Brain Advance Access originally published online on August 28, 2009
Brain 2009 132(10):2798-2804; doi:10.1093/brain/awp216
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Increased risk and worse prognosis of myocardial infarction in patients with prior hospitalization for epilepsy—The Stockholm Heart Epidemiology Program
1 Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden 2 Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden 3 Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden 4 Department of Epidemiology, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden 5 Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Boston, MA, USA
Correspondence to: Dr Imre Janszky, Department of Public Health Sciences, Karolinska Institutet, Norrbacka, 6th Floor, Karolinska University Hospital, SE-171 76 Stockholm, Sweden E-mail: imre.janszky{at}ki.se
The association of epilepsy with risk of acute myocardial infarction (AMI) remains uncertain, and its association with myocardial infarction prognosis has not been evaluated. In this study, we performed a population-based case–control study that included 1799 cases with first AMI and 2339 controls, frequency matched by age, sex and hospital catchment area. A history of epilepsy was identified using the Swedish hospital discharge registry. Information on lifestyle and biomarkers was determined from questionnaires and standardized clinic examinations. The cohort of cases was followed for 8 years to evaluate the relationship between epilepsy and post AMI prognosis. A diagnosis of epilepsy was associated with higher risk of incident AMI, with an odds ratio (OR) of 4.92 [95% confidence interval (CI) 2.34–10.31] after adjustment for age, gender, hospital catchment area, and education. There was a graded positive relation between number of hospitalizations for epilepsy and risk of AMI. Adjustment for smoking and levels of tissue plasminogen activator (tPA)/plasminogen activator inhibitor 1 (PAI-1) complex, von Willebrand factor and homocysteine weakened, and adjustment for high-density lipoprotein (HDL) and fibrinogen strengthened, the relationship between epilepsy and AMI. The OR for epilepsy was 4.83 (95% CI 1.62–14.43) when age, gender, hospital catchment area, education and established, clinically relevant AMI risk factors, i.e. diabetes mellitus, smoking, hypertension, physical activity, obesity, high-density lipoprotein, total cholesterol and alcohol consumption were simultaneously controlled for. Epilepsy was also associated with AMI prognosis. Multivariable adjusted hazard ratios for total and cardiac mortality and for a combined outcome of cardiac death and non-fatal reinfarction, heart failure and stroke during follow up, were 1.95 (0.70–5.43), 3.49 (1.05–11.65) and 2.39 (1.16–4.90), respectively. We conclude that epilepsy might be a risk and an adverse prognostic factor for AMI. Smoking and increase in the level of homocysteine, tPA/PAI-1 complex and von Willebrand factor are candidate mechanisms linking epilepsy to increased AMI risk. Physicians should be aware of the potential cardiovascular implications of epilepsy.
Key Words: epilepsy; acute myocardial infarction; risk; prognosis
Abbreviations: AED, antiepileptic drug; AMI, acute myocardial infarction; CI, confidence interval; CHD, coronary heart disease; HDL, high density lipoprotein; OR, odds ratio; PAI-1, plasminogen activator inhibitor 1; SHEEP, Stockholm Heart Epidemiology Program; tPA, tissue plasminogen activator
Received March 6, 2009. Revised June 29, 2009. Accepted July 5, 2009.