Study: Italian Patients With COPD at High Risk of Severe Cardiovascular Events

Italian patients with chronic obstructive pulmonary disease (COPD) are at a high risk of severe cardiovascular (CV) events following exacerbations, according to a study published in the European Journal of Internal Medicine.¹

The researchers explained that patients with COPD often face comorbidities. More specifically, over 80% of patients with COPD have at least 1 comorbidity, including cardiovascular diseases (CVDs), depression, and diabetes. CVDs, like hypertension and heart failure (HF), are the most common comorbidities in those with COPD as their onset risk is doubled.

Patients with COPD also periodically experience exacerbations, “a worsening of respiratory symptoms, characterized by increased dyspnea, cough, and sputum production.”² The researchers noted that exacerbations lead to disease progression, have negative consequences on the mental and physical status of patients, and increase the rate of both hospitalizations and readmissions.¹

A previous study found a correlation between reduced lung function, increased CV mortality, and ventricular arrhythmia risk.² Therefore, further research is needed regarding the relationship between COPD exacerbations, CVDs, and CV events.¹ Consequently, the researchers evaluated the association between periods following a COPD exacerbation and the occurrence of a severe CV event.

To create their study population, they used the Fondazione Ricerca e Salute (ReS) database,³ which contains Italian administrative health care data from 2013 to 2021 for 5 million inhabitants per year. It contains various information on inhabitants, including hospital and prescription drug records. Eligible patients in the ReS database included those with COPD aged 45 years or older between January 1, 2015, and December 31, 2018.¹

Past evidence found that the highest risk of a severe CV event is within the first 30 days following a COPD exacerbation.⁴ Therefore, the researchers segmented the exposure period into 5 mutually exclusive periods (1-7 days, 8-14 days, 15-30 days, 31-180 days, and 181-365 days). ¹ An exposure period, or exacerbation period, ended if a following exacerbation occurred, the patient was lost to follow-up, or the follow-up period ended. The researchers also calculated crude incidence rates (IRs) of all CV events per 100 person-years for both exposed and unexposed periods.

The researchers included 216,864 patients from the ReS database with COPD in their study population, the majority of which (55.5%) were male and had a mean (standard deviation [SD]) age of 74 (12) years. Of the study population, 129,886 (59.7%) were newly diagnosed with COPD; they had a mean (SD) age of 73 (12) years. CV and metabolic comorbidities were the most frequent, especially hypertension (75.8%) and dyslipidemias (34.4%).

During a mean follow-up duration of 34.4 (20.6; range, 0.03-60.0) months, 69,620 (32.1%) patients experienced at least 1 exacerbation. Of these, 47,953 patients (69.0%) had at least 1 moderate exacerbation, and 32,569 (46.8%) had at least 1 severe exacerbation. Compared to those with at least 1 moderate exacerbation, the researchers noted that patients with at least 1 severe exacerbation had a higher prevalence of all comorbidities of interest.

Additionally, 46,214 (21.3%) patients experienced at least 1 severe acute CV event during follow-up; HF was the most prevalent (13.9%), followed by acute coronary syndrome (5.0%). More specifically, during follow-up, 37,631 (81.4%) of these patients experienced a severe CV event before a moderate or severe exacerbation. Conversely, the remaining patients experienced a CV event within 365 days of an exacerbation (n = 10,269 patients) or more than 365 days following an exacerbation (n = 4428).

The crude IR of a CV event 365 days post-exacerbation was 15.8 per 100 person-years (95% CI, 15.5-16.1). In terms of periods, the crude IR of a CV event was highest within the first 7 days post-exacerbation (252.1 per 100 person-years; 95% CI, 245.3-258.9) and lowest between 181 and 365 days post-exacerbation (5.6 per 100 person-years; 95% CI, 5.3-5.9). Similarly, estimated HRs for severe CV event risk were highest within 7 days post-exacerbation (HR, 34.3; 95% CI, 33.1-35.6), especially for heart failure (HR, 50.6; 95% CI, 48.6-52.7); estimated HRs remained elevated for 365 days (HR, 1.1; 95% CI, 1.02-1.13).

The researchers acknowledged their limitations. For example, they recognized the potential misclassification of severe acute CV events as severe exacerbations within the first 7 days after symptoms. Because of the similarity between cardiac and respiratory symptoms, this 1 to 7-day period is prone to potential misclassification; they noted that the estimated HRs should be interpreted with this in mind. Despite their limitations, the researchers expressed confidence in their findings.

“Our findings emphasize the importance of early interventions and treatment optimization among patients with COPD to reduce cardiopulmonary risk by preventing COPD exacerbations and, in turn, non-fatal and fatal severe acute CV events,” the authors concluded.

References

1. Calabria S, Ronconi G, Dondi L, et al. Cardiovascular events after exacerbations of chronic obstructive pulmonary disease: Results from the Exacerbations of COPD and their outcomes in cardiovascular diseases study in Italy. Eur J Intern Med. doi:10.1016/j.ejim.2024.04.021

2. Hillas G, Perlikos F, Tzanakis N. Acute exacerbation of COPD: is it the "stroke of the lungs"?. Int J Chron Obstruct Pulmon Dis. 2016;11:1579-1586. doi:10.2147/COPD.S106160

3. Calabria S, Dondi L, Ronconi G, et al. Acute lower respiratory infections: real-world evidence of antibiotic prescription pattern and costs from a large administrative Italian database. Fam Pract. 2022;39(4):669-677. doi:10.1093/fampra/cmac002

4. Crisan L, Wong N, Sin DD, Lee HM. Karma of cardiovascular disease risk factors for prevention and management of major cardiovascular events in the context of acute exacerbations of chronic obstructive pulmonary disease. Front Cardiovasc Med. 2019;6:79. doi:10.3389/fcvm.2019.00079