Intracerebral Hemorrhage Linked to Increased Risk of Ischemic Stroke, Myocardial Infarction

The degree of increased risk for subsequent ischemic events following intracerebral hemorrhage persisted after adjusting for basic demographic characteristics and traditional vascular risk factors.

After pooling data from 4 population-based cohort studies, investigators have concluded that intracerebral hemorrhage is associated with an increased risk of subsequent ischemic stroke and myocardial infarction, and therefore may be used as a risk marker for arterial ischemic events.

Lead author Santosh B. Murthy, MD, MPH, assistant professor of neurology, Weill Cornell Medical College, and medical director, Neurosciences Intensive Care Unit, New York-Presbyterian Hospital, and colleagues included 47,866 participants for analysis using an arterial ischemic event, defined as a composite of ischemic stroke or myocardial infarction, as the primary outcome.

During a median follow-up period of 12.7 years (interquartile range [IQR], 7.7-19.5), 318 participants developed intracerebral hemorrhages while arterial ischemic events occurred in 7648 participants (16.0%). Following intracerebral hemorrhage, the incidence rate of an arterial ischemic event was 3.6 events per 100 person-years (95% CI, 2.7-5.0), compared to 1.1 events per 100 person-years (95% CI, 1.1-1.2) in participants without intracerebral hemorrhage.

Using unadjusted Cox proportional hazards regression analysis, intracerebral hemorrhage was associated with an increased risk of an arterial ischemic event (hazard risk [HR], 3.1 [95% CI, 2.3-4.2]). This risk remained consistently elevated even after adjusting for baseline covariates (HR, 2.3 [95% CI, 1.7-3.1]).

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"From a pathophysiological standpoint, hematoma-mediated inflammation, antithrombotic drug interruption, and shared vascular risk factors are some of the possible mechanisms underlying the association between intracerebral hemorrhage and ischemic arterial events,” Murthy et al wrote.

The incidence rate of acute ischemic stroke was 2.3 events per 100 person-years (95% CI, 1.6-3.4) after intracerebral hemorrhage versus 0.5 events per 100 person-years (95% CI, 0.5-0.6) in those without intracerebral hemorrhage. Myocardial infarction, accounting for 4522 of the 7648 participants with ischemic events, had an incidence rate of 1.8 events per 100 person-years (95% CI, 1.2-2.7) after intracerebral hemorrhage compared to 0.7 events per 100 person-years (95% CI, 0.6-0.7) in those without intracerebral hemorrhage.

Of 318 patients who had an index intracerebral hemorrhage, only 15 (4.7%) had a recurrent intracerebral hemorrhage event, equating to an incidence of 1.1% per year, which the authors described as, "much lower than the risk of ischemic events.”

The investigators also found that intracerebral hemorrhage was associated with subsequent arterial ischemic events across subgroups defined by age, sex, race/ethnicity, atrial fibrillation, antiplatelet medication use, and study cohort. There was no significant interactions between intracerebral hemorrhage and the subgroup stratification variables.

In sensitivity analyses, intracerebral hemorrhage was associated with subsequent arterial ischemic events when updating covariates in a time-varying manner (HR, 2.2 [95% CI, 1.6-3.0]) and when using incidence density matching (odds ratio [OR], 2.3 [95% CI, 1.3-4.2]). These associations continued when including participants with prevalent intracerebral hemorrhage, ischemic stroke, or myocardial infarction (HR, 2.2; [95% CI, 1.6-2.9]) and when treating death as a competing risk (subdistribution HR, 1.6 [95% CI, 1.1-2.1]).

The data used was gathered from the Atherosclerosis Risk in Communities (ARIC) study, the Cardiovascular Health Study (CHS), the Northern Manhattan Study (NOMAS), and the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study.

REFERENCE
Murthy SM, Zhang C, Diaz I, et al. Association between intracerebral hemorrhage and subsequent arterial ischemic events in participants from 4 population-based cohort studies. JAMA Neurol. Published online May 3, 2021. doi: 10.1001/jamaneurol.2021.0925