Background and purpose High admission blood pressure (BP) levels have been associated with lower recanalization rates after endovascular treatment (EVT) for patients with acute ischemic stroke (AIS) with emergent large vessel occlusion (ELVO). We sought to evaluate the association of admission BP with early outcomes in patients with ELVO treated with EVT.
Methods Consecutive patients with AIS presenting with ELVO in a tertiary stroke center during a 4-year period were prospectively evaluated. Admission systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured using automated cuff recordings. A blinded neuroradiologist calculated the final infarct volume (FIV) using standardized ABC/2 methodology. A favorable functional outcome (FFO) at 3 months was defined as modified Rankin Scale score of 0–2.
Results Our study population consisted of 116 patients with AIS (mean age 63±13 years, median NIH Stroke Scale score 17 points (IQR 14–21), median FIV 30 cm3 (IQR 8–94)). Higher admission SBP correlated with higher FIV (r +0.225; p=0.020). Patients with FFO had lower admission SBP (151±24 mm Hg vs 165±28 mm Hg; p=0.010), while admission SBP levels were higher in patients who died during hospitalization (169±34 mm Hg vs 156±24 mm Hg; p=0.043). A 10 mm Hg increment in admission SBP was independently (p=0.010) associated with an increase of 12 cm3 in FIV (95% CI 3 to 21) in multiple linear regression models adjusting for potential confounders. A 10 mm Hg increment in admission SBP was independently (p=0.012) associated with a lower likelihood of FFO at 3 months (OR 0.64; 95% CI 0.45 to 0.91) in multiple logistic regression models adjusting for potential confounders.
Conclusions Higher admission SBP is an independent predictor of increased FIV and lower likelihood of 3-month FFO in patients with ELVO treated with EVT.
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A portion of this study's findings was presented at the International Stroke Conference 2016.
Endovascular treatment (EVT) has shown benefit in patients with acute ischemic stroke (AIS) due to anterior circulation emergent large vessel occlusion (ELVO), particularly in those with good collaterals.1–5 However, limited data are available on the relationship between admission blood pressure (BP) and neurological outcome in AIS after EVT. Interestingly, higher baseline systolic blood pressure (SBP) levels have been associated with lower likelihood of recanalization and good functional outcomes in patients with AIS treated with intravenous thrombolysis (IVT).6 ,7 Moreover, the potential association of intensive BP-lowering with 3-month functional outcome of patients with AIS treated with IVT is currently being investigated in a phase III randomized controlled trial (RCT).8 In addition, a pooled analysis of the Mechanical Embolus Removal in Cerebral Ischemia (MERCI) and Multi MERCI trials has indicated that higher admission SBP levels have been associated with a lower likelihood of revascularization.9 In view of these results and ongoing studies, we sought to evaluate the potential association between admission BP levels and outcomes including final infarct volume (FIV) and 3-month favorable functional outcome (FFO) in ELVO patients treated with EVT.
Data from consecutive ELVO patients who underwent EVT in our tertiary care stroke center from February 2011 to December 2014 has been prospectively collected in a database, as previously described.1 ,2 ELVO was diagnosed on pretreatment CT angiography (CTA) as previously described.1 ,2 CT and CTA were performed on a 64-slice scanner. CT slice thickness was 1.25 mm with acquisitions in axial, sagittal, and coronal planes with three-dimensional reformations. Baseline characteristics including demographics, vascular risk factors, admission NIH Stroke Scale (NIHSS) scores, admission serum glucose, and admission SBP and diastolic blood pressure (DBP) levels were recorded as previously described. Admission SBP and DBP values (the first BP on arrival if patient was brought in by family or first BP measured by emergency medical system (EMS) personnel in the field if they were involved) were measured using automated cuffs.10
A blinded neuroradiologist calculated CTA collateral scores (CSs) and FIV using standardized methodology as previous described.1 CSs for anterior circulation ELVO were reported in a dichotomized fashion (ie, poor (CS=0) vs good (CS=1, 2 and 3)) using a methodology that has been shown to predict clinical outcome.11 FIV was calculated by the simplification of the ellipsoid rule: A×B×C/2 on delayed (7 days to 14 days) brain MRI using Fluid Averted Inversion Recovery (FLAIR) sequences.12 Delayed CT head was used in a small number of patients with contraindications to brain MRI. Successful recanalization at the end of the endovascular procedure was defined by Thrombolysis in Cerebral Infarction (TICI) scores of IIb or III.13 Three-month FFO was defined as a modified Rankin Scale (mRS) score of 0–2 at 3 months, which was obtained either from a post-hospital discharge clinic follow-up or from a hospital visit. Deaths during hospitalization and during the 3-month follow-up period were also documented. We defined symptomatic intracranial hemorrhage (sICH) as any evidence of ICH on brain CT accompanied by an increase in NIHSS score of ≥4 points.10 ,14 Investigation review board approval for this study was granted based on the prospectively maintained AIS database at our institution (10–01003-XP).
