Mortality After Admission to Stroke Unit for Intracerebral Hemorrhage: Effect of Age 80 and Older and Multimorbidity

To the Editor: The incidence of spontaneous intracerebral hemorrhage (ICH) increases exponentially with age, so individuals aged 80 and older are expected to represent a growing proportion of all people admitted to stroke units (SU) for ICH. Age of 80 and older is considered to be a major predictor of ICH mortality independent of characteristics related to ICH severity, but supporting evidence is limited to two small noncontemporary cohort studies and a large contemporary cohort study that did not control for any confounders. Findings from noncontemporary cohorts may not be applicable to individuals with ICH currently benefiting from organized inpatient (SU) care, which has improved ICH survival. Another limitation of these studies is the lack of control for prestroke multimorbidity, which is a known predictor of mortality in stroke. This prospective study investigated whether, in individuals with ICH admitted to a SU, age of 80 and older predicts in-SU mortality independent of multimorbidity. The study included 213 participants aged 80 and older (mean age 84.9 4.0, 57.9% male) and 259 participants younger than 80 (mean age 68.7 9.9, 39.9% male) with spontaneous first-episode ICH consecutively admitted to the SU of the Maggiore Hospital (Bologna, Italy) between October 2007 and December 2013. The Maggiore Hospital ethics committee approved the study. All participants (or their representatives) provided informed consent. Information was collected from medical records. Multimorbidity was defined as a Charlson Comorbidity Index of 2 or greater. Other confounders were sex, hypertension, diabetes mellitus, atrial fibrillation, dementia, prestroke functional impairment (modified Rankin Scale), neurological impairment on admission (National Institutes of Health Stroke Scale), anticoagulation-related etiology, pulse pressure, neuroradiological findings (location and intraventricular extension), and recourse to neurosurgical procedures. The association between aged 80 and older and in-SU mortality was estimated using hazard ratios (HRs) and their 95% confidence intervals (CIs) from Cox proportional hazards regression models adjusted for prestroke and ICH-related confounders. Preliminary analyses showed a significant interaction between age and multimorbidity (P = .04). Based on inspection of survival curves and on previous literature, the interaction was modeled as a time-dependent variable to obtain separate mortality risk estimates for stays or 7 or fewer days and longer than 7 days. Analyses were performed using SPSS version 21 (IBM Corp., Armonk, NY). P < . 05 was considered statistically significant. Mortality at 7 days or fewer (69.3% of all deaths) was unrelated to age or multimorbidity (Table 1). By contrast, mortality at longer than 7 days was six times as high for younger than 80 with multimorbidity and aged 80 and older with and without multimorbidity than for younger than 80 without multimorbidity. In individuals with stroke, deaths within the first week are mostly the direct consequence of hemorrhagic injury, whereas deaths in the following weeks are mostly related to medical complications. Therefore, age 80 and older and multimorbidity may fail to affect in-SU mortality during the first week because, at this time, prognosis mainly depends on ICH severity, but after the first week, age 80 and older and multimorbidity may become relevant for managing medical complications. Nevertheless, in the model, the effect of multimorbidity was limited to individuals younger than 80. It may be that, in individuals aged 80 and older, the direct consequences of hemorrhagic injury override those of medical complications for a longer time than in younger individuals. Age-related alterations in cellular architecture and the metabolism of the human brain that may aggravate hematoma expansion and perihematomal edema are consistent with this hypothesis. Moreover, animal models show that brain hemorrhage in older age is associated with excess