Abstract
Introduction:
Mechanical thrombectomy has become standard of care for emergent large vessel occlusive (ELVO) stroke. Estimates of incidence for thrombectomy eligibility vary significantly. NIH Stroke Scale (NIHSS) of 10 or greater is highly predictive of large vessel occlusion. Using our Kentucky Appalachian Stroke Registry (KApSR), we evaluated temporal trends in stroke admissions with NIHSS ≥ 10 to determine patient characteristics amongst that group along with effects and needs in thrombectomy utilization.
Methods:
Using the KApSR database that captures patients throughout the Appalachian region in our stroke network, we evaluated patients admitted with ischemic stroke with NIHSS ≥ 10. We recorded demographics, comorbidities, treatment (thrombectomy, decompressive craniectomy), and county of origin. Change in NIHSS from admission to discharge was used as an indicator of inpatient outcome.
Results:
Between 2010–2016, 1510 patients were admitted with NIHSS ≥ 10. 87.2% had high blood pressure, 69.6% had dyslipidemia and 41.7% used tobacco. There were significant sex differences in the types of patients presenting with NIHSS ≥ 10 with females being older on average, and having more atrial fibrillation and obesity. There was an increase in thrombectomy utilization from 2010 to 2016 but only 7.5% of the potentially eligible patients underwent the procedure. In comparison to the period 2010–2014, the 2015–2016 period had higher rates of obesity and tobacco abuse.
Conclusion:
Among patients with significant burden of ischemic stroke, the most common coexisting medical condition was high blood pressure. Patients who underwent thrombectomy had significantly better inpatient clinical improvement. These data support the need to maximize utilization of thrombectomy along with need to devote increased resources on modifiable stroke risk factors.
Keywords: Stroke, NIH Stroke Scale, Rural health, Thrombectomy
Introduction
Ischemic stroke accounts for approximately 87% of stroke,(1) with emergent large vessel occlusions (ELVO) representing 28–46%.(2) The presence of ELVO has been shown in various studies to increase odds of death by 4.5 fold, and to cause a 3-fold reduction of good outcome in affected populations.(2) The goal of current therapeutic strategies is recanalization of the occlusion before irreversible damage has occurred. Intravenous tissue plasminogen activator (IV-tPA) given up to 4.5 hours after onset of symptoms has been the only standard of care for acute ischemic strokes in the past,(3) even though in cases of proximal vessel occlusion it only results in early reperfusion in 13–50% of cases.(4) More recently, endovascular mechanical thrombectomy (MT) has become a standard of care procedure with established benefits shown in multiple clinical trials.(4–7) More recently, with the use of perfusion based imaging and automated software, this time window has been extended up to 24 hours in a selected patient population with target mismatch.(8, 9) Estimates of incidence for thrombectomy eligibility vary significantly across the nation. The National Institutes of Health Stroke Scale (NIHSS) is a validated tool to assess stroke severity and scores ≥ 10 have been associated with positive predictive value (PPV) of 97% in carotid and 96% in vertebro-basilar occlusions.(10)
High stroke incidence and stroke risk factor burden in West Virginia and rural Kentucky, has led to development of the Kentucky Appalachian Stroke Registry (KApSR) to collect demographic and clinical data in real time from stroke patients’ electronic health records, and to utilize this information for quality of care and research.(11) The aim of this study was to evaluate temporal trends in regional stroke admissions with NIHSS ≥ 10 to determine epidemiologic effects and needs in thrombectomy utilization using the Kentucky Appalachian Stroke Registry (KApSR).
Methods
Using the previously described KApSR methodology(11), a snapshot database was created for cross-sectional analysis of patients over 18 years of age, admitted from January 1, 2010 to December 31, 2016 to the University Hospital with acute ischemic stroke or transient ischemic attack. These patients were studied retrospectively, and the patients with NIHSS ≥ 10 recorded on admission were selected for further analysis. This was based on the hypothesis that the patients with NIHSS ≥ 10 have a very high likelihood of having a proximal vessel occlusion, and are potential thrombectomy candidates. Demographic characteristics were obtained and studied. We also analyzed whether these patients received intravenous thrombolytic (TPA), underwent thrombectomy, or underwent decompressive hemicraniectomy during their hospitalization. Change in NIHSS from admission to discharge was measured as an indicator of inpatient outcome.(12) The data were also analyzed for gender differences. Finally, we analyzed subgroups of epochs before (2010–2014) and after (2015–2016) AHA/ASA guidelines recommended thrombectomy as a standard for ELVO.(13)
Summary statistics and analyses were performed on PC – SAS version 9.1 and p ≤ 0.05 was considered significant. Proportion were compared using chi-square statistics, and means were compared using two sample t-tests. The research protocol was approved by our institutional review board, which waived informed consent for study subjects due to the retrospective nature of the study.
