Association Between Absolute Eosinophil Count and Complex Aortic Arch Plaque in Patients With Acute Ischemic Stroke
Background and Purpose—Eosinophil counts are thought to be associated with atherosclerosis and aortic arch plaques. However, whether these associations exist among patients with acute ischemic stroke remains unclear. We aimed to evaluate the association between absolute eosinophil count (AEC) and aortic arch plaques among these patients.
Methods—Consecutive acute ischemic stroke patients undergoing transesophageal echocardiography were retrospectively analyzed. Complex aortic arch plaques (CAPs) were defined as plaques ≥4 mm in thickness, with ulcer, or with mobile component.
Results—A total of 430 patients (289 male, mean age 69.8±11.4 years) were enrolled. Patients with CAPs (n=169) showed higher mean AEC than those without (167±174/µL versus 127±127/µL; P=0.007). Multivariate analysis showed that increased AEC was independently associated with the presence of CAPs (odds ratio, 2.09; 95% confidence interval, 1.21–3.65).
Conclusions—Among patients with acute ischemic stroke, increased AEC was independently associated with the presence of CAPs. Our results suggest that AEC may be a useful predictor for the presence of CAPs in these patients.
Along with the popularization of endovascular therapy for acute ischemic stroke (AIS), examination and treatment with catheter manipulation are expected to be performed more frequently in the acute phase of ischemic stroke.
Intraprocedural cerebral or systemic embolism is a serious complication of catheter-based cerebral angiography. The positive correlation between severity of aortic plaques and risk of cholesterol crystal embolism (CCE) has been noted.1 Although transesophageal echocardiography (TEE) is useful, it cannot be performed for all patients before urgent catheterization. Therefore, other predictors related to the presence of aortic arch plaques are required in patients with AIS.
Absolute eosinophil count (AEC) is thought to be related to thick aortic arch plaque among patients with heart disease scheduled for catheterization procedures.2 This fact raised the hypothesis that AEC might be also a useful predictor for the presence of aortic arch plaque in the acute phase of ischemic stroke. The aim of this study was to examine whether AEC was related to the presence of aortic arch plaque in patients with acute stroke.
Consecutive 1251 patients with AIS, who were admitted to our hospital, were studied (Figure I in the online-only Data Supplement). Among them, 430 patients (289 male, mean age 69.8±11.4 years) with adequate TEE records were retrospectively analyzed. The decision whether to perform TEE was made by attending physicians based on the necessity of searching for the stroke embolic source, considering the complications of TEE.
We collected patients’ demographics, age, sex, stroke subtype, comorbidities, laboratory findings including AEC on admission, carotid ultrasonography findings, and TEE findings. TEE was performed as previously described.3 The maximum value of plaque thickness was evaluated. Complex aortic arch plaques (CAPs) were defined as plaques ≥4 mm in thickness, with ulcer, or with mobile components. CAPs proximal and distal to subclavian artery were defined as pre- and postcentral, respectively. Patients were divided into 2 groups: those with and those without CAPs. Multivariate logistic analyses were performed to identify the indicators for the presence of CAPs, using a backward selection procedure. The prevalence rates of aortic lesions within each AEC tertile were analyzed. Detailed methods are provided in the online-only Data Supplement.
Characteristics of Patients With and Without CAPs
Among 430 patients, 169 patients (39.3%) had CAPs. Baseline characteristics of patients with and without CAPs are compared in Table. Patients with CAPs had increased AEC compared with patients without (167±174/µL versus 127±127/µL, P=0.007). Patients with CAP were older, more males, more smokers, had higher frequency of hypertension, diabetes mellitus, and history of cerebral infarction or of ischemic heart disease. In addition, serum high-density lipoprotein cholesterol levels were lower, and CRP levels were higher in patients with CAP than in those without.
AEC and Vascular Risks
Patient characteristics stratified according to the AEC tertiles are presented in Table I in the online-only Data Supplement. Serum high-density lipoprotein cholesterol level, triglycerides level, and estimated glomerular filtration rate were associated with AEC tertiles. However, the tendency for abnormal lipid profile and renal function was not significant when patients with CAPs were excluded (Table II in the online-only Data Supplement).
CAPs and AEC
Multivariate logistic regression analysis showed that increased AEC was independently associated with the presence of CAPs after adjustment for related factors selected by stepwise regression (odds ratio, 2.09; 95% confidence interval, 1.21–3.65; P=0.008; Figure 1). The prevalence of aortic ulcer, thick aortic arch plaque (≥4 mm), and plaques with mobile components was higher in patients with higher AEC tertile (P=0.002, 0.008, 0.030, respectively; Figure 2A). Patients with higher AEC tertile also tended to have CAPs (P=0.004; Figure 2B).
In this study, increased AEC was independently associated with the thickness of aortic arch plaques among AIS patients. Elkind et al4 reported that leukocyte count was associated with aortic arch plaque thickness. Several studies raised more attention for leukocytes’ subtypes, especially eosinophils.2
The mechanism of independent association of increased AEC with aortic arch plaque remains unclear, but we assumed that spontaneous CCE may explain the association. CCE refers to the embolization of the contents of an atherosclerotic plaque from a proximal large-caliber artery (eg, CAP), and eosinophilia is commonly seen in patients with CCE.5 CCE is most often seen after invasive procedures involving manipulation of the aorta or its major branches, and mortality from CCE is still high.6 No patients were diagnosed with CCE on admission in this study. However, some reports showed that a small fraction of CCE arises spontaneously and that there are mild forms of CCE.7–9 These spontaneous cholesterol emboli were seen in 1.9% of patients in an autopsy study.10 Preston et al11 reported that 4.2% had cholesterol emboli among old patients with renal failure. These subclinical spontaneous CCE would be more frequent among patients with CAPs than among those without, which may result in the elevation of AEC in patients with CAPs.
It is reported that abnormal lipid profile (ie, higher serum triglyceride and lower serum high-density lipoprotein cholesterol levels) and chronic kidney disease were associated with AEC.12,13 These associations were also shown in this study. As for lipid profile, it might arise because patients with higher AEC tertile had higher prevalence of CAPs, which is strongly associated with abnormal lipid profile. The association between decreased renal function and elevated AEC might also be explained by the involvement of spontaneous CCE because kidney damage is a feature of CCE. These hypotheses are supported by the fact that the associations became inconsequential when patients with CAPs were excluded from the analysis.
This study has several limitations. First, some underdiagnosed specific conditions might have affected AEC, although we eliminated them whenever possible. Second, selection bias may have affected the rate of detection of CAPs in our series.
Among patients with AIS, AEC was independently correlated with CAPs, which might have been because of subclinical spontaneous CCE. Prospective studies are needed to confirm the predictive value of AEC for the existence of CAPs in the acute phase of ischemic stroke.
The online-only Data Supplement is available with this article at http://stroke.ahajournals.org/lookup/suppl/doi:10.1161/STROKEAHA.116.016436/-/DC1.
- Received October 1, 2016.
- Revision received December 20, 2016.
- Accepted January 4, 2016.
- © 2017 American Heart Association, Inc.
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