Depression, stroke, and dementia in patients with myocardial infarction

The connection between the heart and mind has been studied since Sir William Harvey observed more than 350 years ago that negative emotions adversely affect the heart. Today, we know that diseases of the mind can affect the heart and, conversely, that heart diseases can cause both physical and mental diseases of the brain. To explore this relation further, we examined how previous depression affects survival in patients with myocardial infarction (MI) (study II), and how the occurrence of MI affects the risk of ischemic and hemorrhagic stroke (study III) and dementia (study IV). These studies were preceded by a validation study including all major cardiovascular diagnoses in the Danish National Patient Registry (study I). Studies II-IV are population-based cohort studies, of which studies III-IV are matched cohort studies. We identified antidepressant use from prescription registries and used nationwide databases to identify study populations and retrieve data on outcomes and comorbidity. 
In study I (2010-2012), we reviewed a total of 2,153 medical records from one university hospital and two regional hospitals in the Central Denmark Region. We randomly sampled up to 100 cases for each cardiovascular diagnosis. Medical record review served as reference standard to compute the positive predictive value for each diagnosis. For first-time MI, the positive predictive value was 97% (95% CI 91%-99%) and exceeded 90% for the most common cardiovascular disease entities. 
In study II (1995-2014), we identified 170,771 patients with first-time MI. Previous depression was identified by either a depression diagnosis or the use of antidepressants. Patients with MI and a previous depression diagnosis had higher 19-year mortality risks (87% vs. 78%). The overall adjusted mortality rate ratio was 1.11 (95% CI 1.07-1.15), increasing to 1.22 (95% CI 1.17-1.27) when including the use of antidepressants in the definition of depression. The association was stronger in patients with recent depression but was not influenced by depression severity or type of MI.
In study III (1980-2009), we identified 258,806 patients with a first-time MI and 1,244,773 sex-, age-, and calendar year-matched individuals from the general population, and followed them for development ischemic or hemorrhagic stroke. During the first 30 days after MI, the adjusted stroke rate ratio was 31.9 (95% CI 28.4-35.8) for ischemic stroke, 21.8 (95% CI 16.6-28.5) for intracerebral hemorrhage (ICH), and 16.6 (95% CI 8.7-32.0) for subarachnoid hemorrhage (SAH) compared with the general population. The adjusted stroke rate ratio remained increased during 31 to 365 days (3-fold for ischemic stroke, 2-fold for ICH, and 1.5-fold for SAH). During the following 1-30 years, the risk remained 1.6-fold increased for ischemic stroke but decreased to near unity for ICH and SAH.
In study IV (1980-2012), we identified 314,911 patients with first-time MI and 1,573,193 sex-, age-, and calendar year-matched individuals from the general population and followed 1-year survivors for development of dementia. Compared with the general population cohort, MI patients were not at increased risk of all-cause dementia (adjusted hazard ratio = 1.01, 95% CI 0.98-1.03). In subgroups of dementia, we observed no substantial association with Alzheimer's disease (adjusted hazard ratio = 0.92, 95% CI 0.88-0.95) or other dementias (adjusted hazard ratio = 0.98, 95% CI 0.95-1.01). However, patients with MI had an increased risk of vascular dementia (adjusted hazard ratio = 1.35, 95% CI 1.28-1.43). 
In conclusion, we found that preceding depression was associated with moderately increased mortality after MI, and that 
was associated with an increased risk of stroke and vascular dementia, but not dementia from other causes.