Predictive Value of the Systemic Immune-Inflammation Index for Periprocedural Complications in Flow Diverter Treatment for Patients with Intracranial Aneurysms

doi:10.21203/rs.3.rs-4833682/v1

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Predictive Value of the Systemic Immune-Inflammation Index for Periprocedural Complications in Flow Diverter Treatment for Patients with Intracranial Aneurysms

https://doi.org/10.21203/rs.3.rs-4833682/v1

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Flow-diverter devices (FDs) are effective in treating intracranial aneurysms (IAs) but carry substantial periprocedural risks, particularly ischemic complications. This study aimed to determine if elevated Systemic Immune-Inflammation Index (SII) can independently predict these risks and assess the impact of age and dual antiplatelet therapy on this association. We conducted a retrospective analysis of patients treated with FDs between February 2016 and August 2023, using blood samples taken within six days before surgery to calculate SII. Logistic regression and decision tree analyses assessed the link between SII and periprocedural complications, with subgroups exploring influencing factors. Multivariable analysis identified high SII as an independent predictor of periprocedural complications (OR=5.306, 95% CI: 1.367-18.455; P=0.009). The decision tree model confirmed SII > 0.437 as a critical threshold. Subgroup analysis showed a pronounced association of SII with periprocedural complications in patients ≥65 years (OR=36.979, 95% CI: 2.103-650.134; P=0.014) and in those on clopidogrel therapy (OR=16.921, 95% CI: 2.733-104.746; P=0.002). An elevated Systemic Immune-Inflammation Index (SII) >0.437 significantly correlates with increased periprocedural complications (6.5% vs. 1.8%, P=0.017). Although not statistically significant, higher SII is associated with a greater rate of ischemic events (3.9% vs. 0.9%). Elevated preoperative SII independently predicts periprocedural complications, particularly ischemic events, in patients undergoing FDs treatment for intracranial aneurysms. This association is especially significant in older patients and those on clopidogrel therapy.

Trial Registration: ClinicalTrials.gov (NCT06446778). Registered on May 22, 2024.

Systemic immunity-inflammation index

Flow diverter

Periprocedural complications

Intracranial aneurysms

Flow-diverter devices (FDs) have gained global recognition for their safety and efficacy in aneurysm management, with occlusion rates ranging from 76–90%.[1–3] Despite these promising outcomes, flow-diversion treatment is associated with an overall complication rate of 10.1%.[4] Consequently, the identification of risk factors for such adverse events is paramount to optimize therapeutic outcomes.

Previous studies have predominantly concentrated on demographic, clinical, and morphological determinants, with the role of immune-inflammatory status receiving less attention.[5] Inflammatory responses, mediated by immune cells and platelet activation, are crucial for aneurysm repair through endothelial proliferation, yet may also precipitate in-stent stenosis and thrombosis.[6] Moreover, heightened inflammation could destabilize aneurysms, increasing the risk of periprocedural hemorrhage.[7] The significance of inflammation in periprocedural management has been well established in the context of percutaneous coronary intervention.[8] However, the association between inflammation and periprocedural complications in FDs treatment remains unclear.

The systemic immune-inflammation index (SII), which incorporates neutrophil, lymphocyte, and platelet counts, reflects the complex interactions among immunity, inflammation, and coagulation processes. This complexity suggests that SII may be more sensitive in assessing the risk of vascular events.[9] While it shows promise in predicting complications in cardiovascular interventions and cerebrovascular incidents,[8, 10] further research is needed to determine its prognostic value in cerebrovascular interventions. Hence, this study aims to elucidate the correlation between preoperative SII and periprocedural complications in patients treated with FDs, refining intervention strategies and enhancing patient prognosis.

Study design

We conducted a retrospective analysis of a prospectively maintained database at our center. Consecutive patients treated with FDs between February 2016 and August 2023 were retrospectively reviewed.

