Abstract
In Japan, which has become a super-aging society, the incidence of spontaneous intracerebral hemorrhage among older adults is increasing. Managing these patients is often complicated by frailty and systemic comorbidities. Although these issues pose unique challenges, there is limited research on spontaneous intracerebral hemorrhage in this population, leaving their clinical characteristics and prognoses unclear. This retrospective study reviewed spontaneous intracerebral hemorrhage patients aged ≥75 years who were admitted to our institution from April 2004 to March 2024. Demographics, clinical presentation, imaging findings, and in-hospital outcomes were analyzed to identify risk factors for both 30-day and complication-related mortality. A total of 501 patients were included in the study, with 213 (42.5%) categorized as the oldest-old (age ≥85 years). Over the 2-decade study period, the proportion of oldest-old spontaneous intracerebral hemorrhage patients increased, and this age group exhibited a high risk of complication-related mortality (16.9%). Multivariate analysis identified age ≥85 years (odds ratio: 4.25, 95% confidence interval: 2.12-8.51, p < 0.001), Glasgow Coma Scale score ≤8 at admission (odds ratio: 2.27, 95% confidence interval: 1.19-4.34, p = 0.013), and serum albumin ≤3.5 g/dL at admission (odds ratio: 2.12, 95% confidence interval: 1.07-4.19, p = 0.031) as independent risk factors for complication-related mortality. The prognosis of spontaneous intracerebral hemorrhage in older adults is significantly worse in individuals aged ≥85 years. Older patients with spontaneous intracerebral hemorrhage are at a heightened risk of complication-related mortality, which is primarily associated with advanced age, neurological severity, and hypoalbuminemia.
Keywords: spontaneous intracerebral hemorrhage, older age, mortality, albumin
Introduction
Japan is undergoing a super-aging society, a trend expected to persist.1) In 2023, individuals aged ≥75 years constituted 16.1% of Japan's total population.2) Spontaneous intracerebral hemorrhage (SICH) is the second most common type of stroke after cerebral infarction, with its incidence increasing with age.3-5) Consequently, the number of SICH cases among older adults is increasing and is expected to increase further as populations age. Older patients with SICH are particularly vulnerable to comorbidities and frailty, which substantially complicate treatment and management.6) These patients often have limited physiological reserve, and in-hospital complications can directly lead to mortality. Therefore, managing older patients with SICH requires particular attention and tailored strategies. Despite these challenges, studies addressing SICH in older adults are limited.7,8) Furthermore, the proportion of the oldest-old (aged ≥85 years) included in previous studies is relatively small, leaving the clinical characteristics and prognoses of this population largely unknown. This study aims to elucidate the clinical characteristics of SICH in older adults and to identify risk factors for short-term prognosis and complication-related mortality, thereby providing a foundation for improved management of this vulnerable population.
Materials and Methods
Patients
Patients aged ≥75 years who presented with SICH and were admitted to Teraoka Memorial Hospital from April 2004 to March 2024 were retrospectively reviewed. SICH was defined as an intraparenchymal hemorrhage identified by computed tomography (CT) in patients admitted within 24 hours of symptom onset. Intracerebral hemorrhage (ICH) due to hypertension and amyloid angiopathy, as diagnosed using the Modified Boston Criteria, was included as SICH. Patients with ICH resulting from trauma, vascular malformations, moyamoya disease, ruptured aneurysms, tumor bleeding, vasculitis, or hemorrhagic transformation of ischemic stroke were excluded. The study was approved by the Ethics Committee of Teraoka Memorial Hospital (FY2024-07), which waived the requirement for individual informed consent. The study followed the opt-out method for consent, as detailed on Teraoka Memorial Hospital's website.
Demographic data
To investigate the proportion of older patients with SICH by age over 2 decades, the study period was divided into four 5-year intervals: April 2004 to March 2009, April 2009 to March 2014, April 2014 to March 2019, and April 2019 to March 2024. Age was categorized into 3 groups: 75-79 years, 80-84 years, and ≥85 years. The distribution of the older population within the medical care zone was based on national census data conducted every 5 years. The medical care zone was defined as the combined area of Fukuyama City, where Teraoka Memorial Hospital is located, and Fuchu City (Figure 1A). Population trends were estimated using census data from Fukuyama and Fuchu City.
