Felipe De Los Rios La Rosa

Age at stroke: Temporal trends in stroke incidence in a large, biracial population

Objectives: We describe temporal trends in stroke incidence stratified by age from our population-based stroke epidemiology study. We hypothesized that stroke incidence in younger adults (age 20–54) increased over time, most notably between 1999 and 2005. Methods: The Greater Cincinnati/Northern Kentucky region includes an estimated population of 1.3 million. Strokes were ascertained in the population between July 1, 1993, and June 30, 1994, and in calendar years 1999 and 2005. Age-, race-, and gender-specific incidence rates with 95 confidence intervals were calculated assuming a Poisson distribution. We tested for differences in age trends over time using a mixed-model approach, with appropriate link functions. Results: The mean age at stroke significantly decreased from 71.2 years in 1993/1994 to 69.2 years in 2005 (p < 0.0001). The proportion of all strokes under age 55 increased from 12.9% in 1993/1994 to 18.6% in 2005. Regression modeling showed a significant change over time (p = 0.002), characterized as a shift to younger strokes in 2005 compared with earlier study periods. Stroke incidence rates in those 20–54 years of age were significantly increased in both black and white patients in 2005 compared to earlier periods. Conclusions: We found trends toward increasing stroke incidence at younger ages. This is of great public health significance because strokes in younger patients carry the potential for greater lifetime burden of disability and because some potential contributors identified for this trend are modifiable.

Eligibility for Intravenous Recombinant Tissue-Type Plasminogen Activator Within a Population The Effect of the European Cooperative Acute Stroke Study (ECASS) III Trial

Background and Purpose The publication of the European Cooperative Acute Stroke Study (ECASS III) expanded the treatment time to thrombolysis for acute ischemic stroke from 3 to 4.5 hours from symptom onset. The impact of the expanded time window on treatment rates has not been comprehensively evaluated in a population based study.Background and Purpose— The publication of the European Cooperative Acute Stroke Study (ECASS III) expanded the treatment time to thrombolysis for acute ischemic stroke from 3 to 4.5 hours from symptom onset. The impact of the expanded time window on treatment rates has not been comprehensively evaluated in a population-based study. Methods— All patients with an ischemic stroke presenting to an emergency department during calendar year 2005 in the 17 hospitals that compromise the large 1.3 million Greater Cincinnati/Northern Kentucky population were included in the analysis. Criteria for exclusion from thrombolytic therapy are analyzed retrospectively for both the standard and expanded timeframes with varying door-to-needle times. Results— During the study period, 1838 ischemic strokes presenting to an emergency department were identified. A small proportion of them arrived in the expanded time window (3.4%) compared with the standard time window (22%). Only 0.5% of those who arrived in this timeframe met eligibility criteria for thrombolysis compared with 5.9% using standard eligibility criteria in the standard timeframe. These results did not vary significantly by repeated analysis varying the door-to-needle time or the expanded time windows exclusion criteria. Conclusions— In reality, the expanded time window for thrombolysis in acute ischemic stroke benefits few patients. If we are to improve recombinant tissue-type plasminogen activator administration rates, our focus should be on improving stroke awareness, transport to facilities with ability to administer thrombolysis, and familiarity of physicians with acute stroke treatment guidelines.

Genome-Wide Association Study of Intracranial Aneurysms Confirms Role of Anril and SOX17 in Disease Risk

Background— Genomewide association studies have identified novel genetic factors that contribute to intracranial aneurysm (IA) susceptibility. We sought to confirm previously reported loci, to identify novel risk factors, and to evaluate the contribution of these factors to familial and sporadic IA. Method— We utilized 2 complementary samples, one recruited on the basis of a dense family history of IA (discovery sample 1: 388 IA cases and 397 controls) and the other without regard to family history (discovery sample 2: 1095 IA cases and 1286 controls). Imputation was used to generate a common set of single nucleotide polymorphisms (SNP) across samples, and a logistic regression model was used to test for association in each sample. Results from each sample were then combined in a metaanalysis. Results— There was only modest overlap in the association results obtained in the 2 samples. In neither sample did results reach genomewide significance. However, the metaanalysis yielded genomewide significance for SNP on chromosome 9p (CDKN2BAS; rs6475606; P=3.6 × 10−8) and provided further evidence to support the previously reported association of IA with SNP in SOX17 on chromosome 8q (rs1072737; P=8.7 × 10−5). Analyses suggest that the effect of smoking acts multiplicatively with the SNP genotype, and smoking has a greater effect on risk than SNP genotype. Conclusion— In addition to replicating several previously reported loci, we provide further evidence that the association on chromosome 9p is attributable to variants in CDKN2BAS (also known as ANRIL, an antisense noncoding RNA).

