The role of COPD and inhaled corticosteroids in major adverse cardiovascular events in cardiovascular-kidney-metabolic populations
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Author(s)
Type
Journal Article
Abstract
Background
Cardiovascular-kidney-metabolic (CKM) disease and chronic obstructive pulmonary disease (COPD) are associated with major adverse cardiovascular events (MACE). Whether COPD further increases MACE risk within CKM populations, and whether this potential risk is modifiable through inhaled corticosteroids (ICS), is unknown. Within CKM populations, we investigated the relationship between (1) COPD and subsequent MACE, and (2) amongst concurrent CKM-COPD populations, we investigated the relationship between ICS and subsequent MACE.
Methods
We used Clinical Practice Research Datalink (CPRD) Aurum, Hospital Episode Statistics and Office of National Statistics data, between January 1st, 2010, and March 29th, 2021. We created five discrete cohorts: chronic kidney disease (CKD), type-II diabetes mellitus (T2DM), obesity, MACE history, and older adults (aged ≥ 65 years old [“Age65 + ”]). CKD, T2DM, obesity, and Age65 + cohorts were MACE-naïve at the time of inclusion. Aim (1) exposures were (a) COPD, (b) incident COPD, and (c) being at risk of COPD without diagnosis (defined as age ≥ 40 years old, smoking history, no evidence of asthma, and frequent respiratory infections requiring antibiotics). Aim (2) exposure was ICS prescription (control group: long-acting bronchodilators). The outcome was MACE (acute coronary syndrome, arrhythmia, heart failure, ischaemic stroke, or cardiovascular-specific mortality). We implemented Cox proportional hazards models.
Results
COPD was associated with MACE amongst all cohorts, but was comparatively weak in the MACE history cohort (cohort total; adjusted hazard ratio [95% confidence interval]): CKD (N = 573,626; 1.29 [1.26, 1.32]), T2DM (N = 649,506; 1.30 [1.26, 1.35], obesity (N = 225,273; 1.41 [1.34, 1.48]), MACE history (N = 507,889; 1.04 [1.02, 1.06]), and Age65 + (N = 592,123, 1.59 [1.52, 1.66]). Incident COPD was associated with subsequent MACE in CKD only (1.28 [1.13, 1.45]). Being at risk of COPD was associated with subsequent MACE in CKD (1.18 [1.07, 1.30]), MACE history (1.16 [1.08, 1.25]), and Age65 + (1.28 [1.13, 1.46]). ICS prescription was not associated with subsequent MACE in any concurrent CKM-COPD cohort.
Conclusions
COPD was an independent risk factor for MACE in CKM populations. ICS did not attenuate MACE amongst CKM-COPD groups. Incident COPD was associated with MACE in CKD, and being at risk of COPD was associated with MACE in CKD, MACE history, and Age65 + cohorts.
Cardiovascular-kidney-metabolic (CKM) disease and chronic obstructive pulmonary disease (COPD) are associated with major adverse cardiovascular events (MACE). Whether COPD further increases MACE risk within CKM populations, and whether this potential risk is modifiable through inhaled corticosteroids (ICS), is unknown. Within CKM populations, we investigated the relationship between (1) COPD and subsequent MACE, and (2) amongst concurrent CKM-COPD populations, we investigated the relationship between ICS and subsequent MACE.
Methods
We used Clinical Practice Research Datalink (CPRD) Aurum, Hospital Episode Statistics and Office of National Statistics data, between January 1st, 2010, and March 29th, 2021. We created five discrete cohorts: chronic kidney disease (CKD), type-II diabetes mellitus (T2DM), obesity, MACE history, and older adults (aged ≥ 65 years old [“Age65 + ”]). CKD, T2DM, obesity, and Age65 + cohorts were MACE-naïve at the time of inclusion. Aim (1) exposures were (a) COPD, (b) incident COPD, and (c) being at risk of COPD without diagnosis (defined as age ≥ 40 years old, smoking history, no evidence of asthma, and frequent respiratory infections requiring antibiotics). Aim (2) exposure was ICS prescription (control group: long-acting bronchodilators). The outcome was MACE (acute coronary syndrome, arrhythmia, heart failure, ischaemic stroke, or cardiovascular-specific mortality). We implemented Cox proportional hazards models.
Results
COPD was associated with MACE amongst all cohorts, but was comparatively weak in the MACE history cohort (cohort total; adjusted hazard ratio [95% confidence interval]): CKD (N = 573,626; 1.29 [1.26, 1.32]), T2DM (N = 649,506; 1.30 [1.26, 1.35], obesity (N = 225,273; 1.41 [1.34, 1.48]), MACE history (N = 507,889; 1.04 [1.02, 1.06]), and Age65 + (N = 592,123, 1.59 [1.52, 1.66]). Incident COPD was associated with subsequent MACE in CKD only (1.28 [1.13, 1.45]). Being at risk of COPD was associated with subsequent MACE in CKD (1.18 [1.07, 1.30]), MACE history (1.16 [1.08, 1.25]), and Age65 + (1.28 [1.13, 1.46]). ICS prescription was not associated with subsequent MACE in any concurrent CKM-COPD cohort.
Conclusions
COPD was an independent risk factor for MACE in CKM populations. ICS did not attenuate MACE amongst CKM-COPD groups. Incident COPD was associated with MACE in CKD, and being at risk of COPD was associated with MACE in CKD, MACE history, and Age65 + cohorts.
Date Issued
2026-04-10
Date Acceptance
2026-02-24
Citation
BMC Medicine, 2026, 24
ISSN
1741-7015
Publisher
BMC
Journal / Book Title
BMC Medicine
Volume
24
Copyright Statement
© The Author(s) 2026 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
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Publication Status
Published
Article Number
221
Date Publish Online
2026-03-04