Figure 1.
(A) Demographic distribution of older patients with spontaneous intracerebral hemorrhage (SICH) within the medical care zone of Teraoka Memorial Hospital. The map highlights the locations of Fukuyama City and Fuchu City, which constitute the hospital’s primary catchment area. (B) The proportion of oldest-old (aged ≥85 years) SICH patients among the older age group (aged ≥75 years) has significantly increased over the past two decades (p = 0.027). (C) Within the medical care zone, the proportion of oldest-old (aged ≥85 years) individuals among the older age group (aged ≥75 years) has also steadily risen over time (p < 0.001).
Clinical data
The baseline clinical information collected included age, sex, medical history (hypertension, diabetes mellitus, dyslipidemia, atrial fibrillation, chronic heart failure, artificial dialysis due to chronic renal failure, dementia, history of ischemic stroke, and history of intracerebral hemorrhage), prestroke modified Rankin Scale (mRS) score, and the use of anticoagulant or antiplatelet agents. The location of hemorrhage was classified as thalamus, subcortical, putamen, cerebellum, brainstem, caudate, or primary ventricle. For cases where a hematoma occupied ≥2 brain regions, the location was determined based on the region with the largest hematoma size. Hematoma volume was measured using initial brain CT scans and calculated by assuming the hematoma to be an ellipsoid and applying the ABC/2 method.9) Intraventricular extension was assessed on the initial CT scan. Obstructive hydrocephalus (ventricular enlargement due to intraventricular hematoma or infratentorial ICH) was assessed using an Evans index ≥0.3 on axial images or a callosal angle ≤90° on coronal images. Hematoma expansion was defined as an increase of >33% or an absolute increase of >0.006 L (6 mL) in hematoma volume.10) A Glasgow Coma Scale (GCS) score and systolic/diastolic blood pressure were assessed at admission. The GCS score was categorized into 3 groups: 3-8, 9-12, and 13-15. Blood tests were performed upon hospital arrival, prior to any crystalloid infusion therapy. Blood test parameters included blood glucose, white blood cell, hemoglobin, platelet count, Controlling Nutritional Status (CONUT) components (serum albumin, total cholesterol, creatinine, and total lymphocyte count), a recent nutritional marker.11) The cutoff points for laboratory parameters were determined based on established criteria for laboratory tests, particularly those aligned with the CONUT score for serum albumin, total cholesterol, and total lymphocyte count. Surgical procedures were performed only on patients who met established surgical criteria, as outlined in the Japanese Stroke Guidelines.12) Length of hospital stay was calculated from the date of admission to discharge. In-hospital complications analyzed in this study included pulmonary infections, urinary tract infections, acute heart failure, ischemic stroke, gastrointestinal bleeding, and coronavirus disease 2019 (COVID-19) infection. Clinical outcome measures were 30-day mortality and complication-related mortality. The 30-day mortality was defined as death from any cause within 30 days of admission. Complication-related mortality was defined as deaths caused by in-hospital complications or of unknown cause, provided that the death was not directly attributable to SICH. Complication-related deaths occurring within 30 days were included only in 30-day mortality, whereas those occurring after 30 days were classified as complication-related mortality. Functional outcomes were assessed using mRS scores, categorized as 0-3 (favorable), 4-5 (unfavorable), and 6 (death). Discharge disposition (home, institutionalization, transfer to another hospital, or death) was obtained from medical records.
Statistical analysis
Summary statistics were reported as mean and standard deviation or median and interquartile range for continuous variables and as frequencies and percentages for categorical variables. To compare clinical characteristics, etiology, risk factors, and clinical outcomes among older patients with SICH across age groups, age was categorized into 3 groups: 75-79 years, 80-84 years, and ≥85 years. Univariate comparisons were conducted using the χ2 test or Fisher's exact test for categorical variables and the Kruskal-Wallis rank-sum test for continuous variables. Risk factors for 30-day mortality and complication-related mortality in older patients with SICH were analyzed. Continuous variables were dichotomized based on cutoff values and converted into categorical variables. Univariate analyses were performed using the χ2 test or Fisher's exact test. Multivariate logistic regression models were constructed to identify independent predictors of 30-day mortality and complication-related mortality. The model included all variables with statistically significant differences (p < 0.05) in univariate analyses. All statistical analyses were performed using R software (version 4.0.2; The R Project for Statistical Computing, Vienna, Austria), and statistical significance was defined as a p < 0.05.
