Skip Navigation

European Journal of Heart Failure 2007 9(9):942-948; doi:10.1016/j.ejheart.2007.06.004
This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (9)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Macchia, A.
Right arrow Articles by Tognoni, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Macchia, A.
Right arrow Articles by Tognoni, G.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2007 European Society of Cardiology

The prognostic influence of chronic obstructive pulmonary disease in patients hospitalised for chronic heart failure

Alejandro Macchia*, Simona Monte, Marilena Romero, Antonio D'Ettorre and Gianni Tognoni

Department of Clinical Pharmacology and Epidemiology, Consorzio Mario Negri Sud Santa Maria Imbaro, Chieti, Italy

* Corresponding author. Tel.: +39 0872570300; fax: +39 0872570248. E-mail address: macchia{at}negrisud.it


   Abstract
Top
 Abstract
1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Study limitations
 References
 
Aims: To investigate the prevalence and the prognostic impact of chronic obstructive pulmonary disease (COPD), in patients hospitalised with chronic heart failure (CHF).

Methods and results: In an observational study based on longitudinal information from administrative registers, 1020 patients aged ≥60 years, who were chronically treated for and hospitalised with CHF were identified and followed-up for major events up to 1 year.

Median age was 80 years, half of the patients were female and 241 patients (23.6%) had concomitant COPD. There were no differences in the prevalence of cardiovascular and non-cardiovascular comorbidities between CHF patients with or without COPD. However, COPD patients were more often male (60.6% vs. 46.3%), more frequently treated with diuretics (95.9% vs. 91.5%) but less often exposed to β-blockers (16.2% vs. 22.0%). Significantly higher adjusted in-hospital (HR 1.50 [95%CI 1.00–2.26]) and out-of-hospital (1.42 [1.09–1.86]) mortality rates were found in CHF patients with concomitant COPD. A higher occurrence of non-fatal AMI/stroke/rehospitalisation for CHF (1.26 [1.01–1.58]) as well as hospitalisation for CHF (1.35 [1.00–1.82]) was associated with COPD.

Conclusions: COPD is a frequent concomitant disease in patients with heart failure and it is an independent short-term prognostic indicator of mortality and cardiovascular comorbidity in patients who have been admitted to hospital for heart failure.

Key Words: Medical record-linkage • Chronic heart failure • Chronic obstructive pulmonary disease

Received November 19, 2006; Revised March 21, 2007; Accepted June 7, 2007


   1. Introduction
Top
 Abstract
 1. Introduction
2. Methods
 3. Results
 4. Discussion
 5. Study limitations
 References
 
According to epidemiological surveys and global burden of disease projections, chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD) are leading causes of morbidity and mortality [1-5]. The importance of CHF and COPD as major public health problems and as critical components of the burden of care for health systems is expected to increase, due to population ageing [6].

Several investigations have documented the presence of CHF as well as unrecognized left ventricular systolic dysfunction (LVSD) among COPD patients [7-9]. In general, these studies have shown that almost 20% of COPD patients have either CHF or LVSD. However, relatively little attention has been given to specifically evaluating the prevalence and the prognostic impact of COPD in patients with CHF as the main current problem [10]. This lack of focus on the interplay between the two conditions is surprising, not only because they share many clinical symptoms, but also because systemic inflammation plays a major role in disease development [11-13].

The prognosis of patients with CHF is most frequently described in relation to well-known cardiovascular factors [14-17]. Other common diseases such as COPD, a chronic disease with high morbidity [18], are rarely included in risk stratification models.

Observational studies with record-linked databases provide the opportunity to assess the impact of COPD and other comorbidities on morbidity and mortality in patients with CHF, following a hospital admission for CHF [19,20].

In this study, we aimed to investigate the prevalence of COPD in patients with CHF and to assess the impact of COPD on survival and on non-fatal clinical outcomes in these CHF patients.


   2. Methods
Top
 Abstract
 1. Introduction
 2. Methods
3. Results
 4. Discussion
 5. Study limitations
 References
 
We carried out a record-linkage analysis of hospital discharge records, prescription databases and mortality registers, which included data on 181,718 subjects aged ≥60 years. The analysis was performed in three Local Health Authorities (LHAs) from Northern Italy (Piemonte and Veneto) between January 1st 2000 and December 31st 2003.

