Changing paradigms in intracerebral hemorrhage management : from acute care to prevention

Abstract

Intracerebral hemorrhage (ICH) is the second most common form of stroke and is an important disease in Asia due to its high incidence rates. ICH results in significant mortality and disability, accounting for 50% of all stroke mortality and a greater disability burden compared to ischemic stroke. Although numerous therapeutic studies aimed at improving neurological outcomes of ICH have been conducted, effective treatments remain elusive. Moreover, those who survive their ICH have a high risk of ICH recurrence, as well as ischemic cardiovascular events. Research gaps and therapeutic challenges remain for treatment strategies that could significantly improve the neurological outcome and long-term prognosis of ICH. As the therapeutic effect of acute ICH treatment is modest, the lack of treatment benefit could be due to an unaccounted factor that confounds therapeutic effect. It is increasingly recognized that the exact ICH location is crucial in determining neurological outcomes. Hence, this thesis will first explore the interaction between ICH location and volume as a determinant factor of ICH outcomes. After surviving an ICH, blood pressure (BP) control is the cornerstone for alleviating the risk of recurrent ICH, cardiovascular risk, and mortality. However, there is limited research in this area, and the current BP target of <130/80mmHg in the American Heart Association ICH Guideline is mainly driven by data from ischemic stroke trials. Apart from BP control, as ischemic cardiovascular diseases share common risk factors with ICH, addressing hyperlipidemia is pivotal in minimizing the cardiovascular risk of ICH survivors. Yet, the optimal low-density lipoprotein cholesterol (LDL-C) target after ICH remains uninvestigated. Therefore, the remainder of my thesis will address the optimal hypertension and hyperlipidemia management after ICH. For this thesis, I established the University of Hong Kong (HKU) ICH cohort with the HKU Stroke Research Group. I was responsible for patient recruitment, data collection and analysis. For the topic of BP control after ICH, I analyzed data from HKU in combination with the ICH cohort of Massachusetts General Hospital (MGH) during my time as a visiting research fellow there. Patients in the HKU cohort were recruited from 2011-2019, while those from MGH were from 2006-2017. This thesis produced several novel and clinically relevant findings. First, I highlighted the crucial interaction between ICH location and volume with neurological outcomes. A small strategic bleed at the thalamus would have devastating neurological deficits, while a similar-sized ICH at the frontal lobe could have a more favorable outcome. Applying this concept by accounting for location-specific outcome heterogeneity in treatment decisions could optimize therapeutic outcomes in ICH. Second, I have shown the importance of early BP control after ICH as it can predict long-term vascular outcomes. I also established long-term BP variability as a potent risk factor for recurrent ICH, and targeting systolic BP <120mmHg could result in decreased recurrent ICH and cardiovascular events. Finally, I found that LDL-C <1.8mmol/L was associated with recurrent ICH, but this association was mainly attributed to cerebral amyloid angiopathy patients and non-statin users, demonstrating the importance of individualized treatment of hypercholesterolemia following ICH.