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1School of Pharmacy, Sungkyunkwan University, Suwon, Korea
2Division of Infectious Diseases, Department of Social and Preventive Medicine, Hallym University College of Medicine, Chuncheon, Korea
3Lemuel Shattuck Hospital, Boston, MA, USA
4Brigham and Women’s Hospital, Boston, MA, USA
5Department of Clinical Research Design and Evaluation, Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University, Seoul, Korea
©2021, Korean Society of Epidemiology
This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
CONFLICT OF INTEREST
The authors have no conflicts of interest to declare for this study.
FUNDING
This study was supported by the Government-wide R&D Fund project for infectious disease research through the Government-wide R&D Fund for Infectious Disease Research (GFID) funded by the Korea Health Industry Development Institute of Republic of Korea (No. HG18C0068).
AUTHOR CONTRIBUTIONS
Conceptualization: JHK, YHB, HL, JYS. Data curation: JHK, YHB, HL, JYS. Formal analysis: HL, YHB. Funding acquisition: JYS. Methodology: JHK, YHB, HL, JYS. Project administration: JHK, YHB, HL, JYS. Visualization: JHK, YHB, HL, JYS. Writing – original draft: JHK, YHB. Writing – review & editing: JHK, YHB, HL, YJC, HJS, JYS.
Characteristics |
Unweighted, n (%) |
IPTW1, % |
||||
---|---|---|---|---|---|---|
ACEI/ARB (n=682)2 | Non-use (n=608) | aSD | ACEI/ARB2 | Non-use | aSD | |
Age (yr) | 62.8±14.4 | 61.3±16.6 | 0.09 | 63.4±23.9 | 62.3±22.6 | 0.05 |
<40 | 42 (6.2) | 72 (11.8) | 3.9 | 8.7 | ||
40-64 | 325 (46.7) | 257 (42.3) | 50.8 | 46.0 | ||
65-84 | 273 (40.0) | 244 (40.1) | 38.8 | 39.6 | ||
≥85 | 42 (6.2) | 35 (5.8) | 6.6 | 5.7 | ||
Sex | 0.07 | 0.02 | ||||
Male | 364 (53.4) | 303 (49.8) | 54.9 | 53.9 | ||
Female | 318 (46.6) | 305 (50.2) | 45.1 | 46.1 | ||
Medical history | ||||||
Hyperlipidemia | 263 (38.6) | 204 (33.6) | 0.10 | 41.2 | 35.5 | 0.12 |
Diabetes | 252 (37.0) | 156 (25.7) | 0.25 | 43.3 | 33.5 | 0.20 |
Cancer | 62 (9.1) | 76 (12.5) | 0.11 | 7.3 | 10.7 | 0.12 |
Respiratory disease | 222 (32.6) | 210 (34.5) | 0.04 | 31.8 | 32.9 | 0.02 |
Asthma | 59 (8.7) | 73 (12.0) | 0.11 | 7.1 | 10.1 | 0.11 |
COPD | 137 (20.1) | 146 (24.0) | 0.10 | 17.8 | 21.4 | 0.09 |
Bronchiectasis | 10 (1.5) | 5 (0.8) | 0.06 | 2.2 | 1.0 | 0.10 |
Pneumonia | 83 (12.2) | 60 (9.9) | 0.07 | 13.7 | 11.8 | 0.06 |
Interstitial lung disease | 8 (1.2) | 8 (1.3) | 0.01 | 1.0 | 1.2 | 0.02 |