Results
Population Characteristics and risk factors
1510 adult patients had NIHSS ≥ 10 recorded at presentation between 2010–2016, and were selected for analysis. Table 1 provides the demographic, co-morbidity, and treatment details for the cohort. The mean age of patients was 68.15 ± 14.65 with average NIHSS on admission of 17.58 ± 6.24. The most common co-morbidity was hypertension (87.2% of patients), followed by dyslipidemia (69.6%), tobacco use (41.7%) and coronary artery disease (CAD; 41.1%). Females were, on average, 5 years older, and were significantly more likely to have atrial fibrillation (AF) and obesity. Conversely, males used tobacco more frequently and were more likely to have CAD. Figure 1 illustrates significant differences in patients admitted with NIHSS ≥ 10 between the two time periods 2010–2014 and 2015–2016. Patients admitted in the later epoch had lower rates of CAD (44.1% vs 34.9%; p<0.001) and dyslipidemia (71.7% vs 65.3%; p=0.01). However, comparing time epochs, patients in the later cohort were younger (68.8 vs 66.9 years, p=0.02), had higher rates of tobacco use (38.5% vs 48.0%; p<0.001), and had higher rates of obesity (8.9% vs 18.7%; p<0.001).
Table 1:
Population Demographics with comparisons between the male and female patient population.
| VARIABLE | TOTAL (n=1510) | MALE (n=715) | FEMALE (n=795) | P-VALUE |
|---|---|---|---|---|
| AGE | 68.15 ± 14.65 | 65.39 ± 14.09 | 70.64 ± 14.81 | <0.001 |
| NIHSS AT TIME OF ADMISSION | 17.58 ± 6.24 | 17.22 ± 6.06 | 17.90 ± 6.38 | 0.0319 |
| NIHSS AT TIME OF DISCHARGE | 13.46 ± 9.00 | 13.13 ± 9.09 | 13.77 ± 8.91 | 0.1657 |
| IMPROVEMENT IN NIHSS (NIHSS AT TIME OF DISCHARGE - NIHSS AT TIME OF ADMISSION) | − 4.11 ± 7.80 | − 4.09 ± 7.85 | − 4.13 ± 7.75 | 0.9135 |
| HISTORY OF HYPERTENSION (Y/N) | 1316/194 (87.2/12.8) | 612/103 (85.6/14.4) | 704/91 (88.6/11.4) | 0.1013 |
| HISTORY OF AF (Y/N) | 539/971 (35.7/64.3) | 222/493 (31.0/69.0) | 317/478 (39.9/60.1) | <0.001 |
| HISTORY OF PRIOR STROKE (Y/N) | 202/1308 (13.4/86.6) | 87/628 (12.2/87.8) | 115/680 (14.5/85.5) | 0.2173 |
| HISTORY OF CAD (Y/N) | 620/890 (41.1/58.9) | 319/396 (44.6/55.4) | 301/494 (37.9/62.1) | 0.0090 |
| TOBACCO USE (Y/N) | 629/881 (41.7/58.3) | 369/346 (51.6/48.4) | 260/535 (32.7/67.3) | <0.001 |
| OBESITY (Y/N) | 184/1326 (12.2/87.8) | 70/645 (9.8/90.2) | 114/681 (14.3/85.7) | 0.0088 |
| HISTORY OF DYSLIPIDEMIA(Y/N) | 1051/459 (69.6/30.4) | 508/207 (71.0/29.0) | 543/252 (68.3/31.7) | 0.2702 |
| HISTORY OF CAROTID STENOSIS (Y/N) | 144/1366 (9.5/90.5) | 79/636 (11.0/89.0) | 65/730 (8.2/91.8) | 0.0703 |
| HISTORY OF HEART FAILURE (Y/N) | 338/1172 (22.4/77.6) | 155/560 (21.7/78.3) | 183/612 (23.0/77.0) | 0.5740 |
| HISTORY OF PVD (Y/N) | 74/1436 (4.9/95.1) | 41/674 (5.7/94.3) | 33/762 (4.2/95.8) | 0.1924 |
| PROSTHETIC HEART VALVE (Y/N) | 24/1486 (1.6/98.4) | 10/705 (1.4/98.6) | 14/781 (1.8/98.2) | 0.7217 |
| TPA ADMINISTERED (Y/N) | 308/1202 (20.4/79.6) | 135/580 (18.9/81.1) | 173/622 (21.8/78.2) | 0.1859 |