The inclusion criteria included the following: (1) Aged over 18 years old; (2) IAs treated with FDs. Exclusion criteria for the study were: (1) patients complicated by other cerebrovascular diseases (e.g., Moyamoya disease, arteriovenous malformation, or arteriovenous fistula); (2) patients with other conditions affecting inflammatory cell counts, such as acute infectious inflammation (e.g., pneumonia or urinary tract infection), autoimmune diseases, or a history of cancer; (3) patients with inadequate venous blood samples collected upon admission, poor image quality, or incomplete medical records. This study received approval from the institutional review boards of centers, and informed consent was waived owing to the anonymous design of the study.

Data collection and definitions

On the admission day, demographic and clinical characteristics were systematically recorded for all participants. These included age, gender, BMI, and medical history (hypertension, diabetes mellitus, dyslipidemia, history of smoking, drinking, hemorrhage, ischemic, and coronary artery disease). Angiographic evaluations of IAs such as location, morphology, neck width, tandem aneurysms (multiple IAs in close proximity to one another on the same or adjacent vascular segments that are not interconnected), regular aneurysms (without daughter sacs or lobulations), vessel diameter (the mean diameter of the parent vessel at the proximal and distal ends of the aneurysms) were conducted. The angiographic data was analyzed by two researchers, while three seasoned neurointerventionalists, each with over a decade of experience, supervised the measurements. Detailed procedural data were extracted from the electronic medical records, documenting dual antiplatelet therapy, FDs specifics, nominal stent diameter and length, coiling assistance, and balloon angioplasty usage.

Periprocedural complications, defined as cerebrovascular incidents within 30 days post-procedure, included intraoperative aneurysm rupture, intraprocedural thrombosis, hemorrhagic events (subarachnoid and intraparenchymal hemorrhage), and ischemic strokes (transient ischemic attacks [TIA], mild ischemia with National Institutes of Health Stroke Scale (NIHSS) score ≤ 4, and severe ischemia with NIHSS > 4). Severe functional impairment was also evaluated.[11]

The blood laboratory data were collected within 6 days before surgery, including neutrophil count, lymphocyte count, monocyte count, and platelet count. The neutrophil-to-lymphocyte ratio (NLR) was defined as the number of neutrophils divided by the number of lymphocytes. Systemic inflammation response index (SIRI) was defined as the number of Monocyte count multiplied by the neutrophil-to-lymphocyte ratio. The systemic immune-inflammation index (SII) is defined as the product of platelet count multiplied by the neutrophil-to-lymphocyte ratio, divided by 1000. [9, 12]

Endovascular treatment procedure

Before the procedure, patients were administered dual antiplatelet therapy (DAPT) comprising daily doses of aspirin (100 mg) and clopidogrel (75 mg) for at least three days. Preoperative assessment for platelet function testing conducted at least one day prior to the procedure. For those exhibiting clopidogrel resistance, ticagrelor was employed as an alternative antiplatelet agent. General anesthesia was administered, and patients were fully heparinized during the operation.

The preferred method for accessing the target aneurysm was the transfemoral arterial approach utilizing a triaxial system. Stent deployment was generally achieved using the non-compacting technique, with the pushing–compaction operation employed infrequently. The stents were sized to extend at least 5mm beyond both the proximal and distal ends of the aneurysms. Balloon angioplasty was commonly used to correct severely poor wall apposition. Adjunctive coiling was considered under specific circumstances: (1) the potential risk of stent shortening or migration, and (2) an increased likelihood of aneurysm recurrence or rupture, which could be attributed to elevated blood flow velocities at the aneurysm neck. A group of neurointerventionalists, each boasting over 15 years of experience in treating aneurysms, made the decisions regarding the ultimate choice of stents and the approach to treatment.

Post-procedure management involved continuing dual antiplatelet therapy for 6 to 12 months, followed by a single antiplatelet regimen of daily aspirin (100 mg) for an additional 6 to 9 months.

