WSO - March 2023 - 355

Liu et al.
355
Keywords
Stroke, HHcy, mortality, glomerular filtration rate
Received: 5 March 2022; accepted: 13 May 2022
Introduction
Stroke remains one of the leading causes of adult deaths in
the world.1 Data of Get With The Guideline (GWTG)Stroke
Program 2003 to 2009 showed that the in-hospital
mortality rate was highest among patients with intracerebral
hemorrhage (ICH) (25.0%), intermediate among
patients with ischemic stroke (IS) (5.5%), and lowest
among patients with transient ischemic attack (TIA)
(0.3%).2 In addition to the current strategies recommended
by the guidelines, more studies are needed to explore new
interventions. Hyperhomocysteinemia (HHcy) is common
among patients with stroke. Observational studies have
indicated that HHcy is a modified risk factor for mortality
after ischemic or hemorrhagic stroke.3,4 Although clinical
trials of secondary prevention of stroke with vitamin B supplementation
have shown moderate to prominent reductions
in the concentrations of total homocysteine (tHcy),
lowering tHcy showed no effect on the composite of stroke,
myocardial infarction, and vascular death.5,6
As an independent risk factor for HHcy, impaired renal
function is prevalent in patients with stroke. Up to 35% of
stroke patients had coexistent chronic kidney disease
(CKD)7 which was documented as a strong independent
predictor of mortality in patients with acute stroke. The
shared pathogenic mechanisms and causal relationships
between impaired kidney function and cerebrovascular disease
phenotypes were verified by large-scale genetic data.8
Whether HHcy acts as a proxy of impaired kidney function
or an independent risk factor for mortality of IS, TIA, and
ICH remains unknown. The aim of this study was to investigate
the association between tHcy in blood and in-hospital
mortality of patients with IS/TIA or ICH and whether the
association was confounded by renal function using data
from the Chinese Stroke Center Alliance (CSCA).
Methods
Ethical approval
Hospitals enrolled in this study received either research
approval and healthcare quality assessment to collect data
in the CSCA project without requiring individual patient
informed consent under the common rule or a waiver of
authorization and exemption from subsequent review by
their institutional review board.9
Study cohort and population
The CSCA is a large hospital-based, multicenter, voluntary,
multifaceted, intervention, and continuous quality improvement
Statistical analysis
We described the characteristics of patients with IS/TIA or
ICH according to a blood tHcy level of 15 µmol/L.
Categorical variables are reported as absolute numbers with
percentages, and continuous variables are reported as the
mean along with standard deviation or median along with the
interquartile range when appropriate. Given the extensive
data set, comparison using p < 0.05 indicates statistical significance
but
may not have any clinical
significance.
Therefore, baseline characteristics were compared using
absolute standardized differences (ASDs), with ASD ⩾ 10
considered to be clinically significant.12 The baseline table
International Journal of Stroke, 18(3)
initiative that was conducted from 1 August 2015 to 31 July
2019. Details on the rationale, design, and major results of
the CSCA have been published previously.9 Among
1,006,798 patients enrolled in the study from secondary or
tertiary hospitals across 31 provinces, autonomous regions,
or municipalities in mainland China, we excluded patients
with stroke not classified (6694, 0.7%); patients with missing
information on key variables, including blood tHcy
(92,525, 9.2%), the eGFR (9913, 1.0%), in-hospital outcomes
(62,803, 6.2%), or covariates (2570, 0.3%); and
patients diagnosed with subarachnoid hemorrhage (SAH)
(8671, 0.9%). The final
analysis sample consisted of
823,622 patients, of whom 752,343 (90.4%) and 71,279
(8.6%) were diagnosed with IS/TIA and ICH, respectively
(Figure 1).
Study variables and outcomes
In this study, baseline information on demographics, risk
factors, stroke severity, medical history, complications,
treatment, and diagnosis was collected at enrollment and
discharge by trained examiners using standardized protocols
at each institute. The vascular risk factors analyzed
included a history of stroke/TIA, hypertension, diabetes,
coronary heart disease/myocardial infarction (CHD/MI),
atrial fibrillation/flutter, dyslipidemia, and current or previous
smoking and drinking.
Fasting whole blood samples were taken within 24 h of
admission. Afterward, tHcy and serum creatinine were
measured at each research center. HHcy is defined as blood
levels exceeding 15 µmol/L.10 We calculated the eGFR
using the new Chronic Kidney Disease Epidemiology
Collaboration (CKD-EPI) equation.11 All measurements
were performed by laboratory personnel blinded to the subjects'
clinical situations. The in-hospital outcome assessed
in this study was all-cause death.
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