Steven J. Kittner

Heart Disease and Stroke Statistics—2009 Update A Report From the American Heart Association Statistics Committee and Stroke Statistics Subcommittee

We thank Drs Robert Adams, Gary Friday, Philip Gorelick, and Sylvia Wasserthiel-Smoller, members of Stroke Statistics Subcommittee; Drs Joe Broderick, Brian Eigel, Kimberlee Gauveau, Jane Khoury, Jerry Potts, Jane Newburger, and Kathryn Taubert; and Sean Coady and Michael Wolz for their valuable comments and contributions. We acknowledge Tim Anderson and Tom Schneider for their editorial contributions and Karen Modesitt for her administrative assistance. View this table: Writing Group Disclosures # Summary {#article-title-2} Each year the American Heart Association, in conjunction with the Centers for Disease Control and Prevention, the National Institutes of Health, and other government agencies, brings together the most up-to-date statistics on heart disease, stroke, and their risk factors and presents them in its Heart Disease and Stroke Statistical Update. The Statistical Update is a valuable resource for researchers, clinicians, healthcare policy makers, media, the lay public, and many others who seek the …

Heart Disease and Stroke Statistics—2013 Update A Report From the American Heart Association

Author(s): Go, Alan S; Mozaffarian, Dariush; Roger, Veronique L; Benjamin, Emelia J; Berry, Jarett D; Borden, William B; Bravata, Dawn M; Dai, Shifan; Ford, Earl S; Fox, Caroline S; Franco, Sheila; Fullerton, Heather J; Gillespie, Cathleen; Hailpern, Susan M; Heit, John A; Howard, Virginia J; Huffman, Mark D; Kissela, Brett M; Kittner, Steven J; Lackland, Daniel T; Lichtman, Judith H; Lisabeth, Lynda D; Magid, David; Marcus, Gregory M; Marelli, Ariane; Matchar, David B; McGuire, Darren K; Mohler, Emile R; Moy, Claudia S; Mussolino, Michael E; Nichol, Graham; Paynter, Nina P; Schreiner, Pamela J; Sorlie, Paul D; Stein, Joel; Turan, Tanya N; Virani, Salim S; Wong, Nathan D; Woo, Daniel; Turner, Melanie B; American Heart Association Statistics Committee and Stroke Statistics Subcommittee

Factors Influencing the Decline in Stroke Mortality A Statement From the American Heart Association/American Stroke Association

Background and Purpose— Stroke mortality has been declining since the early 20th century. The reasons for this are not completely understood, although the decline is welcome. As a result of recent striking and more accelerated decreases in stroke mortality, stroke has fallen from the third to the fourth leading cause of death in the United States. This has prompted a detailed assessment of the factors associated with the change in stroke risk and mortality. This statement considers the evidence for factors that have contributed to the decline and how they can be used in the design of future interventions for this major public health burden. Methods— Writing group members were nominated by the committee chair and co-chair on the basis of their previous work in relevant topic areas and were approved by the American Heart Association Stroke Council’s Scientific Statements Oversight Committee and the American Heart Association Manuscript Oversight Committee. The writers used systematic literature reviews, references to published clinical and epidemiological studies, morbidity and mortality reports, clinical and public health guidelines, authoritative statements, personal files, and expert opinion to summarize evidence and to indicate gaps in current knowledge. All members of the writing group had the opportunity to comment on this document and approved the final version. 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— The decline in stroke mortality over the past decades represents a major improvement in population health and is observed for both sexes and for all racial/ethnic and age groups. In addition to the overall impact on fewer lives lost to stroke, the major decline in stroke mortality seen among people <65 years of age represents a reduction in years of potential life lost. The decline in mortality results from reduced incidence of stroke and lower case-fatality rates. These significant improvements in stroke outcomes are concurrent with cardiovascular risk factor control interventions. Although it is difficult to calculate specific attributable risk estimates, efforts in hypertension control initiated in the 1970s appear to have had the most substantial influence on the accelerated decline in stroke mortality. Although implemented later, diabetes mellitus and dyslipidemia control and smoking cessation programs, particularly in combination with treatment of hypertension, also appear to have contributed to the decline in stroke mortality. The potential effects of telemedicine and stroke systems of care appear to be strong but have not been in place long enough to indicate their influence on the decline. Other factors had probable effects, but additional studies are needed to determine their contributions. Conclusions— The decline in stroke mortality is real and represents a major public health and clinical medicine success story. The repositioning of stroke from third to fourth leading cause of death is the result of true mortality decline and not an increase in mortality from chronic lung disease, which is now the third leading cause of death in the United States. There is strong evidence that the decline can be attributed to a combination of interventions and programs based on scientific findings and implemented with the purpose of reducing stroke risks, the most likely being improved control of hypertension. Thus, research studies and the application of their findings in developing intervention programs have improved the health of the population. The continued application of aggressive evidence-based public health programs and clinical interventions is expected to result in further declines in stroke mortality.

