Figures
- FIGURE 1
Flowchart of included patients, cohorts with and without prior cardiovascular disease, and propensity-score match. DrCOPD: Danish Register of Chronic Obstructive Pulmonary Disease.
- FIGURE 2
Cumulated incidence plots of severe and any major adverse cardiac events (MACE) occurring in the propensity-matched cohorts stratified by pre-existing cardiovascular disease with other-cause mortality as a competing risk. Patients with COPD and asthma and with COPD without asthma were propensity matched 1:2 by age, gender, tobacco exposure, Medical Research Council dyspnoea score, body mass index and forced expiratory volume in 1 s stratified into populations based on pre-existing cardiovascular disease. “Severe MACE” was defined as lethal cardiovascular events, and cardiovascular events requiring revascularisation or hospitalisation; “any MACE” was defined as severe MACE or an event requiring a prescription of ADP receptor inhibitors or nitrates. a) Severe MACE in the propensity score matched cohort of patients with pre-existing cardiovascular disease (n=10 926); b) any MACE in the propensity score matched cohort of patients with pre-existing cardiovascular disease (n=10 926); c) severe MACE in the propensity score matched cohort of patients without pre-existing cardiovascular disease (n=19 980); d) any MACE in the propensity score matched cohort of patients without pre-existing cardiovascular disease (n=19 980).
- FIGURE 3
Forest plots showing hazard ratios for severe major adverse cardiac events (MACE) in cohorts of all included patients with COPD and asthma compared to patients with COPD without asthma stratified by pre-existing cardiovascular disease. Hazard ratios were calculated by adjusted Cox analysis. a) Patients with pre-existing cardiovascular disease (n=18 176). b) Patients without pre-existing cardiovascular disease (n=34 210). Age, body mass index (BMI) and forced expiratory volume in 1 s (FEV1) were analysed as continuous variables; gender, asthma, tobacco exposure and Medical Research Council (MRC) dyspnoea score as binary variables. For tobacco exposure, current and previous smokers were compared to never-smokers, passive smokers and patients with unknown smoking status (the latter comprising 9.1% of patients with prior cardiovascular disease and 8.5% in patients without prior cardiovascular disease). Patients with MRC ≥3 were compared to patients with MRC ≤2.
Tables
- TABLE 1
Baseline characteristics of the propensity-matched cohorts stratified by pre-existing cardiovascular disease
Patients with pre-existing cardiovascular disease Patients without pre-existing cardiovascular disease Patients with COPD and asthma Patients with COPD without asthma Patients with COPD and asthma Patients with COPD without asthma Patients 3690 7236 6775 13 205 Age years 72.4 (65.2–79.1) 72.6 (65.7–78.9) 66.2 (57.1–74.7) 66.4 (58.4–74.3) Female 2058 (55.8) 3989 (55.1) 4024 (59.4) 7761 (58.8) Tobacco exposure Never smoking 219 (5.9) 241 (3.3) 334 (4.9) 432 (3.3) Passive smoking 1 (0.0) 0 (0.0) 1 (0.0) 0 (0.0) Previous smoking 2156 (58.4) 4529 (62.6) 3675 (54.2) 7367 (55.8) Active smoking 981 (26.6) 1998 (27.6) 2217 (32.7) 4581 (34.7) Unknown tobacco exposure 333 (9.0) 468 (6.5) 548 (8.1) 825 (6.2) MRC dyspnoea score 3 (3–4) 3 (3–4) 3 (2–3) 3 (2–4) BMI kg·m−2 25 (23–29) 25 (22–30) 25 (22–29) 25 (21–29) FEV1 % pred 49 (37–61) 49 (37–61) 49 (36–61) 49 (35–61) Comorbidities Hypertension 1898 (51.4) 3622 (50.1) 1525 (22.5) 2872 (21.7) Hypercholesterolaemia 1018 (27.6) 2188 (30.2) 326 (4.8) 571 (4.3) Atrial fibrillation 864 (23.4) 1695 (23.4) 618 (9.1) 1261 (9.5) Diabetes 724 (19.6) 1305 (18.0) 660 (9.7) 1136 (8.6) Osteoporosis or osteopenia 1013 (27.5) 1584 (21.9) 1438 (21.2) 2339 (17.7) Renal insufficiency 2017 (54.7) 3843 (53.1) 1807 (26.7) 3338 (25.3) Liver insufficiency 114 (3.1) 258 (3.6) 210 (3.1) 372 (2.8) Malignancy 854 (23.1) 1561 (21.6) 1131 (16.7) 2111 (16.0) Atopy or allergy 562 (15.2) 264 (3.6) 1042 (15.4) 377 (2.9) Depression 292 (7.9) 442 (6.1) 333 (4.9) 516 (3.9) Exacerbations requiring admission within the year prior to inclusion 1426 (38.6) 2334 (32.3) 2146 (31.7) 3613 (27.4) Medical treatment for respiratory disease within the year prior to inclusion Oral corticosteroid 2207 (59.8) 3113 (43.0) 3703 (54.7) 5276 (40.0) Inhaled corticosteroid 3252 (88.1) 4892 (67.6) 5983 (88.3) 8887 (67.3) Long-acting β2-agonist 3253 (88.2) 5435 (75.1) 5920 (87.4) 9736 (73.7) Long acting muscarinic receptor antagonist 2715 (73.6) 5167 (71.4) 4730 (69.8) 9074 (68.7) Short-acting β2-agonist 2905 (78.7) 4590 (63.4) 5172 (76.3) 8194 (62.1) Short-acting muscarinic receptor antagonist 208 (5.6) 249 (3.4) 250 (3.7) 357 (2.7) Medical treatment for cardiovascular disease within the year prior to inclusion Blood pressure medication 3070 (83.2) 6212 (85.8) 3739 (55.2) 7631 (57.8) Cholesterol-lowering medication 2080 (56.4) 4458 (61.6) 1403 (20.7) 3157 (23.9) ADP-receptor inhibitors 666 (18.0) 1532 (21.2) NA NA Acetyl sialic acid 1841 (49.9) 3838 (53.0) 1002 (14.8) 2213 (16.8) Nitrates 964 (26.1) 1799 (24.9) NA NA Medical treatment for diabetes within the year prior to inclusion Insulin 229 (6.2) 448 (6.2) 225 (3.3) 392 (3.0) Non-insulin antidiabetics 637 (17.3) 1185 (16.4) 657 (9.7) 1311 (9.9) Data are presented as n, median (interquartile range) or n (%). Patients with COPD and asthma and with COPD without asthma were propensity matched 1:2 by age, gender, tobacco exposure, Medical Research Council (MRC) dyspnoea score, body mass index (BMI) and forced expiratory volume in 1 s (FEV1) % stratified into populations based on pre-existing cardiovascular disease. NA: not applicable.