Cardiovascular disease | 190 (27.9) | 158 (26.0) | 0.04 | 27.3 | 26.5 | 0.02 |
Peripheral vascular disease | 64 (9.4) | 49 (8.1) | 0.05 | 9.5 | 9.9 | 0.01 |
Coronary artery disease | 72 (10.6) | 78 (12.8) | 0.04 | 8.8 | 12.9 | 0.13 |
Atrial fibrillation | 19 (2.8) | 21 (3.5) | 0.04 | 2.8 | 3.1 | 0.02 |
Valvular heart disease | 8 (1.2) | 2 (0.3) | 0.10 | 2.5 | 0.7 | 0.15 |
Heart failure | 59 (8.7) | 41 (6.7) | 0.07 | 10.0 | 7.5 | 0.09 |
Arrhythmia | 18 (2.6) | 20 (3.3) | 0.04 | 2.2 | 2.8 | 0.04 |
Chronic kidney disease | 128 (18.8) | 95 (15.6) | 0.08 | 18.5 | 21.0 | 0.06 |
Chronic liver disease | 80 (11.7) | 84 (13.8) | 0.06 | 10.7 | 13.2 | 0.08 |
Stroke | 63 (9.2) | 74 (12.2) | 0.10 | 7.6 | 10.5 | 0.10 |
Other cerebrovascular diseases | 44 (6.5) | 43 (7.1) | 0.03 | 5.9 | 6.6 | 0.03 |
Comedications | ||||||
CCBs | 228 (33.4) | 248 (40.8) | 0.15 | 26.5 | 38.9 | 0.27 |
Diuretics | 149 (21.9) | 133 (21.9) | 0.00 | 22.0 | 23.2 | 0.03 |
β-blockers | 182 (26.7) | 186 (30.6) | 0.09 | 23.8 | 29.7 | 0.14 |
α-blockers | 106 (15.5) | 81 (13.3) | 0.06 | 16.5 | 15.9 | 0.02 |
CHA2DS2-VASc score | 2.7±1.4 | 2.4±1.7 | 0.35 | 2.8±2.3 | 2.5±2.3 | 0.33 |
0-1 | 148 (21.7) | 223 (36.7) | 14.9 | 27.4 | ||
2-5 | 507 (74.3) | 353 (58.1) | 81.9 | 67.9 | ||
6-9 | 27 (4.0) | 32 (5.3) | 3.3 | 4.7 | ||
Duration of hypertension (yr) | 0.33 | 0.31 | ||||
<1 | 40 (5.9) | 74 (12.2) | 3.8 | 8.5 | ||
≥1 and <3 | 106 (15.5) | 141 (23.2) | 11.0 | 19.2 | ||
≥3 and <5 | 149 (21.9) | 141 (23.2) | 21.1 | 20.6 | ||
≥5 | 387 (56.7) | 252 (41.5) | 64.2 | 51.7 |
Values are presented as mean±standard deviation or number (%).
ACEIs, angiotensin-converting enzyme inhibitors; ARBs, angiotensin II receptor blockers; IPTW, inverse probability of treatment weighting; aSD, absolute standardized difference; COPD, chronic obstructive pulmonary disease; CCBs, calcium channel blockers.
1 To generate IPTW, age at cohort entry, sex, income level, CHA2DS2-VASc score, medical history (including diabetes, cardiovascular disease, stroke, other cerebrovascular disease, hyperlipidemia, respiratory disease, chronic kidney disease, cancer, thromboembolism, and dementia), comedications (including other antihypertensives (CCBs, diuretics, β-blockers, and α-blockers), antidiabetics, antibiotics, antiarrhythmics, antiplatelets, anticoagulants, lipid-lowering agents, and antianginal agents), dialysis, and duration of hypertension (<1, ≥1 and <3, ≥3 and <5, and ≥5 years) were used (c-statistics: 0.723 for ACEI/ARB users vs. non-users).
