Chronic obstructive pulmonary disease (COPD) is a progressive and common breathing disorder characterised by cough, sputum, and breathlessness. It is predominantly caused by smoking and many people who have COPD also have cardiovascular disease. Although we know COPD increases cardiovascular disease risk, what is less clear is whether people who have cardiovascular event first (such as a heart attack or stroke) are then at greater risk of a future cardiovascular event if they have COPD or at-risk for COPD. Furthermore, we do not know whether people who have other chronic diseases putting them at-risk of cardiovascular comorbidities (such as type II diabetes or chronic kidney disease) are at a greater risk of a future cardiovascular event if they are then diagnosed with COPD. Finally, it is unclear whether management of COPD (such as pharmacological intervention with inhaled corticosteroids or being hospitalised for different reasons) influence the risk of later cardiovascular events.
Therefore, using primary and secondary electronic healthcare records (including GP patient records and hospital data), this research aims to understand what the cardiovascular event risk profile looks like in: 1) people who have already had a previous cardiovascular event and are then diagnosed with COPD; 2) people who are at high risk of a cardiovascular event (due to another disease or other risk factors such as old age) who are diagnosed with or at risk of COPD, 3) people who are on various treatment regimens for their COPD, or 4) people with COPD who are hospitalized for various reasons.
Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disease resulting in airway obstruction. Cardiovascular comorbidities (i.e., heart failure, ischaemic stroke, arrhythmias) are common in people with COPD: there is an estimated two- to three-fold increase in cardiovascular disease in COPD patients compared with the non-COPD population.
Given established associations between cardiovascular comorbidities and COPD, expanding the understanding of major adverse cardiovascular event (MACE) risk in COPD patients is necessary. Firstly, understanding risk of MACE in COPD patients with already an index MACE, and in whom COPD is therefore the “second hit” in the risk profile, would illustrate how COPD affects pre-existing cardiovascular risk. Additionally, given the systemic inflammation-related overlap between COPD and cardiovascular disease, people at-risk of MACE due to other conditions causing systemic inflammation - such as chronic kidney disease (CKD) or type II diabetes mellitus (T2DM) - may also be at risk of MACE after COPD diagnosis. Finally, it is unknown how management of COPD (i.e., medications prescribed or hospitalizations) affects subsequent MACE risk.
We will conduct a retrospective cohort study using linked Clinical Practice Research Datalink (CPRD) Aurum and Hospital Episode Statistics (HES) data, between 1 January 2004 and 31 December 2019 in England. We will firstly include patients who have had a previous MACE and compare the risk of future MACE, in those with or are at-risk of COPD, compared to those without. Regarding COPD management, we will examine whether inhaled corticosteroids affect secondary MACE risk in COPD patients, and whether MACE risk is greatest in COPD patients hospitalized for various reasons. We will also look at MACE-naïve patients at risk of MACE (i.e., those with diabetes or CKD) to evaluate whether COPD predisposes them to MACE. We will also examine the relationship between hospitalisations, and future MACE, among people with COPD previously hospitalised.
1. The primary outcome is a major adverse cardiovascular event (MACE), including death. The primary endpoint is MACE overall. The secondary endpoints are death or the four individual components of MACE [Acute Coronary Syndrome, Arrythmias, Heart Failure, Ischaemic Stroke].
2. Secondary outcomes are adverse respiratory events in patients with COPD (AECOPD, and increased treatment regiments), and subsequent COPD diagnoses in undiagnosed patients at-risk for COPD.
3. Thirdly, we will examine management of cardiovascular events, including secondary prevention, revascularisation and rehospitalisation, where applicable
Outcomes will be measured using Clinical Practice Research Datalink (CPRD) Aurum data, Hospital Episode Statistics (HES) data, and Office for National Statistics (ONS) data for death data.
Jennifer Quint - Chief Investigator - Imperial College London
Anne Ioannides - Corresponding Applicant - Imperial College London
Constantinos Kallis - Collaborator - Imperial College London
Emily Graul - Collaborator - Imperial College London
Hannah Whittaker - Collaborator - Imperial College London
Yuxiao Alice Wang - Collaborator - Imperial College London
Anne Ioannides - Collaborator - Imperial College London
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation