Homocysteine and Clinical Outcomes in Intracerebral Hemorrhage Patients: Results from the China Stroke Center Alliance

Dandan Wang,1,2 Zhentang Cao,3 Zixiao Li,1,2,4 Hongqiu Gu,2 Qi Zhou,2 Xingquan Zhao,1,2,4 Yongjun Wang1,2,4 1Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2China National Clinical Research Center for Neurological Diseases, Beijing, People’s Republic of China; 3Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 4Research Unit of Artificial Intelligence in Cerebrovascular Disease, Chinese Academy of Medical Sciences, Beijing, People’s Republic of ChinaCorrespondence: Xingquan Zhao; Yongjun Wang, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, No. 119 South 4th Ring West Road, Fengtai District, Beijing, 100070, People’s Republic of China, Tel +86-010-59978891 ; +86-010-59978330, Email zxq@vip.163.com; yongjunwang@ncrcnd.org.cnObjective: Elevated homocysteine (Hcy) levels play a detrimental role in ischemic stroke. Acute spontaneous intracerebral hemorrhage (ICH) accounts for nearly 25% of all stroke cases. However, the influence of Hcy levels and ICH severity on clinical outcomes is unclear.Participants and Study Location: Data were obtained from 85,705 ICH patients enrolled in the China Stroke Center Alliance (CSCA) study, a national, hospital-based, multicenter, voluntary, quality assessment and improvement initiative performed in China. Patients were divided into high and normal Hcy groups according to their Hcy levels observed at admission.Outcome Measures: The outcome indices included severe ICH, in-hospital mortality, and a poor functional outcome at discharge. Multivariable logistic regression was used to analyze the association of different Hcy levels with outcomes.Results: The final analysis included 55,793 ICH patients. High homocysteine (HHcy) levels had higher adjusted odds ratios for severe ICH (OR 1.09, 95% CI 1.01– 1.10, P< 0.0001) and a poor functional outcome at discharge (OR 1.06, 95% CI 1.01– 1.10, P=0.0100) compared with normal Hcy levels. There was no significant difference between HHcy and in-hospital mortality. In the subgroup analysis, stratified by sex and history of hypertension, significant interactions were observed between HHcy and severe ICH (P for interactions was 0.0138 and 0.0120, respectively). HHcy levels exhibited greater associations for severe ICH in female patients (OR 1.07, 95% CI 1.02– 1.12) and patients without hypertension (OR 1.20, 95% CI 1.09– 1.33).Conclusion: An elevated Hcy level exhibited significant association with severe ICH on admission and a poor functional outcome at discharge. The relationship between HHcy and ICH severity on admission was more robust in female patients and patients without hypertension. Hcy might be a valuable biomarker for ICH patients to predict severity at onset and functional outcome at discharge.Keywords: intracerebral hemorrhage, homocysteine, stroke severity, outcom