2 There were 37 (5.4%) ACEI users, 642 (94.1%) ARB users, and 3 (0.4%) ACEI and ARB users.
Variables | No. of patients | Events, n (%) |
Unweighted model |
IPTW model1 |
||
---|---|---|---|---|---|---|
Crude RR (95% CI) | Adjusted RR (95% CI)2 | Crude RR (95% CI) | Adjusted RR (95% CI)2 | |||
All-cause mortality, mechanical ventilation, ICU admission, sepsis | ||||||
Non-use | 608 | 28 (4.6) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) |
ACEIs or ARBs use | 682 | 23 (3.4) | 0.73 (0.42, 1.27) | 0.71 (0.41, 1.24) | 0.60 (0.42, 0.85) | 0.60 (0.42, 0.85)* |
All-cause mortality | ||||||
Non-use | 608 | 12 (2.0) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) |
ACEIs or ARBs use | 682 | 10 (1.5) | 0.74 (0.32, 1.72) | 0.71 (0.31, 1.67) | 0.64 (0.37, 1.12) | 0.62 (0.35, 1.09) |
Respiratory events3 | ||||||
Non-use | 608 | 108 (17.8) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) |
ACEIs or ARBs use | 682 | 126 (18.5) | 1.04 (0.80, 1.35) | 1.02 (0.79, 1.32) | 0.99 (0.84, 1.16) | 0.99 (0.84, 1.17) |
RR, relative risk; ACEIs, angiotensin-converting enzyme inhibitors; ARBs, angiotensin II receptor blockers; IPTW, inverse probability of treatment weighting; CI, confidence interval; ICU, intensive care unit.
1 To generate IPTW, age at cohort entry, sex, income level, CHA₂DS₂-VASc score, medical history (including diabetes, cardiovascular disease, stroke, other cerebrovascular disease, hyperlipidemia, respiratory disease, chronic kidney disease, cancer, thromboembolism, and dementia), comedications (including other antihypertensives [calcium channel blockers, diuretics, β-blockers, and α-blockers], antidiabetics, antibiotics, antiarrhythmics, antiplatelets, anticoagulants, lipid-lowering agents, and antianginal agents), dialysis, and duration of hypertension (<1, ≥1 and <3, ≥3 and <5, and ≥5 years) were used.
2 For the adjusted RR, multivariable Poisson regression was used and adjusted for age, sex, CHA2DS2-VASc score, diabetes, cardiovascular disease, and respiratory disease.
3 Respiratory events included acute respiratory distress syndrome, interstitial lung disease, pneumonia, and respiratory failure. *p<0.05.
Variables | No. of patients | Events, n (%) |
Unweighted model |
IPTW model1 |
||
---|---|---|---|---|---|---|
Crude RR (95% CI) | Adjusted RR (95% CI)2 | Crude RR (95% CI) | Adjusted RR (95% CI)2 | |||
All-cause mortality, mechanical ventilation, ICU admission, sepsis | ||||||
Non-use | 523 | 23 (4.4) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) |
ACEIs or ARBs use | 767 | 28 (3.7) | 0.83 (0.48, 1.44) | 0.79 (0.45, 1.38) | 0.68 (0.49, 0.94)* | 0.65 (0.46, 0.90)* |
All-cause mortality | ||||||
Non-use | 523 | 12 (2.3) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) |
ACEIs or ARBs use | 767 | 10 (1.3) | 0.57 (0.25, 1.32) | 0.52 (0.22, 1.22) | 0.45 (0.27, 0.74)* | 0.41 (0.25, 0.68)* |
Respiratory events3 | ||||||
Non-use | 523 | 92 (17.6) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) |
ACEIs or ARBs use | 767 | 142 (18.5) | 1.05 (0.81, 1.37) | 1.08 (0.77, 1.32) | 0.98 (0.84, 1.13) | 0.94 (0.81, 1.09) |
RR, relative risk; ACEIs, angiotensin-converting enzyme inhibitors; ARBs, angiotensin II receptor blockers; IPTW, inverse probability of treatment weighting; CI, confidence interval; ICU, intensive care unit.
