scholarly journals Cholesterol reducer and Thrombolytic therapy in acute ischemic stroke

2020 ◽  
Author(s):  
Nicolas Poupore ◽  
Dan Strat ◽  
Tristan Mackey ◽  
Katherine Brown ◽  
Ashley Snell ◽  
...  

Abstract Background Specific clinical risk factors may contribute to worsening or improving neurological functions in an acute ischemic stroke (AIS) patient pre-treated with a cholesterol reducer with a subsequent recombinant tissue plasminogen activator (rtPA) treatment. We investigated clinical risk factors associated with good or poor presenting neurological symptoms in ischemic stroke patients with prior cholesterol reducer use, specifically a statin and rtPA therapy.Methods We retrospectively analyzed baseline clinical and demographic data of 630 patients with AIS taking cholesterol reducers prior to rtPA treatment from January 2010 to June 2016 in a regional stroke center. Progressing (NIHSS ≤ 7) or worsening (NIHSS > 7) scores for neurologic improvement determined measures for treatment outcome. Multivariate logistic regression models identified demographic and clinical factors associated with worsening or progressing neurologic functions.Results Adjusted multivariate analysis showed that in an ischemic stroke population with a combined rtPA and cholesterol reducer medication history, increasing age (OR = 1.032, 95% CI, 1.015-1.048, P < 0.001) and atrial fibrillation (OR = 1.859, 95% CI, 1.098-3.149, P = 0.021) demonstrated a likely association with worsening neurologic functions, while direct admission (OR = 0.411, 95% CI, 0.246-0.686, P = 0.001) and being Caucasian (OR = 0.496, 95% CI, 0.297-0.827, P = 0.007) showed an association with improving or progressing neurologic functions.Conclusion A prior cholesterol reducer, namely a statin, plus rtPA combination may be associated with worsening neurological function for elderly AIS patients with atrial fibrillation, while Caucasians directly admitted to a neurology unit are more likely to show an association with progress or improvements in neurologic functions.

2020 ◽  
Author(s):  
Nicolas Poupore ◽  
Dan Strat ◽  
Tristan Mackey ◽  
Katherine Brown ◽  
Ashley Snell ◽  
...  

Abstract Background Specific clinical risk factors may contribute to worsening or improving neurological functions in an acute ischemic stroke (AIS) patient pre-treated with a cholesterol reducer with a subsequent recombinant tissue plasminogen activator (rtPA) treatment. We investigated clinical risk factors associated with good or poor presenting neurological symptoms in ischemic stroke patients with prior cholesterol reducer use, specifically a statin and rtPA therapy. Methods We retrospectively analyzed baseline clinical and demographic data of 630 patients with AIS taking cholesterol reducers prior to rtPA treatment from January 2010 to June 2016 in a regional stroke center. Progressing (NIHSS ≤ 7) or worsening (NIHSS > 7) scores for neurologic improvement determined measures for treatment outcome. Multivariate logistic regression models identified demographic and clinical factors associated with worsening or progressing neurologic functions. Results Adjusted multivariate analysis showed that in an ischemic stroke population with a combined rtPA and cholesterol reducer medication history, increasing age (OR = 1.032, 95% CI, 1.015-1.048, P < 0.001) and atrial fibrillation (OR = 1.859, 95% CI, 1.098-3.149, P = 0.021) demonstrated a likely association with worsening neurologic functions, while direct admission (OR = 0.411, 95% CI, 0.246-0.686, P = 0.001) and being Caucasian (OR = 0.496, 95% CI, 0.297-0.827, P = 0.007) showed an association with improving or progressing neurologic functions. Conclusion A prior cholesterol reducer, namely a statin, plus rtPA combination may be associated with worsening neurological function for elderly AIS patients with atrial fibrillation, while Caucasians directly admitted to a neurology unit are more likely to show an association with progress or improvements in neurologic functions.


Author(s):  
Nicholas A. Marston ◽  
Parth N. Patel ◽  
Frederick K. Kamanu ◽  
Francesco Nordio ◽  
Giorgio M. Melloni ◽  
...  

