Mitchell S.V. Elkind

Guidelines for the Primary Prevention of Stroke A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association

The aim of this updated statement is to provide comprehensive and timely evidence-based recommendations on the prevention of stroke among individuals who have not previously experienced a stroke or transient ischemic attack. Evidence-based recommendations are included for the control of risk factors, interventional approaches to atherosclerotic disease of the cervicocephalic circulation, and antithrombotic treatments for preventing thrombotic and thromboembolic stroke. Further recommendations are provided for genetic and pharmacogenetic testing and for the prevention of stroke in a variety of other specific circumstances, including sickle cell disease and patent foramen ovale.

Criteria for Evaluation of Novel Markers of Cardiovascular Risk A Scientific Statement From the American Heart Association

There is increasing interest in utilizing novel markers of cardiovascular disease risk, and consequently, there is a need to assess the value of their use. This scientific statement reviews current concepts of risk evaluation and proposes standards for the critical appraisal of risk assessment methods. An adequate evaluation of a novel risk marker requires a sound research design, a representative at-risk population, and an adequate number of outcome events. Studies of a novel marker should report the degree to which it adds to the prognostic information provided by standard risk markers. No single statistical measure provides all the information needed to assess a novel marker, so measures of both discrimination and accuracy should be reported. The clinical value of a marker should be assessed by its effect on patient management and outcomes. In general, a novel risk marker should be evaluated in several phases, including initial proof of concept, prospective validation in independent populations, documentation of incremental information when added to standard risk markers, assessment of effects on patient management and outcomes, and ultimately, cost-effectiveness.

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.

Ischemic Stroke Subtype Incidence Among Whites, Blacks, and Hispanics The Northern Manhattan Study

Background—Stroke incidence is greater in blacks than in whites; data on Hispanics are limited. Comparing subtype-specific ischemic stroke incidence rates may help to explain race-ethnic differences in stroke risk. The aim of this population-based study was to determine ischemic stroke subtype incidence rates for whites, blacks, and Hispanics living in one community. Methods and Results—A comprehensive stroke surveillance system incorporating multiple overlapping strategies was used to identify all cases of first ischemic stroke occurring between July 1, 1993, and June 30, 1997, in northern Manhattan. Ischemic stroke subtypes were determined according to a modified NINDS scheme, and age-adjusted, race-specific incidence rates calculated. The annual age-adjusted incidence of first ischemic stroke per 100 000 was 88 (95% CI, 75 to 101) in whites, 149 (95% CI, 132 to 165) in Hispanics, and 191 (95% CI, 160 to 221) in blacks. Among blacks compared with whites, the relative rate of intracranial atherosclerotic stroke was 5.85 (95% CI, 1.82 to 18.73); extracranial atherosclerotic stroke, 3.18 (95% CI, 1.42 to 7.13); lacunar stroke, 3.09 (95% CI, 1.86 to 5.11); and cardioembolic stroke, 1.58 (95% CI, 0.99 to 2.52). Among Hispanics compared with whites, the relative rate of intracranial atherosclerotic stroke was 5.00 (95% CI, 1.69 to 14.76); extracranial atherosclerotic stroke, 1.71 (95% CI, 0.80 to 3.63); lacunar stroke, 2.32 (95% CI, 1.48 to 3.63); and cardioembolic stroke, 1.42 (95% CI, 0.97 to 2.09). Conclusions—The high ischemic stroke incidence among blacks and Hispanics compared with whites is due to higher rates of all ischemic stroke subtypes.

Race-ethnic disparities in the impact of stroke risk factors: the northern Manhattan stroke study.

Background and Purpose— Stroke risk factors have been determined in large part through epidemiological studies in white cohorts; as a result, race-ethnic disparities in stroke incidence and mortality rates remained unexplained. The aim in the present study was to compare the prevalence, OR, and etiological fraction (EF) of stroke risk factors among white, blacks, and Caribbean Hispanics living in the same urban community of northern Manhattan. Methods— In this population-based incident case-control study, cases (n=688) of first ischemic stroke were prospectively matched 1:2 by age, sex, and race-ethnicity with community controls (n=1156). Risk factors were determined through in-person assessment. Conditional logistic regression was used to calculate adjusted ORs in each race-ethnic group. Prevalence and multivariate EFs were determined in each race-ethnic group. Results— Hypertension was an independent risk factor for whites (OR 1.8, EF 25%), blacks (OR 2.0, EF 37%), and Caribbean Hispanics (OR 2.1, EF 32%), but greater prevalence led to elevated EFs among blacks and Caribbean Hispanics. Greater prevalence rates of diabetes increased stroke risk in blacks (OR 1.8, EF 14%) and Caribbean Hispanics (OR 2.1 P <0.05, EF 10%) compared with whites (OR 1.0, EF 0%), whereas atrial fibrillation had a greater prevalence and EF for whites (OR 4.4, EF 20%) compared with blacks (OR 1.7, EF 3%) and Caribbean Hispanics (OR 3.0, EF 2%). Coronary artery disease was most important for whites (OR 1.3, EF 16%), followed by Caribbean Hispanics (OR 1.5, EF 6%) and then blacks (OR 1.1, EF 2%). Prevalence of physical inactivity was greater in Caribbean Hispanics, but an elevated EF was found in all groups. Conclusions— The prevalence, OR, and EF for stroke risk factors vary by race-ethnicity. These differences are crucial to the etiology of stroke, as well as to the design and implementation of stroke prevention programs.

Abdominal Obesity and Risk of Ischemic Stroke: The Northern Manhattan Stroke Study

Background and Purpose— Obesity is well recognized as a risk factor for coronary heart disease and mortality. The relationship between abdominal obesity and ischemic stroke remains less clear. Our aim was to evaluate abdominal obesity as an independent risk factor for ischemic stroke in a multiethnic community. Methods— A population-based, incident case-control study was conducted July 1993 through June 1997 in northern Manhattan, New York, NY. Cases (n=576) of first ischemic stroke (66% ≥65 years of age; 56% women; 17% whites; 26% blacks; 55% Hispanics) were enrolled and matched by age, sex, and race-ethnicity to stroke-free community controls (n=1142). All subjects were interviewed and examined and had measurements of waist-to-hip ratio (WHR). Odds ratios (ORs) of ischemic stroke were calculated with gender-specific quartiles (GQs) and gender-specific medians of WHR adjusted for stroke risk factors and body mass index (BMI). Results— Compared with the first quartile, the third and fourth quartiles of WHR had an increased risk of stroke (GQ3: OR, 2.4; 95% CI, 1.5 to 3.9; GQ4: OR, 3.0; 95% CI, 1.8 to 4.8) adjusted for other risk factors and BMI. Those with WHR equal to or greater than the median had an overall OR of 3.0 (95% CI, 2.1 to 4.2) for ischemic stroke even after adjustment for other risk factors and BMI. Increased WHR was associated with a greater risk of stroke in men and women and in all race-ethnic groups. The effect of WHR was stronger among younger persons (test for heterogeneity, P <0.0002) (<65 years of age: OR, 4.4; 95%CI, 2.2 to 9.0; ≥65 years of age: OR, 2.2; 95% CI, 1.4 to 3.2). WHR was associated with an increased risk among those with and without large-artery atherosclerotic stroke. Conclusions— Abdominal obesity is an independent, potent risk factor for ischemic stroke in all race-ethnic groups. It is a stronger risk factor than BMI and has a greater effect among younger persons. Prevention of obesity and weight reduction need greater emphasis in stroke prevention programs.

Racial-Ethnic Disparities in Stroke Care: The American Experience: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association

Purpose— Our goal is to describe the effect of race and ethnicity on stroke epidemiology, personal beliefs, access to care, response to treatment, and participation in clinical research. In addition, we seek to determine the state of knowledge on the main factors that may explain disparities in stroke care, with the goal of identifying gaps in knowledge to guide future research. The intended audience includes physicians, nurses, other healthcare professionals, and policy makers. Methods— Members of the writing group were appointed by the American Heart Association Stroke Council Scientific Statement Oversight Committee and represent different areas of expertise in relation to racial-ethnic disparities in stroke care. The writing group reviewed the relevant literature, with an emphasis on reports published since 1972. The statement was approved by the writing group; the statement underwent peer review, then was approved by the American Heart Association Science Advisory and Coordinating Committee. Results— There are limitations in the definitions of racial and ethnic categories currently in use. For the purpose of this statement, we used the racial categories defined by the US federal government: white, black or African American, Asian, American Indian/Alaskan Native, and Native Hawaiian/other Pacific Islander. There are 2 ethnic categories: people of Hispanic/Latino origin or not of Hispanic/Latino origin. There are differences in the distribution of the burden of risk factors, stroke incidence and prevalence, and stroke mortality among different racial and ethnic groups. In addition, there are disparities in stroke care between minority groups compared with whites. These disparities include lack of awareness of stroke symptoms and signs and lack of knowledge about the need for urgent treatment and the causal role of risk factors. There are also differences in attitudes, beliefs, and compliance among minorities compared with whites. Differences in socioeconomic status and insurance coverage, mistrust of the healthcare system, the relatively limited number of providers who are members of minority groups, and system limitations may contribute to disparities in access to or quality of care, which in turn might result in different rates of stroke morbidity and mortality. Cultural and language barriers probably also contribute to some of these disparities. Minorities use emergency medical services systems less, are often delayed in arriving at the emergency department, have longer waiting times in the emergency department, and are less likely to receive thrombolysis for acute ischemic stroke. Although unmeasured factors may play a role in these delays, the presence of bias in the delivery of care cannot be excluded. Minorities have equal access to rehabilitation services, although they experience longer stays and have poorer functional status than whites. Minorities are inadequately treated with both primary and secondary stroke prevention strategies compared with whites. Sparse data exist on racial-ethnic disparities in access to surgical care after intracerebral hemorrhage and subarachnoid hemorrhage. Participation of minorities in clinical research is limited. Barriers to participation in clinical research include beliefs, lack of trust, and limited awareness. Race is a contentious topic in biomedical research because race is not proven to be a surrogate for genetic constitution. Conclusions— There are limitations in the current definitions of race and ethnicity. Nevertheless, racial and ethnic disparities in stroke exist and include differences in the biological determinants of disease and disparities throughout the continuum of care, including access to and quality of care. Access to and participation in research is also limited among minority groups. Acknowledging the presence of disparities and understanding the factors that contribute to them are necessary first steps. More research is required to understand these differences and find solutions.

Carotid plaque, a subclinical precursor of vascular events: The Northern Manhattan Study

Background: Carotid atherosclerosis is a known biomarker associated with future vascular disease. The risk associated with small, nonstenotic carotid plaques is less clear. The objective of this study was to examine the association between maximum carotid plaque thickness and risk of vascular events in an urban multiethnic cohort. Methods: As part of the population-based Northern Manhattan Study, carotid plaque was analyzed among 2,189 subjects. Maximum carotid plaque thickness was evaluated at the cutoff level of 1.9 mm, a prespecified value of the 75th percentile of the plaque thickness distribution. The primary outcome measure was combined vascular events (ischemic stroke, myocardial infarction, or vascular death). Results: Carotid plaque was present in 1,263 (58%) subjects. After a mean follow-up of 6.9 years, vascular events occurred among 319 subjects; 121 had fatal or nonfatal ischemic stroke, 118 had fatal or nonfatal myocardial infarction, and 166 died of vascular causes. Subjects with maximum carotid plaque thickness greater than 1.9 mm had a 2.8-fold increased risk of combined vascular events in comparison to the subjects without carotid plaque (hazard ratio, 2.80; 95% CI, 2.04–3.84). In fully adjusted models, this association was significant only among Hispanics. Approximately 44% of the low-risk individuals by Framingham risk score had a 10-year vascular risk of 18.3% if having carotid plaque. Conclusions: Maximum carotid plaque thickness is a simple and noninvasive marker of subclinical atherosclerosis associated with increased risk of vascular outcomes in a multiethnic cohort. Maximum carotid plaque thickness may be a simple and nonexpensive tool to assist with vascular risk stratification in preventive strategies and a surrogate endpoint in clinical trials.

Recurrent stroke and cardiac risks after first ischemic stroke The Northern Manhattan Study

Background: Few population-based studies with long-term follow-up have compared risk of recurrent stroke and cardiac events after first ischemic stroke. The relative risk of these two outcomes may inform treatment decisions. Methods: In the population-based Northern Manhattan Study, first ischemic stroke patients age 40 or older were prospectively followed for recurrent stroke, myocardial infarction (MI), and cause-specific mortality. Fatal cardiac events were defined as death secondary to MI, congestive heart failure, sudden death/arrhythmia, and cardiopulmonary arrest. Risk of events (with 95% CIs) was calculated using Kaplan–Meier survival analysis and adjusted for sex and age using Cox proportional hazard models. Results: Mean age (n = 655; median follow-up 4.0 years) was 69.7 ± 12.7 years. The risk of recurrent stroke was more than twice that of cardiac events (including nonfatal MI) at 30 days and approximately twice cardiac risk at 5 years. The age- and sex-adjusted 5-year risk of fatal or nonfatal recurrent stroke was 18.3% (14.8 to 21.7%), and the 5-year risk of MI or fatal cardiac event was 8.6% (6.0 to 11.2%). The adjusted 5-year risk of nonfatal stroke (14.8%, 11.6 to 17.9%) was approximately twice as high as fatal cardiac events (6.4%, 4.1 to 8.6%) and four times higher than risk of fatal stroke (3.7%, 2.1 to 5.4%). Conclusions: Cardiac mortality is nearly twice as high as mortality owing to recurrent stroke, but long-term risk of all stroke, fatal or nonfatal, is approximately twice the risk of all cardiac events. The high risk of nonfatal recurrent stroke reinforces the importance of therapies aimed at preventing stroke recurrence in addition to preventing cardiac events.

Carotid Intima-Media Thickness Is Associated With Allelic Variants of Stromelysin-1, Interleukin-6, and Hepatic Lipase Genes The Northern Manhattan Prospective Cohort Study

Background and Purpose— Atherosclerosis is a complex disorder with hereditary and environmental causes. Carotid artery intima-media wall thickness (IMT) is a useful measure of atherosclerosis. The objective of this study was to determine the association between carotid IMT and functional promoter variants of stromelysin-1 (MMP3: −1612 5A>6A), interleukin-6 (IL6: −174G>C), and hepatic lipase (HL: −480C>T) genes. Methods— B-mode carotid ultrasound was performed among 87 subjects (mean age, 70±12 years; 55% women; 60% Caribbean-Hispanic, 25% black, and 13% white) from the Northern Manhattan Prospective Cohort Study. Carotid IMT was calculated as a composite measure (mean of the maximum IMT in the bifurcation, the common carotid artery, and the internal carotid artery). Results— For all polymorphisms, genotype distribution was not significantly different from Hardy-Weinberg equilibrium. The frequencies of the rare alleles were as follows:MMP3 −1612 5A>6A, 0.31 (95% CI, 0.25 to 0.39);IL6 −174 G>C, 0.20 (95% CI, 0.13 to 0.25); and HL −480 C>T, 0.45 (95% CI, 0.35 to 0.50). Carotid IMT in the sample was 0.78±0.18 mm. Subjects with the MMP3 genotype 6A6A had 8% greater mean carotid IMT than the other MMP3 genotypes combined (0.95±0.17 versus 0.87±0.15 mm;P =0.04). Subjects with the IL6 genotype GG had 11% greater IMT (0.85±0.17 versus 0.76±0.16 mm;P =0.03), and those with the HL genotype CC had 13% greater IMT (0.87±20 versus 0.76±0.18 mm;P =0.02) than the other genotypes combined. Adjustment for other risk factors did not change these associations. Conclusions— Carotid IMT is higher among subjects homozygous for functional variants in genes related to matrix deposition (MMP3 −16126A), inflammation (IL6 −174G), and lipid metabolism (HL −480C). These associations were independent of race-ethnicity and some environmental exposures. Further studies are needed to confirm these genotype-phenotype associations.