Impact of Cerebral Small Vessel Disease on Functional Recovery After Intracerebral Hemorrhage.

Background and Purpose- In this study, we aim to investigate the association of computed tomography-based markers of cerebral small vessel disease with functional outcome and recovery after intracerebral hemorrhage. Methods- Computed tomographic scans of patients in the ERICH study (Ethnic and Racial Variations of Intracerebral Hemorrhage) were evaluated for the extent of leukoaraiosis and cerebral atrophy using visual rating scales. Poor functional outcome was defined as a modified Rankin Scale (mRS) of ≥3. Multivariable logistic and linear regression models were used to explore the associations of cerebral small vessel disease imaging markers with poor functional outcome at discharge and, as a measure of recovery, change in mRS from discharge to 90 days poststroke. Results- After excluding in-hospital deaths, data from 2344 patients, 583 (24.9%) with good functional outcome (mRS of 0-2) at discharge and 1761 (75.1%) with poor functional outcome (mRS of 3-5) at discharge, were included. Increasing extent of leukoaraiosis (P for trend, 0.01) and only severe (grade 4) global atrophy (odds ratio, 2.02; 95% CI, 1.22-3.39, P=0.007) were independently associated with poor functional outcome at discharge. Mean (SD) mRS change from discharge to 90-day follow-up was 0.57 (1.18). Increasing extent of leukoaraiosis (P for trend, 0.002) and severe global atrophy (ß [SE], -0.23 [0.115]; P=0.045) were independently associated with less improvement in mRS from discharge to 90 days poststroke. Conclusions- In intracerebral hemorrhage survivors, the extent of cerebral small vessel disease at the time of intracerebral hemorrhage is associated with poor functional outcome at hospital discharge and impaired functional recovery from discharge to 90 days poststroke.

Men Experience Higher Risk of Pneumonia and Death After Intracerebral Hemorrhage.

BACKGROUND: Infectious complications worsen outcome after intracerebral hemorrhage (ICH). We investigated the impact of sex on post-ICH infections and mortality. METHODS: Consecutive ICH patients (admitted to a single hospital between 1994 and 2015) were retrospectively assessed via chart review to ascertain the following in-hospital infections: urinary tract infection (UTI), pneumonia, and sepsis. Adjusted logistic regression was performed to identify associations between sex, infection, and mortality at 90 days. RESULTS: Two thousand and four patients were investigated, 1071 (53.7%) males. Men were more likely to develop pneumonia (21.9 vs 15.5% p < 0.001) and sepsis (3.4 vs 1.6%, p = 0.009), whereas women had higher risk of UTI (19.9 vs 11.7% p < 0.001). Multivariate analyses confirmed association between male sex and pneumonia (Odds Ratio (OR) 1.37, 95% confidence interval (CI) 1.08-1.74, p = 0.011). Male sex (OR 1.40; CI 1.07-1.85; p = 0.015) and infection (OR 1.56; CI 1.11-1.85; p = 0.011) were independently associated with higher 90-day mortality. CONCLUSIONS: Types and rates of infection following ICH differ by sex. Male sex independently increases pneumonia risk, which subsequently increases 90-day mortality. Sex-specific preventive strategies to reduce the risk of these complications may be one strategy to improve ICH outcomes.

Comparison of Genetic and Self-Identified Ancestry in Modeling Intracerebral Hemorrhage Risk.