Statistical analysis

Statistical analysis was performed using R (v4.3.2), with normality assessed by the Kolmogorov-Smirnov test. Continuous variables were presented as mean ± SD or median (IQR) and analyzed with the t-test or Wilcoxon test. Categorical variables were reported as frequencies and proportions and analyzed using the Χ2 or Fisher’s exact test. The study cohort of 452 IAs was divided into derivation (70%) and validation (30%) subsets. Variables that had P value < 0.1 and demonstrated clinical significance were incorporated into three separate multivariate logistic regression models—Model 1, Model 2, and Model 3—each evaluating the NLR, SIRI and SII, respectively. Subgroup analyses were conducted to explore SII's association with complications in the elderly and those on dual antiplatelet regimens. The Decision Tree model was developed using 'caret' and 'rpart' packages, with feature selection guided by a P value < 0.1 and tenfold cross-validation. The model used the 'Gini' criterion and a maximum depth of 10. ROC analysis evaluated the predictive accuracy of the DT and multivariate models for complications. SII values were dichotomized based on Decision Tree outcomes to further investigate their association with periprocedural complications.

Demographic and aneurysm characteristics

In our study, we evaluated 488 IAs treated with FDs in 449 patients. Out of these, 452 IAs (92.6%) met our stringent inclusion criteria (Supplemental Figure. 1). In the total cohort, the mean age was 56(IQR:46.8–64.0) years, and 306 patients (67.7%) were female, 19 patients (4.20%) presented with periprocedural complications and 433(95.8%) did not. The characteristics of 452 IAs from 418 patients in the derivation and validation cohorts have been compared in Supplemental Table 1. No significant differences were noted between the derivation and validation cohort.

The results of univariate analysis are shown in Table 1. In the derivation cohort, compared with those without periprocedural complications, patients with periprocedural complications tended to have a diabetes (42.9% vs 11.9%, P = 0.005), hemorrhagic history (35.7% vs 6.9%, P = 0.003), larger neck width of the aneurysm (7.58 vs 4.27, P = 0.039), different dual antiplatelet regimen (P = 0.035) and worse preoperative mRS score (P < 0.001). Patients with complications also showed a trend towards increased neutrophil and platelet counts, though these did not statistically differ (p = 0.067, 0.350 respectively). Notably, preoperative SII differed significantly between two groups (0.54 vs 0.43 ×10⁹/L, P = 0.056). Other baseline characteristics were similar between the two groups. ROC analysis was performed to determine ability of SII index to distinguish patients who did or did not periprocedural complications (AUC of 0.651 on the derivation cohort and 0.758 on the validation cohort, Fig. 3c, d).