Continuous variables are presented as mean±SD (normal distribution) and as median with IQR (skewed distribution). Categorical variables are presented as percentages with their corresponding 95% CIs. Statistical comparisons between two groups were performed using the χ2 test or, in case of small expected frequencies, the Fisher' exact test. Continuous variables were compared by the use of the unpaired t test or Mann–Whitney U test, as indicated. Furthermore, the associations of BP parameters with different binary outcomes (eg, 3-month FFO) were assessed using univariable and multivariable logistic regression models adjusting for potential confounders. In multivariable analyses we tested the statistical significance hypothesis under the likelihood ratio test with an α value of 0.05. We reported all associations as ORs with their corresponding 95% CIs. Finally, the association between BP parameters and FIV was evaluated using Spearman's correlation coefficient (r) and multiple linear regression models. Statistical significance was achieved in multiple linear regression models with a two-tailed value of p<0.05. The associations between FIV and other variables are presented by means of standardized and unstandardized linear regression coefficients. The corresponding 95% CI of unstandardized linear regression coefficients are also provided. The Statistical Package for Social Science (SPSS) V.22.0 for Windows was used for statistical analyses.
Our study population consisted of 116 patients with AIS with anterior circulation ELVO (mean age 63±13 years, 51% male, median admission NIHSS score 17 points (IQR 14–21), median FIV 30 cm3 (IQR 8–94)) who were treated with EVT (table 1). The MRI FLAIR sequence was used to calculate FIV in 99 patients and delayed CT head was used in the remaining 17 patients. Of the 116 patients with AIS, 41 had internal carotid artery (ICA) occlusion (35%), 58 had middle cerebral artery (MCA) M1 occlusions (50%), and the remaining 17 patients had M2 MCA occlusion (15%). Newer generation thrombectomy devices (stent retrievers) were used in 76 patients (66%), 12 patients (10%) underwent direct aspiration thrombectomy alone, and older generation thrombectomy devices were used in 28 patients (24%). Presenting BP levels did not differ between patients with proximal (ICA or M1 MCA) and distal occlusions (M2MCA) (p=0.426). Systemic thrombolysis prior to EVT was administered in 75 patients (65%). Successful recanalization (TICI IIb or III) was achieved in 73 patients (63%). A total of 38 patients (33%) achieved FFO, while in-hospital and 3-month mortality were 27% and 31%, respectively.
Admission SBP and DBP levels in patients with efficacy (revascularization, 3-month FFO) and safety (sICH, in-hospital mortality and 3-month mortality) outcomes are summarized in table 2. Patients with FFO had lower admission SBP (151±24 mm Hg vs 165±28 mm Hg; p=0.010), while admission DBP did not differ between the two groups (89±18 mm Hg vs 89±22 mm Hg; p=0.999). Admission SBP levels were higher in patients who died during hospitalization (169±34 mm Hg vs 156±24 mm Hg; p=0.043), but the two groups did not differ in terms of admission DBP levels (94±24 mm Hg vs 86±18 mm Hg; p=0.80). Admission SBP and DBP levels did not differ between alive and dead patients at 3 months ((166±35 mm Hg vs 156±23 mm Hg; p=0.160) and (91±24 mm Hg vs 86±18 mm Hg; p=0.315)) as well as in patients with and without sICH (p>0.05). Admission SBP tended to be lower in patients who had successful revascularization compared with those who did not (157±26 mm Hg vs 163±29 mm Hg), but this difference did not reach statistical significance (p=0.284). Finally, patients with good and poor collaterals did not differ in terms of admission SBP levels (153±29 mm Hg vs 150±26 mm Hg) in both univariate analysis (p=0.525) and continuous grading of collaterals (p=0.396).