Background: Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) that are associated with an increased risk of stroke. We sought to determine whether a genetic risk score (GRS) could identify subjects at higher risk for ischemic stroke after accounting for traditional clinical risk factors in five trials across the spectrum of cardiometabolic disease. Methods: Subjects who had consented for genetic testing and who were of European ancestry from the ENGAGE AF-TIMI 48, SOLID-TIMI 52, SAVOR-TIMI 53, PEGASUS-TIMI 54, and FOURIER trials were included in this analysis. A set of 32 SNPs associated with ischemic stroke was used to calculate a GRS in each patient and identify tertiles of genetic risk. A Cox model was used to calculate hazard ratios for ischemic stroke across genetic risk groups, adjusted for clinical risk factors. Results: In 51,288 subjects across the five trials, a total of 960 subjects had an ischemic stroke over a median follow-up period of 2.5 years. After adjusting for clinical risk factors, increasing genetic risk was strongly and independently associated with increased risk for ischemic stroke (p-trend=0.009). When compared to individuals in the lowest third of genetic risk, individuals in the middle and top tertiles of genetic risk had adjusted hazard ratios of 1.15 (95% CI 0.98-1.36) and 1.24 (95% CI 1.05-1.45) for ischemic stroke, respectively. Stratification into subgroups revealed the performance of the GRS appeared stronger in the primary prevention cohort with an adjusted HR for the top versus lowest tertile of 1.27 (95% CI 1.04-1.53), compared with an adjusted HR of 1.06 (95% CI 0.81-1.41) in subjects with prior stroke. In an exploratory analysis of patients with atrial fibrillation and CHA 2 DS 2 -VASc of 2, high genetic risk conferred a 4-fold higher risk of stroke and an absolute risk equivalent to those with CHA 2 DS 2 -VASc of 3. Conclusions: Across a broad spectrum of subjects with cardiometabolic disease, a 32-SNP GRS was a strong, independent predictor of ischemic stroke. In patients with atrial fibrillation but lower CHA 2 DS 2 -VASc scores, the GRS identified patients with risk comparable to those with higher CHA 2 DS 2 -VASc scores.


Medicine ◽  
2020 ◽  
Vol 99 (26) ◽  
pp. e20830
Author(s):  
Yuanyuan Zhuo ◽  
Jiaman Wu ◽  
Yimin Qu ◽  
Haibo Yu ◽  
Xingxian Huang ◽  
...  

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Nicolas Poupore ◽  
Bridgette Allen ◽  
Thomas I Nathaniel

Background: The aim of this study is to identify clinical risk factors in acute ischemic stroke ( AIS) pretreated with anti-hypertensive (anti-HTN) medications with a subsequent thrombolytic therapy that are associated with potential worsening or improving neurological functions. Methods: We analyzed retrospectively collected data from consecutive AIS patients with a combined anti-HTN medications and recombinant tissue plasminogen activator (rtPA) therapy for AIS. We used logistic regression model to identify demographic and clinical risk factors that are associated with improving or worsening neurologic functions in AIS patients with a combined anti-HTN and thrombolytic therapy. The overall correct classification of the logistic regression models was determined using the Hosmer-Lemeshow test, while the area under the receiver operating characteristic curve was used to test the sensitivity of the model. The variance inflation factor was used to check for multicollinearity. Results: In the adjusted analysis, patients with increasing age (Odd ratio (OR)=1.035, 95% CI, 1.022-1.049, P <0.001), female AIS patients (OR = 1.630, 95% CI, 1.182-2.248, P =0.002) with a history of substance abuse (OR = 2.315, 95% CI, 1.107-4.842, P = 0.026) were associated with worsening neurologic functions. However, Caucasians (OR = 0.535, 95% CI, 0.361-0.793, P = 0.002) with dyslipidemia (OR = 0.655, 95% CI, 0.479-0.897, P = 0.008), obesity (OR = 0.642, 95% CI, 0.472-0.873, P = 0.005), high-density lipoproteins (HDL; OR = 0.988, 95% CI, 0.976-1.000, P = 0.045), and with a direct admission (OR = 0.509, 95% CI, 0.341-0.761, P = 0.001) were associated with improving neurologic function in AIS patients with a combined anti-HTN medications and rtPA therapy. Conclusion: Our findings reveal specific demographic and clinical risk factors that are associated with worsening or improving neurological functions in AIS pretreated anti-HTN medications with a subsequent thrombolytic therapy. This finding suggests the development of management strategies to manage identified clinical risk factors in AIS patients pretreated with anti-HTN medications prior to thrombolytic therapy.