Results
A total of 501 patients (aged ≥75 years) with SICH admitted to Teraoka Memorial Hospital from April 2004 to March 2024 were included in the study. During the same period, 409 patients with SICH aged ≤74 years were admitted to the institution. The mean overall age of the older cohort was 83.9 (±5.7) years, with 309 (61.7%) being female (Table 1). Comorbidities included hypertension in 237 patients (47.3%), diabetes mellitus in 69 (13.8%), dyslipidemia in 42 (8.4%), atrial fibrillation in 41 (8.2%), chronic heart failure in 22 (4.4%), artificial dialysis in 16 (3.2%), dementia in 98 (19.6%), history of ischemic stroke in 128 (25.5%), and history of intracerebral hemorrhage in 53 (10.6%). A total of 116 patients (23.2%) were on antiplatelet agents, and 65 (13.0%) were on anticoagulant agents. The most common location of hemorrhage was the thalamus (154, 30.7%), followed by the subcortical region (140, 27.9%), putamen (113, 22.6%), cerebellum (53, 10.6%), brainstem (31, 6.2%), caudate nucleus (5, 1.0%), and primary ventricle (5, 1.0%). The mean hematoma volume was 28.7 mL, with 149 patients (29.7%) having hematoma volumes exceeding 30 mL. At admission, the GCS scores indicated severe impairment (GCS: 3-8) in 126 patients (25.1%), moderate impairment (GCS: 9-12) in 92 (18.4%), and mild impairment (GCS: 13-15) in 283 (56.5%). Blood test results at admission were as follows: albumin 3.9 (±0.5) g/dL, creatinine 1.0 (±1.1) mg/dL, blood glucose 144.4 (±48.8) mg/dL, white blood cell 8.1 (±3.5) ×103/μL, hemoglobin 12.8 (±1.8) g/dL, and platelet count 21.1 (±9.8) ×104/μL. The surgical procedure was performed in 82 patients (16.4%). The types of surgical procedures included 61 craniotomies (74.4%), 4 endoscopic surgeries (4.9%), 4 stereotactic aspirations (4.9%), and 13 external ventricular drainages (15.9%). The distribution of surgical procedures by age group is presented in Supplementary Table S1. The mRS score at 30 days was 0-3 (favorable outcome) in 157 patients (31.9%), 4-5 (unfavorable outcome) in 263 patients (53.5%), and 6 (death) in 72 patients (14.6%). The incidence of in-hospital complications was as follows: pulmonary infection in 83 patients (16.6%), urinary tract infection in 63 (12.6%), acute heart failure in 19 (3.8%), ischemic stroke in 8 (1.6%), gastrointestinal bleeding in 7 (1.4%), and COVID-19 infection in 6 (1.2%). Complication-related mortality was observed in 48 patients (9.6%). Discharge disposition was categorized as follows: home in 158 patients (31.5%), institutionalization in 192 (38.3%), transfer to another hospital in 37 (7.4%), and death in 114 (22.8%).
Table 1.
Clinical Characteristics of Older Patients with SICH (≥75 Years) and Univariate Analysis Classified by Age Group
| Variable | Overall | 75-79 years | 80-84 years | ≥85 years | p-value |
|---|---|---|---|---|---|
| Number of patients, n (%) | 501 (100%) | 133 (26.2%) | 155 (30.9%) | 213 (42.5%) | |
| Age at onset, years (mean ± SD) | 83.9 ± 5.7 | 77.2 ± 1.5 | 82.1 ± 1.4 | 89.3 ± 3.5 | <0.001 |
| Female, n (%) | 309 (61.7%) | 70 (52.6%) | 86 (55.5%) | 153 (71.8%) | <0.001 |
| Comorbidities, n (%) | |||||
| Hypertension | 237 (47.3%) | 65 (48.9%) | 73 (47.1%) | 99 (46.5%) | 0.908 |
| Diabetes mellitus | 69 (13.8%) | 24 (18.0%) | 31 (20.0%) | 14 (6.6%) | <0.001 |
| Dyslipidemia | 42 (8.4%) | 7 (5.3%) | 16 (10.3%) | 19 (8.9%) | 0.283 |
| Atrial fibrillation | 41 (8.2%) | 8 (6.0%) | 17 (11.0%) | 16 (7.5%) | 0.278 |
| Chronic heart failure | 22 (4.4%) | 3 (2.3%) | 4 (2.6%) | 15 (7.0%) | 0.062 |
| Artificial dialysis | 16 (3.2%) | 8 (6.0%) | 5 (3.2%) | 3 (1.4%) | 0.058 |
| Dementia | 98 (19.6%) | 12 (9.0%) | 34 (21.9%) | 52 (24.4%) | 0.001 |
| History of ischemic stroke | 128 (25.5%) | 26 (19.5%) | 41 (26.5%) | 61 (28.6%) | 0.161 |
| History of intracerebral hemorrhage | 53 (10.6%) | 13 (9.8%) | 18 (11.6%) | 22 (10.3%) | 0.869 |
| Antiplatelet use, n (%) | 116 (23.2%) | 29 (21.8%) | 33 (21.3%) | 54 (25.4%) | 0.601 |
| Anticoagulant use, n (%) | 65 (13.0%) | 16 (12.0%) | 19 (12.3%) | 30 (14.1%) | 0.815 |
| Pre-stroke mRS score ≤2, n (%) | 380 (75.8%) | 110 (82.7%) | 121 (78.1%) | 149 (70.0%) | 0.017 |
| Location of hemorrhage, n (%) | 0.899 | ||||
| Thalamus | 154 (30.7%) | 39 (29.3%) | 40 (25.8%) | 75 (35.2%) | |
| Subcortical region | 140 (27.9%) | 34 (25.6%) | 48 (31.0%) | 58 (27.2%) | |
| Putamen | 113 (22.6%) | 35 (26.3%) | 37 (23.9%) | 41 (19.2%) | |
| Cerebellum | 53 (10.6%) | 14 (10.5%) | 17 (11.0%) | 22 (10.3%) | |
| Brainstem | 31 (6.2%) | 8 (6.0%) | 10 (6.5%) | 13 (6.1%) | |
| Caudate nucleus | 5 (1.0%) | 2 (1.5%) | 1 (0.6%) | 2 (0.9%) | |
| Primary ventricle | 5 (1.0%) | 1 (0.8%) | 2 (1.3%) | 2 (0.9%) | |
| Intraventricular extension, n (%) | 177 (35.3%) | 47 (35.3%) | 49 (31.6%) | 81 (38.0%) | 0.446 |
| Hematoma volume, mL (mean ± SD) | 28.7 ± 39.9 | 25.9 ± 37.3 | 31.1 ± 40.1 | 28.8 ± 41.1 | 0.290 |
| Hematoma volume >30 mL, n (%) | 149 (29.7%) | 34 (25.6%) | 52 (33.5%) | 63 (29.6%) | 0.335 |
| Obstructive hydrocephalus, n (%) | 39 (7.8%) | 8 (6.0%) | 13 (8.4%) | 18 (8.5%) | 0.674 |
| Hematoma expansion, n (%) | 10 (2.0%) | 2 (1.5%) | 5 (3.2%) | 3 (1.4%) | 0.431 |
| GCS score at admission, n (%) | 0.471 | ||||
| 3-8 | 126 (25.1%) | 36 (27.1%) | 34 (21.9%) | 56 (26.3%) | |
| 9-12 | 92 (18.4%) | 19 (14.3%) | 29 (18.7%) | 44 (20.7%) | |
| 13-15 | 283 (56.5%) | 78 (58.6%) | 92 (59.4%) | 113 (53.1%) | |
| Systolic blood pressure, mmHg (mean ± SD) | 176.5 ± 35.7 | 174.8 ± 38.9 | 174.9 ± 36.1 | 178.7 ± 33.2 | 0.478 |
| Diastolic blood pressure, mmHg (mean ± SD) | 95.2 ± 21.4 | 96.4 ± 22.5 | 94.9 ± 22.2 | 94.8 ± 20.0 | 0.703 |
| Blood test results (mean ± SD) | |||||
| Albumin, g/dL | 3.9 ± 0.5 | 4.0 ± 0.5 | 4.0 ± 0.4 | 3.8 ± 0.5 | 0.001 |
| Total cholesterol, mg/dL | 185.1 ± 38.2 | 187.2 ± 40.6 | 184.9 ± 36.8 | 184.0 ± 37.6 | 0.666 |
| Creatinine, mg/dL | 1.0 ± 1.1 | 1.2 ± 1.6 | 0.9 ± 1.0 | 0.9 ± 0.9 | 0.927 |
| Blood glucose, mg/dL | 144.4 ± 48.8 | 147.0 ± 48.7 | 145.1 ± 47.8 | 142.2 ± 49.6 | 0.245 |
| White blood cell, 103/μL | 8.1 ± 3.5 | 8.1 ± 3.4 | 8.4 ± 3.4 | 8.0 ± 3.6 | 0.406 |
| Hemoglobin, g/dL | 12.8 ± 1.8 | 13.5 ± 1.8 | 13.0 ± 1.7 | 12.2 ± 1.5 | <0.001 |
| Platelet count, 104/μL | 21.1 ± 9.8 | 20.5 ± 7.2 | 20.8 ± 11.2 | 21.7 ± 10.1 | 0.252 |
| Total lymphocyte count, 103/μL | 1.5 ± 0.9 | 1.6 ± 1.1 | 1.4 ± 0.7 | 1.4 ± 0.9 | 0.910 |
| Surgery, n (%) | 82 (16.4%) | 26 (19.5%) | 35 (22.6%) | 21 (9.9%) | 0.003 |
| Hospital stay, days, median (IQR) | 73 (20-125) | 68 (16-121) | 76 (33-137) | 71 (16-123) | 0.150 |
| mRS score at 30 days, n (%) | 0.007 | ||||
| 0-3 | 157 (31.9%) | 56 (42.1%) | 47 (30.3%) | 54 (25.4%) | |
| 4-5 | 263 (53.5%) | 58 (43.6%) | 88 (56.8%) | 117 (54.9%) | |
| 6 | 72 (14.6%) | 16 (12.0%) | 17 (11.0%) | 39 (18.3%) | |
| In-hospital complications, n (%) | |||||
| Pulmonary infection | 83 (16.6%) | 18 (13.5%) | 20 (12.9%) | 45 (21.1%) | 0.061 |
| Urinary tract infection | 63 (12.6%) | 10 (7.5%) | 24 (15.5%) | 29 (13.6%) | 0.106 |
| Acute heart failure | 19 (3.8%) | 1 (0.8%) | 4 (2.6%) | 14 (6.6%) | 0.015 |
| Ischemic stroke | 8 (1.6%) | 3 (2.3%) | 1 (0.6%) | 4 (1.9%) | 0.548 |
| Gastrointestinal bleeding | 7 (1.4%) | 0 (0.0%) | 5 (3.2%) | 2 (0.9%) | 0.048 |
| COVID-19 infection | 6 (1.2%) | 2 (1.5%) | 3 (1.9%) | 1 (0.5%) | 0.440 |
| Complication related mortality, n (%) | 48 (9.6%) | 3 (2.3%) | 9 (5.8%) | 36 (16.9%) | <0.001 |
| Discharge disposition, n (%) | 0.028 | ||||
| Home | 158 (31.5%) | 52 (39.1%) | 53 (34.2%) | 53 (26.1%) | |
| Institutionalization | 192 (38.3%) | 52 (39.1%) | 58 (37.4%) | 82 (40.4%) | |
| Transfer to another hospital | 37 (7.4%) | 9 (6.8%) | 16 (10.3%) | 12 (5.9%) | |
| Dead | 114 (22.8%) | 20 (15.0%) | 28 (18.1%) | 56 (27.6%) | |
| Follow-up period, days, median (IQR) | 248 (70-1184) | 553 (97-1796) | 303 (79-1591) | 162 (53-777) | <0.001 |
Statistically significant values are in bold.
Post-hoc pairwise comparisons were not performed.
COVID-19: coronavirus disease 2019; GCS: Glasgow Coma Scale; IQR: interquartile range; mRS: modified Rankin Scale; SD: standard division; SICH: spontaneous intracerebral hemorrhage
In the univariate analysis of SICH patients classified by age group (75-79 years, 80-84 years, and ≥85 years), significant differences were observed in age, sex, comorbidities (diabetes mellitus and dementia), pre-stroke mRS score ≤2, blood test results (albumin and hemoglobin), surgical intervention, 30-day mRS score, in-hospital complications (acute heart failure and gastrointestinal bleeding), complication-related mortality, discharge disposition, and follow-up period (Table 1). Notably, the proportion of complication-related mortality among the oldest-old (aged ≥85 years) SICH patients was 16.9%.
The proportion of oldest-old (aged ≥85 years) SICH patients among the older age group (≥75 years) has significantly increased over the past 2 decades (χ2 test, p = 0.027, Figure 1B). From April 2004 to March 2009, the proportion of oldest-old SICH patients was 31.8% (approximately 1 in 3 individuals). In contrast, from April 2019 to March 2024, this proportion had increased to 49.5% (approximately 1 in 2 individuals). Even within the medical care zone of our hospital, encompassing Fukuyama and Fuchu City, the proportion of oldest-old individuals (aged ≥85 years) among the older population (≥75 years) has been steadily increasing (χ2 test, p < 0.001, Figure 1C). In 2005, this proportion was 26.6%, increasing to 32.9% in 2020.
Univariate analysis of 30-day mortality in older patients with SICH (≥75 years) revealed the following factors as significantly associated with 30-day mortality (Supplementary Table S2): age ≥85 years (p = 0.045), pre-stroke mRS score ≤2 (p = 0.005), intraventricular extension (p < 0.001), hematoma volume >30 mL (p < 0.001), obstructive hydrocephalus (p < 0.001), GCS score ≤8 at admission (p < 0.001), albumin ≤3.5 g/dL (p = 0.033), blood glucose >150 mg/dL (p < 0.001), white blood cell >10,000/μL (p < 0.001), and hemoglobin ≤12.0 g/dL (p = 0.005). Multivariate analysis, incorporating variables that showed significant differences in univariate analysis, identified the following as independent risk factors for 30-day mortality (Supplementary Table S3): age ≥85 years (odds ratio [OR]: 2.59, 95% confidence interval [CI]: 1.22-5.51, p = 0.014), intraventricular extension (OR: 3.20, 95% CI: 1.31-7.53, p = 0.006), hematoma volume >30 mL (OR: 2.48, 95% CI: 1.12-5.46, p = 0.025), GCS score ≤8 at admission (OR: 27.40, 95% CI: 9.93-75.70, p < 0.001), and white blood cell >10,000/μL (OR: 2.65, 95% CI: 1.23-5.71, p = 0.013).
Univariate analysis of complication-related mortality in older patients with SICH (≥75 years) revealed the following factors as significantly associated with complication-related mortality (Table 2): age ≥85 years (p < 0.001), pre-stroke mRS score ≤2 (p = 0.005), GCS score ≤8 at admission (p = 0.003), and albumin ≤3.5 g/dL (p = 0.002). Multivariate analysis, incorporating variables that showed significant differences in univariate analysis, identified the following as independent risk factors for complication-related mortality (Table 3): age ≥85 years (OR: 4.25, 95% CI: 2.12-8.51, p < 0.001), GCS score ≤8 at admission (OR: 2.27, 95% CI: 1.19-4.34, p = 0.013), and albumin ≤3.5 g/dL (OR: 2.12, 95% CI: 1.07-4.19, p = 0.031).
Table 2.
Univariate Analysis of Complication Related Mortality in Older Patients with SICH (≥75 Years)
| Variable | No complication related mortality (n = 453) | Complication related mortality (n = 48) | p-value |
|---|---|---|---|
| Age ≥85 years, n (%) | 177 (39.1%) | 36 (75.0%) | <0.001 |
| Female, n (%) | 279 (61.6%) | 30 (62.5%) | >0.999 |
| Comorbidities, n (%) | |||
| Hypertension | 210 (46.4%) | 27 (56.2%) | 0.249 |
| Diabetes mellitus | 63 (13.9%) | 6 (12.5%) | 0.961 |
| Dyslipidemia | 39 (8.6%) | 3 (6.2%) | 0.786 |
| Atrial fibrillation | 38 (8.4%) | 3 (6.2%) | 0.785 |
| Chronic heart failure | 20 (4.4%) | 2 (4.2%) | >0.999 |
| Artificial dialysis | 15 (3.3%) | 1 (2.1%) | >0.999 |
| Dementia | 87 (19.2%) | 11 (22.9%) | 0.671 |
| History of ischemic stroke | 114 (25.2%) | 14 (29.2%) | 0.667 |
| History of intracerebral hemorrhage | 46 (10.2%) | 7 (14.6%) | 0.483 |
| Antiplatelet use, n (%) | 103 (22.7%) | 13 (27.1%) | 0.618 |
| Anticoagulant use, n (%) | 59 (12.4%) | 9 (18.8%) | 0.305 |
| Pre-stroke mRS score ≤2, n (%) | 352 (77.9%) | 28 (58.3%) | 0.005 |
| Intraventricular extension, n (%) | 154 (34.0%) | 23 (47.9%) | 0.078 |
| Hematoma volume >30 mL, n (%) | 129 (28.5%) | 20 (41.7%) | 0.083 |
| Obstructive hydrocephalus, n (%) | 34 (7.5%) | 5 (10.4%) | 0.406 |
| Hematoma expansion, n (%) | 9 (2.0%) | 1 (2.1%) | >0.999 |
| GCS score ≤8 at admission, n (%) | 105 (23.2%) | 21 (43.8%) | 0.003 |
| Blood test results, n (%) | |||
| Albumin ≤3.5 g/dL | 73 (16.4%) | 17 (35.4%) | 0.002 |
| Total cholesterol ≤180 mg/dL | 198 (46.5%) | 17 (37.8%) | 0.339 |
| Creatinine >0.9 mg/dL | 110 (24.4%) | 18 (37.5%) | 0.073 |
| Blood glucose >150 mg /dL | 151 (34.3%) | 19 (41.3%) | 0.434 |
| White blood cell >10,000/μL | 113 (25.0%) | 14 (29.2%) | 0.648 |
| Hemoglobin ≤12.0 g/dL | 134 (29.8%) | 19 (39.6%) | 0.217 |
| Platelet count ≤10.0 × 104/μL | 23 (5.1%) | 2 (4.2%) | >0.999 |
| Total lymphocyte count ≤1,600/μL | 271 (66.4%) | 29 (70.7) | 0.700 |
| Surgery, n (%) | 69 (15.2%) | 13 (27.1%) | 0.057 |
Statistically significant values are in bold.
mRS: modified Rankin Scale, GCS: Glasgow Coma Scale; SICH: spontaneous intracerebral hemorrhage
Table 3.
Multivariate Analysis of Complication Related Mortality in Older Patients with SICH (≥75 Years)
| Variable | OR (95% CI) | p-value |
|---|---|---|
| Age ≥85 years | 4.25 (2.12-8.51) | <0.001 |
| Pre-stroke mRS score ≤2 | 0.54 (0.28-1.03) | 0.062 |
| GCS score ≤8 at admission | 2.27 (1.19-4.34) | 0.013 |
| Albumin ≤3.5 g/dL | 2.12 (1.07-4.19) | 0.031 |
Statistically significant values are in bold.
mRS: modified Rankin Scale, GCS: Glasgow Coma Scale; SICH: spontaneous intracerebral hemorrhage
Discussion
This study elucidated the clinical characteristics, short-term prognosis, and risk factors for complication-related mortality in older patients with SICH in a suburban Japanese region. The thalamus was the most common location of hemorrhage (30.7%), followed by the subcortical region (27.9%), putamen (22.6%), and cerebellum (10.6%). Consistent with our findings, a previous large-scale Japanese study reported an increase in thalamic hemorrhages with age.13) The analysis, which included patients across all age groups, revealed that younger patients (aged ≤74 years) exhibited a lower incidence of subcortical and cerebellar hemorrhages but a higher incidence of putaminal hemorrhages. This age-related variation in hemorrhage location may reflect differences in underlying pathophysiological mechanisms, such as age-related vascular changes, including cerebral amyloid angiopathy in some older patients and hypertensive arteriopathy predominantly affecting the basal ganglia in younger patients.
