Assessment of lipoprotein-associated phospholipase A2 level and its changes in the early stages as predictors of delayed cerebral ischemia in patients with aneurysmal subarachnoid hemorrhage

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OBJECTIVE

The relationship between lipoprotein-associated phospholipase A2 (Lp-PLA2) and various cardiovascular and cerebrovascular diseases is inconsistent. However, the connection between Lp-PLA2 level and delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH) remains unclear. The objective of this study was to investigate the relationships between the Lp-PLA2 levels in the early stages of aSAH and the occurrence of DCI.

METHODS

The authors evaluated 114 patients with aSAH who were enrolled into a prospective observational cohort study. Serum Lp-PLA2 level at admission (D0), on the first morning (D1), and on the second morning of hospitalization (D2) were determined using commercial enzyme-linked immunosorbent assay kits. The relationship between Lp-PLA2 levels and DCI was analyzed.

RESULTS

Forty-three patients with aSAH (37.72%) experienced DCI. Mean serum Lp-PLA2 level decreased from 183.06 ± 61.36 μg/L at D0 (D0 vs D1, p = 0.303), to 175.32 ± 51.49 μg/L at D1 and 167.24 ± 54.10 μg/L at D2 (D0 vs D2, p = 0.040). The Lp-PLA2 level changes (D0-D1 and D0-D2) were comparable between patients with and without DCI. Multivariate model analysis revealed Lp-PLA2 level (D0) > 200 μg/L was a more significant factor of DCI compared with Lp-PLA2 (D1) and Lp-PLA2 (D2), and was a strong predictor of DCI (odds ratio [OR] 6.24, 95% confidence interval [CI] 2.05–18.94, p = 0.001) after controlling for World Federation of Neurosurgical Societies (WFNS) grade (OR 3.35, 95% CI 1.18–9.51, p = 0.023) and modified Fisher grade (OR 6.07, 95% CI 2.03–18.14, p = 0.001). WFNS grade (area under the curve [AUC] = 0.792), modified Fisher grade (AUC = 0.731), and Lp-PLA2 level (D0; AUC = 0.710) were all strong predictors of DCI. The predictive powers of WFNS grade, modified Fisher grade, and Lp-PLA2 (D0) were comparable (WFNS grade vs Lp-PLA2: p = 0.233; modified Fisher grade vs Lp-PLA2: p = 0.771). The poor-grade patients with Lp-PLA2 (D0) > 200 μg/L had significantly worse DCI survival rate than poor-grade patients with Lp-PLA2 (D0) ≤ 200 μg/L (p < 0.001).

CONCLUSIONS

The serum level of Lp-PLA2 was significantly elevated in patients with DCI, and decreased within the first 2 days after admission. Lp-PLA2 in the early stages of aSAH might be a novel predictive biomarker for the occurrence of DCI.

ABBREVIATIONS aSAH = aneurysmal subarachnoid hemorrhage; AUC = area under the curve; CI = confidence interval; COV = coefficient of variation; CTA = CT angiography; D0 = at admission; D1 = on the first morning of hospitalization; D2 = on the second morning of hospitalization; DCI = delayed cerebral ischemia; DSA = digital subtraction angiography; ELISA = enzyme-linked immunosorbent assay; Lp-PLA2 = lipoprotein-associated phospholipase A2; OR = odds ratio; ROC = receiver operating characteristic; WFNS = World Federation of Neurosurgical Societies.

Article Information

Correspondence De-Zhi Kang: The First Affiliated Hospital of Fujian Medical University, Fuzhou, China. kdz99988@vip.sina.com.

INCLUDE WHEN CITING Published online January 18, 2019; DOI: 10.3171/2018.8.JNS181839.

C.Y.D. and H.P.C. contributed equally to this work and share first authorship.

Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

© AANS, except where prohibited by US copyright law.

Headings

Figures

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    ROC curve analysis comparing WFNS grade and Lp-PLA2 at admission (D0) for identifying DCI following SAH. The AUCs of WFNS grade, modified Fisher grade, and Lp-PLA2 (D0) were 0.792 (95% CI 0.702–0.882), 0.731 (95% CI 0.632–0.830), and 0.710 (95% CI 0.610–0.810), respectively. The AUCs of WFNS grade, modified Fisher grade and Lp-PLA2 (D0) were not significantly different (Z tests: Lp-PLA2 [D0] vs WFNS grade, Z = 1.194, p = 0.233; Lp-PLA2 [D0] vs modified Fisher grade, Z = 0.291, p = 0.771; WFNS grade vs modified Fisher grade, Z = 0.888, p = 0.374). The greater distance between the ROC curve and the gray diagonal line indicates better diagnosis accuracy.

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    Kaplan-Meier curves of the 30-day DCI survival rates of patients with and without Lp-PLA2 levels at admission (D0) > 200 μg/L. The Kaplan-Meier curve shows a 30-day DCI survival rate of 16.0% (4/25) for poor-grade patients having Lp-PLA2 (D0) levels > 200 μg/L, 58.8% (20/34) for poor-grade patients having Lp-PLA2 (D0) levels ≤ 200 μg/L, 88.9% (8/9) for good-grade patients having Lp-PLA2 (D0) levels > 200 μg/L, and 84.8% (39/46) for good-grade patients having Lp-PLA2 (D0) levels ≤ 200 μg/L. The log-rank test showed a p value < 0.001. Post hoc log-rank testing revealed that the good-grade patients with Lp-PLA2 (D0) levels > 200 μg/L had a similar DCI survival rate compared to that of good-grade patients with Lp-PLA2 (D0) levels ≤ 200 μg/L (p = 0.712), but the poor-grade patients with Lp-PLA2 (D0) levels > 200 μg/L had significantly worse DCI survival rates than poor-grade patients having Lp-PLA2 (D0) levels ≤ 200 μg/L (p = 0.001).

References

1

Boluijt JMeijers JCRinkel GJVergouwen MD: Hemostasis and fibrinolysis in delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage: a systematic review. J Cereb Blood Flow Metab 35:7247332015

2

Budohoski KPCzosnyka MSmielewski PKasprowicz MHelmy ABulters D: Impairment of cerebral autoregulation predicts delayed cerebral ischemia after subarachnoid hemorrhage: a prospective observational study. Stroke 43:323032372012

3

Budohoski KPGuilfoyle MHelmy AHuuskonen TCzosnyka MKirollos R: The pathophysiology and treatment of delayed cerebral ischaemia following subarachnoid haemorrhage. J Neurol Neurosurg Psychiatry 85:134313532014

4

Cai HZheng SCai BYao PDing CChen F: Neuroglobin as a novel biomarker for predicting poor outcomes in aneurysmal subarachnoid hemorrhage. World Neurosurg 116:e258e2652018

5

Carpenter KLCzosnyka MJalloh INewcombe VFHelmy AShannon RJ: Systemic, local, and imaging biomarkers of brain injury: more needed, and better use of those already established? Front Neurol 6:262015

6

Chamling BGross SStoffel-Wagner BSchubert GAClusmann HCoburn M: Early diagnosis of delayed cerebral ischemia: possible relevance for inflammatory biomarkers in routine clinical practice? World Neurosurg 104:1521572017

7

Chen KWu YWang QWang JLi XZhao Z: The methodology and pharmacokinetics study of intraventricular administration of vancomycin in patients with intracranial infections after craniotomy. J Crit Care 30:218.e1218.e52015

8

Claassen JBernardini GLKreiter KBates JDu YECopeland D: Effect of cisternal and ventricular blood on risk of delayed cerebral ischemia after subarachnoid hemorrhage: the Fisher scale revisited. Stroke 32:201220202001

9

Connolly ES JrRabinstein AACarhuapoma JRDerdeyn CPDion JHigashida RT: Guidelines for the management of aneurysmal subarachnoid hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 43:171117372012

10

Dallmeier DKoenig W: Strategies for vascular disease prevention: the role of lipids and related markers including apolipoproteins, low-density lipoproteins (LDL)-particle size, high sensitivity C-reactive protein (hs-CRP), lipoprotein-associated phospholipase A2 (Lp-PLA2) and lipoprotein(a) (Lp(a)). Best Pract Res Clin Endocrinol Metab 28:2812942014

11

Diringer MNBleck TPClaude Hemphill J IIIMenon DShutter LVespa P: Critical care management of patients following aneurysmal subarachnoid hemorrhage: recommendations from the Neurocritical Care Society’s Multidisciplinary Consensus Conference. Neurocrit Care 15:2112402011

12

Dorhout Mees SMMolyneux AJKerr RSAlgra ARinkel GJ: Timing of aneurysm treatment after subarachnoid hemorrhage: relationship with delayed cerebral ischemia and poor outcome. Stroke 43:212621292012

13

Drenckhahn CBrabetz CMajor SWiesenthal DWoitzik JDreier JP: Criteria for the diagnosis of noninfectious and infectious complications after aneurysmal subarachnoid hemorrhage in DISCHARGE-1. Acta Neurochir Suppl 115:1531592013

