The role of COPD and inhaled corticosteroids in major adverse cardiovascular events in cardiovascular-kidney-metabolic populations.

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.