Non-cardiovascular Comorbidity, Severity and Prognosis in Non-selected Heart Failure Populations: A Systematic Review and Meta-analysis

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.