2.1. Data sources
Hospital discharge records included information on primary diagnoses and up to five coexisting conditions, diagnostic and therapeutic interventions, date of admission, discharge and in-hospital death. All diagnoses were coded according to the International Classification of Disease, Ninth Revision [ICD-9 CM] [21].

The prescription database documented all community prescriptions reimbursed by the National Health System with drugs coded according to the Anatomical Therapeutic Chemical (ATC) Classification [22] and qualified with respect to dosages, date of first prescription and duration of exposure.

Mortality statistics were available as death certificates from each LHA.

A linkage of these three databases was carried out, and pharmacological history for each patient was obtained. The reliability of this strategy to produce an epidemiological survey has been previously validated and reported [23-27].

All security and protection measures for patient data were performed, according to national law.

2.2. Identification of CHF
Patients were classified as CHF patients if they were (a) discharged, between January 1st and December 31st 2002 (index year) with a primary or secondary diagnosis of CHF (code 428), and (b) chronically exposed to specific medication for CHF over the two previous years. Repeat prescriptions of any combination of the following drugs: ACE-inhibitors, digoxin, furosemide, carvedilol, bisoprolol, spironolactone, and angiotensin receptor blockers (ARBs) were considered as specific treatments for CHF. Combination therapy was defined as prescription of at least one other of the specified drugs within 45 days of the prescription date of the first drug, as reported elsewhere [25,27]. The first hospital admission during 2002 was considered the index date (day 0) for including the patient in the study.

2.3. Identification of COPD in patients with CHF
A patient was classified as having COPD, if he/she was chronically exposed to inhaled/oral bronchodilators or inhaled steroids, or both [28] over the two years preceding the index date, with or without intercurrent hospitalisations for any COPD related conditions (ICD-9 code: 491.2, 491, 492, 494, 496, 518).

2.4. Other comorbid conditions
Cardiovascular (CV) and non-cardiovascular (NCV) conditions that are known indicators of additional CV risk were included in the analysis, if documented over the 24-month period preceding the index date. Hypertension and diabetes were identified from hospitalisations and/or chronic exposure to pharmacological treatments. For all other CV conditions for which a specific prescription pattern was not identifiable, only hospitalisation-associated diagnoses were considered.

Cancer was identified from hospitalisation data.

The prescription of psychotropic drugs (mainly antidepressants) was also considered, because of the reported specific association of the related clinical conditions with both CHF and COPD [29,30].

No information about smoking habit was available in the administrative registers.

2.5. Statistical analysis
The baseline characteristics of patients with and without COPD were compared using the chi square test for discrete variables and the Wilcoxon rank sum test for continuous variables. The median and the 25 to 75 percentiles are quoted for continuous variables. A multivariate logistic regression was used for the analysis of factors influencing in-hospital mortality. For each patient, follow-up was extended from the index date to day 360 or until the occurrence of one of the following events, if earlier than day 360: 1) death for any reason, 2) either non-fatal AMI, non-fatal stroke or (re)hospitalisation for CHF; 3) (re)hospitalisation for CHF, 4) (re)hospitalisation for any reason. Time-to-event analyses were conducted for survival as well as for survival free of major events using a Cox proportional hazard model with COPD as the reference. For both logistic regression and Cox models, we always adjusted for the same covariates, including only those that were significant (p<0.10) in the univariate analysis, specifically age, sex, diabetes, peripheral vascular disease, stroke and malignancy. Survival curves were generated by plotting the results of the Cox analysis.

A sensitivity analysis was performed to assess the robustness of the model after accounting for potential residual confounding deriving from the effect of an unmeasured binary covariate. This analysis assumes that the unmeasured confounder is both binary and independent of measured confounders [31].

All computations were performed using SPSS 10.0 statistical package and SAS Statistical Package Release 9.1 (SAS Institute, Cary, NC, USA).


   3. Results
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
4. Discussion
 5. Study limitations
 References
 
One thousand and twenty patients were chronically treated for and hospitalised with CHF. Of these, 671 patients (66%) had the CHF diagnosis in the first position of the hospital discharge record.

Two hundred and forty one patients (23.6%) had COPD, according to our predefined criteria. A broader definition (including hospitalisations in the absence of documented chronic drug exposure) increased the prevalence of COPD to 31.4% (N=320) (data not shown).

