Dawn Kleindorfer

An Updated Definition of Stroke for the 21st Century A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association

Despite the global impact and advances in understanding the pathophysiology of cerebrovascular diseases, the term “stroke” is not consistently defined in clinical practice, in clinical research, or in assessments of the public health. The classic definition is mainly clinical and does not account for advances in science and technology. The Stroke Council of the American Heart Association/American Stroke Association convened a writing group to develop an expert consensus document for an updated definition of stroke for the 21st century. Central nervous system infarction is defined as brain, spinal cord, or retinal cell death attributable to ischemia, based on neuropathological, neuroimaging, and/or clinical evidence of permanent injury. Central nervous system infarction occurs over a clinical spectrum: Ischemic stroke specifically refers to central nervous system infarction accompanied by overt symptoms, while silent infarction by definition causes no known symptoms. Stroke also broadly includes intracerebral hemorrhage and subarachnoid hemorrhage. The updated definition of stroke incorporates clinical and tissue criteria and can be incorporated into practice, research, and assessments of the public health.

Incidence and Short-Term Prognosis of Transient Ischemic Attack in a Population-Based Study

Background and Purpose— Transient ischemic attacks (TIAs) have been shown to be a strong predictor of subsequent stroke and death. We present the incidence and short-term prognosis of TIA within a large population with a significant proportion of minorities with out-of-hospital TIA. Methods— TIA cases were identified between July 1, 1993 and June 30, 1994 from the Greater Cincinnati/Northern Kentucky population of 1.3 million inhabitants by previously published surveillance methods, including inpatient and out-of-hospital events. Incidence rates were adjusted to the 1990 population, and life-table analyses were used for prognosis. Results— The overall race, age, and gender-adjusted incidence rate for TIA within our population was 83 per 100 000, with age, race, and gender adjusted to the 1990 US population. Blacks and men had significantly higher rates of TIA than whites and women. Risk of stroke after TIA was 14.6% at 3 months, and risk of TIA/stroke/death was 25.2%. Age, race, and sex were not associated with recurrent TIA or subsequent stroke in our population, but age was associated with mortality. Conclusions— Using our incidence rates for TIA in blacks and whites, we conservatively estimate that ≈240 000 TIAs occurred in 2002 in the United States. Our incidence rate of TIA is slightly higher than previously reported, which may be related to the inclusion of blacks and out-of-hospital events. There are racial and gender-related differences in the incidence of TIA. We found a striking risk of adverse events after TIA; however, there were no racial or gender differences predicting these events. Further study is warranted in interventions to prevent these adverse events after TIA.

The increasing incidence of anticoagulant-associated intracerebral hemorrhage

Objective: To define temporal trends in the incidence of anticoagulant-associated intracerebral hemorrhage (AAICH) during the 1990s and relate them to rates of cardioembolic ischemic stroke. Methods: We identified all patients hospitalized with first-ever intracerebral hemorrhage (ICH) in greater Cincinnati during 1988, from July 1993 through June 1994, and during 1999. AAICH was defined as ICH in patients receiving warfarin or heparin. Patients from the same region hospitalized with first-ever ischemic stroke of cardioembolic mechanism were identified during 1993/1994 and 1999. Incidence rates were calculated and adjusted to the 2000 US population. Estimates of warfarin distribution in the United States were obtained for the years 1988 through 2004. Results: AAICH occurred in 9 of 184 ICH cases (5%) in 1988, 23 of 267 cases (9%) in 1993/1994, and 54 of 311 cases (17%) in 1999 (p < 0.001). The annual incidence of AAICH per 100,000 persons was 0.8 (95% CI 0.3 to 1.3) in 1988, 1.9 (1.1 to 2.7) in 1993/1994, and 4.4 (3.2 to 5.5) in 1999 (p < 0.001 for trend). Among persons aged ≥80, the AAICH rate increased from 2.5 (0 to 7.4) in 1988 to 45.9 (25.6 to 66.2) in 1999 (p < 0.001 for trend). Incidence rates of cardioembolic ischemic stroke were similar in 1993/1994 and 1999 (31.1 vs 30.4, p = 0.65). Warfarin distribution in the United States quadrupled on a per-capita basis between 1988 and 1999. Conclusions: The incidence of anticoagulant-associated intracerebral hemorrhage quintupled in our population during the 1990s. The majority of this change can be explained by increasing warfarin use. Anticoagulant-associated intracerebral hemorrhage now occurs at a frequency comparable to subarachnoid hemorrhage.

Recombinant Tissue-Type Plasminogen Activator Use for Ischemic Stroke in the United States A Doubling of Treatment Rates Over the Course of 5 Years

Background and Purpose— Recombinant tissue-type plasminogen activator (rtPA) is the only approved therapy for acute ischemic stroke (AIS). In 2004, 1.8% to 2.1% of AIS patients in the United States received rtPA. Given incentives from regulatory agencies and payors to increase rtPA use, we hypothesized that rtPA use in the United States would increase from 2005 to 2009. Methods— AIS cases were defined by exclusion of hemorrhagic stroke and transient ischemic attack International Classification of Diseases 9th revision codes (430, 431, 432, and 435) from diagnosis-related groups 14, 15, 524, and 559 discharges. Patients receiving thrombolytics were identified using International Classification of Diseases 9th revision code 99.10 (Medicare Provider and Analysis Review and Premier databases) and pharmacy billing records (Premier). Change over time and differences between databases were tested using negative binomial regression. Results— Within Medicare Provider and Analysis Review, thrombolytic use increased from 1.1% in 2005 to 3.4% in 2009 (P<0.001 for trend). Within Premier, thrombolytic use increased from 1.4% in 2005 to 3.7% in 2009 for all cases (P<0.001). Analysis of pharmacy billing records in Premier for 50-mg or 100-mg doses of rtPA showed that 3.4% of AIS cases were treated in 2009. Inclusion of patients with transient ischemic attack or hemorrhagic stroke International Classification of Diseases 9th revision codes who received any thrombolytic as “ischemic stroke patients receiving rtPA” changed the rate of thrombolysis to 5.2%. Conclusions— In 2009, 3.4% to 5.2% of AIS patients in the United States received thrombolytics, approximately double the rate of treatment in 2005. Rapid recognition and transport and quick treatment in the emergency department remain goals for further improving treatment rates.

Stroke in a Biracial Population The Excess Burden of Stroke Among Blacks

Background and Purpose— Excess mortality resulting from stroke is an important reason why blacks have higher age-adjusted mortality rates than whites. This observation has 2 possible explanations: Strokes occur more commonly among blacks or blacks have higher mortality rates after stroke. Our population-based epidemiological study is set in the Greater Cincinnati/Northern Kentucky region of 1.31 million people, which is representative of the US white and black populations with regard to many demographic and socioeconomic characteristics. Methods— Hospitalized cases were ascertained by International Classification of Diseases (ninth revision) discharge codes, prospective screening of emergency department admission logs, and review of coroner’s cases. A sampling scheme was used to ascertain cases in the out-of-hospital setting. All potential cases underwent detailed chart abstraction by study nurses, followed by physician review. Race-specific incidence and case fatality rates were calculated. Results— We identified 3136 strokes during the study period (January 1, 1993, to June 30, 1994). Stroke incidence rates were higher for blacks at every age, with the greatest risk (2- to 5-fold) seen in young and middle-aged blacks (<65 years of age). Case fatality rates did not differ significantly in blacks compared with whites. Applying the resulting age- and race-specific rates to the US population in 2002, we estimate that 705 000 to 740 000 strokes have occurred in the United States, with a minimum of 616 000 cerebral infarctions, 67 000 intracerebral hemorrhages, and 22 000 subarachnoid hemorrhages. Conclusions— Excess stroke-related mortality in blacks is due to higher stroke incidence rates, particularly in the young and middle-aged. This excess burden of stroke incidence among blacks represents one of the most serious public health problems facing the United States.

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 Recombinant Tissue Plasminogen Activator in Acute Ischemic Stroke: A Population-Based Study

Background and Purpose— Acute ischemic stroke patients are infrequently treated with recombinant tissue plasminogen activator (rtPA). We present unique population-based data regarding the eligibility of ischemic stroke patients for rtPA treatment. Methods— All ischemic strokes presenting to an emergency department (ED) within a biracial population of 1.3 million were identified. The patient was considered eligible for rtPA on the basis of exclusion criteria from the National Institute of Neurological Disorders and Stroke rtPA trial. Results— Of 2308 ischemic strokes, 1849 presented to an ED. Only 22% of all ischemic strokes in the population arrived in the ED in <3 hours from symptom onset; of these, 209 (51%) were ineligible for rtPA on the basis of mild stroke severity, medical and surgical history, or blood tests. Conclusions— In our population in 1993 to 1994, 8% of all ischemic stroke patients presented to an ED within 3 hours and met other eligibility criteria for rtPA. Even if time were not an exclusion for rtPA, only 29% of all ischemic strokes in our population would have otherwise been eligible for rtPA.

Disparities in stroke incidence contributing to disparities in stroke mortality.

While black‐white and regional disparities in U.S. stroke mortality rates are well documented, the contribution of disparities in stroke incidence is unknown. We provide national estimates of stroke incidence by race and region, contrasting these to publicly available stroke mortality data.

Scientific Rationale for the Inclusion and Exclusion Criteria for Intravenous Alteplase in Acute Ischemic Stroke A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association

Purpose— To critically review and evaluate the science behind individual eligibility criteria (indication/inclusion and contraindications/exclusion criteria) for intravenous recombinant tissue-type plasminogen activator (alteplase) treatment in acute ischemic stroke. This will allow us to better inform stroke providers of quantitative and qualitative risks associated with alteplase administration under selected commonly and uncommonly encountered clinical circumstances and to identify future research priorities concerning these eligibility criteria, which could potentially expand the safe and judicious use of alteplase and improve outcomes after stroke. Methods— Writing group members were nominated by the committee chair on the basis of their previous work in relevant topic areas and were approved by the American Heart Association Stroke Council’s Scientific Statement Oversight Committee and the American Heart Association’s Manuscript Oversight Committee. The writers used systematic literature reviews, references to published clinical and epidemiology studies, morbidity and mortality reports, clinical and public health guidelines, authoritative statements, personal files, and expert opinion to summarize existing evidence and to indicate gaps in current knowledge and, when appropriate, formulated recommendations using standard American Heart Association criteria. All members of the writing group had the opportunity to comment on and approved the final version of this document. The document underwent extensive American Heart Association internal peer review, Stroke Council Leadership review, and Scientific Statements Oversight Committee review before consideration and approval by the American Heart Association Science Advisory and Coordinating Committee. Results— After a review of the current literature, it was clearly evident that the levels of evidence supporting individual exclusion criteria for intravenous alteplase vary widely. Several exclusionary criteria have already undergone extensive scientific study such as the clear benefit of alteplase treatment in elderly stroke patients, those with severe stroke, those with diabetes mellitus and hyperglycemia, and those with minor early ischemic changes evident on computed tomography. Some exclusions such as recent intracranial surgery are likely based on common sense and sound judgment and are unlikely to ever be subjected to a randomized, clinical trial to evaluate safety. Most other contraindications or warnings range somewhere in between. However, the differential impact of each exclusion criterion varies not only with the evidence base behind it but also with the frequency of the exclusion within the stroke population, the probability of coexistence of multiple exclusion factors in a single patient, and the variation in practice among treating clinicians.

Ischemic Stroke Subtypes. A Population-Based Study of Incidence Rates Among Blacks and Whites

Background and Purpose— Blacks have an excess burden of stroke compared with whites; however, data comparing ischemic stroke subtypes among the 2 groups are limited and typically involve relative frequencies. The objective of this study is to compare the incidence rates of ischemic stroke subtypes between blacks and whites within a large, representative, biracial population. Methods— The Greater Cincinnati/Northern Kentucky Stroke Study is designed to measure incidence rates and trends of all strokes within a well-defined, large, biracial population. Hospitalized cases were ascertained by International Classification of Disease (9th revision; ICD-9) discharge codes. Out-of-hospital events were ascertained by prospective screening of emergency department admission logs, review of coroners’ cases, and monitoring all public health and hospital-based primary care clinics. A sampling scheme was used to ascertain events from nursing homes and all other primary care physician offices. All potential cases underwent detailed chart abstraction and confirmed by physician review. Based on all available clinical, laboratory, and radiographic information, ischemic stroke cases were subtyped into the following categories: cardioembolic, large-vessel, small-vessel, other, and stroke of undetermined cause. Race-specific incidence rates were calculated and compared after adjusting for age and gender, and standardizing to the 1990 US population. Results— Between July 1, 1993, and June 30, 1994, 1956 first-ever ischemic strokes occurred among blacks and whites in the study population. Small-vessel strokes and strokes of undetermined cause were nearly twice as common among blacks. Large-vessel strokes were 40% more common among blacks than whites, and there was a trend toward cardioembolic strokes being more common among blacks. Conclusions— The excess burden of ischemic strokes among blacks compared with whites is not uniformly spread across the different subtypes. Large-vessel strokes are more common and cardioembolic stroke are as common among blacks, traditionally thought to be more common among whites.