Abstract
BACKGROUND: Covert brain infarction (CBI) increases the risk of atherosclerotic cardiovascular disease (ASCVD), but optimal clinical management is uncertain. To enable tailored preventive measures, we aimed to determine whether the co-occurrence of CBI with unrecognized myocardial infarction (UMI) identifies a subgroup at especially high risk of ASCVD. METHODS: We included participants from the population-based Rotterdam Study, who were aged ≥45 years and without a history of stroke, transient ischemic attack or myocardial infarction. Participants underwent electrocardiography and brain magnetic resonance imaging between 2006 and 2012 and were followed up for first-ever ASCVD (ie, composite of ischemic stroke and recognized myocardial infarction). We used Cox models adjusted for cardiovascular risk factors to determine ASCVD risk. RESULTS: Among 4627 participants (mean age, 64.1 years; 57% women), 359 (7.8%) had CBI and 92 (2.0%) UMI. Compared with individuals without CBI, those with CBI were twice as likely to have UMI (odds ratio, 2.3 [95% CI, 1.2-3.9]). During a mean 9.9-year follow-up, 344 ASCVD events occurred. Compared with individuals with neither CBI nor UMI, individuals with CBI or UMI were at higher risk of ASCVD (hazard ratio [HR] for CBI, 1.7 [95% CI, 1.2-2.3]; and HR for UMI, 1.7 [95% CI, 0.9-3.3]), and individuals with co-occurring CBI and UMI were at highest risk (HR, 5.6 [95% CI, 2.9-10.7]). Among 359 individuals with CBI, those with UMI were at higher risk of ASCVD than those without UMI (HR, 3.4 [95% CI, 1.7-6.7]). CONCLUSIONS: Individuals with CBI are at increased risk of ASCVD, particularly in the presence of co-occurring UMI. These findings mark a subgroup of patients with CBI that could benefit most from stringent preventive therapy.