3.1. Baseline clinical characteristics
The clinical profile of the overall population, as described in Table 1, is characterized by very old age (3/4 of the subjects were aged ≥75 years), with a large number of CV comorbidities. Specifically AF, CAD and diabetes were present in 38.8%, 32.7% and 31.4% of patients, respectively. The prevalence of other CV conditions (stroke, TIA, peripheral artery disease, previous embolic episodes) ranged from 3.8% to 10.4%. NCV conditions, such as malignancy and depression, were present in 8.9% and 7.5% of the population respectively. There was no difference in the incidence of cardiovascular and non-cardiovascular comorbidities between CHF patients with or without COPD.


View this table:
[in this window]
[in a new window]

  		Table 1 Baseline clinical characteristics of patients with CHF according to the presence or absence of concomitant COPD

 
Analysis of data on previous treatments, showed a significant difference in diuretic exposure and an indication of a difference in beta blockers exposure (Table 1).

Of the 241 patients with COPD, the most prescribed respiratory drugs were methylxanthines (78.8%), followed by inhaled (49.4%) and oral (32.8%) steroids. Additionally, 25.7% of patients received long acting-β2, 21.2% short acting-β2, and 16.2% anticholinergic agents (Table 2).


View this table:
[in this window]
[in a new window]

  		Table 2 Respiratory medications in CHF patients with concomitant COPD.

 
3.2. In-hospital mortality and length of stay
During the index hospitalisation, 147 (14.4%) patients died. For CHF patients without COPD, hospital mortality was 13.2% (103 out of 779) and for those with COPD 18.3% (44 out of 241), corresponding to an adjusted probability (OR (95% CI), p value) of death among COPD patients of 1.50 (1.00-2.26, p=0.05). The median in-hospital length of stay was 9 days in both groups (p=0.15).

3.3. Mortality during follow-up
Eight hundred and seventy three patients survived the index hospitalisation and were available for follow-up. The mean duration of follow-up was 287±121 days. Survival at 1, 3, 6 and 12 months was 95.2%±0.7%, 88.2%±1.1% and 80.9%±1.3%, 68.2%±1.6%, respectively.

Age, diabetes, peripheral vascular disease, stroke and COPD were significantly associated with mortality during follow-up in both unadjusted and adjusted analyses (Table 3). Specifically, the probability of death was increased by 6% for each incremental year. Peripheral vascular disease, diabetes and stroke were independently associated with an increase in the hazard of mortality: HR 1.74 (95%CI, 1.19-2.55), 1.44 (95%CI, 1.12-1.84), and 1.48 (95%CI, 1.03-2.14), respectively.


View this table:
[in this window]
[in a new window]

  		Table 3 Predictors of mortality, after a mean follow up of 287±121 days, in CHF patients with concomitant COPD who survived the index CHF hospitalisation

 
3.4. Effect of COPD on fatal and major non-fatal events
Chronic obstructive pulmonary disease was associated with an independent increased likelihood of death with a HR of 1.42 (95%CI, 1.09-1.86) (Table 3).

The adjusted survival curves of patients with and without COPD are shown in Fig. 1.


Figure 01
View larger version (15K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 1 Effect (hazard ratio [HR (95% CI)], p) of COPD on mortality and major events. Patients without COPD thick solid line, patients with COPD thin dotted line. (A) One-year survival. HR 1.42 (1.09-1.86), p=0.010. (B) One-year survival free of either myocardial infarction, stroke or rehospitalisation for CHF. HR 1.26 (1.01-1.58), p=0.04. (C) One-year survival free of rehospitalisation for CHF. HR 1.35 (1.00-1.82), p=0.05. (D) One-year survival free rehospitalisation for any cause. HR 1.14 (0.94-1.40), p=0.19.

 
Chronic obstructive lung disease also significantly increased the risk of first non-fatal AMI, non-fatal stroke or (re)hospitalisation for CHF (HR 1.26 [95%CI, 1.01-1.58]), as well as of (re)hospitalisation for CHF (HR 1.35 [95%CI, 1.00-1.82]) but not hospitalisations for any reason (HR 1.14 [95%CI, 0.94-1.40]), (Table 4).