Surgical procedures were less frequently performed in the oldest-old age group compared to other age groups. This may reflect patient preference for less aggressive treatment due to advanced age and life expectancy.14) Additionally, the risks associated with general anesthesia often outweigh the potential benefits in this age group, particularly for patients with pre-existing systemic comorbidities. Previous studies have suggested that endoscopic surgery under local anesthesia may be a beneficial option for older patients with SICH who are at high risk for complications associated with general anesthesia.15-17)
Our study included the largest number of oldest-old patients (aged ≥85 years) to date (213 patients), whereas previous studies in this age group were fewer than 100 patients.8,18) The independent risk factors for 30-day mortality in our cohort included age (≥85 years), intraventricular extension, hematoma volume >30 mL, neurological severity (GCS score ≤8 at admission), and elevated white blood cell (>10,000/μL). Previous studies have identified similar predictors of poor short-term outcome in older SICH patients. For example, larger hematoma volume has been associated with poor prognosis,18,19) and low admission GCS as well as elevated white blood cell count have been reported as risk factors for mortality in older SICH patients.20) These prior findings are consistent with our results, suggesting that in older patients, greater stroke severity and systemic inflammatory response contribute to worse outcomes. In contrast, previous studies reported no difference in 30-day mortality between younger and older ICH patients.8,20) In contrast, our data indicate that advanced age itself is associated with short-term prognosis. Specifically, we found that patients aged ≥85 years had a significantly higher 30-day mortality risk compared to those aged 75-84 years.21) This discrepancy may reflect differences in study populations or methodologies, underscoring the need for further research to explore the impact of advanced age on short-term outcomes in SICH.
The independent risk factors for complication-related mortality were identified as age (≥85 years), neurological severity (GCS score ≤8 at admission), and malnutrition (albumin ≤3.5 g/dL). Previous studies have demonstrated that low serum albumin levels on admission are strongly associated with stroke-associated pneumonia and in-hospital mortality.22,23) In contrast, total cholesterol and total lymphocyte count, which are included in the criteria for evaluating the CONUT score, were not associated with complication-related mortality in this study. Our findings underscore the critical importance of serum albumin levels when assessing prognosis in older patients with SICH. Hypoalbuminemia reflects malnutrition and frailty, increasing the risk of infection, disuse, and aspiration due to impaired immunity and dysphagia.24) This combination of factors contributes significantly to complication-related mortality.6,25) Importantly, these 3 risk factors, age, neurological severity, and malnutrition, are all readily available at the time of admission. This highlights the necessity of providing families with clear, advanced information about the potential for sudden deterioration and the high risk of in-hospital mortality in patients presenting with these risk factors. Paying close attention to these risk factors may improve early risk stratification and facilitate more tailored approaches to patient management. Although the present study could not determine whether nutritional interventions for patients with hypoalbuminemia at admission may reduce complication-related mortality, future studies should investigate this possibility to provide novel strategies for improving outcomes in this vulnerable population.
Our study had some limitations that should be addressed in future research. First, as a single-center retrospective study, the incidence of SICH in the medical care zone is an estimate. However, our hospital serves as a core stroke center in the region. Second, this study had a relatively short follow-up period, with a median follow-up of 248 days. Future studies should aim to assess the long-term prognosis of patients with SICH through extended follow-up periods to provide a more comprehensive understanding of outcomes over time.
Conclusions
The prognosis of SICH in older adults are significantly worse in individuals aged ≥85 years. Older patients with SICH are at a heightened risk of complication-related mortality, primarily driven by advanced age, neurological severity, and hypoalbuminemia. These findings highlight the necessity of integrating nutritional assessments, including serum albumin levels, into routine clinical evaluations and tailoring management strategies to improve outcomes for this vulnerable population.
Conflicts of Interest Disclosure
All authors have no conflict of interest.
Ethics Approval
This study was approved by the Ethics Committee of Teraoka Memorial Hospital (FY2024-07).
Consent for Publication
Informed consent was obtained from all individual participants included in the study.
Supplementary Material
References
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