Association Between Plasma Lipoprotein-Associated Phospholipase A2 and Plaque Vulnerability in TIA Patients With Unilateral Middle Cerebral Artery Stenosis

Abstract

Background: Plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) has emerged as a novel biomarker for coronary atherosclerosis. However, the association between Lp-PLA2 and plaque vulnerability in atherosclerosis of cervicocerebral arteries remains poorly defined, especially for intracranial atherosclerotic stenosis (ICAS). We aimed to investigate the association between Lp-PLA2 and plaque vulnerability in transient ischemic attack (TIA) patients with unilateral middle cerebral artery stenoses (MCAs). Methods: In this study, a total of 207 patients were enrolled from April 2017 to April 2020. Clinical data were collected, and MCA plaques were examined with high-resolution magnetic resonance imaging (HRMRI). Baseline characteristics of patients were collected during hospitalization. Statistical comparisons were performed using Pearson's chi-squared test, Mann-Whitney U test, and the Breslow-Day/Tarone's test for the determination of heterogeneity in different age strata. Multivariate binary logistic analysis was used to investigate the potential independent predictors that were highly correlated to plaque vulnerability. Results: The results showed that a high Lp-PLA2 level (>221 ng/ml) was associated with plaque vulnerability in TIA patients with unilateral MCAs. High Lp-PLA2 was independently associated with plaque vulnerability in patients ≤ 60 years old [multivariate adjusted odds ratio (OR) = 9.854; 95% CI, 2.458-39.501] but not in patients >60 years old (multivariate adjusted OR = 1.901; 95% CI, 0.640-5.650). Predictors of plaque vulnerability in different age strata were also different. Conclusion: Lp-PLA2 levels may be correlated to plaque vulnerability in TIA patients with unilateral MCAs and might be a diagnostic biomarker for plaque vulnerability in this kind of patients, especially for ones aged ≤ 60 years old.

Keywords: HRMRI; ICAs; Lp-PLA2; middle cerebral artery; transient ischemic attack.

Figure 1

Illustration of HRMRI images showing atherosclerotic plaques in patients with unilateral MCAs. (A) A 30 year-old man with non-vulnerable plaque: no high signal intensity on PDWI, T1WI, and T2WI. (B) A 70 year-old man with intraplaque hemorrhage: isointensity on PDWI, eccentric high signal intensity on T1WI, and hypointensity on T2WI. (C) A 42 year-old man with plaque enhancement: isointensity on PDWI, eccentric slight hyperintensity on T1WI, and slight hyperintensity on T2WI. (D) A 47 year-old man with heterogeneous signal intensity: mixed signal intensity on PDWI, T1WI, and T2WI. Arrowhead: non-vulnerable plaque; arrow: vulnerable plaque. HRMRI, high-resolution MRI; PDWI, proton density weighted imaging; TOF, time-of-flight; T2WI, T2-weighted imaging; T1WI, T1-weighted imaging; MCAs, middle cerebral artery stenosis.

Figure 2

Receiver operating characteristic (ROC) analysis of Lp-PLA2 in TIA patients with unilateral MCAs. Area under the ROC curve for Lp-PLA2 was 0.746 (95% CI, 0.669–0.822, p < 0.001). Lp-PLA2, lipoprotein-associated phospholipase A2; TIA, transient ischemic attack; MCAs, middle cerebral artery stenoses.

Figure 3

Receiver operating characteristic (ROC) analyses of Lp-PLA2 in studied patients aged ≤ 60 and >60 years old. AUC for Lp-PLA2 was 0.878 (≤ 60, 95% CI, 0.802–0.954, p < 0.001) and 0.5899 (>60, 95% CI 0.4645–0.7153, p = 0.1457). AUC, area under the ROC curve; Lp-PLA2, lipoprotein-associated phospholipase A2.