View this table:
[in this window]
[in a new window]

  		Table 4 Effect of the presence of COPD on mortality and major events during follow-up, in CHF patients discharged from hospital and then chronically treated for CHF

 
The sensitivity analysis showed that to affect the association between COPD comorbidity and mortality, an unmeasured binary confounder should have an absolute difference of 40% in prevalence between patients with and without COPD and should be associated with 30% increase risk of death. Of course such a scenario, though unlikely to occur, cannot be ruled out.


   4. Discussion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
5. Study limitations
 References
 
The main results of this analysis can be summarized as follows. Firstly, the prevalence of COPD among patients with CHF is very high: one in four high-risk elderly patients with CHF has been treated for concomitant COPD. Secondly, chronic obstructive pulmonary disease strongly and independently worsens survival and major outcomes in CHF patients.

This population-based approach, has provided robust answers to most of the questions which stimulated initiation of this project [1-5,7-10].

In a very elderly population with CHF, COPD is present in approximately 25% of the population, suggesting that joint consideration of the two clinical conditions should be part of the current research agenda, both from a public health point of view (burden of care) and when considering strategies for routine and/or experimental management (both in-hospital and out of hospital).

The prevalence of COPD comorbidity in the CHF population in our study broadly agrees with recent epidemiological data from ad hoc surveys. Although real estimates of the burden of COPD are quite difficult to assess [32], mostly due to the different criteria used for diagnosis (prescription patterns, self-reported, physician's assessment and spirometry), the prevalence of COPD in the general population appears to be between 4% and 10% [33], and is strongly influenced by age. A large US survey [34] reported a COPD prevalence of 20.7% at 65-74 years, and 22.9% at 75 years or older, which corresponds with our data in older patients.

Even more important, is the finding that COPD strongly increases the burden of care and overall mortality in the CHF population (despite reported intensive treatment with recommended drugs). COPD independently increased the adjusted risk of in-hospital death by 50% and out-of hospital mortality by 42%. The burden of COPD in CHF is also highlighted by data on re-hospitalisation, as those CHF patients with concomitant COPD had a 35% increased risk of rehospitalisation for CHF.

Other comorbid conditions, including diabetes, PVD, stroke and malignancy, were also associated with an increased risk of death of the same magnitude as that of COPD.

These data are in agreement with other studies [35], which also reported that comorbid conditions had the greatest independent impact on mortality in community-based patients with heart failure. However, of the comorbid conditions commonly associated with CHF, COPD raises major diagnostic and therapeutic problems [36,37]. In a study by Kjoller et al. [38], COPD was a predictor of long-term mortality in patients with acute myocardial infarction without CHF, but was also a confounding factor for the diagnosis of CHF. In our study, all patients had CHF and the results suggested that COPD was a predictor of short-term mortality in these patients, as underlined in a recently published review [37].

Most probably, the impaired prognosis observed in patients with CHF and COPD represents a combination of both pathophysiological and treatment related factors. Patients with CHF usually have a restrictive ventilatory defect and the concomitant presence of COPD imposes an airflow obstruction that leads to lung hyperinflation and further reduced ventilatory response [39]. From the therapeutic point of view, the coexistence of CHF and COPD could result in suboptimal therapy of both conditions: beta-adrenergic blockade could induce severe broncho-constriction and beta-adrenergic agonists could be associated with increased risk of myocardial infarction, heart failure, cardiac arrest and sudden cardiac death [40].

Despite sharing many similarities, CHF and COPD remain separate conditions in terms of epidemiology, organization of care and research strategies. Guidelines and recommendations for both conditions often disregard each other, which further increases uncertainties. The results presented here emphasize the importance of considering the coexistence of these pathologies, which may advocate non-adherence to treatment guidelines. A formal collaboration between scientific associations and research groups in cardiology, pneumonology and internal medicine is urgently needed in order to facilitate understanding of both the burden and the optimal management strategy for patients with COPD and CHF.


   5. Study limitations
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Study limitations
References
 
Some advantages of using administrative data are; the breadth of population coverage, the ability to perform lifetime follow-up and the capture of mortality data. Additionally, this type of study provides important information about daily practice in a "real-life" population, in our case CHF patients, aged 80 years with several comorbidities. Nonetheless, our results should be considered in light of a number of study limitations.