1 To generate IPTW, age at cohort entry, sex, income level, CHA2DS2-VASc score, medical history (including diabetes, cardiovascular disease, stroke, other cerebrovascular disease, hyperlipidemia, respiratory disease, chronic kidney disease, cancer, thromboembolism, and dementia), comedications (including other antihypertensives [calcium channel blockers, diuretics, β-blockers, and α-blockers], antidiabetics, antibiotics, antiarrhythmics, antiplatelets, anticoagulants, lipid-lowering agents, and antianginal agents), dialysis, and duration of hypertension (<1, ≥1 and <3, ≥3 and <5, and ≥5 years) were used.
2 For the adjusted RR, multivariable Poisson regression was used and adjusted for age, sex, CHA2DS2-VASc score, diabetes, cardiovascular disease, and respiratory disease.
3 Respiratory events included acute respiratory distress syndrome, interstitial lung disease, pneumonia, and respiratory failure.
* p<0.05.
Characteristics | Unweighted, n (%) |
IPTW |
||||
---|---|---|---|---|---|---|
ACEI/ARB (n=682) |
Non-use (n=608) | aSD | ACEI/ARB |
Non-use | aSD | |
Age (yr) | 62.8±14.4 | 61.3±16.6 | 0.09 | 63.4±23.9 | 62.3±22.6 | 0.05 |
<40 | 42 (6.2) | 72 (11.8) | 3.9 | 8.7 | ||
40-64 | 325 (46.7) | 257 (42.3) | 50.8 | 46.0 | ||
65-84 | 273 (40.0) | 244 (40.1) | 38.8 | 39.6 | ||
≥85 | 42 (6.2) | 35 (5.8) | 6.6 | 5.7 | ||
Sex | 0.07 | 0.02 | ||||
Male | 364 (53.4) | 303 (49.8) | 54.9 | 53.9 | ||
Female | 318 (46.6) | 305 (50.2) | 45.1 | 46.1 | ||
Medical history | ||||||
Hyperlipidemia | 263 (38.6) | 204 (33.6) | 0.10 | 41.2 | 35.5 | 0.12 |
Diabetes | 252 (37.0) | 156 (25.7) | 0.25 | 43.3 | 33.5 | 0.20 |
Cancer | 62 (9.1) | 76 (12.5) | 0.11 | 7.3 | 10.7 | 0.12 |
Respiratory disease | 222 (32.6) | 210 (34.5) | 0.04 | 31.8 | 32.9 | 0.02 |
Asthma | 59 (8.7) | 73 (12.0) | 0.11 | 7.1 | 10.1 | 0.11 |
COPD | 137 (20.1) | 146 (24.0) | 0.10 | 17.8 | 21.4 | 0.09 |
Bronchiectasis | 10 (1.5) | 5 (0.8) | 0.06 | 2.2 | 1.0 | 0.10 |
Pneumonia | 83 (12.2) | 60 (9.9) | 0.07 | 13.7 | 11.8 | 0.06 |
Interstitial lung disease | 8 (1.2) | 8 (1.3) | 0.01 | 1.0 | 1.2 | 0.02 |
Cardiovascular disease | 190 (27.9) | 158 (26.0) | 0.04 | 27.3 | 26.5 | 0.02 |
Peripheral vascular disease | 64 (9.4) | 49 (8.1) | 0.05 | 9.5 | 9.9 | 0.01 |
Coronary artery disease | 72 (10.6) | 78 (12.8) | 0.04 | 8.8 | 12.9 | 0.13 |
Atrial fibrillation | 19 (2.8) | 21 (3.5) | 0.04 | 2.8 | 3.1 | 0.02 |
Valvular heart disease | 8 (1.2) | 2 (0.3) | 0.10 | 2.5 | 0.7 | 0.15 |
Heart failure | 59 (8.7) | 41 (6.7) | 0.07 | 10.0 | 7.5 | 0.09 |
Arrhythmia | 18 (2.6) | 20 (3.3) | 0.04 | 2.2 | 2.8 | 0.04 |
Chronic kidney disease | 128 (18.8) | 95 (15.6) | 0.08 | 18.5 | 21.0 | 0.06 |
Chronic liver disease | 80 (11.7) | 84 (13.8) | 0.06 | 10.7 | 13.2 | 0.08 |
Stroke | 63 (9.2) | 74 (12.2) | 0.10 | 7.6 | 10.5 | 0.10 |
Other cerebrovascular diseases | 44 (6.5) | 43 (7.1) | 0.03 | 5.9 | 6.6 | 0.03 |
Comedications | ||||||
