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Importance: Influenza-like illness (ILI) activity has been associated with increased risk of cardiopulmonary (CP) events during the influenza season. High-dose trivalent influenza vaccine was not superior to standard-dose quadrivalent vaccine for reducing these events in patients with high-risk cardiovascular (CV) disease in the Influenza Vaccine to Effectively Stop Cardio Thoracic Events and Decompensated Heart Failure (INVESTED) trial., Objective: To evaluate whether high-dose trivalent influenza vaccination is associated with benefit over standard-dose quadrivalent vaccination in reducing CP events during periods of high, local influenza activity., Design, Setting, and Participants: This study was a prespecified secondary analysis of INVESTED, a multicenter, double-blind, active comparator randomized clinical trial conducted over 3 consecutive influenza seasons from September 2016 to July 2019. Follow-up was completed in July 2019, and data were analyzed from September 21, 2016, to July 31, 2019. Weekly Centers for Disease Control and Prevention (CDC)-reported, state-level ILI activity was ascertained to assess the weekly odds of the primary outcome. The study population included 3094 patients with high-risk CV disease from participating centers in the US., Intervention: Participants were randomized to high-dose trivalent or standard-dose quadrivalent influenza vaccine and revaccinated for up to 3 seasons., Main Outcomes and Measures: The primary outcome was the time to composite of all-cause death or CP hospitalization within each season. Additional measures included weekly CDC-reported ILI activity data by state., Results: Among 3094 participants (mean [SD] age, 65 [12] years; 2309 male [75%]), we analyzed 129 285 person-weeks of enrollment, including 1396 composite primary outcome events (1278 CP hospitalization, 118 deaths). A 1% ILI increase in the prior week was associated with an increased risk in the primary outcome (odds ratio [OR], 1.14; 95% CI, 1.07-1.21; P < .001), CP hospitalization (OR, 1.13; 95% CI, 1.06-1.21; P < .001), and CV hospitalization (OR, 1.12; 95% CI, 1.04-1.19; P = .001), after adjusting for state, demographic characteristics, enrollment strata, and CV risk factors. Increased ILI activity was not associated with all-cause death (OR, 1.00; 95% CI, 0.88-1.13; P > .99). High-dose compared with standard-dose vaccine did not significantly reduce the primary outcome, even when the analysis was restricted to weeks of high ILI activity (OR, 0.88; 95% CI, 0.65-1.20; P = .43). Traditionally warmer months in the US were associated with lower CV risk independent of local ILI activity., Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, ILI activity was temporally associated with increased CP events in patients with high-risk CV disease, and a higher influenza vaccine dose did not significantly reduce temporal CV risk. Other seasonal factors may play a role in the coincident high rates of ILI and CV events., Trial Registration: ClinicalTrials.gov Identifier: NCT02787044.

Atrial fibrillation (AF) is one of the strongest risk factors for ischemic stroke, which is a leading cause of disability and death. Given the aging population, increasing prevalence of AF risk factors, and improved survival in those with cardiovascular disease, the number of individuals affected by AF will continue increasing over time. While multiple proven stroke prevention therapies exist, important questions remain about the optimal approach to stroke prevention at the population and individual patient levels. Our report summarizes the National Heart, Lung, and Blood Institute virtual workshop focused on identifying key research opportunities related to stroke prevention in AF. The workshop reviewed major knowledge gaps and identified targeted research opportunities to advance stroke prevention in AF in the following areas: (1) improving risk stratification tools for stroke and intracranial hemorrhage; (2) addressing challenges with oral anticoagulants; and (3) delineating the optimal roles of percutaneous left atrial appendage occlusion and surgical left atrial appendage closure/excision. This report aims to promote innovative, impactful research that will lead to more personalized, effective use of stroke prevention strategies in people with AF.

Importance: Only modest attention has been paid to the contributions of social determinants of health to atrial fibrillation (AF) risk factors, diagnosis, symptoms, management, and outcomes. The diagnosis of AF provides unique challenges exacerbated by the arrhythmia's often paroxysmal nature and individuals' disparate access to health care and technologies that facilitate detection. Social determinants of health affect access to care and management decisions for AF, increasing the likelihood of adverse outcomes among individuals who experience systemic disadvantages. Developing effective approaches to address modifiable social determinants of health requires research to eliminate the substantive inequities in health care delivery and outcomes in AF., Observations: The National Heart, Lung, and Blood Institute convened an expert panel to identify major knowledge gaps and research opportunities in the field of social determinants of AF. The workshop addressed the following social determinants: (1) socioeconomic status and access to care; (2) health literacy; (3) race, ethnicity, and racism; (4) sex and gender; (5) shared decision-making in systemically disadvantaged populations; and (6) place, including rurality, neighborhood, and community. Many individuals with AF have multiple adverse social determinants, which may cluster in the individual and in systemically disadvantaged places (eg, rural locations, urban neighborhoods). Cumulative disadvantages may accumulate over the life course and contribute to inequities in the diagnosis, management, and outcomes in AF., Conclusions and Relevance: Workshop participants identified multiple critical research questions and approaches to catalyze social determinants of health research that address the distinctive aspects of AF. The long-term aspiration of this work is to eradicate the substantive inequities in AF diagnosis, management, and outcomes across populations.