Particular disadvantages are the lack of some baseline clinical measurements, such as weight and spirometry, and the potential for diagnostic inaccuracy when prescription patterns are used. Another important limitation is the lack of data on smoking habit.

In our study the presence of COPD was not validated by spirometry, which is the gold standard for diagnosis. Reliance on prescription patterns could potentially result in under or over-estimations of the real burden of disease, since milder forms of the disease may not be included (underestimation) and other pathologies such as asthma which are treated with similar agents could lead to overestimation of the prevalence of COPD. However, in an epidemiological context, there is no uniform method for assessing the "exact" prevalence of COPD [32]. Moreover, there is a lack of consensus among the various spirometric definitions of COPD provided by different scientific societies.

Validations studies [41] suggest that for population-based research, only those with a primary diagnosis of CHF in the hospital discharge register should be regarded as definite CHF cases. We used a very specific (albeit less sensible) form of identification of CHF: the patients had to be both, chronically treated (at least two years with combination therapy) and discharged with a primary or secondary diagnosis of CHF, which reduces the possibility of misclassification.

Finally, a fully adjusted multivariate statistical model and a sensitivity analysis were applied to reduce confounding bias, even though they do not completely rule out the possibility of residual confounding.

In conclusion, our data demonstrate that COPD is a frequent concomitant disease and an independent short-term prognostic indicator of mortality and cardiovascular comorbidity in patients chronically treated for and hospitalised with heart failure.


   References
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Study limitations
 References
 