| TTHROMBECTOMY PERFORMED (Y/N) | 113/1397 (7.5/92.5) | 61/654 (8.5/91.5) | 52/743 (6.5/93.5) | 0.1707 |
| DECOMPRESSIVE CRANIOTOMY PERFORMED (Y/N) | 14/1496 (0.9/99.1) | 8/707 (1.1/98.9) | 6/789 (0.8/99.2) | 0.6396 |
Abbreviations: NIHSS (National Institutes of Health Stoke Scale), AF (Atrial Fibrillation), CAD (coronary artery disease), TPA (Tissue plasminogen activator), PVD (peripheral vascular disease), Y (Yes) and N (No)
Figure 1:
Comparison between 2010–2014 vs 2015–2016 with significant differences
Treatments administered
Among 1510 patients, 308 patients (20.4%) with NIHSS ≥ 10 on admission underwent treatment with intravenous thrombolysis between 2010–2016. Thrombectomy was performed in 113 patients (7.5%) only with no significant difference between sexes in terms of utilization. Annual utilization of thrombectomy was plotted, and showed an increase over time from 0.8% in 2010 to 9.4% in 2016 (Figure 2). On comparison between the 2010–2014 and 2015–2016 periods, it was found that patients in the later epoch were almost twice as likely to get a thrombectomy (12.2% versus 5.2%; p<0.001) along with increase in decompressive craniectomy (2.4% vs 0.2%; p<0.001). The percentage use of tPA declined in the later time period (from 25.8% to 9.6%; p<0.001).
Figure 2:
The figure shows number of thrombectomies performed per year since 2010. The annual rate of mechanical thrombectomy significantly increased from 2010 to 2016 with maximum increase from 2014 to 2015.
Outcome Measures
Comparison of the mean NIHSS score change from admission to discharge between those who underwent mechanical thrombectomy and those who did not show a significant difference (−5.78 ± 9.09 vs −3.98 ± 7.67; p=0.04) with the biggest difference noted in year 2015–2016 (NIHSS decrease of 6.4 in thrombectomy patients versus 4.0 in non-thrombectomy patients; p=0.05). The ‘No Thrombectomy’ group had a slightly but not significantly shorter length of stay. Analysis of LOS and NIHSS change by sex showed a significant difference in mean LOS, with males having longer LOS (14.55 vs 10.2;p=0.0054; Table 2).
Table 2:
Inpatient NIHSS outcomes and length of stay in patients that underwent thrombectomy as compared to the patients that did not undergo the procedure.
| THROMBECTOMY GROUP | NO THROMBECTOMY GROUP | p value | |
|---|---|---|---|
| NIHSS SCORE CHANGE (n=1510) | − 5.78 ± 9.09 | − 3.98 ± 7.67 | 0.04 |
| NIHSS SCORE CHANGE in year 2010–2014 (n=1008) | − 5.00 ± 9.17 | − 3.97 ± 7.74 | 0.43 |
| NIHSS SCORE CHANGE in year 2015–2016 (n=502) | − 6.44 ± 9.04 | − 3.99 ± 7.53 | 0.047 |
| LOS (n=1510) | 14.75 ± 36.42 | 10.14 ± 14.30 | 0.18 |
| LOS in year 2010 – 2014 (n=1008) | 13.52 ± 24.36 | 10.10 ± 12.41 | 0.32 |
| LOS in year 2015 – 2016 (n=502) | 15.80 ± 44.38 | 10.23 ± 17.76 | 0.34 |
Abbreviations: NIHSS (National Institutes of Health Stoke Scale), MTY (mechanical thrombectomy yes), MTN (mechanical thrombectomy no), LOS (length of stay).