Author(s):  
Jack W. O'Sullivan ◽  
Anna Shcherbina ◽  
Johanne M. Justesen ◽  
Mintu Turakhia ◽  
Marco Perez ◽  
...  

Background - Atrial fibrillation (AF) is associated with a five-fold increased risk of ischemic stroke. A portion of this risk is heritable, however current risk stratification tools (CHA 2 DS 2 -VASc) don't include family history or genetic risk. We hypothesized that we could improve ischemic stroke prediction in patients with AF by incorporating polygenic risk scores (PRS). Methods - Using data from the largest available GWAS in Europeans, we combined over half a million genetic variants to construct a PRS to predict ischemic stroke in patients with AF. We externally validated this PRS in independent data from the UK Biobank, both independently and integrated with clinical risk factors. The integrated PRS and clinical risk factors risk tool had the greatest predictive ability. Results - Compared with the currently recommended risk tool (CHA 2 DS 2 -VASc), the integrated tool significantly improved net reclassification (NRI: 2.3% (95%CI: 1.3% to 3.0%)), and fit (χ2 P =0.002). Using this improved tool, >115,000 people with AF would have improved risk classification in the US. Independently, PRS was a significant predictor of ischemic stroke in patients with AF prospectively (Hazard Ratio: 1.13 per 1 SD (95%CI: 1.06 to 1.23)). Lastly, polygenic risk scores were uncorrelated with clinical risk factors (Pearson's correlation coefficient: -0.018). Conclusions - In patients with AF, there appears to be a significant association between PRS and risk of ischemic stroke. The greatest predictive ability was found with the integration of PRS and clinical risk factors, however the prediction of stroke remains challenging.


Author(s):  
Carolyn B Sanders ◽  
Camron Edrissi ◽  
Chase Rathfoot ◽  
Krista Knisely ◽  
Nicolas Poupore ◽  
...  

Introduction : It is estimated that approximately 10–24% of acute ischemic stroke (AIS) patients have comorbid heart failure (HF). However, it is currently unknown if certain clinical risk factors associated with rtPA thrombolytic therapy differ based on HF diagnosis. The purpose of this study is to determine the clinical factors associated with rtPA inclusion in AIS patients with and without heart failure. Methods : Retrospective data for baseline clinical and demographic factors from January 2010 to January 2016 in a regional stroke center were analyzed. Of the 5,469 patients identified with AIS, 590 presented with heart failure while 4,879 did not. Odds ratios and 95% confidence intervals were used to determine which clinical factors were associated with rtPA inclusion. Results : Adjusted multivariate analysis demonstrated that within the AIS population, those without HF who received rtPA were more likely to be associated with Hispanic ethnicity (OR = 0.464, 95% CI, 0.247‐0.87, P = 0.017), coronary artery stenosis (OR = 0.55, 95% CI, 0.366‐0.83, P = 0.004), previous stroke (OR = 0.745, 95% CI, 0.609‐0.91, P = 0.004), previous TIA (OR = 1.447, 95% CI, 1.094‐1.91, P = 0.010), total cholesterol (OR = 1.487, 95% CI, 1.175‐1.88, P = 0.001), lipids (OR = 0.998, 95% CI, 0.996‐1, P = 0.038), serum creatinine (OR = 0.899, 95% CI, 0.854‐0.95, P<0.001), INR (OR = 0.825, 95% CI, 0.73‐0.93, P = 0.002), heart rate (OR = 0.13, 95% CI, 0.071‐0.24, P<0.001), and direct admission (OR = 2.87, 95% CI, 2.432‐3.39, P<0.001). AIS patients with HF who received rtPA were more likely to be associated with increasing age (OR = 0.982, 95% CI, 0.966‐1, P = 0.020), coronary artery disease (OR = 0.618, 95% CI, 0.391‐0.98, P = 0.0.040), INR (OR = 0.326, 95% CI, 0.129‐0.82, P = 0.018), and ambulatory improvement (OR = 1.69, 95% CI, 1.058‐2.7, P = 0.0.028). Conclusions : The results of this study demonstrate that within the AIS population, there are certain clinical risk factors that influence the likelihood of receiving rtPA in patients with and without HF. These findings provide further insight into AIS and HF and suggest the need for further research into the role the identified factors play in influencing clinical outcome.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Jack W Osullivan ◽  
Anna Shcherbina ◽  
Johanne M Justesen ◽  
Mintu Turakhia ◽  
Marco V Perez ◽  
...  