Table 1

Univariate analysis between periprocedural complications and no periprocedural complications group of 452 aneurysms in the derivation and validation cohort.
Variable	Derivation cohort				Validation cohort
	Overall	No PPC Group	PPC Group	p	Overall	No PPC Group	PPC Group	p
	318	304	14	p	134	129	5	p
Age (years)	57.00 [47.00, 64.00]	56.00 [47.00, 63.00]	61.50 [55.25, 66.00]	0.107	56.00 [46.00, 63.50]	56.00 [46.00, 63.75]	51.00 [46.00, 57.00]	0.445
Gender, female	214 (67.5)	207 (68.3)	7 (50.0)	0.157	92 (68.1)	89 (68.5)	3 (60.0)	0.653
BMI (kg/m²)	23.44 [21.51, 25.09]	23.44 [21.66, 25.12]	23.54 [20.43, 24.72]	0.916	23.44 [21.59, 25.55]	23.41 [21.59, 25.53]	23.52 [22.04, 28.04]	0.775
Hypertension	117 (36.9)	109 (36.0)	8 (57.1)	0.155	57 (42.2)	54 (41.5)	3 (60.0)	0.650
Hyperlipidemia	98 (30.9)	96 (31.7)	2 (14.3)	0.240	39 (28.9)	37 (28.5)	2 (40.0)	0.626
Diabetes	42 (13.2)	36 (11.9)	6 (42.9)	0.005*	16 (11.9)	14 (10.8)	2 (40.0)	0.107
Coronary disease	8 (2.5)	7 (2.3)	1 (7.1)	0.306	8 (5.9)	8 (6.2)	0 (0.0)	> 0.999
History of smoking	40 (12.6)	36 (11.9)	4 (28.6)	0.085	14 (10.4)	13 (10.0)	1 (20.0)	0.427
History of drinking	31 (9.8)	29 (9.6)	2 (14.3)	0.636	12 (8.9)	11 (8.5)	1 (20.0)	0.377
Hemorrhagic history	26 (8.2)	21 (6.9)	5 (35.7)	0.003*	12 (8.9)	9 (6.9)	3 (60.0)	0.005
Ischemic stroke history	66 (20.8)	60 (19.8)	6 (42.9)	0.084	22 (16.3)	18 (13.8)	4 (80.0)	0.002
Preoperative mRS score				< 0.001*				0.244
0	146 (46.1)	144 (47.5)	2 (14.3)		53 (39.3)	50 (38.5)	3 (60.0)
1	130 (41.0)	126 (41.6)	4 (28.6)		65 (48.1)	64 (49.2)	1 (20.0)
2	27 (8.5)	26 (8.6)	1 (7.1)		10 (7.4)	10 (7.7)	0 (0.0)
3	8 (2.5)	5 (1.7)	3 (21.4)		1 (0.7)	1 (0.8)	0 (0.0)
4	6 (1.9)	2 (0.7)	4 (28.6)		6 (4.4)	5 (3.8)	1 (20.0)
Posterior circulation	36 (11.4)	33 (10.9)	3 (21.4)	0.204	22 (16.3)	21 (16.2)	1 (20.0)	> 0.999
Regular aneurysm	256 (80.8)	247 (81.5)	9 (64.3)	0.156	97 (71.9)	94 (72.3)	3 (60.0)	0.620
Morphological feature, saccular	287 (90.5)	276 (91.1)	11 (78.6)	0.136	118 (87.4)	115 (88.5)	3 (60.0)	0.119
Tandem IAs†	81 (25.6)	78 (25.7)	3 (21.4)	> 0.999	25 (18.5)	24 (18.5)	1 (20.0)	> 0.999
Neck width (mm)	4.37 [3.20, 6.10]	4.27 [3.18, 5.90]	7.58 [3.76, 9.39]	0.039*	5.09 [3.77, 6.92]	5.04 [3.75, 6.89]	14.17 [4.58, 22.50]	0.113
Vessel diameter (mm)‡	3.95 [3.48, 4.45]	3.95 [3.49, 4.48]	3.95 [3.36, 4.24]	0.728	3.95 [3.38, 4.50]	3.95 [3.38, 4.50]	4.21 [3.80, 4.25]	0.958
Dual antiplatelet regimen				0.035*				0.084
Clopidogrel	170 (53.6)	164 (54.1)	6 (42.9)		73 (54.1)	72 (55.4)	1 (20.0)
Ticagrelor	94 (29.7)	92 (30.4)	2 (14.3)		45 (33.3)	43 (33.1)	2 (40.0)
Others	53 (16.7)	47 (15.5)	6 (42.9)		17 (12.6)	15 (11.5)	2 (40.0)
Stent type, TED	186 (58.7)	179 (59.1)	7 (50.0)	0.583	71 (52.6)	70 (53.8)	1 (20.0)	0.190
Nominal stent diameter (mm)	4.00 [3.75, 4.50]	4.00 [3.75, 4.50]	4.00 [3.75, 4.50]	0.903	4.00 [3.50, 4.50]	4.00 [3.50, 4.50]	4.00 [3.75, 4.25]	0.976
Nominal stent length (mm)	20.00 [20.00, 30.00]	20.00 [20.00, 30.00]	25.00 [20.00, 30.00]	0.224	20.00 [20.00, 30.00]	20.00 [20.00, 30.00]	30.00 [18.00, 35.00]	0.484
Balloon angioplasty	12 (3.8)	10 (3.3)	2 (14.3)	0.093	2 (1.5)	2 (1.5)	0 (0.0)	> 0.999
Adjunctive coiling	58 (18.4)	54 (17.8)	4 (30.8)	0.268	31 (23.0)	29 (22.3)	2 (40.0)	0.324
Neutrophils, 10⁹/L	3.45 [2.65, 4.49]	3.43 [2.63, 4.44]	4.37 [3.36, 5.49]	0.067	3.78 [2.92, 5.14]	3.78 [2.92, 5.15]	3.78 [3.73, 4.44]	0.829
Lymphocytes, 10⁹/L	1.88 [1.51, 2.30]	1.88 [1.52, 2.30]	1.82 [1.37, 2.31]	0.704	1.98 [1.58, 2.48]	1.99 [1.59, 2.50]	1.18 [0.99, 1.93]	0.028
Monocytes, 10⁹/L	0.49 [0.39, 0.58]	0.49 [0.39, 0.58]	0.47 [0.41, 0.58]	0.911	0.50 [0.42, 0.65]	0.50 [0.41, 0.65]	0.54 [0.45, 0.57]	0.731
Platelets, 10⁹/L	239.00 [208.00, 279.00]	237.00 [208.00, 279.00]	269.00 [238.00, 276.00]	0.138	249.00 [204.00, 283.00]	247.50 [204.00, 280.75]	250.00 [198.00, 306.00]	0.889
NLR	1.76 [1.36, 2.56]	1.75 [1.35, 2.48]	2.23 [1.46, 3.22]	0.148	1.89 [1.47, 2.64]	1.85 [1.46, 2.59]	3.02 [2.25, 3.81]	0.037
SIRI, 10⁹/L	0.90 [0.59, 1.35]	0.90 [0.58, 1.35]	0.99 [0.76, 1.46]	0.384	0.98 [0.65, 1.52]	0.98 [0.64, 1.47]	1.71 [1.22, 2.06]	0.069
SII, 10⁹/L	0.44 [0.32, 0.66]	0.43 [0.32, 0.66]	0.54 [0.40, 0.87]	0.056	0.46 [0.35, 0.68]	0.45 [0.32, 0.67]	0.74 [0.66, 0.76]	0.050
Values are shown as median (IQR) or frequency (%) unless indicated otherwise.
* Statistic difference.