We further evaluated the association between admission SBP levels and 3-month FFO as well as in-hospital mortality in univariable and multivariable logistic regression analyses. The association between demographics, vascular risk factors, admission SBP, admission DBP, admission NIHSS, serum blood glucose, IVT, onset to groin time, CS (good vs bad), and successful revascularization (defined as TICI grade IIB or III at the end of the endovascular procedure) with FFO was evaluated initially in univariable logistic regression models. The following variables with a p value of <0.1 were selected for inclusion in the multivariable logistic regression model: admission SBP, successful revascularization, IVT, and good CS. Two variables retained their independent association with FFO in multivariable logistic regression analyses (table 3): admission SBP and successful revascularization. More specifically, a 10 mm Hg increment in admission SBP was independently (p=0.012) associated with a lower likelihood of FFO at 3 months (OR 0.64; 95% CI 0.45 to 0.91), while successful revascularization was independently (p=0.006) related to a higher odds of FFO (OR 14.46; 95% CI 2.18 to 95.85). The association of admission SBP with in-hospital mortality did not reach statistical significance in multivariable logistic regression models adjusting for potential confounders (OR per 10 mm Hg increase: 1.40; 95% CI 0.99 to 1.98; p=0.057).
We also investigated the association between admission SBP levels and FIV in simple and multiple linear regression analyses. The association between demographics, vascular risk factors, admission SBP, admission DBP, admission NIHSS, serum blood glucose, IVT, onset to groin time, CS (good vs bad) and successful revascularization with FIV was evaluated initially in simple linear regression models. The following variables with a p value of <0.1 were selected for inclusion in the multiple linear regression model: admission SBP, admission DBP, successful revascularization, onset to groin time, and good CS. Two variables retained their independent association with FIV in multiple linear regression analyses (table 4): admission SBP and successful revascularization. More specifically, a 10 mm Hg increment in admission SBP was independently (p=0.010) associated with an increment of 12 cm3 (95% CI 3 to 21) in FIV, while successful revascularization was independently (p=0.002) related to a reduction in FIV of 60 cm3 (95% CI 22 to 98).
Our findings indicate that higher admission SBP levels are independently associated with increased FIV and lower likelihood of 3-month FFO in patients with ELVO who undergo EVT. The former association was independent of demographics, vascular risk factors, baseline stroke severity, admission serum glucose, collateral status, symptom onset to groin puncture time, and successful revascularization. This observation is in agreement with other reports, underscoring the adverse impact of elevated baseline SBP levels on FFO in patients with AIS treated with systemic thrombolysis.7 ,15
Several mechanisms have been proposed to explain the potential correlation of admission BP with recanalization and outcomes in patients treated with intravenous or intra-arterial therapies. Experimental and clinical studies have demonstrated that higher BP increases blood brain permeability and cerebral edema in the immediate post-stroke period.16 ,17 Early cerebral swelling may increase resistance to residual blood flow and impair the recanalization process leading to worse outcomes. On the other hand, it has been argued that cellular swelling is unlikely to develop within the first few hours of cerebral ischemia. Greater thrombus burden in the occluded artery may lead to higher admission SBP levels and thus the association between increased SBP levels and adverse outcomes may reflect the increased underlying clot burden.18 We were unable to validate this hypothesis using the present data since thrombus length was not measured in our patients. However, admission SBP and DBP levels did not differ between patients with distal and proximal occlusions in our dataset.
Another plausible hypothesis is that higher admission SBP may lead to a stronger hemodynamic force resulting in higher impaction of clot and thereby increasing the difficulty of mechanical retrieval.9 An alternative explanation may be related to the observations of Liebeskind et al19 who documented a strong association between higher admission SBP levels and poorer degrees of collateral flow, which in turn were related to a lower likelihood of recanalization and functional independence. Animal experiments showing that increased intraluminal pressure during the first hours of acute cerebral ischemia may impair the endogenous capacity for fibrinolysis and adversely impact spontaneous vessel recanalization also highlight the potential detrimental effect of elevated admission BP on revascularization of proximal intracranial arterial occlusions.20–22 Although patients with persisting occlusion at the end of the endovascular procedure tended to have higher admission SBP levels, this difference did not reach statistical significance and the association between higher admission SBP and worse functional outcomes cannot be attributed to lower revascularization rates in our dataset. Another possible explanation is that higher admission SBP in this group of patients may suggest that these patients are unhealthier or that acutely raised SBP is a marker of intense ischemia pre-EVT, but we could not provide evidence to support this hypothesis.
