title: Non-cardiovascular comorbidity, severity and prognosis in non-selected heart failure populations: A systematic review and meta-analysis.
abstract: BACKGROUND
  Non-cardiovascular comorbidities are recognised as independent prognostic factors in selected heart failure (HF) populations, but the evidence on non-selected HF and how comorbid disease severity and change impacts on outcomes has not been synthesised. We identified primary HF comorbidity follow-up studies to compare the impact of non-cardiovascular comorbidity, severity and change on the outcomes of quality of life, all-cause hospital admissions and all-cause mortality.
  
  
  METHODS
  Literature databases (Jan 1990-May 2013) were screened using validated strategies and quality appraisal (QUIPS tool). Adjusted hazard ratios for the main HF outcomes were combined using random effects meta-analysis and inclusion of comorbidity in prognostic models was described.
  
  
  RESULTS
  There were 68 primary HF studies covering nine non-cardiovascular comorbidities. Most were on diabetes mellitus (DM), chronic obstructive pulmonary disease (COPD) and renal dysfunction (RD) for the outcome of mortality (93%) and hospital admissions (16%), median follow-up of 4 years. The adjusted associations between HF comorbidity and mortality were DM (HR 1.34; 95% CI 1.2, 1.5), COPD (1.39; 1.2, 1.6) and RD (1.52; 1.3, 1.7). Comorbidity severity increased mortality from moderate to severe disease by an estimated 78%, 42% and 80% respectively. The risk of hospital admissions increased up to 50% for each disease. Few studies or prognostic models included comorbidity change.
  
  
  CONCLUSIONS
  Non-cardiovascular comorbidity and severity significantly increases the prognostic risk of poor outcomes in non-selected HF populations but there is a major gap in investigating change in comorbid status over time. The evidence supports a step-change for the inclusion of comorbidity severity in new HF interventions to improve prognostic outcomes.
authors.affiliation: Health Services Research Unit, Keele University, England, United Kingdom. Electronic address: c.a.rushton@keele.ac.uk.
authors.forename: C A
authors.initials: CA
authors.lastname: Rushton
authors.affiliation: University Hospital North Midlands, England, United Kingdom.
authors.forename: D K
authors.initials: DK
authors.lastname: Satchithananda
authors.affiliation: Health Services Research Unit, Keele University, England, United Kingdom.
authors.forename: P W
authors.initials: PW
authors.lastname: Jones
authors.affiliation: Health Services Research Unit, Keele University, England, United Kingdom.
authors.forename: U T
authors.initials: UT
authors.lastname: Kadam
mesh_terms: D015897:Comorbidity; D003920:Diabetes Mellitus / Q000453:epidemiology; D006333:Heart Failure / Q000453:epidemiology*; D006801:Humans; D007674:Kidney Diseases / Q000453:epidemiology; D011379:Prognosis; D029424:Pulmonary Disease, Chronic Obstructive / Q000453:epidemiology; D011788:Quality of Life
keywords: Comorbidity; Heart failure; Meta-analysis; Prognosis; Systematic review