Discussion
We analyzed the temporal trends in thrombectomy at a regional stroke center serving a primarily rural US population. Our Comprehensive Stroke Center receives thrombectomy patients from central Kentucky, northern Tennessee, and western West Virginia. As such, many of our patients originate from the Appalachian region, where stroke represents a major health disparity. Rural cohorts in regions such as Appalachia have been shown to have higher rates of stroke, even after accounting for comorbidities and other risk factors.(14) Furthermore, unlike large urban environments, central Kentucky has only two Comprehensive Stroke Centers (with only four in the entire state). Treatment of severe stroke, therefore, tends to be centralized in the two largest cities (Louisville for western Kentucky, and Lexington for central and eastern Kentucky). In that setting, we aimed to understand the patient population presenting with high NIH stroke scales, which represents patients most likely to have an Emergent Large Vessel Occlusion. Despite the growing evidence supporting mechanical thrombectomy, only 7.5% of the patients that presented to our hospital with NIHSS ≥ 10 underwent thrombectomy, highlighting the need for additional education and collaboration with referring hospitals and emergency medical service providers; this is particularly important, as the window for thrombectomy has been expanded to 24 hours.(9)
As shown by our data, the burden of co-morbidities suffered by patients in the rural Kentucky and broader Appalachian region with acute ischemic stroke is significant. Even though atrial fibrillation is one of the main causes of vessel occlusion, the incidence of atrial fibrillation in our patient population was low as compared to hypertension, dyslipidemia and tobacco abuse. This stresses the need to devote more resources towards management of these chronic medical conditions. Furthermore, we showed significant differences in the rates and types of co-morbidities among men and women in our region. While men had higher rates of CAD and tobacco use, women had higher rates of atrial fibrillation and obesity. These findings are consistent with some other published studies evaluating sex differences in stroke.(15–17) Tobacco use, CAD, atrial fibrillation and obesity are all linked to increased inflammation, which is a major factor in stroke susceptibility(18–21). Interestingly, the behaviors or pathologies associated with inflammation linked to stroke differ between the sexes. These represent important sex-specific modifiable risk factors, which should be targets for public policy intervention regarding stroke prevention.
In addition to sex-based differences in high-NIHSS stroke incidence, we also noted changing characteristics among the patients in two sequential epochs. While overall rates of CAD and dyslipidemia decreased from 2011–2014 to 2015–2016 among the cohort, rates of obesity and tobacco usage increased. Elevated body mass index (BMI) in particular has been linked to increased stroke mortality in younger patients.(22) As stated above, obesity and tobacco use are both associated with inflammation.(20) Since inflammation is prothrombotic(23), obesity and tobacco use among younger people could be synergistic in decreasing the age of onset for stroke. This reflects the growing and important role that obesity has in the rural population as a modifiable stroke risk factor. Most importantly, the mean age of patients presenting with NIHSS of 10 or more was lower in the later cohort. This is concerning, since it reflects an epidemiologic shift toward younger age severe stroke incidence in our region.
There are several limitations to our study. First, the retrospective nature limits the ability to perform well-controlled and designed comparisons. Second, our analysis reflects patients presenting with NIHSS ≥ 10 specifically rather than confirmed ELVO. While the two have been shown to be closely associated, they are not the same. This limitation of data extrapolation through this methodology is that individual patients cannot be evaluated in terms of protected health information. Therefore, there are variables we could not incorporate. For example, the rate of tPA usage in this population went down from the earlier to later epoch. However, this is likely explained by expanded indications for transfer of ELVO patients for thrombectomy. If more patients arrived at our institution in the > 4.5 hour window, then the number of tPA-eligible patients with high NIHSS would be lower as a result. Finally, while our goal was to provide a region-specific analysis of patients with severe ischemic stroke, extrapolation of our results to another geographic region may not be valid.
Conclusions
Estimates of thrombectomy eligibility and utilization differ across geographic regions. In Appalachia, evaluation of the patients with severe NIH stroke scales suggests gross underutilization of mechanical thrombectomy. As the age of stroke patients in the region is decreasing, the need for additional resources to treat severe stroke as a community burden is intensifying. In creating prevention and treatment policies, we should consider notable sex differences in known risk factors, and use that information to design specific strategies to reduce severe ischemic stroke incidence, and to rapidly treat it with thrombectomy when appropriate.
Acknowledgements:
This publication was supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant UL1TR001998. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
Footnotes
Statement of Ethics: The research protocol was approved by our institutional review board.