Abbreviations: PPC, periprocedural complications; No PPC, no periprocedural complications; NLR, neutrophil to lymphocyte ratio; SII, systemic immune-inflammation index; SIRI, Systemic inflammation response index.

†Multiple IAs in close proximity to one another on the same or adjacent vascular segments that are not interconnected.

‡The mean diameter of the vessel at the proximal and distal ends of the aneurysms.

In the entire cohort, the relationships between neutrophil count, lymphocyte count, platelet count, NLR, SIRI and SII with periprocedural complications were visualized using violin plots (Fig. 1). The conclusions drawn were consistent with those from the derivation cohort, with significant differences observed in NLR and SII between two groups (P = 0.022; P = 0.010), respectively.

Characteristics of Periprocedural Complications in 19 Cases

In this study, we investigated periprocedural complications in 19 patients treated with flow diverters (FDs) for cerebral aneurysms (Table 2). Complications were categorized as ischemic, hemorrhagic, and other types, and monitored during the periprocedural period. Ischemic complications were the most prevalent, occurring in 12 patients (63.16%). These included intraprocedural thrombosis in four cases (21.05%), which rapidly resolved following intraoperative administration of tirofiban, without subsequent adverse events. Transient ischemic attacks (TIAs) or minor strokes were observed in four patients (21.05%), and four cases (21.05%) were confirmed as major ischemic strokes. Hemorrhagic events were observed in 5 patients (26.32%), with subarachnoid hemorrhage (SAH) occurring in 4 patients (21.05%). These hemorrhages occurred either immediately or up to 11 hours post-procedure. Furthermore, intraparenchymal hemorrhage was recorded in 1 patient (5.26%). Other types of complications affected 2 patients (10.53%), including cranial nerve palsy and cerebellar edema, each identified within a day of the procedure. For a detailed overview of baseline characteristics, aneurysm locations, types of devices utilized, and pharmaceutical regimens are shown in Supplemental Table 2.