To the best of our knowledge, this is the first study investigating the potential association between admission BP and FIV in patients with AIS treated with EVT. Our findings are in line with an earlier study (not all with ELVO or underwent EVT) documenting that both excessively high and excessively low acute BP levels were independently associated with increased infarct volumes in consecutive patients with AIS.23 Moreover, the investigators of the International Stroke Trial have reported an independent relationship between baseline SBP and early recurrent ischemic stroke occurring within 14 days from symptom onset.24 These observations, in combination with our findings, lend support to the assumption that higher baseline SBP levels may lead to infarct expansion and early recurrent cerebral ischemia in patients with AIS with ELVO.23 ,24
The present results should be cautiously interpreted, since excessive BP lowering in patients with ELVO prior to revascularization may reduce cerebral blood flow with the risk of exacerbating cerebral hypoperfusion and increasing ischemic injury.25 Consequently, our findings underline the importance of BP monitoring before, during, and after revascularization in order to avoid both excessively high and low BP levels. Moreover, our data allowed us to detect only a statistical association between elevated admission SBP and adverse outcomes in patients with ELVO treated with EVT. The observational study design did not allow us to establish a cause-effect relationship between baseline BP and FFO in ELVO treated with EVT. This question can only be answered in the setting of a RCT including ELVO patients with a design similar to the ENCHANTED (ENhanced Control of Hypertension ANd Thrombolysis strokE study) trial that attempts to answer a similar research question in patients with AIS treated with IVT.
Several limitations of the present study need to be acknowledged. We did not measure the correlation between clot burden and presenting BP and their impact on the final outcome. Also, we did not assess other components of BP including pulse pressure, mean arterial pressure, and (more specifically) BP variability, which has been associated with early neurological deterioration in patients with AIS.26 Moreover, we did not record serial BP measurements after admission and the variability of BP levels prior to and during EVT, and consequently we were unable to assess the potential impact of periprocedural BP fluctuations on stroke outcome. Last, our sample size was moderate and comprised only patients with anterior circulation ELVO. This potential shortcoming may not have allowed us to detect possible associations between admission SBP and collateral status or complete revascularization.
In conclusion, our findings indicate that elevated admission SBP may be associated with worse early outcomes in terms of FIV and unfavorable functional outcome in patients with ELVO treated with EVT. This preliminary observation needs to be independently validated in larger multicenter registries. Additional research is also required to investigate more broadly the role of BP beyond the pre-procedure period, with an expanded focus on the entire periprocedural period and BP levels and trends as they relate to outcomes in patients with AIS with proximal intracranial occlusions treated with endovascular procedures.
Contributors NG, DH, and AVA: literature search, study design, data analysis, data interpretation, figures, manuscript writing, manuscript revisions. GT and SI: literature search, study design, data analysis, data interpretation, figures, manuscript revisions. YK, FI, VTD, RZ, JC, and KA: literature search, study design, figures, manuscript revisions. AC: literature search, study design, figures, manuscript writing, manuscript revisions. ASA: study idea, literature search, study design, data analysis, data interpretation, figures, manuscript writing, manuscript revisions. LE: study supervision, study idea, design and critical manuscript revisions.
Competing interests DH has served as a consultant for Covidien. AAA has served as a consultant for Covidien, Johnson and Johnson, Siemens, Stryker, and Terumo; and received grants from Siemens and Terumo. LE has served as a consultant for Stryker Neurovascular, Microvention, and Codman Neurovascular.
Ethics approval Institutional Investigation Review Board approval for this study was granted based on the prospectively maintained University of Tennessee Health Sciences Center Acute Ischemic Stroke Database (10-01003-XP).
Provenance and peer review Not commissioned; externally peer reviewed.
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