Conflict of interest statement: L.M.F. received payment for consultancy from: Boehringer Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline Beech, Merck Sharp & Dhome, Novartis, Nycomed, Pearl Therapeutics, SigmaTau, Sterna, Peer Voice Europe, Pearl Therapeutic, OM Pharma Sa, TEVA; payment for lectures, Advisory Boards or Travel Expenses Reimbursements from: AstraZeneca, Dey Pharma, Novartis, Schering Plough, SigmaTau, Roche, German Aerospace Center, Mundipharma Int., Genetech Inc, Elevation Pharmaceutical, Ferrer Group; his institution received grants from Boehringer Ingelheim, ScheringPlough, Pfizer, Nycomed, Menarini Industrie Farmaceutiche, Chiesi Farmaceutici, GlaxoSmithKline, Merck Sharp & Dhome, Roche, AstraZeneca, Novartis, SigmaTau, Italian Ministry for University and Research, Italian Ministry of Health.
Occurrence and impact of chronic obstructive pulmonary disease in elderly patients with stable heart failure
Article first published online: 26 DEC 2012
© 2012 The Authors. Respirology © 2012 Asian Pacific Society of Respirology
Volume 18, Issue 1, pages 125–130, January 2013
How to Cite
BOSCHETTO, P., FUCILI, A., STENDARDO, M., MALAGÙ, M., PARRINELLO, G., CASIMIRRI, E., POTENA, A., BALLERIN, L., FABBRI, L. M., FERRARI, R. and CECONI, C. (2013), Occurrence and impact of chronic obstructive pulmonary disease in elderly patients with stable heart failure. Respirology, 18: 125–130. doi: 10.1111/j.1440-1843.2012.02264.x
- Issue published online: 26 DEC 2012
- Article first published online: 26 DEC 2012
- Accepted manuscript online: 18 SEP 2012 03:52AM EST
- Received 4 April 2012; invited to revise 14 May 2012, 20 August 2012; revised 7 June 2012, 21 August 2012; accepted 28 August 2012 (Associate Editor: Neil Eves).
- chronic heart failure;
- chronic obstructive pulmonary disease;
- functional capacity;
Background and objective: The coexistence of chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) increases with age. The occurrence, prognosis and therapeutic implications of concurrent COPD in elderly patients with CHF were investigated.
Methods: One hundred and eighteen consecutive patients, ≥65 years old with ≥10 pack/years of smoking and with a verified diagnosis of CHF in stable condition, were enrolled. They were followed for a mean of 1029 (range 758–1064) days. All patients had spirometry and the diagnosis and classification of COPD were made according to Global Initiative for Chronic Obstructive Lung Disease guidelines.
Results: The mean occurrence of COPD was 30% (90% confidence interval: 24–37%). At baseline in patients with CHF and COPD, there was a shorter 6-min walk distance, lower arterial oxygen tension, glomerular filtration rate and higher N-terminal pro-B-type natriuretic peptide (all P < 0.05). The prescription of CHF therapies, including β-blockers, was similar in the two groups. After follow up, the presence of COPD in patients with CHF did not appear to influence survival.
Conclusions: COPD is relatively frequent in elderly patients with CHF. COPD did not alter survival.
6-min walk distance
chronic heart failure
chronic obstructive pulmonary disease
The prevalence of chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD) may increase substantially with age. These diseases share dyspnoea and functional impairment as common presenting symptoms, making the coexistence of both conditions difficult to diagnose regardless of patient age. The coexistence of CHF and COPD is presumed to be higher if patients are smokers or ex-smokers, smoking being a common causal factor.1,2 It has been difficult to obtain accurate data on the prevalence of COPD in patients with heart failure.3,4 There is also limited information about the prognosis of elderly patients with CHF and concomitant COPD.
We investigated the occurrence of COPD in elderly patients with CHF. The impact of COPD on prognosis was then evaluated over 3 years.