Table 2

Periprocedural complications in 19 patients.
Event		n	%	n
Ischemic complications	Intraprocedural thrombosis	4	21.05%	12
	TIA/minor stroke	4	21.05%
	Major ischemic stroke	4	21.05%
Hemorrhagic complications	Subarachnoid hemorrhage	4	21.05%	5
Hemorrhagic complications	Intraparenchymal hemorrhage	1	5.26%	5
Other complications	Other complications	2	10.53%	2
Total		19	100.00%

Logistic regression and decision tree for prediction of periprocedural Complications

The logistic regression analysis showed that, after adjusting for baseline differences (history of smoking, diabetes, hemorrhagic history, ischemic stroke history, neck width, stent type and balloon angioplasty), diabetes (OR: 5.885, 95%CI: 1.563–22.042; P = 0.007), and hemorrhagic history (OR: 15.102, 95%CI: 3.485–68.228; P < 0.001) as significant predictors of complications, with SII showing the highest odds ratio (OR) of 5.306 (95%CI:1.367–18.455; P = 0.009) across all models (Fig. 2). The model demonstrated reliable performance with an AUC of 0.792 in the derivation cohort and 0.898 in the validation cohort, achieving a sensitivity of 0.80 and a specificity of 0.986 at the optimal cutoff (Fig. 3c, d).

DT with four nodes and five leaves was constructed, using SII、neck of aneurysm as predictors, as shown in Fig. 3a. According to the DT, participants with aneurysm neck diameters between 6.68 and 10.985 had a 33.0% chance of experiencing periprocedural complications if their SII exceeded 0.437. The DT model's AUC of 0.797 in the derivation cohort and 0.830 in the validation cohort (Fig. 3c, d).

SII index and periprocedural complication events in the overall population

In this subgroup analysis from Table 3, the SII demonstrates a significant association with periprocedural complications among patients aged ≥ 65, exhibiting a notably high adjusted OR of 36.979 (95% CI: 2.103-650.134; P = 0.014). Similarly, the SII serves as a significant predictor of complications in patients receiving clopidogrel, with an adjusted OR of 16.921 (95% CI: 2.733-104.746; P = 0.002). These findings underscore the substantial predictive value of SII for periprocedural risks within these specific patient cohorts.

Table 3

Subgroup analysis for association between SII and periprocedural complications in the elderly and those on dual antiplatelet regimens.
Factor	Subgroup	n total	PPC case n (%)	P value	Adjusted OR (95% CI)
SII	Age < 65	350	13 (3.71%)	0.343	2.448 (0.384–15.601)
	Age ≥ 65	102	6 (5.88%)	0.014	36.979 (2.103-650.134)
	Clopidogrel	243	7 (2.88%)	0.002	16.921 (2.733-104.746)
	Ticagrelor	139	4 (2.88%)	0.355	4.269 (0.197–92.543)
	Others	70	8 (11.43%)	0.355	4.269 (0.197–92.543)
Adjusted for baseline differences (history of smoking, diabetes, hemorrhagic history, ischemic stroke history, neck width, stent type and balloon angioplasty).

Abbreviations: SII, systemic immune-inflammation index; PPC, periprocedural complications; OR, odds ratio; CI, confidence interval.

Figure 3b demonstrates the relationship between the SII and periprocedural complications. An elevated SII (> 0.437) is significantly correlated with increased periprocedural complications (p = 0.017). Although not statistically significant across all categories, the incidence of complications, especially ischemic ones (p = 0.063), is higher in the group with an SII > 0.437 compared to the group with an SII < 0.437.

This is the first study to explore the prognostic value of the SII in patients undergoing FDs treatment for IAs. We found a significant association between SII and periprocedural complications, first validating SII as an independent prognostic factor through logistic regression and decision tree analysis. These findings not only offer a potential risk assessment tool for clinical applications but also underscore the important role of inflammation in periprocedural complications following endovascular treatment.

