mortality Among Patients With Hypertension Hospitalized With COVID-19. Circ Res. 2020. doi:10.1161/CIRCRESAHA.120.317134.\u003c/li\u003e\n\u003cli\u003eCannata F, Chiarito M, Reimers B, Azzolini E, Ferrante G, My I et al. Continuation versus discontinuation of ACE inhibitors or angiotensin II receptor blockers in COVID-19: effects on blood pressure control and mortality. Eur Heart J Cardiovasc Pharmacother. 2020. doi:10.1093/ehjcvp/pvaa056.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp style=\"margin: 0in;font-family: Calibri, sans-serif;text-align: justify;line-height: 24px;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 10px; font-family: Verdana, Geneva, sans-serif; color: rgb(0, 0, 0);\"\u003eTable 1\u003c/span\u003e\u003c/strong\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e: Patients\u0026rsquo; general characteristics, clinical parameters at baseline and treatment distribution.\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" style=\"width: 444.95pt;border-collapse: collapse;border: none;\" width=\"593\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 125.8pt;border: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"28.282828282828284%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top-width: 1pt;border-right-width: 1pt;border-bottom-width: 1pt;border-style: solid solid solid none;border-top-color: windowtext;border-right-color: windowtext;border-bottom-color: windowtext;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"12.794612794612794%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 20px;\"\u003eOverall population (n=69)\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.3pt;border-top-width: 1pt;border-right-width: 1pt;border-bottom-width: 1pt;border-style: solid solid solid none;border-top-color: windowtext;border-right-color: windowtext;border-bottom-color: windowtext;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"14.478114478114477%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 20px;\"\u003eGroup 1 (n=39/69)\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51.95pt;border-top-width: 1pt;border-right-width: 1pt;border-bottom-width: 1pt;border-style: solid solid solid none;border-top-color: windowtext;border-right-color: windowtext;border-bottom-color: windowtext;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"11.616161616161616%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 20px;\"\u003eGroup 2 (n=30/69)\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97.75pt;border-top-width: 1pt;border-right-width: 1pt;border-bottom-width: 1pt;border-style: solid solid solid none;border-top-color: windowtext;border-right-color: windowtext;border-bottom-color: windowtext;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"21.885521885521886%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 20px;\"\u003eGroup 1 vs Group 2\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.45pt;border-top-width: 1pt;border-right-width: 1pt;border-bottom-width: 1pt;border-style: solid solid solid none;border-top-color: windowtext;border-right-color: windowtext;border-bottom-color: windowtext;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"10.942760942760943%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 20px;\"\u003ed-cohen\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 125.8pt;border-right-width: 1pt;border-bottom-width: 1pt;border-left-width: 1pt;border-style: none solid solid;border-right-color: windowtext;border-bottom-color: windowtext;border-left-color: windowtext;background-color: rgb(217, 217, 217);padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"28.282828282828284%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 20px;\"\u003eGeneral characteristics\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: rgb(217, 217, 217);padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"12.794612794612794%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.3pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: rgb(217, 217, 217);padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"14.478114478114477%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51.95pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: rgb(217, 217, 217);padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"11.616161616161616%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97.75pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: rgb(217, 217, 217);padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"21.885521885521886%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.45pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: rgb(217, 217, 217);padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"10.942760942760943%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 125.8pt;border-right-width: 1pt;border-bottom-width: 1pt;border-left-width: 1pt;border-style: none solid solid;border-right-color: windowtext;border-bottom-color: windowtext;border-left-color: windowtext;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"28.282828282828284%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003eSex, m (%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"12.794612794612794%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e50 (72)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.3pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"14.478114478114477%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e26 (67)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51.95pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"11.616161616161616%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e24 (80)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97.75pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"21.885521885521886%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e0.219 \u003csup\u003ec\u003c/sup\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.45pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"10.942760942760943%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 125.8pt;border-right-width: 1pt;border-bottom-width: 1pt;border-left-width: 1pt;border-style: none solid solid;border-right-color: windowtext;border-bottom-color: windowtext;border-left-color: windowtext;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"28.282828282828284%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003eAge, years, mean \u0026plusmn; SD\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"12.794612794612794%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e61 \u0026plusmn;12\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.3pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"14.478114478114477%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e60 \u0026plusmn;12\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51.95pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"11.616161616161616%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e62 \u0026plusmn;12\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97.75pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"21.885521885521886%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e0.311\u003cem\u003e\u003csup\u003ew\u003c/sup\u003e\u003c/em\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.45pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"10.942760942760943%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e0.13\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 125.8pt;border-right-width: 1pt;border-bottom-width: 1pt;border-left-width: 1pt;border-style: none solid solid;border-right-color: windowtext;border-bottom-color: windowtext;border-left-color: windowtext;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"28.282828282828284%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003eHypertension, n (%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"12.794612794612794%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e31 (45)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.3pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"14.478114478114477%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e18 (46)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51.95pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"11.616161616161616%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e13 (43)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97.75pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"21.885521885521886%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e0.815 \u003csup\u003ec\u003c/sup\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.45pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"10.942760942760943%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 125.8pt;border-right-width: 1pt;border-bottom-width: 1pt;border-left-width: 1pt;border-style: none solid solid;border-right-color: windowtext;border-bottom-color: windowtext;border-left-color: windowtext;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"28.282828282828284%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003eDyslipidemia, n (%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"12.794612794612794%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e14 (20)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.3pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"14.478114478114477%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e8 (21)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51.95pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"11.616161616161616%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e6 (20)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97.75pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"21.885521885521886%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e0.958 \u003csup\u003ec\u003c/sup\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.45pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"10.942760942760943%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 125.8pt;border-right-width: 1pt;border-bottom-width: 1pt;border-left-width: 1pt;border-style: none solid solid;border-right-color: windowtext;border-bottom-color: windowtext;border-left-color: windowtext;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"28.282828282828284%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003eObesity, n (%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"12.794612794612794%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e16 (23)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.3pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"14.478114478114477%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e9 (23)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51.95pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"11.616161616161616%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e7 (23)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97.75pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"21.885521885521886%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e0.980 \u003csup\u003ec\u003c/sup\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.45pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"10.942760942760943%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 125.8pt;border-right-width: 1pt;border-bottom-width: 1pt;border-left-width: 1pt;border-style: none solid solid;border-right-color: windowtext;border-bottom-color: windowtext;border-left-color: windowtext;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"28.282828282828284%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003eCardiovascular disease, n (%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"12.794612794612794%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e8 (12)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.3pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"14.478114478114477%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e5 (13)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51.95pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"11.616161616161616%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e3 (10)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97.75pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"21.885521885521886%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e1.000 \u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.45pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"10.942760942760943%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 125.8pt;border-right-width: 1pt;border-bottom-width: 1pt;border-left-width: 1pt;border-style: none solid solid;border-right-color: windowtext;border-bottom-color: windowtext;border-left-color: windowtext;background-color: rgb(217, 217, 217);padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"28.282828282828284%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 20px;\"\u003eClinical assessment at baseline\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: rgb(217, 217, 217);padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"12.794612794612794%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.3pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: rgb(217, 217, 217);padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"14.478114478114477%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51.95pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: rgb(217, 217, 217);padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"11.616161616161616%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97.75pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: rgb(217, 217, 217);padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"21.885521885521886%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.45pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: rgb(217, 217, 217);padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"10.942760942760943%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 125.8pt;border-right-width: 1pt;border-bottom-width: 1pt;border-left-width: 1pt;border-style: none solid solid;border-right-color: windowtext;border-bottom-color: windowtext;border-left-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"28.282828282828284%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003ePaO\u003csub\u003e2\u003c/sub\u003e/FiO\u003csub\u003e2\u003c/sub\u003e, mmHg, median (IQR)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"12.794612794612794%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e190 (99)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.3pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"14.478114478114477%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e182 (110)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51.95pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"11.616161616161616%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e214 (116)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97.75pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"21.885521885521886%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e0.023 \u003cem\u003e*\u003c/em\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.45pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"10.942760942760943%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e0.47\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 125.8pt;border-right-width: 1pt;border-bottom-width: 1pt;border-left-width: 1pt;border-style: none solid solid;border-right-color: windowtext;border-bottom-color: windowtext;border-left-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"28.282828282828284%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e\u0026Delta;A-aO\u003csub\u003e2\u003c/sub\u003e, mmHg,\u0026nbsp;median (IQR)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"12.794612794612794%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e219 (102)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.3pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"14.478114478114477%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e234 (151)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51.95pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"11.616161616161616%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e197 (86)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97.75pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"21.885521885521886%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e0.133 \u003cem\u003e*\u003c/em\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.45pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"10.942760942760943%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e0.40\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 125.8pt;border-right-width: 1pt;border-bottom-width: 1pt;border-left-width: 1pt;border-style: none solid solid;border-right-color: windowtext;border-bottom-color: windowtext;border-left-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"28.282828282828284%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003emeanBP, mmHg, mean \u0026plusmn; SD\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"12.794612794612794%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e97 \u0026plusmn;13\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.3pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"14.478114478114477%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e97 \u0026plusmn;13\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51.95pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"11.616161616161616%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e96 \u0026plusmn;13\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97.75pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"21.885521885521886%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e0.406\u003csup\u003ew\u003c/sup\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.45pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"10.942760942760943%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e0.03\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 125.8pt;border-right-width: 1pt;border-bottom-width: 1pt;border-left-width: 1pt;border-style: none solid solid;border-right-color: windowtext;border-bottom-color: windowtext;border-left-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"28.282828282828284%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e[K\u003csup\u003e+\u003c/sup\u003e]\u003csub\u003eplasma\u003c/sub\u003e, mmol/L, mean \u0026plusmn; SD\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"12.794612794612794%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e4.1 \u0026plusmn;0.5\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.3pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"14.478114478114477%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e4.2 \u0026plusmn; 0.6\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51.95pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"11.616161616161616%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e4.0 \u0026plusmn;0.4\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97.75pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"21.885521885521886%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e0.111\u003csup\u003ew\u003c/sup\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.45pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"10.942760942760943%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e0.38\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 125.8pt;border-right-width: 1pt;border-bottom-width: 1pt;border-left-width: 1pt;border-style: none solid solid;border-right-color: windowtext;border-bottom-color: windowtext;border-left-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"28.282828282828284%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003eCRP, mg/dL,\u0026nbsp;median (IQR)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"12.794612794612794%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e12 (10)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.3pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"14.478114478114477%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e11 (10)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51.95pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"11.616161616161616%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e13 (10)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97.75pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"21.885521885521886%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e0.186 \u003cem\u003e*\u003c/em\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.45pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"10.942760942760943%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e0.28\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 125.8pt;border-right-width: 1pt;border-bottom-width: 1pt;border-left-width: 1pt;border-style: none solid solid;border-right-color: windowtext;border-bottom-color: windowtext;border-left-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"28.282828282828284%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003eIL-6, pg/mL, median (IQR)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"12.794612794612794%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e83 (91)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.3pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"14.478114478114477%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e88 (139)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51.95pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"11.616161616161616%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e83 (64)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97.75pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"21.885521885521886%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e0.757 \u003cem\u003e*\u003c/em\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.45pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"10.942760942760943%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e0.16\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 125.8pt;border-right-width: 1pt;border-bottom-width: 1pt;border-left-width: 1pt;border-style: none solid solid;border-right-color: windowtext;border-bottom-color: windowtext;border-left-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"28.282828282828284%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003eD-dimer,\u0026nbsp;g/L,\u0026nbsp;median (IQR)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"12.794612794612794%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e992 (1079)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.3pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"14.478114478114477%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e939 (890)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51.95pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"11.616161616161616%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e1057 (1135)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97.75pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"21.885521885521886%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e0.215\u003cem\u003e*\u003c/em\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.45pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"10.942760942760943%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e0.33\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 125.8pt;border-right-width: 1pt;border-bottom-width: 1pt;border-left-width: 1pt;border-style: none solid solid;border-right-color: windowtext;border-bottom-color: windowtext;border-left-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"28.282828282828284%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003eFerritin, ng/mL,\u0026nbsp;median (IQR)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"12.794612794612794%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e1421 (2121)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.3pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"14.478114478114477%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e1262 (2495)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51.95pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"11.616161616161616%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e1704 (1866)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97.75pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"21.885521885521886%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e0.380 \u003cem\u003e*\u003c/em\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.45pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"10.942760942760943%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e0.02\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 125.8pt;border-right-width: 1pt;border-bottom-width: 1pt;border-left-width: 1pt;border-style: none solid solid;border-right-color: windowtext;border-bottom-color: windowtext;border-left-color: windowtext;background-color: rgb(217, 217, 217);padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"28.282828282828284%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 20px;\"\u003eTreatment distribution\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: rgb(217, 217, 217);padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"12.794612794612794%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.3pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: rgb(217, 217, 217);padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"14.478114478114477%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51.95pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: rgb(217, 217, 217);padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"11.616161616161616%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97.75pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: rgb(217, 217, 217);padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"21.885521885521886%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.45pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: rgb(217, 217, 217);padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"10.942760942760943%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 125.8pt;border-right-width: 1pt;border-bottom-width: 1pt;border-left-width: 1pt;border-style: none solid solid;border-right-color: windowtext;border-bottom-color: windowtext;border-left-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"28.282828282828284%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003eACEi or ARBs, n (%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"12.794612794612794%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e25 (36)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.3pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"14.478114478114477%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e6 (15)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51.95pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"11.616161616161616%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e19 (63)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97.75pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"21.885521885521886%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e\u0026lt;0.001 \u003csup\u003ec\u003c/sup\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.45pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"10.942760942760943%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 125.8pt;border-right-width: 1pt;border-bottom-width: 1pt;border-left-width: 1pt;border-style: none solid solid;border-right-color: windowtext;border-bottom-color: windowtext;border-left-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"28.282828282828284%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003eCa\u003csup\u003e2+\u0026nbsp;\u003c/sup\u003echannel blockers, n (%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"12.794612794612794%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e11 (16)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.3pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"14.478114478114477%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e11 (28)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51.95pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"11.616161616161616%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e0 (0.0)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97.75pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"21.885521885521886%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e0.002 \u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.45pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"10.942760942760943%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 125.8pt;border-right-width: 1pt;border-bottom-width: 1pt;border-left-width: 1pt;border-style: none solid solid;border-right-color: windowtext;border-bottom-color: windowtext;border-left-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"28.282828282828284%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003ealpha-1-adrenergic antagonist, n (%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"12.794612794612794%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e4 (6)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.3pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"14.478114478114477%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e4 (10)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51.95pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"11.616161616161616%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e0 (0.0)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97.75pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"21.885521885521886%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e0.127 \u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.45pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"10.942760942760943%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 125.8pt;border-right-width: 1pt;border-bottom-width: 1pt;border-left-width: 1pt;border-style: none solid solid;border-right-color: windowtext;border-bottom-color: windowtext;border-left-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"28.282828282828284%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003eHydroxychloroquine, n (%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"12.794612794612794%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e69 (100)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.3pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"14.478114478114477%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e39 (100)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51.95pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"11.616161616161616%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e30 (100)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97.75pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"21.885521885521886%\"\u003e\n \u003cp style=\"margin: 0in 0in 0in 40.8pt;font-size:16px;font-family: Calibri, sans-serif;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e-\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.45pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"10.942760942760943%\"\u003e\n \u003cp style=\"margin: 0in 0in 0in 40.8pt;font-size:16px;font-family: Calibri, sans-serif;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 125.8pt;border-right-width: 1pt;border-bottom-width: 1pt;border-left-width: 1pt;border-style: none solid solid;border-right-color: windowtext;border-bottom-color: windowtext;border-left-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"28.282828282828284%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003eLopinavir/Ritonavir, n (%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"12.794612794612794%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e24 (35)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.3pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"14.478114478114477%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e23 (59)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51.95pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"11.616161616161616%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e1 (3)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97.75pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"21.885521885521886%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e\u0026lt;0.001\u0026nbsp;\u003c/span\u003e\u003cem\u003e\u003cspan style=\"line-height: 20px;\"\u003e*\u003c/span\u003e\u003c/em\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.45pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"10.942760942760943%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 125.8pt;border-right-width: 1pt;border-bottom-width: 1pt;border-left-width: 1pt;border-style: none solid solid;border-right-color: windowtext;border-bottom-color: windowtext;border-left-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"28.282828282828284%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003eAnakinra, n (%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"12.794612794612794%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e20 (29)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.3pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"14.478114478114477%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e9 (23)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51.95pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"11.616161616161616%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e11 (37)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97.75pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"21.885521885521886%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e0.217\u0026nbsp;\u003c/span\u003e\u003cem\u003e\u003cspan style=\"line-height: 20px;\"\u003e*\u003c/span\u003e\u003c/em\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.45pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"10.942760942760943%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 125.8pt;border-right-width: 1pt;border-bottom-width: 1pt;border-left-width: 1pt;border-style: none solid solid;border-right-color: windowtext;border-bottom-color: windowtext;border-left-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"28.282828282828284%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003eCortisone, n (%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"12.794612794612794%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e24 (35)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64.3pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"14.478114478114477%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e10 (26)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51.95pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"11.616161616161616%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e14 (47)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97.75pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"21.885521885521886%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e0.069\u0026nbsp;\u003c/span\u003e\u003cem\u003e\u003cspan style=\"line-height: 20px;\"\u003e*\u003c/span\u003e\u003c/em\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.45pt;border-style: none solid solid none;border-bottom-width: 1pt;border-bottom-color: windowtext;border-right-width: 1pt;border-right-color: windowtext;background-color: white;padding: 0in 5.4pt;vertical-align: top;\" valign=\"top\" width=\"10.942760942760943%\"\u003e\n \u003cp style=\"margin: 0in;font-size:16px;font-family: Calibri, sans-serif;text-align: center;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 20px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style=\"margin: 0in;font-family: Calibri, sans-serif;text-align: justify;line-height: 24px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eSD, standard deviation; PaO\u003csub\u003e2\u003c/sub\u003e/FiO\u003csub\u003e2\u003c/sub\u003e, partial pressure of oxygen to inspiratory fraction of oxygen ratio; IQR, interquartile range; \u0026Delta;A-aO\u003csub\u003e2\u003c/sub\u003e, alveolar-arterial oxygen gradient (\u0026Delta;A-aO2); meanBP, mean blood pressure; [K\u003csup\u003e+\u003c/sup\u003e]\u003csub\u003eplasma\u003c/sub\u003e, plasma concentration of potassium; CRP, C-reactive protein; IL-6, interleukin 6; ACEi, inhibitors of angiotensin converting enzyme; ARBs, angiotensin receptor antagonists.\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"margin: 0in;font-family: Calibri, sans-serif;text-align: justify;line-height: 24px;\"\u003e\u003cspan style=\"font-size: 10px; font-family: Verdana, Geneva, sans-serif; color: rgb(0, 0, 0);\"\u003e\u003csup\u003ec\u003c/sup\u003ep-value from Pearson\u0026rsquo;s chi-square test. \u003csup\u003ew\u003c/sup\u003ep-value from Welch\u0026#39;s t-test. \u003csup\u003e\u0026sect;\u003c/sup\u003ep-value from Fisher\u0026rsquo;s Exact test. *p-value from Mann-Whitney U-test. Cohen\u0026rsquo;s d effect size for unequal group size \u003c/span\u003e\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"COVID-19, Angiotensin-Converting Enzyme-2, Renin-Angiotensin-Aldosterone System, Mineral Corticoid Receptor Antagonist, aldosterone","lastPublishedDoi":"10.21203/rs.3.rs-45837/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-45837/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose:\u0026nbsp;\u003c/strong\u003eDespite the spread of SARS-CoV-2 global pandemic and the volume of clinical trials launched, no specific therapeutic drug approaches improving outcomes have been so far approved. In COVID-19 patients, aldosterone via ACE2 deregulation may be responsible for systemic and pulmonary vasoconstriction, inflammation and oxidative organ damage.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eAim\u003c/strong\u003e: To verify retrospectively the impact of the mineral corticoid receptor antagonist canrerone\u0026nbsp;\u003cem\u003ei.v.\u003c/em\u003e\u0026nbsp;on the need of invasive ventilatory support and/or all-cause in-hospital mortality.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eStudy design\u003c/strong\u003e: In this retrospective study (CARDIOVID-19, ID-107162),\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eCOVID-19\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003epatients hospitalized for severe respiratory failure were taken care by pneumologists or cardiologists and received two different therapeutic approaches according to personal skill of referral medical team on pharmacological management. Group 1 (n=39) were given vasodilator agents or RAAS-inhibitors and group 2 (n=30) were given canrenone i.v.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: Among 69 consecutive COVID-19 patients, enrolled in COVID-19 NETWORK registry, the group given canrenone (200 mg/q.d. for a median of 14±11) showed a free event rate of 83% with a survival percentage of 90%. In group 1, not receiving canrenone, free event rate was 51% and survival 64%. Kaplan-Meier analysis for composite outcomes showed a Log Rank of 0.0004 and for mortality, Log Rank was 0.005.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e: The novelty of our observation relies on the independent positive impact of the canrenone, a mineral corticoid receptor antagonist, on all-cause mortality and clinical improvement in COVID-19 patients.\u003c/p\u003e","manuscriptTitle":"The efficacy of mineral corticoid receptor antagonist, canrenone, in COVID-19 patients","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2020-07-22 15:02:28","doi":"10.21203/rs.3.rs-45837/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6830ff38-9770-4d62-8332-85b1f9982a69","owner":[],"postedDate":"July 22nd, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":176824,"name":"Preventive Medicine"}],"tags":[],"updatedAt":"2020-07-22T15:02:28+00:00","versionOfRecord":[],"versionCreatedAt":"2020-07-22 15:02:28","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-45837","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-45837","identity":"rs-45837","version":["v1"]},"buildId":"ApUGefWb6u5IBVtyqm6d5","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}