Subjects and study design
The study was designed as an observational cohort study. From 31 January 2007 to 31 January 2008, consecutive patients (n = 168) at the first visit to the outpatient Heart Failure Clinic (University Hospital of Ferrara, Italy) with age ≥ 65 years and a smoking history ≥10 pack/years were enrolled after giving informed consent. The patients had a confirmed recent diagnosis (<3 months) of heart failure. Thirty-nine subjects (23%) declined participation. The 129 patients enrolled were in stable clinical condition and the diagnosis of heart failure was made according to the European Society of Cardiology guidelines.5 Pulmonary function tests were performed within a month of the patient's first clinic visit and COPD was diagnosed and staged according to Global Initiative for Chronic Obstructive Lung Disease guidelines.6 Eleven participants whose spirometry did not fulfil current quality control standards were excluded.7
Demographic data, smoking history, 6-min walk distance (6MWD), electrocardiogram and echocardiography were recorded during the patient's first visit. Spirometry, arterial blood gas assessment, comorbid diseases and ongoing pharmacological treatments were noted. Patient treatment was optimized by following the European Society of Cardiology guidelines for management of patients with CHF. Physicians were blinded to the results of the spirometric assessment.5
Patients were reviewed every 12 weeks.
Follow up was censored when the last recruited patient completed the 42-month visit. All participants signed informed consent. The study complies with the Declaration of Helsinki and the research protocol was approved by the ethics committee of the University Hospital of Ferrara. (ClinicalTrials.gov number, NCT01114386).
The glomerular filtration rate was estimated by determining serum creatinine using the Cockcroft–Gault equation.8
Echocardiographic evaluation included standard mono, two-dimensional views and Doppler measurement. The diastolic and systolic diameters of the left ventricle were measured in M-mode recordings obtained in the parasternal long-axis view. The end-diastolic volume and end-systolic volume of the left ventricle were obtained in an apical four-chamber view by using the single-plane area-length method. The left ventricular ejection fraction was calculated as (end-diastolic volume – end-systolic volume)/end-diastolic volume × 100%. Left ventricular ejection fraction was considered as an indication of systolic dysfunction with values ≤ 40%. The tricuspid annular plane systolic excursion was used as an indicator of right ventricular function and the peak pulmonary artery pressure was estimated from the maximum systolic gradient across the tricuspid valve.9,10
CHF stages were defined by the New York Heart Association functional classification.
Spirometry (Biomedin, Padova, Italy) and partial arterial pressure of oxygen and carbon dioxide (Instrumentations Laboratories, Milan, Italy) were measured according to current international guidelines.7
6MWD was assessed as per guidelines.11
The Charlson Index was computed to obtain a synthetic index which allowed the evaluation of the prognostic role of one or more comorbidities present at baseline12 but did not include COPD in the individual's score.
Medicines were classified into therapeutic groups according to the Anatomical Therapeutic Chemical classification system. Particular attention was given to β-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and diuretics. With regards to β-blockers, the daily prescribed dose was expressed as a percentage of the target dose as per the guidelines for the different active components.5
Continuous variables were compared by the Wilcoxon rank sum test with corrections for multiple testing and categorical variables by chi-square analysis or Fisher's exact test, when suitable.
Survival curves were generated by the Kaplan–Meier methods and differences in survival between subgroups were evaluated using the log–rank test. We applied univariable and multivariable Cox proportional hazards regression models to assess the relation between death (the primary end-point) and a broad range of potential confounders as presented in Table 3.