CCBs | 228 (33.4) | 248 (40.8) | 0.15 | 26.5 | 38.9 | 0.27 |
Diuretics | 149 (21.9) | 133 (21.9) | 0.00 | 22.0 | 23.2 | 0.03 |
β-blockers | 182 (26.7) | 186 (30.6) | 0.09 | 23.8 | 29.7 | 0.14 |
α-blockers | 106 (15.5) | 81 (13.3) | 0.06 | 16.5 | 15.9 | 0.02 |
CHA2DS2-VASc score | 2.7±1.4 | 2.4±1.7 | 0.35 | 2.8±2.3 | 2.5±2.3 | 0.33 |
0-1 | 148 (21.7) | 223 (36.7) | 14.9 | 27.4 | ||
2-5 | 507 (74.3) | 353 (58.1) | 81.9 | 67.9 | ||
6-9 | 27 (4.0) | 32 (5.3) | 3.3 | 4.7 | ||
Duration of hypertension (yr) | 0.33 | 0.31 | ||||
<1 | 40 (5.9) | 74 (12.2) | 3.8 | 8.5 | ||
≥1 and <3 | 106 (15.5) | 141 (23.2) | 11.0 | 19.2 | ||
≥3 and <5 | 149 (21.9) | 141 (23.2) | 21.1 | 20.6 | ||
≥5 | 387 (56.7) | 252 (41.5) | 64.2 | 51.7 |
Variables | No. of patients | Events, n (%) | Unweighted model |
IPTW model |
||
---|---|---|---|---|---|---|
Crude RR (95% CI) | Adjusted RR (95% CI) |
Crude RR (95% CI) | Adjusted RR (95% CI) |
|||
All-cause mortality, mechanical ventilation, ICU admission, sepsis | ||||||
Non-use | 608 | 28 (4.6) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) |
ACEIs or ARBs use | 682 | 23 (3.4) | 0.73 (0.42, 1.27) | 0.71 (0.41, 1.24) | 0.60 (0.42, 0.85) | 0.60 (0.42, 0.85)* |
All-cause mortality | ||||||
Non-use | 608 | 12 (2.0) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) |
ACEIs or ARBs use | 682 | 10 (1.5) | 0.74 (0.32, 1.72) | 0.71 (0.31, 1.67) | 0.64 (0.37, 1.12) | 0.62 (0.35, 1.09) |
Respiratory events |
||||||
Non-use | 608 | 108 (17.8) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) |
ACEIs or ARBs use | 682 | 126 (18.5) | 1.04 (0.80, 1.35) | 1.02 (0.79, 1.32) | 0.99 (0.84, 1.16) | 0.99 (0.84, 1.17) |
Variables | No. of patients | Events, n (%) | Unweighted model |
IPTW model |
||
---|---|---|---|---|---|---|
Crude RR (95% CI) | Adjusted RR (95% CI) |
Crude RR (95% CI) | Adjusted RR (95% CI) |
|||
All-cause mortality, mechanical ventilation, ICU admission, sepsis | ||||||
Non-use | 523 | 23 (4.4) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) |
ACEIs or ARBs use | 767 | 28 (3.7) | 0.83 (0.48, 1.44) | 0.79 (0.45, 1.38) | 0.68 (0.49, 0.94) |
0.65 (0.46, 0.90) |
All-cause mortality | ||||||
Non-use | 523 | 12 (2.3) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) |
ACEIs or ARBs use | 767 | 10 (1.3) | 0.57 (0.25, 1.32) | 0.52 (0.22, 1.22) | 0.45 (0.27, 0.74) |
0.41 (0.25, 0.68) |
Respiratory events |
||||||
Non-use | 523 | 92 (17.6) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) |
ACEIs or ARBs use | 767 | 142 (18.5) | 1.05 (0.81, 1.37) | 1.08 (0.77, 1.32) | 0.98 (0.84, 1.13) | 0.94 (0.81, 1.09) |
