Cardiovascular Disease Does Not Predict Exacerbation Rate or Mortality in Chronic Obstructive Pulmonary Disease

Abstract

Cardiovascular disease (CVD) is common in patients with chronic obstructive pulmonary disease (COPD) (1-4), yet it is unclear whether its presence increases the incidence of acute exacerbations (AECOPD) or the risk of death. Observational studies have shown that COPD is associated with a 2-5 times higher risk of ischaemic heart disease (IHD), cardiac dysrhythmia, heart failure, diseases of the pulmonary circulation, and diseases of the arteries, compared with non-COPD populations (4,5). A prospective evaluation of COPD exacerbations in patients with comorbid IHD from the London COPD Cohort reported longer duration but not an increased frequency of AECOPD in patients with IHD (6).This prospective study was designed to test the hypothesis that the presence of CVD increases the risk of AECOPD and/or death in COPD patients recruited in a primary care setting. MethodsThe ACCESS study (Assessment of Comorbidities in COPD in European Symptomatic Subjects; NCT01516528; 115058 study) was a prospective, longitudinal, observational, non-drug interventional, two-year study in COPD patients enrolled from primary care in Belgium, France, Germany, the Netherlands, Poland, and Spain. Patients, visiting their general practitioner (GP) for any reason, were invited to participate if they were ≥40 years old, current or ex-smoker (smoking history of ≥10 pack-years), a minimum of 12 months of prior history of COPD, and a forced expiratory volume in one second (FEV 1 )/forced vital capacity (FVC) postbronchodilator ratio <0.70. Patients with a primary diagnosis of asthma, pulmonary fibrosis, asbestosis, any cancer or clinically significant bronchiectasis were excluded. Page 3 of 12 3Patients were followed up for 27 months through clinic visits at screening (-3 months), baseline (0 months), 12 months and 24 months, and by phone at 3, 6, 9, 15, 18 and 21 months. Written informed consent was obtained from all subjects and the study was approved by independent ethics committees as per the requirements in each country.The prevalence of CVD at baseline was defined using a composite measure with previously published criteria (7). The primary outcome was the annual rate of moderate-severe AECOPD during the 24-month follow-up period. Moderate AECOPD was defined as a worsening of symptoms that required oral corticosteroids and/or antibiotics, whilst severe exacerbations were defined as those that included hospitalization. Mortality was a secondary outcome; details of patient deaths were obtained from the GP.To derive event rates and test associations, we applied multivariable negative binomial regression and Cox proportional hazards regression models, respectively.All analysis was pre-specified except hospitalizations and mortality outcome modeling which were post-hoc. Results2,887 evaluable patients were included in this analysis. Their mean age was 66 years, 70% were male, and 47% were current smokers with a mean postbronchodilator FEV 1 % predicted of approximately 60% (Table 1). The mean number of moderate-severe AECOPD episodes in the prev...

Understanding low COPD exacerbation rates in Japan: a review and comparison with other countries

“…The primary care-based ACCESS study in European patients with COPD, with and without cardiovascular disease (CVD), reported an acute exacerbation rate of 0.63 per patient per year ( Figure 1B ). 30 This is similar to the exacerbation rate reported for the Japanese cohort in the UPLIFT study (0.61 per patient per year). 7 However, it should again be noted that baseline characteristics of the two study populations were different: patients in ACCESS had a mean age of 66.1 years, mean BMI 27.2 kg/m 2 , 70% were male, 26.6% were GOLD stage III, and 6.3% were GOLD stage IV, 30 while those in the Japanese cohort of UPLIFT had a mean age of 68.0 years, mean BMI 20.7 kg/m 2 , 96% were male, 56% were GOLD stage III, and none were GOLD stage IV.…”

Hospitalisation and mortality in patients with comorbid COPD and heart failure: a systematic review and meta-analysis

“…This is further supported by Cerezo Lajas et al who reported that COPD patients with destabilised HF were at 5.25 times greater odds (95%CI: 1.11, 24.75) of frequent rehospitalisation, defined as ≥2 rehospitalisation within 30 days of index hospitalisation [8]. Many previous studies have investigated the effect of a compound variable representing 'cardiovascular comorbidities' on AECOPD incidence and severity; however, the heterogeneity of the various cardiovascular conditions included within such a compound variable may explain why these studies have found conflicting evidence [11,53,54].…”

“…Several studies have shown that COPD patients with HF experience more AECOPD and hospitalisations than those without HF [8][9][10]. Meanwhile, Jones et al did not find an association between cardiovascular comorbidity and AECOPD or mortality [11]; however, a composite cardiovascular exposure may not be indicative of the effects of individual cardiac conditions on COPD patients. Patel et al found that COPD patients with ischaemic heart disease, a precursor to HF, experienced longer exacerbations than COPD patients without ischaemic heart disease, but not more exacerbations [12].…”

Risk factors of chronic obstructive pulmonary disease exacerbations

“…In a large‐scale study Jones et al investigated the correlation between CVD and exacerbation rates and mortality in COPD cohort. They concluded that the presence of CVD was not associated with increased risk of exacerbations or death, but with a higher risk of hospitalisation.…”

“…Mortality was higher in patients with systolic dysfunction (19.2%) compared with subjects who had preserved ejection fraction (4.8%). 96 In a large-scale study Jones et al 97 investigated the correlation between CVD and exacerbation rates and mortality in COPD cohort. They concluded that the presence of CVD was not associated with increased risk of exacerbations or death, but with a higher risk of hospitalisation.…”