To avoid data overfitting, we followed a stepwise modelling approach by applying a variable selection using the Akaike Information Criterion and a bootstrapped variance estimation of the final model.13
All tests are two sided with a significance level of 0.05. Statistical analyses were performed as described.14
Baseline characteristics of patients with incipient CHF according to the presence or absence of COPD
Baseline clinical characteristics of 118 outpatients are presented in Table 1.
|All||CHF and no COPD||CHF and COPD||P-value|
|(n = 118)||(n = 82)||(n = 36)|
|Age (years)||72.6 ± 6.8||72.1 ± 6.6||73.8 ± 7.1||0.16|
|Males (n (%))||101 (86)||71 (87)||30 (83)||0.64|
|Pack/years||42.3 ± 25.5||39.2 ± 22.2||49.2 ± 31.0||0.16|
|CHF aetiology (n (%))|
|Ischaemic||75 (64)||55 (67)||20 (56)||0.22|
|Idiopathic||21 (18)||14 (17)||7 (19)|
|Hypertensive||19 (16)||10 (12)||9 (25)|
|Other and unknown||3 (2)||3 (4)||0 (0)|
|GOLD stage (n (%))|
|I||20 (17)||—||20 (56)||—|
|II||14 (12)||—||14 (39)|
|III||2 (2)||—||2 (6)|
|IV||0 (0)||—||0 (0)|
|MAP (mm Hg)||93 (86–100)||93 (88–100)||91 (86–96)||0.12|
|Heart rate (bpm)||68 (58–77)||68 (59–77)||68 (57–80)||0.11|
|BMI||28.1 ± 3.7||28.4 ± 3.6||27.6 ± 3.8||0.18|
|Diabetes (n (%))||32 (27)||24 (29)||8 (22)||0.43|
|Charlson Index (n (%))†|
|1||32 (27)||24 (30)||8 (22)||0.8|
|2||42 (36)||26 (32)||16 (45)|
|3||9 (8)||6 (7)||3 (8)|
|4||23 (19)||18 (22)||5 (14)|
|5||8 (7)||5 (6)||3 (8)|
|6||3 (2)||2 (2)||1 (3)|
|7||1 (1)||1 (1)||0 (0)|
|BODE index||1.2 ± 1.5||1.1 ± 1.4||1.5 ± 1.7||0.25|
The patients' mean age was 72.6 ± 6.8 years; more than half had CHF of ischaemic aetiology (64%) and 86% were men. A total of 36 patients had criteria for the diagnosis of COPD (prevalence 30%), 23 (64%) were unaware of having any pulmonary disease. Almost all of the patients (95%) were classified as Global Initiative for Chronic Obstructive Lung Disease stages I and II.
Most baseline clinical features, including diabetes, BODE (Body mass index, Obstruction, Dyspnoea, Exercise capacity) and Charlson Index, were not different in patients having CHF with and without COPD. Conversely, CHF patients with COPD had a lower partial arterial pressure of oxygen (P < 0.005) and glomerular filtration rate (P < 0.01), a higher N-terminal pro-B-type natriuretic peptide (P < 0.05) and a shorter 6MWD (P < 0.05) as compared with those without COPD (Table 2).
|All (n = 118)||CHF and no COPD||CHF and COPD||P-value|
|(n = 82)||(n = 36)|
|NYHA class (n (%))|
|I and II||103 (87)||73 (89)||30 (83)||0.39|
|III and IV||15 (13)||9 (11)||6 (17)|
|GFR (mL/min/1.73 m2)||61.1 ± 23.5||64.1 ± 23.1||54.3 ± 23.0||0.006|
|NT-pro-BNP (pg/mL)||2208.8 ± 3365.3||1642.9 ± 1871.4||3534.6 ± 5264.5||0.03|
|6MWD (m)||362.5 ± 159.9||374.4 ± 165.0||332.8 ± 144.4||0.04|
|Haemoglobin (g/dL)||13.2 (12.1–14.3)||13.3 (12.2–14.5)||13.1 (11.9–14.1)||0.48|
|HsCRP (mg/mL)||0.8 ± 2.5||0.5 ± 0.7||1.5 ± 4.4||0.17|
|LVEF (%)||39.9 ± 11.2||40.7 ± 11.2||38.2 ± 11.0||0.38|
|EDV (mL)||165.5 (122.2–200.7)||171.5 (134.7–203.2)||133 (100–187.5)||0.06|
|ESV(mL)||95 (62–130)||100 (66–135)||78 (57.5–119)||0.21|
|TAPSE (mm)†||18 (15–20)||18 (14.5–20)||17.5 (15.2–20.7)||0.98|
|sPAP(mm Hg)||35 ± 9.4||33.9 ± 8.5||37.8 ± 11.3||0.19|
|FEV1 post-bronchodilator (% predicted)||89.2 ± 20.0||93.8 ± 19.0||78.8 ± 18.7||0.001|
|FVC post-bronchodilator (% predicted)||95.6 ± 20.1||94.8 ± 18.9||98.2 ± 23.6||0.48|
|FEV1/FVC (%)||72.9 ± 8.2||77.1 ± 4.6||63.4 ± 6.4||0.001|
|ΔFEV1 post-bronchodilator (%)||—||—||4.9 ± 1.2||—|
|PaO2 (mm Hg)‡||83.6 ± 11.2||85.6 ± 12.2||79.3 ± 7.2||0.004|
|PaCO2 (mm Hg)‡||39.5 ± 7.8||40.6 ± 8.8||37.35 ± 4.7||0.09|
In the study sample, 98 patients (83%) were treated with β-blockers, with no difference based on the presence or absence of COPD. Moreover, the CHF target dose was similar.
Univariate and multivariate Cox proportional hazards regression model analysis for predictors of all-cause mortality in patients with incipient CHF
The median follow up was 1029 days (758–1064, percentiles 25–75) and 39 patients (33%) demised. Table 3 summarizes the unadjusted associations for all-cause mortality of different clinical and functional variables. New York Heart Association functional classification, partial arterial pressure of carbon dioxide, glomerular filtration rate, pulmonary artery pressure, 6MWD, N-terminal pro-B-type natriuretic peptide, forced expiratory volume in 1 s post-bronchodilator and age had a significant prognostic value. However, there was no significant association between COPD and all-cause mortality. Multivariate analysis revealed that glomerular filtration rate, 6MWD and age were of independent prognostic value; forced expiratory volume in 1 s post-bronchodilator was very close to the statistical significance (P = 0.065) (Table 3).
|Univariate analysis||Multivariate analysis|
|Hazard ratio (95% CI)||P-value||Hazard ratio (95% CI)||P-value|
|Age (years)||1.103 (1.04–1.17)||0.006||1.067 (1.01–1.13)||0.021|
|NYHA||1.268 (0.51–3.14)||0.002||0.773 (0.29–2.07)||0.607|
|PaO2 (mm Hg)||0.999 (0.96–1.04)||0.115||—||—|
|PaCO2 (mm Hg)||0.890 (0.80–0.98)||0.037||0.954 (0.85–1.06)||0.394|
|GFR (mL/min/1.73 m2)||0.957 (0.94–0.98)||0.001||0.969 (0.95–0.99)||0.005|
|sPAP(mm Hg)||1.034 (0.99–1.07)||0.007||0.995 (0.95–1.04)||0.810|
|TAPSE (mm)||0.878 (0.80–0.96)||0.521||—||—|
|6MWD (m)||0.996 (0.993–0.998)||0.001||0.997 (0.995–0.999)||0.008|
|Haemoglobin (g/dL)||0.844 (0.70–1.01)||0.174||—||—|
|NT-pro BNP (pg/mL)||1.000 (1.00–1.00)||0.001||1.000 (1.00–1.00)||0.596|
|HsCRP (mg/mL)||1.101 (1.02–1.19)||0.084||—||—|
|FEV1 post-bronchodilator (% predicted)||0.975 (0.96–0.99)||0.013||0.983 (0.96–1.00)||0.065|
|FEV1/FVC (%)||0.977 (0.94–1.01)||0.096||—||—|
If COPD was defined according to the cut-off based on the lower limit of normal values for forced expiratory volume in 1 s/forced vital capacity, that is, values below the 5th percentile of the frequency distribution of values measured in the reference population,15 the number of patients with CHF and COPD was reduced from 36 to 34. Results of the statistical analysis were unchanged.
This observational study assessed 118 outpatients with CHF and COPD. Coexistent COPD did not appear to affect cardiac parameters, except for N-terminal pro-B-type natriuretic peptide. COPD did impact functional capacity as shown by a lower partial arterial pressure of oxygen and a shorter 6MWD. Over a 3-year period of follow up, coexistent COPD did not appear to reduce the prognosis of patients with stable CHF.
This study had some unique features. We assessed coexistent COPD in elderly patients with verified CHF at an outpatient setting. Previous reports had been based on retrospective or cross-sectional cohort studies,16,17 involved hospitalized cohorts with worsening heart failure18,19 or were done in subjects enrolled in clinical trials.20,21
There is a well-known association between CHF and COPD, but many factors influence the estimates of COPD prevalence.6,22 Our results in elderly patients with CHF and a history of smoking found COPD in 30% of patients. This is within the reported range in North America (11 to 52%) and in European cohorts (9 to 41%)3 and is in agreement with that recently described in stable patients with CHF.23
Increased B-type natriuretic peptide is known to be associated with COPD, both in the stable condition and during exacerbations.24 We performed 6MWD because it is a practical simple test and, despite its known limitations, a reliable index of functional status and quality of life.11 6MWD was significantly lower in the COPD and CHF group, indicating a reduction in functional status—as can be expected.
The majority of the previous studies reported a strong association between the presence of non-cardiac comorbidities (including COPD) and the occurrence of adverse clinical outcomes in patients with CHF.25 In a large survey, using the Norwegian Heart Failure registry, De Blois et al.26 confirmed an impact of COPD on survival of patients with heart failure. However, in two recent investigations,23,27 the presence of airway obstruction did not influence the survival in outpatients with CHF. Likewise, we failed to find an adverse association between COPD and prognosis. These results may have a number of explanations. Firstly, there may have been differences in criteria to define COPD. Secondly, the lack of differences in β-blocker treatments among our groups may have played a role. β-blocker use may have resulted in comparable survival in this study.28,29
Thirdly, the period of 3 years may have been too short to see evidence of adverse effects on mortality on COPD with CHF.
Limitations of the study
The limited sample size is a clear limitation of the present study. Another limitation is the underrepresentation of female patients. Although gender imbalance could affect the interpretation of the results of our study, COPD has not been found to impact on mortality in a cohort of heart failure patients where genders were equally represented.27
In summary, COPD is a frequent coexistent disease in older patients with a history of smoking and stable CHF. In this study, survival was not adversely influenced by having COPD in addition to CHF.
The study was supported by the Italian Ministry of Health and the Consorzio Ferrara Ricerche. The authors would like to thank Dr N. Napoli, University Hospital of Ferrara, for providing data about patient hospitalizations during the follow up.
- 5ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the diagnosis and treatment of acute and chronic heart failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Eur. J. Heart Fail. 2008; 10: 933–89., , et al.
- 8National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am. J. Kidney Dis. 2002; 39: S1–266.
- 9Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J. Am. Soc. Echocardiogr. 2005; 18: 1440–63., , et al.
- 14R Development Core Team. R: A Language and Environment for Statistical Computing . The R Foundation for Statistical Computing, Vienna, 2011. Available from URL: http://www.R-project.org/.
- 20Chronic obstructive pulmonary disease is an independent predictor of death but not atherosclerotic events in patients with myocardial infarction: analysis of the Valsartan in Acute Myocardial Infarction Trial (VALIANT). Eur. J. Heart Fail. 2009; 11: 292–8., , et al.
- 27Short-term outcomes in heart failure patients with chronic obstructive pulmonary disease in the community. World J. Cardiol. 2012; 4: 66–71., , et al.