Temporal Trends in Acute Stroke Management

The benefit of intravenous recombinant tissue-type plasminogen activator (rt-PA) for the treatment of acute ischemic stroke is well established.1,2 Unfortunately, the rates of rt-PA use among US patients with ischemic stroke remain quite low. Previously, our group published the rate of rt-PA use among ischemic stroke patients within the large Premier database, which is a 15% sampling of US hospitals that cross-references drug use with administrative data. The rate of rt-PA use was extremely low and did not increase from 2001 to 2004.3 This was despite rt-PA being approved for use in the US since 1996. More recently, we found that the rates of rt-PA have begun to slowly increase from 1.4% in fiscal year (FY) 2001 to 4.5% in FY 2009 (Figure 1).4 The timing of this increase seemed to coincide with primary stroke center certification by the Joint Commission in the United States in 2004, although this is only an association rather than definitive causality. Rates of rt-PA use did not seem to be affected by increased reimbursement given to hospitals for care of rt-PA–treated patients (instituted in 2006), as we had originally hypothesized. Figure 1. National estimates of recombinant tissue-type plasminogen activator (rt-PA) use in the United States. To explore the impact further of …

Analysis of Tissue Plasminogen Activator Eligibility by Sex in the Greater Cincinnati/Northern Kentucky Stroke Study

Background and Purpose— Sex differences in recombinant tissue-type plasminogen activator (r-tPA) administration are present in some populations. It is unknown whether this is because of eligibility differences or the modifiable exclusion criterion of severe hypertension. Our aim was to investigate sex differences in r-tPA eligibility, in individual exclusion criteria, and in the modifiable exclusion criterion, hypertension. Methods— We included all ischemic stroke patients ≥18 years among residents of the Greater Cincinnati/Northern Kentucky region who presented to 16-area emergency departments in 2005. Eligibility for r-tPA and individual exclusion criteria were determined using 2013 American Heart Association (AHA) and European Cooperative Acute Stroke Study (ECASS) III guidelines. Results— Of 1837 ischemic strokes, 58% were women, 24% were black. Mean age in years was 72.2 for women and 66.1 for men. Eligibility for r-tPA was similar by sex (6.8% men and 6.1% women; P=0.55), even after adjusting for age (7.0% and 5.9%; P=0.32). Similar proportions of women and men arrived beyond 3- and 4.5-hour time windows, but more women had severe hypertension. There were no sex differences in blood pressure treatment rates among those with severe hypertension (14.6% women and 20.8% men; P=0.21). More women were >80 years and had National Institutes of Health Stroke Scale (NIHSS) >25. Conclusions— Within a large, biracial population, eligibility for r-tPA was similar by sex. Women were more likely to have the modifiable exclusion criterion of severe hypertension but were not more likely to be treated. Women were more likely to have 2 of the 5 ECASS III exclusion criteria. Undertreatment of hypertension in women is a potentially modifiable contributor to reported differences in r-tPA administration.

Sex-specific stroke incidence over time in the Greater Cincinnati/Northern Kentucky Stroke Study.

Objective: Recent data suggest stroke incidence is decreasing over time, but it is unknown whether incidence is decreasing in women and men to the same extent. Methods: Within our population of 1.3 million, all incident strokes among residents ≥20 years old were ascertained at all hospitals during July 1993–June 1994 and calendar years 1999, 2005, and 2010. A sampling scheme was used to ascertain out-of-hospital cases. Sex-specific incidence rates per 100,000 among black and white participants, age- and race-adjusted, were standardized to the 2000 US Census population. Trends over time by sex were compared; a Bonferroni correction was applied for multiple comparisons. Results: Over the 4 study periods, there were 7,710 incident strokes; 57.2% (n = 4,412) were women. Women were older than men (mean ± SE 72.4 ± 0.34 vs 68.2 ± 0.32, p < 0.001). Incidence of all strokes decreased over time in men (263 [confidence interval 246–281] to 192 [179–205], p < 0.001) but not in women (217 [205–230] to 198 [187–210], p = 0.15). Similar sex differences were seen for ischemic stroke (men, 238 [223–257] to 165 [153–177], p < 0.01; women, 193 [181–205] to 173 [162–184], p = 0.09). Incidence of all strokes and of ischemic strokes was similar between women and men in 2010. Incidence of intracerebral hemorrhage and subarachnoid hemorrhage were stable over time in both sexes. Conclusions: Decreases in stroke incidence over time are driven by a decrease in ischemic stroke in men. Contrary to previous study periods, stroke incidence rates were similar by sex in 2010. Future research is needed to understand why the decrease in ischemic stroke incidence is more pronounced in men.