Background: We sought to determine whether a small pool of ancestry-informative DNA markers (AIMs) improves modeling of intracerebral hemorrhage (ICH) risk in heterogeneous populations, compared with self-identified race/ethnicity (SIRE) alone. Methods: We genotyped 15 preselected AIMs to perform principal component (PC) analysis in the ERICH study (a multi-center case-control study of ICH in whites, blacks, and Hispanics). We used multivariate logistic regression and tests for independent samples to compare associations for genetic ancestry and SIRE with ICH-associated vascular risk factors (VRFs). We then compared the performance of models for ICH risk that included AIMs and SIRE alone. Results: Among 4,935 subjects, 34.7% were non-Hispanic black, 35.1% non-Hispanic white, and 30.2% Hispanic by SIRE. In stratified analysis of these SIRE groups, AIM-defined ancestry was strongly associated with seven of the eight VRFs analyzed (p < 0.001). Within each SIRE group, regression of AIM-derived PCs against VRFs confirmed independent associations of AIMs across at least two race/ethnic groups for seven VRFs. Akaike information criterion (AIC) (6,294 vs. 6,286) and likelihood ratio test (p < 0.001) showed that genetic ancestry defined by AIMs achieved a better ICH risk modeling compared to SIRE alone. Conclusion: Genetically-defined ancestry provides valuable risk exposure information that is not captured by SIRE alone. Particularly among Hispanics and blacks, inclusion of AIMs adds value over self-reported ancestry in controlling for genetic and environmental exposures that influence risk of ICH. While differences are small, this modeling approach may be superior in highly heterogeneous clinical poulations. Additional studies across other ancestries and risk exposures are needed to confirm and extend these findings.

Sex differences in intracerebral hemorrhage expansion and mortality.

BACKGROUND AND OBJECTIVE: Due to conflicting results in multiple studies, uncertainty remains regarding sex differences in severity and mortality after intracerebral hemorrhage (ICH). We investigated the impact of sex on ICH severity, expansion, and mortality. METHODS: We analyzed prospectively collected ICH patients and assessed clinical variables and mortality rate. Mediation analyses were used to examine associations between sex and mortality and sex and hematoma expansion. RESULTS: 2212 patients were investigated, 53.5% male. Men with ICH were younger (72 vs. 77years), had greater smoking and alcohol use, and were more likely to have hypertension, diabetes, hypercholesterolemia and coronary artery disease (all p<0.05). Lobar hemorrhages were more frequent in women (47.6% vs 38.4%, p<0.001). Male sex was a risk factor for hematoma expansion (Odd Ratio (OR) 1.7, 95% confidence interval (CI) 1.15-2.50, p=0.007). Multivariable analysis found that male sex was independently associated with 90-day mortality (OR 2.15 (95% CI 1.46-3.19), p<0.001), and one-year mortality (Hazard Ratio 1.28 (95% CI: 1.09-1.50), p=0.003). Early hematoma expansion mediated a portion of the association between sex and mortality (mediation p=0.02). CONCLUSIONS: Men with ICH experience a higher risk of both expansion and early and late mortality, even after controlling for known risk factors. Further research is needed to explore the biological mechanisms underlying these observed differences.

Significance of admission hypoalbuminemia in acute intracerebral hemorrhage.

Low levels of serum albumin may increase the risk of infections and mortality in critically ill patients. We tested the hypothesis that admission hypoalbuminemia predicted infectious complications and poor outcome in subjects with acute intracerebral hemorrhage (ICH). We analyzed a single center cohort of ICH patients collected between 1994 and 2015. Pneumonia, urinary tract infection and sepsis were retrospectively identified, according to validated criteria. Serum albumin was measured on admission and hypoalbuminemia was defined as total albumin ≤3.5 g/dL. The association between albumin levels, infections, and mortality at 90 days was tested with multivariable logistic regression analyses. A total of 2010 patients were included (median age 74 years, 54.5% males) of whom 444 (22.1%) had hypoalbuminemia on admission and 763 (38%) died within 90 days. The frequency of pneumonia, urinary tract infection, and sepsis was 19.9, 15.1, and 2.7%, respectively. Hypoalbuminemic patients had lower admission Glasgow coma scale, higher frequency of intraventricular hemorrhage and were more likely to have a history of chronic kidney or liver disease. After adjustment for potential confounders, hypoalbuminemia was an independent predictor of pneumonia [odds ratio (OR) 1.76, 95% confidence interval (CI) 1.34-2.33, p < 0.001] and sepsis (OR 2.29, 95% CI 1.22-4.30, p = 0.010). Low levels of albumin were also independently associated with higher mortality at 90 days (OR 1.78, 95% CI 1.30-2.44, p < 0.001). In conclusion, early hypoalbuminemia is common and predicts poor outcome in ICH patients. Increased susceptibility to pneumonia and sepsis may be the pathophysiological mechanism underlying this association.