Albert W. Tsai

Coagulation factors, inflammation markers, and venous thromboembolism: the longitudinal investigation of thromboembolism etiology (LITE)

PURPOSE We sought to assess prospectively whether higher levels of blood coagulation factors and inflammation markers are risk factors for venous thromboembolism. SUBJECTS AND METHODS In two pooled population-based cohort studies, we measured levels of factor VII, factor VIII, von Willebrand factor, fibrinogen, and C-reactive protein, and white blood cell count, in samples obtained from 19,237 adults with no baseline history of venous thromboembolism, cancer, or warfarin use. The endpoint was validated venous thromboembolism during follow-up (median, 7.8 years). RESULTS A total of 159 venous thromboembolism events occurred. Factor VIII and von Willebrand factor were linearly associated with increased risk of venous thromboembolism (P for trend <0.0001). As compared with those in the lowest quartile, the multivariate-adjusted hazard ratio (HR) of venous thromboembolism was 2.6 (95% confidence interval [CI]: 1.6 to 4.3) for factor VIII levels in the highest quartile and 3.8 (95% CI: 2.0 to 7.2) for the highest fifth percentile. For von Willebrand factor, the hazard ratios in middle-aged subjects were 4.6 (95% CI: 2.2 to 9.2) for the highest quartile and 7.6 (95% CI: 3.1 to 18) for the highest fifth percentile. Factor VII levels above the 95th percentile, as compared with the lowest quartile, also conveyed a higher risk of venous thromboembolism (HR = 2.4; 95% CI: 1.2 to 4.8). In contrast, there was no association of venous thromboembolism with fibrinogen or C-reactive protein levels, or white cell count. CONCLUSIONS In this prospective study, elevated factor VIII and von Willebrand factor levels were common, independent, and dose-dependent risk factors for venous thromboembolism, and an elevated factor VII level was a possible risk factor. Venous thromboembolism, unlike arterial disease, was not related to inflammatory markers.

Ankle-brachial index and 7-year ischemic stroke incidence: the ARIC study.

Background and Purpose— Low ankle-brachial index (ABI), which is the ratio of tibial artery systolic blood pressure to brachial systolic artery pressure, is known to be a measure of lower limb peripheral artery disease as well as a marker for other cardiovascular disease events. The ability of ABI to predict incident ischemic stroke, however, is not established in population-based studies. Methods— ABI was measured in a cohort of 14 839 black and white men and women aged 45 to 64 years. Stroke incidence was calculated during approximately 7 years of follow-up. Results— A total of 206 incident strokes occurred. Adjusted stroke incidence rates were markedly higher for those in the lowest versus the highest categories of ABI for men, women, blacks, and whites. The proportional hazards regression model, adjusted for age, race, gender, and field center, showed an inverse linear trend between ABI and ischemic stroke incidence (P <0.0001). The lowest group (ABI <0.80) had a hazard ratio of 5.68 (95% CI 2.77 to 11.66). After adjustment for major risk factors in a multivariate model, the hazard ratio in the lowest group was elevated (1.93) but no longer statistically significant (95% CI 0.78 to 4.78). There was, however, still an indication of an overall inverse linear trend between ABI and incident stroke (P =0.03). Conclusions— Low ABI was strongly associated with increased incidence of ischemic stroke, but the relationship was substantially reduced after adjustment for major cardiovascular risk factors.

Utility of Dysphagia Screening Results in Predicting Poststroke Pneumonia

Background and Purpose— Dysphagia screening before oral intake (DS) is a stroke care quality indicator. The value of DS is unproven. Quality adherence and outcome data from the Paul Coverdell National Acute Stroke Registry were examined to establish value of DS. Methods— Adherence to the DS quality indicator was examined in patients with stroke discharged from Paul Coverdell National Acute Stroke Registry hospitals between March 1 and December 31, 2009. Patients were classified as unscreened (US), screened and passed (S/P), and screened and failed. Associations between screening status and pneumonia rate were assessed by logistic regression models after adjustment for selected variables. Results— A total of 18 017 patients with stroke discharged from 222 hospitals in 6 states were included. A total of 4509 (25%) were US; 8406 (47%) were S/P, and 5099 (28%) were screened and failed. Compared with US patients, screened patients were significantly more impaired. Pneumonia rates were: US 4.2%, S/P 2.0%, and screened and failed 6.8%. After adjustment for demographic and clinical features, US patients were at a higher risk of pneumonia (OR, 2.2; 95% CI, 1.7 to 2.7) compared with S/P patients. Conclusions— Data suggest that patients are selectively screened based on stroke severity. Pneumonia rate was higher in US patients compared with S/P patients. Clinical judgment regarding who should be screened is imperfect. S/P patients have a lower pneumonia rate indicating that DS adds accuracy in predicting pneumonia risk. The Joint Commission recently retired DS as a performance indicator for Primary Stroke Center certification. These results suggest the need to implement a DS performance measure for patients with acute stroke.