Prevalence of Positive Troponin and Echocardiogram Findings and Association With Mortality in Acute Ischemic Stroke

Background and Purpose— Acute ischemic stroke (AIS) patients may have raised serum cardiac troponin levels on admission, although it is unclear what prognostic implications this has, and whether elevated levels are associated with cardiac causes of stroke or structural cardiac disease as seen on echocardiogram. We investigated the positivity of cardiac troponin and echocardiogram testing within a large biracial AIS population and any association with poststroke mortality. Methods— Within a catchment area of 1.3 million, we screened emergency department admissions from 2010 using International Classification of Diseases, Ninth Edition, discharge codes 430 to 436 and ascertained all physician-confirmed AIS cases by retrospective chart review. Hypertroponinemia was defined as elevation in cardiac troponin above the standard 99th percentile. Multiple logistic regression was performed, controlling for stroke severity, history of cardiac disease, and all other stroke risk factors. Results— Of 1999 AIS cases, 1706 (85.3%) had a cardiac troponin drawn and 1590 (79.5%) had echocardiograms. Hypertroponinemia occurred in 353 of 1706 (20.7%) and 160 of 1590 (10.1%) had echocardiogram findings of interest. Among 1377 who had both tests performed, hypertroponinemia was independently associated with echocardiogram findings (odds ratio, 2.9; 95% confidence interval, 2–4.2). When concurrent myocardial infarctions (3.5%) were excluded, hypertroponinemia was also associated with increased mortality at 1 year (35%; odds ratio, 3.45; 95% confidence interval, 2.1–5.6) and 3 years (60%; odds ratio, 2.91; 95% confidence interval, 2.06–4.11). Conclusions— Hypertroponinemia in the context of AIS without concurrent myocardial infarction was associated with structural cardiac disease and long-term mortality. Prospective studies are needed to determine whether further cardiac evaluation might improve the long-term mortality rates seen in this group.

Estimated Impact of Emergency Medical Service Triage of Stroke Patients on Comprehensive Stroke Centers: An Urban Population-Based Study

Background and Purpose— The American Stroke Association recommends that Emergency Medical Service bypass acute stroke–ready hospital (ASRH)/primary stroke center (PSC) for comprehensive stroke centers (CSCs) when transporting appropriate stroke patients, if the additional travel time is ⩽15 minutes. However, data on additional transport time and the effect on hospital census remain unknown. Methods— Stroke patients ≥20 years old who were transported from home to an ASRH/PSC or CSC via Emergency Medical Service in 2010 were identified in the Greater Cincinnati area population of 1.3 million. Addresses of all patients’ residences and hospitals were geocoded, and estimated travel times were calculated. We estimated the mean differences between the travel time for patients taken to an ASRH/PSC and the theoretical time had they been transported directly to the region’s CSC. Results— Of 929 patients with geocoded addresses, 806 were transported via Emergency Medical Service directly to an ASRH/PSC. Mean additional travel time of direct transport to the CSC, compared with transport to an ASRH/PSC, was 7.9±6.8 minutes; 85% would have ⩽15 minutes added transport time. Triage of all stroke patients to the CSC would have added 727 patients to the CSC’s census in 2010. Limiting triage to the CSC to patients with National Institutes of Health Stroke Scale score of ≥10 within 6 hours of onset would have added 116 patients (2.2 per week) to the CSC’s annual census. Conclusions— Emergency Medical Service triage to CSCs based on stroke severity and symptom duration may be feasible. The impact on stroke systems of care and patient outcomes remains to be determined and requires prospective evaluation.

Toward a Modern Delivery of Stroke Care in Emerging Economies

Noncommunicable diseases are now a major source of mortality and disability in the developing world. Stroke incidence and prevalence is on the rise and is of particular interest because of its elevated mortality and morbidity. Developing countries bear the brunt of this disease, which hampers efforts to achieve economic and societal growth. Effective strategies to control this disease should focus on prevention without neglecting acute therapies.

Association Between Acute Kidney Disease and Intravenous Dye Administration in Patients With Acute Stroke: A Population-Based Study

Background and Purpose— Computed tomographic angiography and conventional angiography provide timely vascular anatomic information in patients with stroke. However, iodinated contrast dye may cause acute kidney injury (AKI). Within a large, biracial population, we examined in-hospital incidence of new or worsening kidney disease in patients with stroke and its association with administration of intravenous dye. Methods— All adult residents of the Greater Cincinnati/Northern Kentucky region with acute ischemic stroke or intracerebral hemorrhage who presented to an emergency department in 2010 were included. Prevalence of unsuspected kidney disease at the time of emergency department presentation and the incidence of AKI after admission in 2 groups of patients—those who did and those who did not receive intravenous dye—were determined. Results— In 2010, 2299 patients met inclusion criteria (89% ischemic stroke and 11% intracerebral hemorrhage); mean age 69 years (SD 15), 22% black, and 54% women. Among these patients, 37% had kidney disease at baseline, including 22% (516/2299) in whom this was unsuspected. Two percent (2%; 15/853) of patients with baseline kidney disease developed AKI during the hospital stay. Of those with no baseline kidney disease, 1% (14/14 467) developed AKI. There was no association between dye administration and new or worsening kidney disease. Conclusions— Although 22% of patients in the Greater Cincinnati/Northern Kentucky stroke population had unsuspected kidney disease, the incidence of new or worsening kidney disease was low, and AKI was not associated with dye administration. These findings confirm single-center reports that the risk of severe renal complications after contrast dye is small.