Lobar Intracerebral Hemorrhage and Risk for Major Cardiovascular Events

Patients with history of lobar intracerebral hemorrhage have increased risk for MACEs compared with patients with history of nonlobar intracerebral hemorrhage.

Lobar intracerebral hemorrhage (ICH) is associated with an increased risk for major cardiovascular events (MACEs) compared with nonlobar ICH, and this risk is primarily due to increased rates of recurrent ICH, according to a study published in JAMA Network Open.

Investigators assessed risk for MACEs by hematoma location from a cohort of patients with spontaneous ICH in southern Denmark. Eligible participants were aged 50 years or older and were hospitalized with first-ever spontaneous ICH from January 1, 2009, to December 31, 2018.

Follow-up for the main analysis began at the index ICH and ended on the date of the first outcome event or at censoring (date of death not due to an outcome event, emigration, or end of study on December 31, 2018), whichever came first.

The primary outcomes were MACEs (the composite of ICH, ischemic stroke, spontaneous intracranial extra-axial hemorrhage, myocardial infarction [MI], systemic embolism, or vascular death), spontaneous recurrent ICH, ischemic stroke, and MI.

A total of 2289 patients were eligible, 1034 patients with lobar ICH (47.9% men; mean age, 75.2 [SD, 10.7] years) and 1255 with nonlobar ICH (54.2% men; mean age, 73.5 [SD, 11.4] years).

Our novel observation that the risk of a second stroke after ICH did not differ by index hematoma location and that this risk was higher for IS [ischemic stroke] than ICH merits further study.

After a follow-up of 2048 person-years (mean follow-up, 2.1 years), the lobar group had a higher frequency of MACEs compared with the nonlobar cohort (incidence rate [IR], 10.84 [95% CI, 9.51-12.37] vs 7.91 [95% CI, 6.93-9.03]; adjusted hazard ratio [aHR], 1.26; 95% CI, 1.10-1.44). A total of 115 patients had a recurrent ICH, with crude IRs per 100 person-years of 3.74 (95% CI, 3.01-4.66) in the lobar cohort and 1.24 (95% CI, 0.89-1.73) in the nonlobar cohort (aHR, 2.63; 95% CI, 1.97-3.49).

The IRs per 100 person-years and aHRs were comparable in the 2 cohorts for ischemic stroke (IR, 1.45 [95% CI, 1.02-2.06] vs 1.77 [95% CI, 1.34-2.34]; aHR, 0.81; 95% CI, 0.60-1.10) and MI (IR, 0.42 [95% CI, 0.22-0.81] vs 0.64 [95% CI, 0.40-1.01]; aHR, 0.64; 95% CI, 0.38-1.09).

The risk for MACE, ischemic stroke, and MI (but not recurrent ICH) were increased in patients with atrial fibrillation (AF) compared with those without AF regardless of hematoma location. The risk for all outcomes was greater among patients with vs without previous occlusive vascular disease.

In patients with comorbid AF at time of the index ICH, the relative rates of the main outcomes were not different based on hematoma location, although the rate of ischemic stroke was lower after lobar ICH (aHR, 0.50; 95% CI, 0.26-0.97).

Limitations include use of unverified registry diagnostic codes for MI, and the study being underpowered to robustly assess risk for MI or a second stroke during follow-up. In addition, data are not available for brain scan characteristics other than hematoma location, which could affect short-term mortality and stroke recurrence risk. Also, proxies are used for alcohol and smoking, and the results may not be generalizable to other populations.

”In this cohort study, lobar ICH was associated with a higher risk of MACEs than nonlobar ICH, and this higher risk was largely attributable to higher rates of recurrent ICH,” the study authors wrote. “Our novel observation that the risk of a second stroke after ICH did not differ by index hematoma location and that this risk was higher for IS [ischemic stroke] than ICH merits further study.”

Disclosure: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Boe NJ, Hald SM, Jensen MM, et al. Major cardiovascular events after spontaneous intracerebral hemorrhage by hematoma location. JAMA Netw Open. Published online April 5, 2023. doi: 10.1001/jamanetworkopen.2023.5882