  1. de Giuli F., Khaw K.T., Cowie M.R., Sutton G.C., Ferrari R., Poole-Wilson P.A. Incidence and outcome of persons with a clinical diagnosis of heart failure in a general practice population of 696,884 in the United Kingdom. Eur J Heart Fail (2005) 3:295–302.
  2. Murray C.J., Lopez A.D. Global mortality, disability, and the contribution of risk factors: Global Burden of Disease Study. Lancet (1997) 349:1436–1442.[CrossRef][Web of Science][Medline]
  3. Peruzza S., Sergi G., Vianello A., et al. Chronic obstructive pulmonary disease (COPD) in elderly subjects: impact on functional status and quality of life. Resp Med (2003) 97:612–617.[CrossRef][Web of Science][Medline]
  4. Lee W.C., Chavez Y.E., Baker T., Luce B.R. Economic burden of heart failure: a summary of recent literature. Heart Lung (2004) 33:362–371.[CrossRef][Web of Science][Medline]
  5. Strassels S.A., Smith D.H., Sullivan S.D., Mahajan P.S. The costs of treating COPD in the United States. Chest (2001) 119:344–352.[Abstract/Free Full Text]
  6. Murray C.J., Lopez A.D. Alternative projections of mortality and disability by cause 1990-2020: Global Burden of Disease Study. Lancet (1997) 349:1498–1504.[CrossRef][Web of Science][Medline]
  7. Curkendall S.M., DeLuise C., Jones J.K., et al. Cardiovascular disease in patients with chronic obstructive pulmonary disease, Saskatchewan Canada cardiovascular disease in COPD patients. Ann Epidemiol (2006) 16:63–70.[CrossRef][Web of Science][Medline]
  8. Rutten F.H., Moons K.G., Cramer M.J., et al. Recognising heart failure in elderly patients with stable chronic obstructive pulmonary disease in primary care: cross sectional diagnostic study. BMJ (2005) 331:1379.[Abstract/Free Full Text]
  9. Rutten F.H., Cramer M.J., Grobbee D.E., et al. Unrecognized heart failure in elderly patients with stable chronic obstructive pulmonary disease. Eur Heart J (2005) 26:1887–1894.[Abstract/Free Full Text]
  10. Rutten F.H., Cramer M.J., Lammers J.W., Grobbee D.E., Hoes A.W. Heart failure and chronic obstructive pulmonary disease: an ignored combination? Eur J Heart Fail (2006) 8:706–711.[Abstract/Free Full Text]
  11. Donaldson G.C., Seemungal T.A., Patel I.S., et al. Airway and systemic inflammation and decline in lung function in patients with COPD. Chest (2005) 128:1995–2004.[Abstract/Free Full Text]
  12. Sin D.D., Man S.F. Skeletal muscle weakness, reduced exercise tolerance, and COPD: is systemic inflammation the missing link? Thorax (2006) 61:1–3.[Free Full Text]
  13. Saetta M., Turato G., Maestrelli P., Mapp C.E., Fabbri L.M. Cellular and structural bases of chronic obstructive pulmonary disease. Am J Respir Crit Care Med (2001) 163:1304–1309.[Free Full Text]
  14. Eichhorn E.J. Prognosis determination in heart failure. Am J Med (2001) 110(7A):14S–36S.[CrossRef][Medline]
  15. Brophy J.M., Dagenais G.R., McSherry F., Williford W., Yusuf S. A multivariate model for predicting mortality in patients with heart failure and systolic dysfunction. Am J Med (2004) 116:300–304.[CrossRef][Web of Science][Medline]
  16. Pocock S.J., Wang D., Pfeffer M.A., et al. Predictors of mortality and morbidity in patients with chronic heart failure. Eur Heart J (2006) 27:65–75.[Abstract/Free Full Text]
  17. Nieminen M.S., Brutsaert D., Dickstein K., et al. EuroHeart Failure Survey II (EHFS II): a survey on hospitalized acute heart failure patients: description of population. Eur Heart J (2006) 27:2725–2736.[Abstract/Free Full Text]
  18. Fletcher C., Peto R. The natural history of chronic airflow obstruction. BMJ (1997) 1:1645–1648.
  19. Schneeweiss S., Avorn J. A review of uses of health care utilization databases for epidemiologic research on therapeutics. J Clin Epidemiol (2005) 58:323–337.[CrossRef][Web of Science][Medline]
  20. Ayanian J.Z. Using administrative data to assess health care outcomes. Eur Heart J (1999) 20:1689–1691. Lancet 366 2005 2005-2011.[Free Full Text]
  21. International classification of diseases, 9th revision (clinical modification). (1998) Washington: Public Health Service, US Department of Health and Human Services.
  22. WHO Collaborating Centre for Drug Statistics Methodology. ATC Index with DDDs. (2003) Oslo, Norway: WHO.
  23. D'Ettorre A. ReClust. Technical Report 2005 (2006) http://easi.negrisud.it/software/reclust/index.html (30 September).
  24. CINECA. The Interuniversity Consortium of Northeastern Italy. (2006) Accessed at www.cineca.it/en/area/inf_syst_serv_health.htm (30 September).
  25. Monte S., Macchia A., Pellegrini F., et al. Antithrombotic treatment is strongly underused despite reducing overall mortality among high-risk elderly patients hospitalized with atrial fibrillation. Eur Heart J (2006) 27:2217–2223.[Abstract/Free Full Text]
  26. Lepore V., D'Ettorre A., Valerio M., et al. From pharmacoepidemiology to the epidemiology of delivered care. Ital J Clin Pharm (2002) 16:102–107.
  27. Monte S., Fanizza C., Romero M., Rossi E., De Rosa M., Tognoni G. Administrative databases as a basic tool for the epidemiology of cardiovascular diseases. G Ital Cardiol (2006) 3:206–216.
  28. Scurti V., Font, Monte S., et al. Pharmacoepidemiology of chronic treatments. Definitions, methodology, model scenarios. Ital J Clin Pharm (2005) 19:102–109.
  29. Joynt K.E., Whellan D.J., O'connor C.M. Why is depression bad for the failing heart? A review of the mechanistic relationship between depression and heart failure. J Card Fail (2004) 10:258–271.[CrossRef][Web of Science][Medline]
  30. Kunik M.E., Roundy K., Veazey C., et al. Surprisingly high prevalence of anxiety and depression in chronic breathing disorders. Chest (2005) 127:1205–1211.[Abstract/Free Full Text]
  31. Lin D.Y., Psaty B.M., Krommal R.A. Assessing the sensitivity of regression results to unmeasured confounders in observational studies. Biometrics (1998) 54:948–963.[CrossRef][Web of Science][Medline]
  32. Halbert R.J., Isonaka S., George D., Iqbal A. Interpreting COPD prevalence estimates: what is the true burden of disease? Chest (2003) 123:1684–1692.[Abstract/Free Full Text]
  33. Mannino D.M., Homa D.M., Akinbami L.J., Ford E.S., Redd S.C. Chronic obstructive pulmonary disease surveillance — United States, 1971-2000. Respir Care (2002) 47:1148–1149.[Medline]
  34. Connors A.F. Jr., Dawson N.V., Thomas C., et al. Outcomes following acute exacerbation of severe chronic obstructive lung disease: the SUPPORT investigators (Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments). Am J Respir Crit Care Med (1996) 154:959–967.[Abstract]
  35. Lee D.S., Austin P.C., Rouleau J.L., Liu P.P., Naimark D., Tu J.V. Predicting mortality among patients hospitalized for heart failure: derivation and validation of a clinical model. JAMA (2003) 290:2581–2587.[Abstract/Free Full Text]
  36. Egred M., Shaw S., Mohammad P., Waitt P., Rodriguez E. Under-use of beta blockers in patients with ischaemic heart disease and concomitant chronic obstructive pulmonary disease. QJM (2005) 98:493–497.[Abstract/Free Full Text]
  37. Le Jemtel T.H., Padeletti M., Jelic S. Diagnostic and therapeutic challenges in patients with coexistent chronic obstructive pulmonary disease and chronic heart failure. J Am Coll Cardiol (2007) 49:171–180.[Abstract/Free Full Text]
  38. Kjoller E., Kober L., Iversen K., Torp-Pedersen C. Trace Study Group. Importance of chronic obstructive pulmonary disease for prognosis and diagnosis of congestive heart failure in patients with acute myocardial infarction. Eur J Heart Fail (2004) 6:71–77.[Abstract/Free Full Text]
  39. Sirak T.E., Jelic S., Le Jemtel T.H. Therapeutic update: non-selective beta- and alpha-adrenergic blockade in patients with coexistent chronic obstructive pulmonary disease and chronic heart failure. J Am Coll Cardiol (2004) 44:497–502.[Abstract/Free Full Text]
  40. Salpeter S.R., Salpeter E.E. Cardiovascular effects of β-agonists in patients with asthma and COPD: a meta-analysis. Chest (2004) 125:2309–2321.[Abstract/Free Full Text]
  41. Ingelsson E., Arnlov J., Sundstrom J., Lind L. The validity of a diagnosis of heart failure in a hospital discharge register. Eur J Heart Fail (2005) 7:787–791.[Abstract/Free Full Text]