- TABLE 2
Primary end-point outcomes
Patients with pre-existing cardiovascular disease Patients without pre-existing cardiovascular disease Patients with COPD and asthma Patients with COPD without asthma Patients with COPD and asthma Patients with COPD without asthma Patients n 3690 7236 6775 13 205 Primary outcome Severe MACE 591 (15.9) 978 (6.8) 301 (4.4) 550 (2.0) HR (95% CI) 1.25 (1.13–1.39)# Reference 1.22 (1.06–1.41) Reference Secondary outcome Any MACE 654 (17.6) 1093 (7.6) 388 (5.7) 696 (2.5) HR (95% CI) 1.22 (1.11–1.34)# Reference 1.22 (1.07–1.38) Reference Severe MACE analysis Lethal cardiovascular events 72 (1.9) 148 (1.0) 42 (0.6) 88 (0.3) HR (95% CI) 1.14 (0.86–1.51) Reference 1.09 (0.75–1.57) Reference Nonlethal cardiovascular events requiring revascularisation 102 (2.8) 152 (1.1) 45 (0.7) 113 (0.4) HR (95% CI) 1.53 (1.19–1.97)# Reference 0.92 (0.65–1.29) Reference Non-lethal cardiovascular events requiring admission 417 (11.2) 678 (4.7) 214 (3.1) 349 (1.3) HR (95% CI) 1.28 (1.15–1.43)# Reference 1.25 (1.08–1.45)# Reference All-cause mortality (not MACE) 843 (22.7) 1807 (12.5) 991 (14.5) 2169 (7.9) HR (95% CI) 1.11 (1.03–1.21)# Reference 1.06 (0.98–1.14) Reference Data are presented as n (%), unless otherwise stated. Hazard ratios (HR) analysed by unadjusted Cox method with other cause mortality as a competing risk on the propensity-matched cohorts stratified by pre-existing cardiovascular disease. Patients with COPD and asthma and with COPD without asthma were propensity matched 1:2 by age, gender, tobacco exposure, Medical Research Council dyspnoea score, body mass index and forced expiratory volume in 1 s stratified into populations based on pre-existing cardiovascular disease. “Severe major adverse cardiac events (MACE)” defined as lethal cardiovascular events, and cardiovascular events requiring revascularisation or hospitalisation; “any MACE” defined as a severe MACE or an event requiring a prescription of ADP receptor inhibitors or nitrates. #: statistical significance >0.95 by regression analysis.
- TABLE 3
Secondary outcomes
Patients with pre-existing cardiovascular disease Patients without pre-existing cardiovascular disease Patients with COPD and asthma Patients with COPD without asthma Patients with COPD and asthma Patients with COPD without asthma Patients 3707 14 469 6824 27 386 Severe MACE 593 (16.0) 1984 (13.7) 302 (4.4) 1240 (4.5) HR (95% CI) 1.22 (1.11–1.34)# Reference 1.21 (1.06–1.37)# Reference Any MACE 661 (17.8) 2270 (15.7) 519 (7.6) 2109 (7.7) HR (95% CI) 1.10 (0.86–1.40) Reference 1.26 (1.10–1.45)# Reference Severe MACE subunit analysis Lethal cardiovascular events 72 (1.9) 317 (2.2) 42 (0.6) 218 (0.8) HR (95% CI) 1.16 (0.89–1.50) Reference 1.06 (0.76–1.48) Reference Nonlethal cardiovascular events requiring revascularisation 102 (2.8) 314 (2.2) 45 (0.7) 249 (0.9) HR (95% CI) 1.51 (1.21–1.90)# Reference 0.98 (0.71–1.35) Reference Nonlethal cardiovascular events requiring admission 419 (11.3) 1353 (9.4) 215 (3.2) 737 (2.7) HR (95% CI) 1.23 (1.12–1.36)# Reference 1.25 (1.09–1.43) Reference All-cause mortality (not MACE) 843 (22.7) 3914 (27.1) 993 (14.6) 5422 (19.8) HR (95% CI) 1.08 (1.00–1.17)# Reference 1.02 (0.95–1.09) Reference Data are presented as n (%), unless otherwise stated. Hazard ratios by Cox analysis with other cause mortality as a competing risk adjusting for age, gender, tobacco exposure, Medical Research Council dyspnoea score, body mass index and forced expiratory volume in 1 s on cohorts of all included patients stratified by pre-existing cardiovascular disease. “Severe major adverse cardiac events (MACE)” defined as lethal cardiovascular events, and cardiovascular events requiring revascularisation or hospitalisation; “any MACE” defined as a severe MACE or an event requiring a prescription of ADP receptor inhibitors or nitrates. #: statistical significance >0.95 by regression analysis.