Introduction: Atrial fibrillation (AF) is associated with a five-fold increased risk of ischemic stroke. A portion of this risk is heritable, however current risk stratification tools (CHA 2 DS 2 -VASc) don’t include family history or genetic risk. Hypothesis: A polygenic risk scores (PRS) is both independently, and in integrated with clinical risk factors, predictive of ischemic stroke in patients with Atrial Fibrillation. Methods: Using data from the largest available GWAS in Europeans, we combined over half a million genetic variants to construct a PRS to predict ischemic stroke in patients with AF. We externally validated this PRS in independent data from the UK Biobank (UK Biobank), both independently and integrated with clinical risk factors. Results: The integrated PRS and clinical risk factors risk tool had the greatest predictive ability. Compared with the currently recommended risk tool (CHA 2 DS 2 -VASc), the integrated tool significantly improved net reclassification (NRI: 2.3% (95%CI: 1.3% to 3.0%)), and fit (χ2 P =0.002). Independently, PRS was a significant predictor of ischemic stroke in patients with AF prospectively (Hazard Ratio: 1.13 per 1 SD (95%CI: 1.04 to 1.21)). Lastly, polygenic risk scores were uncorrelated with clinical risk factors (Pearson’s correlation coefficient: -0.018). Conclusions: In patients with AF, there appears to be a significant association between PRS and risk of ischemic stroke. The greatest predictive ability was found with the integration of PRS and clinical risk factors, however the prediction of stroke remains challenging.


2020 ◽  
Vol 26 ◽  
pp. 107602962090686 ◽  
Author(s):  
Nicolas Poupore ◽  
Dan Strat ◽  
Tristan Mackey ◽  
Thomas I. Nathaniel

Background: Specific clinical risk factors linked to transient ischemic attack (TIA) could affect functional ambulatory outcome following thrombolytic therapy in patients having ischemic stroke with a prior TIA (TIA-ischemic stroke). This issue was investigated in this study. Methods: We retrospectively analyzed data from 6379 ischemic stroke patients of which 1387 presented with an antecedent TIA prior to onset of stroke. We used logistic regression model to identify demographic and clinical risk factors that are associated with functional ambulatory outcome in patients with TIA-ischemic stroke treated with thrombolytic therapy. Results: In a population of TIA-ischemic stroke who received recombinant tissue plasminogen activator, patients with a history of stroke (odds ratio [OR] = 3.229, 95% confidence interval [CI] = 1.494-6.98, P = .003) were associated with increasing odds of improvement in functional ambulation, while the female gender (OR = 0.462, 95% CI = 0.223-0.956, P = .037) was associated with reducing odds of improvement. In the non-TIA group, dyslipidemia (OR = 1.351, 95% CI = 1.026-1.781, P = .032) and blood glucose (OR = 1.003, 95% CI = 1.0-1.005, P = .041) were associated with the increasing odds of improvement while older patients (OR = 0.989, 95% CI = 0.98-0.999, P = .029) with heart failure (OR = 0.513, 95% CI = 0.326-0.808, P = .004) and higher lipid level (OR = 0.834, 95% CI = 0.728-0.955, P = .009) were associated with reducing odds of improvement in ambulation. Conclusion: In a population of TIA-ischemic stroke with thrombolytic therapy and a clearly defined TIA without focal ischemic injury, regardless of associated clinical risk factors, a TIA prior to a stroke is not associated with reducing odds of improved ambulatory outcome, except in female patients with TIA-ischemic stroke.


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