Total Homocyst(e)ine Concentration and the Likelihood of Nonfatal Stroke Results From the Third National Health and Nutrition Examination Survey, 1988–1994

BACKGROUND AND PURPOSE Elevated serum total homocyst(e)ine [H(e)] is an independent risk factor for stroke. Few studies, however, have examined this association in blacks. METHODS Data from the Third National Health and Nutrition Examination Survey (n=4534), a nationally representative sample of US adults, were used to examine the relationship between H(e) and a physician diagnosis of stroke (n=185) in both black and white adults. Multivariate-adjusted logistic regression analyses were used to examine this relationship. RESULTS Serum vitamin B12 and folate concentrations were significantly lower among participants in the highest H(e) quartile (>/=12.1 micromol/L) than among participants in the lowest quartile (</=7.4 micromol/L). Those in the highest quartile were older, had higher mean cholesterol and blood pressure levels, and were more likely to smoke and to have completed <12 years of education. After adjustment for age, the odds ratio (OR) for stroke was 2.9 (95% confidence interval [CI], 1.4 to 5.7; highest versus lowest quartile). Adjustment for gender, race/ethnicity, education, systolic blood pressure, cholesterol, diabetes mellitus, and smoking reduced the magnitude of the association (OR, 2.3; 95% CI, 1.2 to 4. 6). The association between H(e) and stroke did not differ by race [P=0.265 for race-H(e) interaction term]. The multivariate adjusted OR for the highest quartile versus the lowest was 2.5 (1.1 to 5.5) among whites and 1.4 (0.4 to 4.7) among blacks. CONCLUSIONS In this nationally representative sample of US adults, H(e) concentration was independently associated with an increased likelihood of nonfatal stroke. This association was present in both black and white adults.

Meta-analysis in more than 17,900 cases of ischemic stroke reveals a novel association at 12q24.12.

Objectives: To perform a genome-wide association study (GWAS) using the Immunochip array in 3,420 cases of ischemic stroke and 6,821 controls, followed by a meta-analysis with data from more than 14,000 additional ischemic stroke cases. Methods: Using the Immunochip, we genotyped 3,420 ischemic stroke cases and 6,821 controls. After imputation we meta-analyzed the results with imputed GWAS data from 3,548 cases and 5,972 controls recruited from the ischemic stroke WTCCC2 study, and with summary statistics from a further 8,480 cases and 56,032 controls in the METASTROKE consortium. A final in silico “look-up” of 2 single nucleotide polymorphisms in 2,522 cases and 1,899 controls was performed. Associations were also examined in 1,088 cases with intracerebral hemorrhage and 1,102 controls. Results: In an overall analysis of 17,970 cases of ischemic stroke and 70,764 controls, we identified a novel association on chromosome 12q24 (rs10744777, odds ratio [OR] 1.10 [1.07–1.13], p = 7.12 × 10−11) with ischemic stroke. The association was with all ischemic stroke rather than an individual stroke subtype, with similar effect sizes seen in different stroke subtypes. There was no association with intracerebral hemorrhage (OR 1.03 [0.90–1.17], p = 0.695). Conclusion: Our results show, for the first time, a genetic risk locus associated with ischemic stroke as a whole, rather than in a subtype-specific manner. This finding was not associated with intracerebral hemorrhage.

Genetics and Genomics for the Prevention and Treatment of Cardiovascular Disease: Update A Scientific Statement From the American Heart Association

Cardiovascular diseases (CVDs) are a major source of morbidity and mortality worldwide. Despite a decline of ≈30% over the past decade, heart disease remains the leading killer of Americans.1 For rare and familial forms of CVD, we are increasingly recognizing single-gene mutations that impart relatively large effects on individual phenotype. Examples include inherited forms of cardiomyopathy, arrhythmias, and aortic diseases. However, the prevalence of monogenic disorders typically accounts for a small proportion of the total CVD observed in the population. CVDs in the general population are complex diseases, with several contributing genetic and environmental factors. Although recent progress in monogenic disorders has occurred, we have seen a period of intense investigation to identify the genetic architecture of more common forms of CVD and related traits. Genomics serves several roles in cardiovascular health and disease, including disease prediction, discovery of genetic loci influencing CVD, functional evaluation of these genetic loci to understand mechanisms, and identification of therapeutic targets. For single-gene CVDs, progress has led to several clinically useful diagnostic tests, extending our ability to inform the management of afflicted patients and their family members. However, there has been little progress in developing genetic testing for complex CVD because individual common variants have only a modest impact on risk. The study of the genomics of complex CVDs is further challenged by the influence of environmental variables, phenotypic heterogeneity, and pathogenic complexity. Characterization of the clinical phenotype requires consideration of the clinical details of the diseases and traits under study. This update expands the prior scientific statement on the relevance of genetics and genomics for the prevention and treatment of CVDs.2 In the earlier report, we focused on the current status of the field, which consisted of predominantly family-based linkage studies and single-gene or mendelian mutations of relatively large phenotypic effect …

Use of Medicare claims data to estimate national trends in stroke incidence, 1985-1991.