The NLR is an established marker for heart failure, cardiovascular diseases, and chronic inflammatory conditions, offering a quick assessment of the inflammatory state.[13] However, NLR primarily focuses on the ratio between neutrophils and lymphocytes, potentially not fully reflecting the full scope of systemic inflammation. The SIRI has shown potential in predicting outcomes in stroke patients but may still miss other inflammatory parameters.[14] In contrast, the SII, which integrates neutrophil, lymphocyte, and platelet counts, provides a more comprehensive evaluation of the inflammatory state. Platelets play a crucial role in both inflammatory responses and thrombus formation, making SII potentially more sensitive in assessing vascular event risks.[9, 15] An elevated SII may reflect a broader inflammatory and vascular response, which is particularly relevant in neurointerventional surgeries involving vascular manipulation and potential injury.

Previous studies on FD treatment have identified major risk factors for periprocedural complications, such as basilar artery aneurysms, hypertension, ischemic stroke, and a history of subarachnoid hemorrhage.[3, 16] However, limited research exists on the systemic immune-inflammatory state of patients. Emerging evidence indicates that inflammatory mechanisms play a significant role in periprocedural ischemic and bleeding events following endovascular treatments. Mechanical injuries from stenting can trigger cerebral vasospasm, leading to TIA,[17] and activate inflammatory pathways that promote thrombogenesis. Inflammatory responses, involving the release of various mediators, can hinder stent endothelialization and exacerbate thrombosis risk.[18] Thrombin amplifies this process by promoting leukocyte adhesion, smooth muscle cell proliferation, and the release of inflammatory cytokines, creating a feedback loop that furthers inflammation and thrombus formation. Even with dual antiplatelet therapy, these phenomena are challenging to completely avoid.[19] Meanwhile, Inflammation is increasingly recognized as a key factor in the pathogenesis and progression of IAs,[7] with inflammatory cell infiltration in the aneurysm wall significantly contributing to its vulnerability.[20] Neutrophils and lymphocytes produce enzymes and cytokines that degrade the extracellular matrix and elevate rupture risk. [21, 22] The exacerbation of the inflammatory response intensifies the activity of these cells in the aneurysm wall, further destabilizing the structure. Platelets further support these inflammatory and immune responses, increasing the potential for aneurysmal instability and hemorrhagic events.[23] Based on the results of a Decision Tree analysis, further stratified analysis was conducted, revealing that patients with a SII exceeding 0.437 face a significantly increased risk of periprocedural complications, particularly ischemic events during the periprocedural period. This finding may offer new insights for clinical management, suggesting that SII could serve as a valuable biomarker for risk stratification in the periprocedural setting.

In cerebrovascular diseases, age is a recognized risk factor, and DAPT affects periprocedural outcomes. Our exploratory subgroup analysis assessed the impact of age and DAPT regimens on periprocedural outcomes. We found that in patients over 65, high SII levels were significantly linked to increased periprocedural complications (adjusted OR = 36.979; P = 0.014), Likely due to age-related oxidative stress and chronic inflammation's impact on surgical outcomes. Age-related decline in antioxidant capacity and chronic inflammation accumulation may weaken the body's regulation and defense against inflammation, increasing periprocedural complications risk.[24, 25] Further analysis of antiplatelet therapy outcomes revealed that patients treated with clopidogrel showed elevated SII levels and a correspondingly increased risk of periprocedural complications (adjusted OR = 16.921; P = 0.002), suggesting suboptimal antiplatelet efficacy under inflammatory stress compared to a baseline cohort risk (adjusted OR = 5.306). In contrast, ticagrelor was associated with a lower risk of complications (adjusted OR = 4.269), evidencing more robust platelet inhibition. Although the precise mechanisms are not yet clear, this phenomenon may be due to ticagrelor's more stable antiplatelet effects at elevated levels of systemic inflammation.[26] Moreover, the association of ticagrelor with reduced inflammatory indices during post-PCI follow-up suggests that its anti-inflammatory properties might contribute to the clinical benefits observed with antiplatelet therapy.[27] Therefore, we recommend a personalized approach for elderly patients with high inflammatory profiles, favoring ticagrelor for its stable antiplatelet effect and potential anti-inflammatory properties, to optimize endovascular treatment outcomes.

