Exposures, Outcomes, and Covariates
Neal S. Parikh, MD
Sato S, Delcourt C, Heeley E, Arima H, Zhang S, Al-Shahi Salman R, et al. Significance of Cerebral Small-Vessel Disease in Acute Intracerebral Hemorrhage. Stroke. 2016
Question & Rationale
Small vessel disease (SVD), as reflected by white matter lesions (WML), brain atrophy and lacunar strokes, is associated with hypertension and possibly abnormal autoregulation. The INTERACT 2 investigators therefore hypothesized that SVD is associated with a poor outcome after intracranial hemorrhage (ICH) and investigated whether this association is mediated by intensive blood pressure lowering in ICH treatment.
The INTERACT2 cohort was used for this study. In this international, multicenter, open, blinded endpoint, randomized trial, patients with spontaneous ICH were randomized within 6 hours to SBP<140 versus SBP<180. The cohort did not include patients with pre-existing advanced dementia or disability.
There were three measures of SVD on baseline CT: WML, atrophy, and lacunar strokes. On baseline CT, WML were graded by the van Swieten scale. Atrophy was measured by linear measurements (frontal ratio, third ventricle Sylvian fissure distance) and visual inspection. Lacunar stroke was defined as a round/ovoid cavity of 3-15 millimeters in diameter. The outcome was defined as 90 days death or major disability. Interaction term analysis was used to determine effect of intensive BP lowering on outcome.
Covariates were age, gender, location, history of ischemic stroke, hypertension, diabetes, use of anti-thrombotic and lipid lowering agents, onset to randomization time, systolic BP, NIHSS, volume/location of hematoma, and intraventricular extension.
In crude and adjusted regression analyses, measures of WML and atrophy were associated with death or major disability. Lacunar stroke was not associated with the outcome in crude or multivariate models. High intensity BP lowering did not result in excess poor outcomes in patients with evidence of SVD.
There was only fair-moderate intra-class correlation for WML, brain atrophy, and especially lacunes. Additionally, the study was not pre-specified and therefore subject to type I error. Last, pre-ICH cognitive and physical disability were not rigorously assessed; however, this is compatible with clinical practice – it is often not possible to thoroughly assess a patient’s pre-ICH function at the time of ICH.
Pre-existing SVD burden may be associated with poor outcome after ICH, and this relationship is not mediated by intensity of blood pressure control. Therefore, these data allay fears regarding intensive BP management after ICH in patients with sequela of chronic hypertension such as SVD.