Acute Stroke Reperfusion Therapy Trends in the Expanded Treatment Window Era

BACKGROUND The American Heart Association/American Stroke Association (AHA/ASA) recommended an expansion of the time window for acute ischemic stroke (AIS) reperfusion with intravenous (IV) recombinant tissue plasminogen activator (rt-PA) from 3 to 4.5 hours after symptom onset. We examine rates of IV and intra-arterial (IA) reperfusion before and after the recommendations to track guideline adoption in community practice. METHODS Patients with AIS in the Paul Coverdell National Acute Stroke Registry spanning years 2007-2012 were identified. Trends in rates of IV rt-PA versus IA therapy were examined. Outcomes included symptomatic intracerebral hemorrhage (sICH), in-hospital mortality, ability to ambulate at discharge, and discharge destination. RESULTS From 2007 to 2012, there were 182,235 AIS patients (median age, 72 years; 51.5% women) in the database at the time of analysis. AIS patients receiving IV rt-PA increased significantly from 3.7% in 2007 to 5.1% in 2012 in the ≤3 hours time window and from .2% in 2007 to 1.3% in 2012 in the 3-4.5 hours time window (P < .001 for both). There was also a significant increase in the rate of IA therapy between 2007 and 2012 (P < .001). There was a significant decrease in the rate of sICH among patients who received any reperfusion between 2007 and 2012. CONCLUSIONS There was a trend for increased utilization of IV rt-PA in the 0-3 hours and the 3-4.5 hours time windows, which began around the same time as the publication of AHA/ASA recommendations in 2009. This increase was associated with an increase in IA treatment rates along with a decrease in overall sICH rates for patients receiving any reperfusion.

Utilization of Intravenous Thrombolysis in 3–4.5 Hours: Analysis of the Minnesota Stroke Registry

Background: The American Heart Association and the American Stroke Association recommend intravenous (IV) thrombolysis up to 4.5 h from acute ischemic stroke symptom onset based on its proven benefit in improving patient outcomes. We analyzed data from the Minnesota Stroke Registry to assess the rates of IV thrombolytic utilization and the process of care in this expanded window. Methods: We identified patients who had received IV recombinant tissue plasminogen activator (rt-PA) at any of the 19 participating hospitals from January 1, 2008 till December 31, 2010. Treatment groups were those actually treated by IV rt-PA in 0–3 h and those treated by IV rt-PA in 3–4.5 h. Duration from symptom onset to arrival in the emergency department (ED) was dichotomized to cohorts of 0–2 and 2–3.5 h. We determined the overall utilization of IV rt-PA in the expanded window and calculated door-to-needle times for the two treatment windows. We also ascertained the rates of symptomatic intracerebral hemorrhage between the two treatment groups. Results: Out of the total 519 patients who received IV rt-PA for acute ischemic stroke, 433 (83%) were treated within 0–3 h and 86 (17%) within 3–4.5 h. Of all the patients who received IV rt-PA within 3–4.5 h, 45% arrived at the ED within 2 h of symptom onset. Median door-to-needle time for the 0- to 3-hour window was 74.5 min [interquartile range (IQR) 57–90] and 54 min (IQR 43.5–70.5) for the 3- to 4.5-hour window. Based on arrival time to the ED, door-to-needle time of ≤60 min was achieved by only 31% (142/458) of patients who arrived within 0–2 h of their symptom onset compared to 61% (37/61) of those who arrived at the ED within 2–3.5 h of their symptom onset. Fifty-nine (14%) patients in the 0- to 3-hour group and 17 (20%) patients in the 3- to 4.5-hour group received a combination of IV rt-PA and endovascular treatments. Among patients with documented admission National Institutes of Health Stroke Scale scores, the values (median with IQR) were different between the 0- to 3- and the 3- to 4.5-hour group, i.e. 10 (IQR 5–18) and 7 (IQR 4–14), respectively. Conclusion: Patients who received IV rt-PA within the 3- to 4.5-hour window comprised 17% of all IV rt-PA cases treated in the Minnesota Stroke Registry hospitals after the new guidelines recommended a time window expansion. Almost half of these patients would have qualified for treatment within the 0- to 3-hour window as they presented within 0–2 h of symptom onset. Patients arriving 2–3.5 h after symptom onset received thrombolysis on average 20 min faster than patients arriving within 2 h of symptom onset.

Impact of an Electronic Medical Record-Based Clinical Decision Support Tool for Dysphagia Screening on Care Quality

Background and Purpose— Dysphagia screening (DS) before oral intake in patients with acute stroke is a hospital-level performance measure. We report outcomes of an initiative to improve compliance to this quality measure. Methods— The design was a pre- versus postintervention comparison study. The Intervention was an electronic medical record-based clinical DS system embedded within stroke admission orders. The clinical DS was designed to facilitate DS in patients with stroke. The primary outcome was compliance to a process measure in patients with ischemic stroke: performance of a swallow screen before oral intake. Results— DS measure compliance increased from 36% to 74% (P=0.001). Chart audits found screened patients were more likely to have clinical DS-embedded admission orders initiated or stroke unit admission. Conclusion— The electronic medical record offers a ready platform for clinical DS implementation. DS is a difficult performance measure to improve. The described clinical DS has the potential for improving performance on this challenging care quality measure.