14

Duan WPan YWang CWang YZhao XWang Y: Risk factors and clinical impact of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage: analysis from the China National Stroke Registry. Neuroepidemiology 50:1281362018

15

Francoeur CLMayer SA: Management of delayed cerebral ischemia after subarachnoid hemorrhage. Crit Care 20:2772016

16

Frontera JAFernandez ASchmidt JMClaassen JWartenberg KEBadjatia N: Defining vasospasm after subarachnoid hemorrhage: what is the most clinically relevant definition? Stroke 40:196319682009

17

Geraghty JRTestai FD: Delayed cerebral ischemia after subarachnoid hemorrhage: beyond vasospasm and towards a multifactorial pathophysiology. Curr Atheroscler Rep 19:502017

18

Jung CSLange BZimmermann MSeifert V: CSF and serum biomarkers focusing on cerebral vasospasm and ischemia after subarachnoid hemorrhage. Stroke Res Treat 2013:5603052013

19

Komotar RJSchmidt JMStarke RMClaassen JWartenberg KELee K: Resuscitation and critical care of poor-grade subarachnoid hemorrhage. Neurosurgery 64:3974112009

20

Li DWei WRan XYu JLi HZhao L: Lipoprotein-associated phospholipase A2 and risks of coronary heart disease and ischemic stroke in the general population: a systematic review and meta-analysis. Clin Chim Acta 471:38452017

21

Roh DJMorris NAClaassen J: Intracranial multimodality monitoring for delayed cerebral ischemia. J Clin Neurophysiol 33:2412492016

22

Ross Eckard ALongenecker CTJiang YDebanne SMLabbato DStorer N: Lipoprotein-associated phospholipase A2 and cardiovascular disease risk in HIV infection. HIV Med 15:5375462014

23

Rosso CRosenbaum DPires CCherfils CKoujah NMestari F: Lipoprotein-associated phospholipase A2 during the hyperacute stage of ischemic and hemorrhagic strokes. J Stroke Cerebrovasc Dis 23:e277e2822014

24

Rostami EEngquist HHowells TJohnson URonne-Engström ENilsson P: Early low cerebral blood flow and high cerebral lactate: prediction of delayed cerebral ischemia in subarachnoid hemorrhage. J Neurosurg 128:176217702018

25

Sabri MAi JLakovic KD’abbondanza JIlodigwe DMacdonald RL: Mechanisms of microthrombi formation after experimental subarachnoid hemorrhage. Neuroscience 224:26372012

26

Srinivasan AAggarwal AGaudihalli SMohanty MDhandapani MSingh H: Impact of early leukocytosis and elevated high-sensitivity C-reactive protein on delayed cerebral ischemia and neurologic outcome after subarachnoid hemorrhage. World Neurosurg 90:91952016

27

Stienen MNSmoll NRWeisshaupt RFandino JHildebrandt GStuderus-Germann A: Delayed cerebral ischemia predicts neurocognitive impairment following aneurysmal subarachnoid hemorrhage. World Neurosurg 82:e599e6052014

28

Tian YJia HLi SWu YGuo LTan G: The associations of stroke, transient ischemic attack, and/or stroke-related recurrent vascular events with Lipoprotein-associated phospholipase A2. A systematic review and meta-analysis. Medicine (Baltimore) 96:e94132017

29

Topbas CSwick ARazavi MAnderson NLPearson TWBystrom C: Measurement of lipoprotein-associated phospholipase A2 by use of 3 different methods: exploration of discordance between ELISA and activity assays. Clin Chem 64:6977042018

30

Tsai AKSteffen BTOrdovas JMStraka RZhou XHanson NQ: Short-term fenofibrate treatment reduces elevated plasma Lp-PLA2 mass and sVCAM-1 levels in a subcohort of hypertriglyceridemic GOLDN participants. Transl Res 158:991052011

31

Wang YZhang JQian YTang XLing HChen K: Association of Lp-PLA2 mass and aysmptomatic intracranial and extracranial arterial stenosis in hypertension patients. PLoS One 10:e01304732015

32

Wang YZhou BZhou PYao YCui QLiu Y: Association of lipoprotein-associated phospholipase A2 mass with asymptomatic cerebral artery stenosis. J Cell Mol Med 22:232923362018

33

Zijlmans JLCoert BAvan den Berg RSprengers MESMajoie CBLMVandertop WP: Unfavorable outcome in patients with aneurysmal subarachnoid hemorrhage WFNS grade I. World Neurosurg 118:e217e2222018

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