Our multivariate analysis confirmed diabetes and a history of bleeding as independent predictors of complication risk, consistent with existing literature.[28] Following aneurysm rupture, vasospasms related to subarachnoid hemorrhage (SAH) and a hypercoagulable state further increase the risk of ischemic complications.[29] These pathological states warrant attention in treatment strategies. Following endovascular treatment in diabetic patients, the increased risk of ischemic events may be attributed to the high expression and aggregation of glycoprotein IIB/IIIA receptors, particularly under hyperglycemic conditions, and an enhanced inflammatory response. These findings underscore the importance of managing diabetes and a history of bleeding in treating IAs.[30] For patients with these risk factors, closer monitoring and more aggressive antiplatelet or anticoagulation therapy may be necessary.

Limitations

Despite valuable insights, this study's single-center, retrospective design may limit the generalizability of the findings. The SII is influenced by various factors, including age, gender, comorbidities, and other inflammatory conditions. Although efforts were made to exclude patients with such conditions, their potential impact cannot be entirely excluded. Thus, caution is warranted when applying SII as an independent predictive factor.

An elevated preoperative SII, along with a history of hemorrhage and diabetes, are independent risk factors for periprocedural complications in patients undergoing FDs for IAs, especially ischemic events. SII, a readily attainable indicator reflecting inflammation and immune status, is valuable for predicting and intervening early in complications. Older patients and those on clopidogrel may require more attention.

Author contributions

Jiwan Huang and Yaxian Huang make equal contributions to this research. Xin Feng and Chuanzhi Duan are co corresponding authors. Jiwan Huang: designed, conceptualized the study and drafted the manuscript; Yaxian Huang, Chi Huang, Mengshi Huang: analyzed and interpreted the data; Zhuohua Wen, Anqi Xu, Runze Ge, Hao Yuan, Hongyu Shi, Gengwu Ma, Can Li, Jiancheng Lin, Ruizhe Yi, Yuqi Hu, Yuheng Jin: collected the data; Shuyin Liang, Yiming Bi, Shixing Su, Xin Zhang and Xifeng Li: critically revised the study outcomes; Xin Feng and Chuanzhi Duan: funding, study supervision, and critical revision of the manuscript.

Ethics approval and consent to participate

This study has been approved by the Ethics Committee of Zhujiang Hospital of Southern Medical University (2023-KY-023-02) and conforms to the ethical standards as per the revised Declaration of Helsinki. The study is registered with ClinicalTrials.gov (NCT06446778). We retrospectively analyzed data collected through January 2023; however, all of these data were initially collected prospectively at the time of patient admission Data after January 2023 were collected in a prospective design. And participants gave informed consent to participate in the study before taking part.

Consent for publication

All authors of the manuscript agreed to its publication.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Natural Science Foundation of China (82201427) and the Foundation of National Heath Commission Capacity Building and Continuing Education Center (GWJJ2022100102).

Competing Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Availability of data and materials

The supporting data of this study is available from the corresponding author on reasonable request.

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No competing interests reported.

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Predictive Value of the Systemic Immune-Inflammation Index for Periprocedural Complications in Flow Diverter Treatment for Patients with Intracranial Aneurysms

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Abstract

Figures

Introduction

MATERIALS AND METHODS

Study design

Data collection and definitions

Endovascular treatment procedure

Statistical analysis

Results

Demographic and aneurysm characteristics

Characteristics of Periprocedural Complications in 19 Cases

Logistic regression and decision tree for prediction of periprocedural Complications

SII index and periprocedural complication events in the overall population

Discussion

Limitations

Conclusions

Declarations

References

Additional Declarations

Supplementary Files

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Version 1