Analysis and application of brain imaging data from a large clinical trial of blood pressure lowering in acute intracerebral haemorrhage

Abstract

Background and rationale«br /» Factors already known to be associated with outcome after intracerebral haemorrhage (ICH) are age, clinical severity, and brain imaging features that include the initial size, growth over 24 hours, infratentorial location, and intraventricular extension of the haematoma. «br /» Despite this knowledge, trials of various therapies that have attempted to limit ICH growth have not produced clear improvements in outcome and in particular, one of the most promising treatments, that of early intensive blood pressure (BP) lowering, suggested an improvement in physical function but without any reduction in ICH growth, the most plausible mechanism of action.«br /» There is a need, therefore, to undertake more detailed analysis of the brain imaging parameters of ICH in the hope of identifying new predictive markers of outcome.«br /» «strong»Research question«/strong»«br /» Characterisation of ICH morphology and location, and of other brain abnormalities, will allow the assessment of associations of these parameters with adverse clinical outcomes, including health-related quality of life (HRQoL). Identification of these prognostic variables might improve patient care and aid clinical research.«br /» «strong»Methods«/strong»«br /» This thesis uses data from the Intensive Blood Pressure Reduction in Acute Intracerebral Haemorrhage Trial (INTERACT) studies which assessed the effectiveness of early intensive BP lowering (target systolic BP <140 mmHg within 1 hour) against the contemporaneous guideline-recommended management of hypertension (target systolic BP <180 mmHg) within 6 hours of onset of an ICH. I re-analyzed baseline digital brain imaging from over 2000 participants in these studies to determine location, shape, density, presence of haematoma sedimentation in the ICH, and of the association of small vessel disease markers that included brain atrophy, white matter disease, and lacunar infarction, with adverse outcomes. The aim was to determine the independent associations of these parameters with various measures of clinical outcome.«br /» «strong»Outcomes and statistical analysis«/strong»«br /» Outcomes were assessed at 90 days from onset of symptoms of ICH, and included measures of death or major disability using the modified Rankin Scale (mRS) scores and the HRQoL using the 5-dimension European Quality of Life scale (EQ5D). Associations with poor outcomes, EQ5D global or utility score (≤ median), and death (mRS 6) and/or major disability (mRS 3-5), were assessed in logistic and linear regression models.«br /» «strong»Results «/strong»«br /» Neurological severity (National Institutes of Health Stroke Scale (NIHSS) score ≥14) was associated with poor HRQoL (Odds Ratio (OR) 3.14 [95% Confidence Interval {CI}] 2.53-3.88) as was the location of the ICH in the posterior limb of the internal capsule (PLIC) (OR 1.87 [1.45-2.40]) or thalamus (OR 2.14 [1.32-3.48]). Death or major disability (mRS 3-6) was associated was PLIC (OR 2.1 [1.65-2.68] ), location in the thalamus (OR 2.24 [1.4-3.57]) and infratentorial areas (OR 3.04 [1.68-5.50]), irregularity of the shape of ICH [OR 1.6 (1.29-1.98)], presence of a sedimentation level [OR 3.94 (1.01-15.37)], extensive white matter disease changes [OR 1.42 (1.02-1.98)], and brain atrophy as measured by both the frontal ratio (frontal horn to midline distance divided by the inner table to midline distance [OR 1.47 (1.08-1.99)] and the third ventricle to Sylvian fissure distance [OR 1.64 (1.21-1.22)].«br /» «strong»Conclusion«/strong»«br /» I have confirmed that clinical severity is the dominant factor associated with poor HRQoL and also identified several radiological markers that are also associated with this outcome and with death or major disability after ICH.«br /» These findings may help to stratify risk, aid clinical prognostication, and improve the selection of patients in clinical practice and research studies.«br /»