Values are presented as mean±standard deviation or number (%). ACEIs, angiotensin-converting enzyme inhibitors; ARBs, angiotensin II receptor blockers; IPTW, inverse probability of treatment weighting; aSD, absolute standardized difference; COPD, chronic obstructive pulmonary disease; CCBs, calcium channel blockers. To generate IPTW, age at cohort entry, sex, income level, CHA2DS2-VASc score, medical history (including diabetes, cardiovascular disease, stroke, other cerebrovascular disease, hyperlipidemia, respiratory disease, chronic kidney disease, cancer, thromboembolism, and dementia), comedications (including other antihypertensives (CCBs, diuretics, β-blockers, and α-blockers), antidiabetics, antibiotics, antiarrhythmics, antiplatelets, anticoagulants, lipid-lowering agents, and antianginal agents), dialysis, and duration of hypertension (<1, ≥1 and <3, ≥3 and <5, and ≥5 years) were used (c-statistics: 0.723 for ACEI/ARB users vs. non-users). There were 37 (5.4%) ACEI users, 642 (94.1%) ARB users, and 3 (0.4%) ACEI and ARB users.
RR, relative risk; ACEIs, angiotensin-converting enzyme inhibitors; ARBs, angiotensin II receptor blockers; IPTW, inverse probability of treatment weighting; CI, confidence interval; ICU, intensive care unit. To generate IPTW, age at cohort entry, sex, income level, CHA₂DS₂-VASc score, medical history (including diabetes, cardiovascular disease, stroke, other cerebrovascular disease, hyperlipidemia, respiratory disease, chronic kidney disease, cancer, thromboembolism, and dementia), comedications (including other antihypertensives [calcium channel blockers, diuretics, β-blockers, and α-blockers], antidiabetics, antibiotics, antiarrhythmics, antiplatelets, anticoagulants, lipid-lowering agents, and antianginal agents), dialysis, and duration of hypertension (<1, ≥1 and <3, ≥3 and <5, and ≥5 years) were used. For the adjusted RR, multivariable Poisson regression was used and adjusted for age, sex, CHA2DS2-VASc score, diabetes, cardiovascular disease, and respiratory disease. Respiratory events included acute respiratory distress syndrome, interstitial lung disease, pneumonia, and respiratory failure.
*p<0.05.
RR, relative risk; ACEIs, angiotensin-converting enzyme inhibitors; ARBs, angiotensin II receptor blockers; IPTW, inverse probability of treatment weighting; CI, confidence interval; ICU, intensive care unit. To generate IPTW, age at cohort entry, sex, income level, CHA2DS2-VASc score, medical history (including diabetes, cardiovascular disease, stroke, other cerebrovascular disease, hyperlipidemia, respiratory disease, chronic kidney disease, cancer, thromboembolism, and dementia), comedications (including other antihypertensives [calcium channel blockers, diuretics, β-blockers, and α-blockers], antidiabetics, antibiotics, antiarrhythmics, antiplatelets, anticoagulants, lipid-lowering agents, and antianginal agents), dialysis, and duration of hypertension (<1, ≥1 and <3, ≥3 and <5, and ≥5 years) were used. For the adjusted RR, multivariable Poisson regression was used and adjusted for age, sex, CHA2DS2-VASc score, diabetes, cardiovascular disease, and respiratory disease. Respiratory events included acute respiratory distress syndrome, interstitial lung disease, pneumonia, and respiratory failure. p<0.05.