Differential distribution of plasma apoA-I and apoB levels and clinical significance of apoB/apoA-I ratio in ischemic stroke subtypes

 I can't see any explanation here that even remotely suggests this does ANYTHING AT ALL for stroke recovery. Totally useless.

Differential distribution of plasma apoA-I and apoB levels and clinical significance of apoB/apoA-I ratio in ischemic stroke subtypes

Nguyen Van Tuyen^1,2Nguyen Hoang Ngoc¹Phan Quoc Hoan³Nguyen Thi Yen⁴Nghiem Xuan Hoan^3,5*†Nguyen Cam Thach^4*†

• 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.