Silent MI Identified as Associated Risk Factor for Ischemic Stroke

Research into silent myocardial infarction may help identify cause of ischemic strokes that lack etiology, as well as identify better therapeutic strategies to combat recurring stroke.

A recent cardiovascular health study (CHS) published in Neurology identified silent myocardial infarction (MI) as an associated risk factor for ischemic stroke.1 The investigators’ findings may help to pinpoint the cause for ischemic strokes that currently lack an identifiable source. 

A total of 4224 community-dwelling individuals over the age of 65 years were enrolled in the study, all of whom did not have prevalent stroke or baseline evidence of MI. Following a median follow-up period of 9.8 years, 362 (8.6%) of participants had an incident silent MI, 421 (10%) had an incident overt MI, and 377 (8.9%) had an incident ischemic stroke. Study findings indicate an independent link between silent MI and subsequent ischemic stroke (hazard ratio [HR], 1.51 [95% CI, 1.03-2.21]), following adjustment for baseline demographics and vascular risk factors. 

“One-fifth of ischemic strokes have no known etiology, but have clinical and radiographic characteristics that suggest they arise from a distant source, and thus are considered to be embolic strokes of undetermined source (ESUS). Failure to identify the mechanism of these strokes precludes targeted secondary stroke preventive strategies, and there is a high risk of recurrent stroke with standard antiplatelet therapy,” lead author Alexander E. Merkler, MD, Weill Cornell Medical College, and colleagues wrote.1 “Our findings suggest that silent MI may predispose to cardiac embolism and subsequent stroke and therefore represent a novel therapeutic target for secondary stroke prevention that is currently inadequately treated with standard antiplatelet regiments.”

A total of 5201 participants were initially selected for the study; however, following baseline adjustments, 199 were excluded due to prevalent stroke, 474 were excluded due to prevalent overt MI, 161 were excluded due to prevalent silent MI, and 143 were missing covariates. The mean number of ECGs was 7.7 amongst the 4224 eligible participants.

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The investigators determined the primary outcome to be incident ischemic stroke. Secondary outcomes were several ischemic stroke subtypes, namely nonlacunar, lacunar, and other/unknown types. 

Following adjustment for baseline demographics, Cox proportional hazards analysis was used to identify association between time-varying MI status (silent, overt, or no MI) and stroke. Of the 377 participants who had an incident ischemic stroke, 136 (36.1%) were nonlacunar, 57 (15.1%) were lacunar, 184 (48.8%) were other or an unknown subtype, and 174 were of indeterminate etiology. An analysis of these subtypes concluded that silent MI was significantly associated with nonlacunar ischemic stroke (HR, 2.40 [95% CI, 1.36-4.22]). There was no significant association found with unknown ischemic stroke subtypes (HR, 1.29 [95% CI, 0.73-2.31]). Significant association between overt MI and incident ischemic stroke remained in both the short term (HR, 80 [95% CI, 53-199]) and long term (HR, 1.60 [CI, 1.04-2.44]).

“Our study adds novel findings supporting the hypothesis that silent MI is a risk factor for ischemic stroke,” the investigators wrote.1 “While there may be residual confounding as we could not adjust for vascular risk factors that occurred subsequent to baseline; and we could not account for the potential contribution of systemic inflammation on stroke as a result of silent MI, the association between silent MI and incident ischemic stroke is consistent with the hypothesis that silent MI may lead to thrombus formation and subsequent cardiac embolism, as also seen in overt MI. Thus, although the MI is silent or unrecognized, it should not be considered benign, but rather a covert risk factor for many adverse outcomes.” 

Limitations of the study were identified, including the age of the participants (all of whom were more than 65 years); lack of continuous heart-rhythm monitoring, details regarding the degree of left ventricular dysfunction/severity of myocardial scarring from the MI, and detailed information on vascular risk factors that developed after baseline; inability to determine the exact date of silent MI; and limited access to intracranial imaging. Additional research will be required with stronger antithrombotic therapy for participants with previously unrecognized MI and stroke, in order to better understand the interaction between heart disease and stroke. 

REFERENCE
Merkler AE, Bertz TM, Kamel H, et al. Silent myocardial infarction and subsequent ischemic stroke in the cardiovascular health study. Neurology. Published online May 24, 2021. doi:10.1212/WNL.0000000000012249