Neurological and psychiatric comorbidity in patients with heart failure: risk and prognosis.

Heart failure is a complex clinical syndrome and one of the leading causes of morbidity and mortality with a prevalence of 1%-2% of the adult population. The prognosis is poor with a 5-year mortality rate of 50%, which partly can be attributed to the presence of concomitant comorbidity, including neurological and psychiatric comorbidities. However, the prognostic impact of depression and the role of heart failure as a risk factor for dementia and stroke are not fully understood.
 Denmark is well-known for its unique health registries. The DNPR has been widely used in cardiovascular research in the past decades, although the accuracy of several diseases and interventions is largely unknown.
 This thesis explored the PPV of a range of cardiovascular diagnoses including heart failure (study I) and cardiac interventions (study II) recorded in the DNPR. In addition, we aimed to provide new insights into the impact of depression on mortality in heart failure patients with reduced and preserved left ventricular ejection fraction (study III). Finally, we studied the association between heart failure and subsequent short-term and long-term risks of dementia (study IV) and ischemic and hemorrhagic stroke (study V).
 In studies I-II, we identified 3386 patients with various cardiovascular diagnoses or cardiac interventions during 2010-2012 using the DNPR. Patient medical charts served as the gold standard for diagnosis confirmation and were adjudicated by physicians. We found a high PPV (≥90%) for the majority of the patients while the PPV was somewhat lower for myocarditis, heart failure, and recurrent events. 
In study III, we analyzed 205,719 patients with incident heart failure during 1995-2014. A history of depression was associated with 15%-20% increased mortality rate in patients with LVEF ≤35% and when defining depression based on a combination of 
redeemed antidepressant prescription and hospital-based diagnoses, but not when depression was ascertained based solely on diagnoses. 
In study IV, we included 324,418 heart failure patients and a general population comparison cohort comprising 1,622,079 individuals matched for age and sex during 1980-2012. The heart failure cohort had a 21% increased rate of all-cause dementia, mainly driven by increased hazards of vascular dementia and other dementia, whereas heart failure was not associated with Alzheimer's disease. 
In study V, we identified and followed 289,353 patients with heart failure and 1,446,765 individuals from the general population matched for age, sex, and calendar year. Heart failure patients had a five-fold elevated rate of ischemic stroke, two-fold increased rate of ICH, and a four-fold increased rate of SAH within 30 days. These associations receded towards the null but persisted over 30 years. 
In conclusion, the DNPR contains data on several cardiovascular diagnoses and cardiac interventions recorded with high PPVs. Our data also suggest that a history of depression is an adverse prognostic factor for death in patients with heart failure and low LVEF. Finally, heart failure emerged as a risk factor for all-cause dementia as well as for both ischemic and hemorrhagic stroke.