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

Abstract

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 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.

Keywords: apoA-I; apoB; apoB/apoA-I ratio; extracranial atherosclerosis; intracranial atherosclerosis; ischemic stroke; small artery occlusion.

Figure 1

Distribution of routine lipid profile in IS patients: (A) Triglyceride; (B) Cholesterol; (C) LDL; (D) HDL. Box-plots illustrate median values with range (min-max) and outliers; NS, not significant; ICAS, intracranial atherosclerosis; ECAS, extracranial atherosclerosis; SAO, small artery occlusion; NICAS, Non-ICAS (ECAS+SAO). p-values were calculated by Kruskal – Wallis tests.

Figure 2

Distribution of apoA-I and apoB levels in IS patients: (A) Distribution of apoA-I in ICAS and NICAS; (B) Distribution of apoA-I in ICAS, ECAS and SAO; (C) Distribution of apoB in ICAS and NICAS; (D) Distribution of apoB in ICAS, ECAS and SAO. Box-plots illustrate median values with range (min-max) and outliers; NS, not significant; ICAS, intracranial atherosclerosis; ECAS, extracranial atherosclerosis; SAO, small artery occlusion; NICAS, Non-ICAS (ECAS+SAO). p-values were calculated by Wilcoxon tests.

Figure 3

Association of apoB/apoA-I ratio with IS patients according to the TOAST classification system: Box-plots illustrate median values with range (min-max) and outliers; NS, not significant; ICAS, intracranial atherosclerosis; ECAS, extracranial atherosclerosis; SAO, small artery occlusion; NICAS, Non-ICAS (ECAS+SAO). p-values were calculated by Wilcoxon tests.

Figure 4

Correlation between apoA-I, apoB, apoB/apoA-I ratio with conventional lipid components in IS patients: (A) correlation between ApoA-I and HDL; (B) correlation between ApoB and Triglyceride; (C) correlation between ApoB and LDL; (D) Correlation between ApoB and Cholesterol; (E) Correlation between apoB/apoA-I ratio and LDL; (F) Correlation between apoB/apoA-I ratio and Cholesterol; (G) correlation between apoB/apoA-I ratio and Triglyceride; (H) correlation between apoB/apoA-I ratio and HDL. The correlation coefficient between two variables was calculated by using spearman’s rank correlation coefficient. Spearman’s rho (rho) and p-value are given.

Figure 5

Correlation between apoA-I, apoB, apoB/apoA-I ratio and conventional lipid in IS patients with triglyceride >6 mmol/L: The correlation coefficients between two variables (correlations between apoB, apoA-I, apoB/apoA-I with triglyceride, LDL, Cholesterol) were calculated by using spearman’s rank correlation coefficient. Spearman’s rho (rho) values are given.

Figure 6

Association of apoA-I, apoB, apoB/apoA-I ratio with the arterial stenosis levels: (A) apoA-I; (B) apoB; (C) apoB/apoA-I ratio. Box-plots illustrate median values with range (min-max) and outliers; NS, not significant; p-values were calculated by Wilcoxon or Kruskal Wallis tests where appropriate.

Figure 7

Association of apoA-I, apoB, apoB/apoA-I ratio with number of stenosis or occlusion sites: Box-plots illustrate median values with range (min-max) and outliers; NS, not significant; p-values were calculated by Wilcoxon tests.

Figure 8

Association apoB/apoA-I ratio with arterial stenosis severity: Performance of different RF models in differentiating extreme stenosis from mild–severe stenosis group (A–C). RF model-1 included variables: apoB/apoA-I ratio, apoA-I, apoB, LDL, cholesterol, triglyceride, age, and gender; RF model-2 included variables: apoB/apoA-I ratio, age, and gender; RF model-3 included only apoB/apoA-I ratio. The AUC values were accordingly presented under the FR model-1 (A), the RF model-2 (B), and the model-3 (C). Variable importance plot (D) and plot of distribution of minimal depth (E). The similar RF models were constructed to differentiate extreme from severe stenosis (F); extreme from mild stenosis (G); severe from mild stenosis (H).

Figure 9

Performance of the RF models in differentiating ICAS from non-ICAS patients: RF model-1 included variables: apoB/apoA-I ratio, apoA-I, apoB, LDL, cholesterol, triglyceride, age, and gender; RF model-2 included variables: apoB/apoA-I ratio, age, and gender; RF model-3 included only apoB/apoA-I ratio. The AUC values were presented under the FR model-1/-2/-3 (A); Variable importance plot (B) and plot of distribution of minimal depth (C).