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Survivors of intracerebral hemorrhage had three times the risk of ischemic stroke compared with the general population, and twice the risk of myocardial infarction (MI), an analysis of U.S. population-based cohort studies found.

In a study of nearly 48,000 participants that adjusted for various factors, intracerebral hemorrhage was associated with an increased risk for later arterial ischemic events (HR 2.3, 95% CI 1.7-3.1), ischemic stroke (HR 3.1, 95% CI 2.1-4.5), and MI (HR 1.9, 95% CI 1.2-2.9), reported Santosh Murthy, MD, MPH, of Weill Cornell Medicine in New York City, and colleagues.

In subgroup analyses, the increased risk was comparable among Black and white individuals, and independent of measured traditional vascular risk factors and use of antithrombotic medication.

"These findings suggest that intracerebral hemorrhage may be a novel risk marker for arterial ischemic events," the group wrote in .

Sensitivity analyses that updated covariates in a time-varying manner; used incidence density matching; examined death as a competing risk; and included participants with prevalent intracerebral hemorrhage, ischemic stroke, or MI confirmed the association between intracerebral hemorrhage and arterial ischemic events.

Nearly 2.9 million patients worldwide experience intracerebral hemorrhage each year, and many of these patients survive initial acute hospitalization and can recover, Murthy and coauthors noted.

"Therefore, our results pertain to a large group of patients who may benefit from improved strategies to prevent arterial ischemic events," they wrote.

While linking intracerebral hemorrhage with subsequent MI and ischemic stroke have been reported, lacked control groups without intracerebral hemorrhage.

"The importance of the findings is that they ignite and inform efforts to improve risk stratification and secondary prevention of ischemic as well as hemorrhagic events after [intracerebral hemorrhage]," commented Graeme Hankey, MD, of the University of Western Australia in Perth, in an .

The current study pooled four U.S. population-based cohort studies -- the Atherosclerosis Risk in Communities (ARIC) study, Cardiovascular Health Study (CHS), Northern Manhattan Study (NOMAS), and Reasons for Geographic and Racial Differences in Stroke (REGARDS) study -- and involved a total of 47,866 eligible participants (57.7% women, mean age 62 years).

There were 318 intracerebral hemorrhages and 7,648 arterial ischemic events over a median follow-up of 12.7 years. The association between intracerebral hemorrhage and risk of an arterial ischemic event was consistent across the four studies. Among patients with an index intracerebral hemorrhage, only 15 (4.7%) had a recurrent intracerebral hemorrhage event, equating to an incidence rate of 1.1% per year, much lower than the risk of ischemic events, wrote Murthy and co-authors.

Given that cerebral small vessel disease (predominantly hypertensive deep perforator arteriopathy and cerebral amyloid angiopathy) are responsible for most cases of spontaneous intracerebral hemorrhage, guidelines emphasize risk assessment, lifestyle management, and maintaining blood pressure below 130/80 mm Hg to prevent recurrent intracerebral hemorrhage.

However, equivocate about the use of established strategies such as and lipid-lowering medications, due to concerns about recurrence of intracerebral hemorrhage, Murthy and colleagues wrote, a risk that these findings suggest is exceeded by patients' risk for arterial ischemic events.

"Our study highlights the need for randomized clinical trials to assess the net clinical benefit of antithrombotic therapy and statin medications in this high-risk population," the group wrote.

Indeed, Hankey suggested that the unresolved question of whether there may be a net benefit of starting, or restarting, intracerebral hemorrhage in patients at risk for ischemic events is "energized by this study, and by a recent exploratory analysis of all vascular events among patients with [intracerebral hemorrhage] enrolled in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels () trial."

Hankey listed several additional potential strategies worthy of investigation, including specific anti-inflammatory therapies and phosphodiesterase-3 inhibitors, that may safely address the risk of ischemic events after intracerebral hemorrhage.

Murthy and colleagues noted several limitations to their work, including the subtle differences in the definition of exposure and outcomes across the four cohorts, as well as possible surveillance bias, given evolving approaches to management of vascular risk factors between the late 1980s up to the late 2000s.

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