Although stroke mortality has been declining in the United States for decades, recent trends in stroke incidence based on national data have not been described. We used Medicare hospitalization data to estimate national trends in the incidence of stroke among Americans aged 70 years or older, and we provide evidence of the validity of the estimate. Methods We defined stroke as a principal diagnosis with International Classification of Diseases, 9th Revision, Clinical Modification codes 430 to 434 or 436 to 437. We excluded many recurrent cases from the analysis by eliminating persons hospitalized for stroke during the 5 years preceding the index stroke. We calculated annual adjusted incidence rates and examined trends graphically. We investigated the effect of different exclusion periods, trends in in-hospital mortality of stroke patients, and trends in out-of-hospital stroke mortality. We examined trends in relation to sex, race, and age. Results The estimated age- and sex-adjusted stroke incidence declined 9.5% from 1985 to 1989, then increased 3.3% to 1991. The pattern did not vary with the length of the exclusion period or when all listed diagnoses rather than principal diagnoses were used to identify stroke cases. Incidence trends resembled the overall trend for both men and women, for 5-year age groups, and for whites; the trend did not change for blacks. Conclusions Stroke incidence declined steadily from 1985 to 1989 and then increased slightly to 1991. Several postulated potential sources of bias were investigated and found to be unlikely to account for the incidence decline, although some may have contributed to the subsequent incidence increase.

The Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) Study Protocol

Background and Purpose— Epidemiological studies of intracerebral hemorrhage (ICH) have consistently demonstrated variation in incidence, location, age at presentation, and outcomes among non-Hispanic white, black, and Hispanic populations. We report here the design and methods for this large, prospective, multi-center case–control study of ICH. Methods— The Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study is a multi-center, prospective case–control study of ICH. Cases are identified by hot-pursuit and enrolled using standard phenotype and risk factor information and include neuroimaging and blood sample collection. Controls are centrally identified by random digit dialing to match cases by age (±5 years), race, ethnicity, sex, and metropolitan region. Results— As of March 22, 2013, 1655 cases of ICH had been recruited into the study, which is 101.5% of the target for that date, and 851 controls had been recruited, which is 67.2% of the target for that date (1267 controls) for a total of 2506 subjects, which is 86.5% of the target for that date (2897 subjects). Of the 1655 cases enrolled, 1640 cases had the case interview entered into the database, of which 628 (38%) were non-Hispanic black, 458 (28%) were non-Hispanic white, and 554 (34%) were Hispanic. Of the 1197 cases with imaging submitted, 876 (73.2%) had a 24 hour follow-up CT available. In addition to CT imaging, 607 cases have had MRI evaluation. Conclusions— The ERICH study is a large, case–control study of ICH with particular emphasis on recruitment of minority populations for the identification of genetic and epidemiological risk factors for ICH and outcomes after ICH.

Measuring alcohol consumption for genomic meta-analyses of alcohol intake: opportunities and challenges

Whereas moderate drinking may have health benefits, excessive alcohol consumption causes many important acute and chronic diseases and is the third leading contributor to preventable death in the United States. Twin studies suggest that alcohol-consumption patterns are heritable (50%); however, multiple genetic variants of modest effect size are likely to contribute to this heritable variation. Genome-wide association studies provide a tool for discovering genetic loci that contribute to variations in alcohol consumption. Opportunities exist to identify susceptibility loci with modest effect by meta-analyzing together multiple studies. However, existing studies assessed many different aspects of alcohol use, such as typical compared with heavy drinking, and these different assessments can be difficult to reconcile. In addition, many studies lack the ability to distinguish between lifetime and recent abstention or to assess the pattern of drinking during the week, and a variety of such concerns surround the appropriateness of developing a common summary measure of alcohol intake. Combining such measures of alcohol intake can cause heterogeneity and exposure misclassification, cause a reduction in power, and affect the magnitude of genetic association signals. In this review, we discuss the challenges associated with harmonizing alcohol-consumption data from studies with widely different assessment instruments, with a particular focus on large-scale genetic studies.

Agreement between TOAST and CCS ischemic stroke classification: The NINDS SiGN Study

Objective: The objective of this study was to assess the level of agreement between stroke subtype classifications made using the Trial of Org 10172 Acute Stroke Treatment (TOAST) and Causative Classification of Stroke (CCS) systems. Methods: Study subjects included 13,596 adult men and women accrued from 20 US and European genetic research centers participating in the National Institute of Neurological Disorders and Stroke (NINDS) Stroke Genetics Network (SiGN). All cases had independently classified TOAST and CCS stroke subtypes. Kappa statistics were calculated for the 5 major ischemic stroke subtypes common to both systems. Results: The overall agreement between TOAST and CCS was moderate (agreement rate, 70%; κ = 0.59, 95% confidence interval [CI] 0.58–0.60). Agreement varied widely across study sites, ranging from 28% to 90%. Agreement on specific subtypes was highest for large-artery atherosclerosis (κ = 0.71, 95% CI 0.69–0.73) and lowest for small-artery occlusion (κ = 0.56, 95% CI 0.54–0.58). Conclusion: Agreement between TOAST and CCS diagnoses was moderate. Caution is warranted when comparing or combining results based on the 2 systems. Replication of study results, for example, genome-wide association studies, should utilize phenotypes determined by the same classification system, ideally applied in the same manner.