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Eur J Heart FailHome page
N. M. Hawkins, P. S. Jhund, C. R. Simpson, M. C. Petrie, M. R. MacDonald, F. G. Dunn, K. MacIntyre, and J. J.V. McMurray
Primary care burden and treatment of patients with heart failure and chronic obstructive pulmonary disease in Scotland
Eur J Heart Fail, January 1, 2010; 12(1): 17 - 24.
[Abstract] [Full Text] [PDF]

Home page
 Eur Heart J SupplHome page
E. Erdmann
Safety and tolerability of beta-blockers: prejudices and reality
Eur. Heart J. Suppl., March 1, 2009; 11(suppl_A): A21 - A25.
[Abstract] [Full Text] [PDF]

Home page
 Eur Heart JHome page
Authors/Task Force Members, K. Dickstein, A. Cohen-Solal, G. Filippatos, J. J.V. McMurray, P. Ponikowski, P. A. Poole-Wilson, A. Stromberg, D. J. van Veldhuisen, D. Atar, et al.
ESC 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. Heart J., October 1, 2008; 29(19): 2388 - 2442.
[Full Text] [PDF]

Home page
 Eur J Heart FailHome page
K. Dickstein, A. Cohen-Solal, G. Filippatos, J. J.V. McMurray, P. Ponikowski, P. A. Poole-Wilson, A. Stromberg, D. J. van Veldhuisen, D. Atar, A. W. Hoes, et al.
ESC 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, October 1, 2008; 10(10): 933 - 989.
[Full Text] [PDF]

Home page
 Eur J Heart FailHome page
A. Macchia, S. Monte, F. Pellegrini, M. Romero, A. D'Ettorre, L. Tavazzi, G. Tognoni, and A. P. Maggioni
Depression worsens outcomes in elderly patients with heart failure: An analysis of 48,117 patients in a community setting
Eur J Heart Fail, July 1, 2008; 10(7): 714 - 721.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (9)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Macchia, A.
Right arrow Articles by Tognoni, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Macchia, A.
Right arrow Articles by Tognoni, G.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?