- 1Department of Stroke, Institute of Neurology, 108 Institute of Clinical Medical and Pharmaceutical Sciences, Hanoi, Vietnam
- 2VNU University of Medicine and Pharmacy, Hanoi, Vietnam
- 3Department of Molecular Biology, 108 Institute of Clinical Medical and Pharmaceutical Sciences, Hanoi, Vietnam
- 4Department of Biochemistry, 108 Institute of Clinical Medical and Pharmaceutical Sciences, Hanoi, Vietnam
- 5Vietnamese-German Center for Medical Research (VG-CARE), Hanoi, Vietnam
Background and purpose: Ischemic stroke (IS) is
classified into clinical subtypes and likely influenced by various lipid
components. Nevertheless, the roles of apolipoprotein A-I (apoA-I),
apolipoprotein B (apoB), and apoB/apoA-I ratio in different IS subtypes
remain underexplored. This study aimed to investigate the differential
distribution of plasma apoA-I and apoB levels among IS subtypes and to
evaluate the predictive value(Does nothing for recovery!) of the apoB/apoA-I ratio in assessing IS
subtypes and disease severity.
Methods: In this study, 406 IS patients were
categorized into three IS-subtypes based on clinical manifestations and
imaging assessment, including intracranial atherosclerosis-related IS
patients (ICAS, n = 193), extracranial atherosclerosis-related IS patients (ECAS, n = 111), and small artery occlusion-related IS patients (SAO, n = 102).
Plasma apoA-I and apoB levels were measured upon hospital admission.
Random forest (RF) models were performed to assess predictive values of
these apolipoproteins apoB, apoA-I and their ratio in assessing IS
subtype stratification and disease severity.
Results: Serum apoA-I levels were significantly lower in ICAS compared to ECAS and SAO patients (p < 0.0001), while apoB levels were higher in ICAS patients (p < 0.0001). The apoB/apoA-I ratio was significantly higher in ICAS compared to ECAS and SAO patients (p < 0.0001).
Correlation analyses found a significant correlation between the
apoB/apoA-I ratio and conventional lipid components. Additionally, RF
models and plots of variable importance and distribution of minimal
depth revealed that the apoB/apoA-I ratio played the most influential
predictor in predicting IS subtypes and stenosis severity.
Conclusion: Our study shows the differential
distribution of apoA-I and apoB IS subtypes and reveals the significance
of the apoB/apoA-I ratio in assessing IS subtypes and arterial stenosis
severity. Further studies are warranted to validate these findings and
enhance their clinical applicability.
Introduction
Globally, stroke stands as the second leading cause of mortality globally, contributing to 11.6% of all deaths (1). In which, ischemic stroke (IS) prevails as the most prevalent, constituting 62.4% of all stroke incidents worldwide in 2019 (1, 2).
Despite significant advances in treatment and therapy for IS, mortality
rates remain high. The critical factor is the time elapsed between
symptom onset and seeking medical attention. This underscores the
importance of swift action in stroke management. Among survivors, the
recurrence rate of stroke patients after the acute event is very high,
with approximately 15–30% at risk within the first 2 years, 25% within
5 years, and doubling after 10 years (3).
Importantly, IS can inflict profound neurological impairment and
persistent disability in these survival individuals, thereby imposing
significant health and economic burdens on societies.
Ischemic stroke is a vascular disorder of the brain’s
circulatory system, with multiple causes leading to this condition, such
as arterial atherosclerosis, cardiac emboli or blood clots originating
from the heart, and coagulation disorders. Among which arterial
atherosclerosis is a known strong risk factor for IS (4).
Arterial atherosclerosis can occur both intracranially and
extracranially, with intracranial atherosclerosis (ICAS) is more
prevalent in Asian patients and is associated with a high risk of
recurrence, whereas extracranial atherosclerosis (ECAS) is more common
in individuals from western countries (4, 5).
Meanwhile, a distinct IS subtype, known as small-artery occlusion
(SAO), resulting in small (<15 mm in axial diameter) subcortical
infarcts, is well categorized by the Trial of ORG10172 in Acute Stroke
Treatment (TOAST classification) (6). This subtype is prevalent in developing nations, particularly accounting for 27.3% of IS cases in China (7, 8).
Atherosclerosis is a chronic lipid-driven and
maladaptive inflammatory disease of arterial intima. Several factors
were considered to contribute to pathogenesis of artery atherosclerosis
formation. It is characterized by the dysfunction of lipid homeostasis
and signaling pathways that control the inflammation. High-risk factors,
such as hypertension, diabetes, and smoking, cause vascular endothelial
dysfunction and increased permeability. This leads to accumulation of
cholesterol-containing low-density lipoproteins (LDL) in the intima,
which initiates a complex series of inflammatory and biochemical
reactions involving accumulation of extracellular matrix, activation of
the endothelium, infiltration of monocytes and T cells, intimal
thickening, fibrous cap formation, and angiogenesis (9–11).
In clinical practice, one of the important measures in
the prevention and treatment of arterial atherosclerotic disease is the
control of lipoproteins (cholesterol, HDL, LDL). These are commonly
measured parameters that help clinicians assess metabolic disorders and
identify risk factors for arterial atherosclerosis (12–14).
Nonetheless, apolipoproteins, in particular, apolipoprotein B (apoB)
may be more useful clinically than LDL cholesterol because it captures
greater information about atherogenic particles and is not influenced by
heterogeneity of particle cholesterol content (15).
Apolipoproteins are integral components of lipoproteins and play
essential roles in lipid metabolism and transport. Unlike lipoproteins,
apolipoproteins are directly involved in the pathophysiology of
atherosclerosis. ApoB is present on atherogenic lipoproteins (such as
LDL and VLDL) and is directly involved in their interaction with
arterial endothelial cells, promoting the formation of atherosclerotic
plaques. Additionally, apolipoprotein A-I (apoA-I), the major protein
component of HDL particles, is associated with reverse cholesterol
transport and has protective effects against atherosclerosis. In recent
years, several investigations have shed light on the significance of
apoA-I, apoB, and the apoB/apoA-I ratio in predicting and assessing
susceptibility to cardiovascular diseases (16–20).
These metrics serve as indicators of the balance between atherogenic
and anti-atherogenic lipoproteins, offering insights into the status of
arterial atherosclerotic disease.
While apoA-I and apoB hold promise as biomarkers,
potentially traditional lipoproteins in terms of enhanced accuracy and
practicality in predicting arterial atherosclerosis in cardiovascular
diseases. However, to date, research on apolipoproteins and their
application in monitoring, prognostication, and preventive treatment of
IS has garnered scant attention. To the best of our knowledge, only a
few studies have investigated apolipoproteins in IS patients (21–23).
Therefore, exploring the potential roles of apoA-I and apoB in IS
patients holds significant value, particularly in the Vietnamese
population where IS represents a substantial medical concern. In
addition to these reasons, we conducted this study aimed to investigate
the differential distribution of plasma apoA-I and apoB levels among IS
subtypes and to evaluate the predictive value of the apoB/apoA-I ratio
in assessing IS subtypes and disease severity.