Disclosures or Conflict(s)-of-Interest: None
References:
- 1.Ovbiagele B, Nguyen-Huynh MN. Stroke epidemiology: advancing our understanding of disease mechanism and therapy. Neurotherapeutics. 2011;8(3):319–29. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Smith WS, Lev MH, English JD, Camargo EC, Chou M, Johnston SC, et al. Significance of large vessel intracranial occlusion causing acute ischemic stroke and TIA. Stroke. 2009;40(12):3834–40. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Hacke W, Kaste M, Bluhmki E, Brozman M, Davalos A, Guidetti D, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. 2008;359(13):1317–29. [DOI] [PubMed] [Google Scholar]
- 4.Saver JL, Goyal M, Bonafe A, Diener HC, Levy EI, Pereira VM, et al. Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med. 2015;372(24):2285–95. [DOI] [PubMed] [Google Scholar]
- 5.Berkhemer OA, Fransen PS, Beumer D, van den Berg LA, Lingsma HF, Yoo AJ, et al. A randomized trial of intraarterial treatment for acute ischemic stroke. The New England journal of medicine. 2015;372(1):11–20. [DOI] [PubMed] [Google Scholar]
- 6.Campbell BC, Mitchell PJ, Kleinig TJ, Dewey HM, Churilov L, Yassi N, et al. Endovascular therapy for ischemic stroke with perfusion-imaging selection. The New England journal of medicine. 2015;372(11):1009–18. [DOI] [PubMed] [Google Scholar]
- 7.Goyal M, Demchuk AM, Menon BK, Eesa M, Rempel JL, Thornton J, et al. Randomized assessment of rapid endovascular treatment of ischemic stroke. The New England journal of medicine. 2015;372(11):1019–30. [DOI] [PubMed] [Google Scholar]
- 8.Albers GW, Marks MP, Kemp S, Christensen S, Tsai JP, Ortega-Gutierrez S, et al. Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging. N Engl J Med. 2018;378(8):708–18. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Nogueira RG, Jadhav AP, Haussen DC, Bonafe A, Budzik RF, Bhuva P, et al. Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct. N Engl J Med. 2018;378(1):11–21. [DOI] [PubMed] [Google Scholar]
- 10.Fischer U, Arnold M, Nedeltchev K, Brekenfeld C, Ballinari P, Remonda L, et al. NIHSS score and arteriographic findings in acute ischemic stroke. Stroke. 2005;36(10):2121–5. [DOI] [PubMed] [Google Scholar]
- 11.Kitzman P, Wolfe M, Elkins K, Fraser JF, Grupke SL, Dobbs MR. The Kentucky Appalachian Stroke Registry (KApSR). J Stroke Cerebrovasc Dis. 2017. [DOI] [PubMed] [Google Scholar]
- 12.Dobbs MR, Krishnamohan P, Jicha G, Cohen AP. Innovation in Stroke Care Quality: NIH Stroke Scale Change and Shewhart Charts. Qual Manag Health Care. 2015;24(3):135–9. [DOI] [PubMed] [Google Scholar]
- 13.Powers WJ, Derdeyn CP, Biller J, Coffey CS, Hoh BL, Jauch EC, et al. 2015 AHA/ASA Focused Update of the 2013 Guidelines for the Early Management of Patients With Acute Ischemic Stroke Regarding Endovascular Treatment: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke; a journal of cerebral circulation. 2015. [DOI] [PubMed] [Google Scholar]
- 14.Kapral MK, Austin PC, Jeyakumar G, Hall R, Chu A, Khan AM, et al. Rural-Urban Differences in Stroke Risk Factors, Incidence, and Mortality in People With and Without Prior Stroke. Circ Cardiovasc Qual Outcomes. 2019;12(2):e004973. [DOI] [PubMed] [Google Scholar]
- 15.Spychala MS, Honarpisheh P, McCullough LD. Sex differences in neuroinflammation and neuroprotection in ischemic stroke. Journal of neuroscience research. 2017;95(1–2):462–71. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Emdin CA, Wong CX, Hsiao AJ, Altman DG, Peters SA, Woodward M, et al. Atrial fibrillation as risk factor for cardiovascular disease and death in women compared with men: systematic review and meta-analysis of cohort studies. BMJ. 2016;532:h7013. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Ball J, Carrington MJ, Wood KA, Stewart S, Investigators S. Women versus men with chronic atrial fibrillation: insights from the Standard versus Atrial Fibrillation spEcific managemenT studY (SAFETY). PloS one. 2013;8(5):e65795. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Smoking and Inflammation. PLoS Med. 2005;2(6):e198. [Google Scholar]
- 19.Hu YF, Chen YJ, Lin YJ, Chen SA. Inflammation and the pathogenesis of atrial fibrillation. Nat Rev Cardiol. 2015;12(4):230–43. [DOI] [PubMed] [Google Scholar]
- 20.Ellulu MS, Patimah I, Khaza’ai H, Rahmat A, Abed Y. Obesity and inflammation: the linking mechanism and the complications. Archives of medical science: AMS. 2017;13(4):851–63. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.McColl BW, Allan SM, Rothwell NJ. Systemic infection, inflammation and acute ischemic stroke. Neuroscience. 2009;158(3):1049–61. [DOI] [PubMed] [Google Scholar]
- 22.Darke S, Duflou J, Kaye S, Farrell M, Lappin J. Body mass index and fatal stroke in young adults: A national study. J Forensic Leg Med. 2019;63:1–6. [DOI] [PubMed] [Google Scholar]
- 23.Libby P, Simon DI. Inflammation and thrombosis: the clot thickens. Circulation. 2001;103(13):1718–20. [DOI] [PubMed] [Google Scholar]