Clinically recognized atrial fibrillation (AF) is associated with higher risk of complications, including ischemic stroke, cognitive decline, heart failure, myocardial infarction, and death. It is increasingly recognized that AF frequently is undetected until complications such as stroke or heart failure occur. Hence, the public and clinicians have an intense interest in detecting AF earlier. However, the most appropriate strategies to detect undiagnosed AF (sometimes referred to as subclinical AF) and the prognostic and therapeutic implications of AF detected by screening are uncertain. Our report summarizes the National Heart, Lung, and Blood Institute's virtual workshop focused on identifying key research priorities related to AF screening. Global experts reviewed major knowledge gaps and identified critical research priorities in the following areas: (1) role of opportunistic screening; (2) AF as a risk factor, risk marker, or both; (3) relationship between AF burden detected with long-term monitoring and outcomes/treatments; (4) designs of potential randomized trials of systematic AF screening with clinically relevant outcomes; and (5) role of AF screening after ischemic stroke. Our report aims to inform and catalyze AF screening research that will advance innovative, resource-efficient, and clinically relevant studies in diverse populations to improve the diagnosis, management, and prognosis of patients with undiagnosed AF.

Hispanics/Latinos are expected to constitute 25% of the U.S. population by 2060. Differences in the prevalence of health risk factors, chronic diseases, and access to and utilization of health-care services between Hispanics/Latinos and other populations in the U.S. have been documented. This study aimed to describe and analyze the landscape of Research Program Grants (RPGs) funded by the National Institutes of Health (NIH) between 2008 and 2015 involving Hispanic/Latino health research in six health condition areas-asthma, cancer, dementia, diabetes, liver/gallbladder disease, and obesity-and to identify opportunities for continued research in these areas. Using an NIH internal search engine, we identified new and renewal Hispanic/Latino health RPGs searching for specific Hispanic/Latino identifiers in the Title, Abstract, and Specific Aims. We used descriptive statistics to examine the distribution of funded RPGs by NIH disease-based classification codes for the six health condition areas of interest, and other selected characteristics. The most prominent clusters of research subtopics were identified within each health condition area, and performance sites were mapped at the city level. Within the selected time frame, 3,221 Hispanic/Latino health-related unique RPGs were funded (constituting 4.4% of all funded RPGs), and of those 625 RPGs were eligible for review and coding in the present study. Cancer and obesity were the most commonly studied health condition areas (72%), while studies on mechanisms of disease-biological and non-biological-(72.6%), behavioral research (42.1%) and epidemiological studies (38.1%) were the most common types of research. Most of the primary performance sites were in California, Texas, the northeastern U.S., and Illinois. The predominance of mechanistic, behavioral, and epidemiological studies in our analysis poses opportunities to evaluate knowledge gained and their clinical application, explore new research questions, or to update some methods or instruments. The findings of the present study suggest opportunities to expand research in understudied mechanisms of disease that could explain differences in prevalence of conditions like diabetes and cancer among different heritage groups. In addition, our findings suggest that the impact of interventions or policies designed to reduce health disparities, innovative multi-level interventions, implementation and dissemination studies, the role of health information technology on health outcomes, and the intersectionality of individual, sociocultural, geographic, and other factors on health outcomes, among others, are understudied approaches, which could potentially advance research in Hispanic/Latino health and contribute to the achievement of better health outcomes in this diverse population., (Copyright © 2020 Avilés-Santa, Hsu, Lam, Arteaga, Artiles, Coady, Cooper, Curry, Desvigne-Nickens, Nicastro and Rosario.)

The interrelationships between atrial fibrillation (AF) and heart failure (HF) are complex and poorly understood, yet the number of patients with AF and HF continues to increase worldwide. Thus, there is a need for initiatives that prioritize research on the intersection between AF and HF. This article summarizes the proceedings of a virtual workshop convened by the US National Heart, Lung, and Blood Institute to identify important research opportunities in AF and HF. Key knowledge gaps were reviewed and research priorities were proposed for characterizing the pathophysiological overlap and deleterious interactions between AF and HF; preventing HF in people with AF; preventing AF in individuals with HF; and addressing symptom burden and health status outcomes in AF and HF. These research priorities will hopefully help inform, encourage, and stimulate innovative, cost-efficient, and transformative studies to enhance the outcomes of patients with AF and HF.

Catheter ablation has brought major advances in the management of patients with atrial fibrillation (AF). As evidenced by multiple randomized trials, AF catheter ablation can reduce the risk of recurrent AF and improve quality of life. In some studies, AF ablation significantly reduced cardiovascular hospitalizations. Despite the existing data on AF catheter ablation, numerous knowledge gaps remain concerning this intervention. This report is based on a recent virtual workshop convened by the National Heart, Lung, and Blood Institute to identify key research opportunities in AF ablation. We outline knowledge gaps related to emerging technologies, the relationship between cardiac structure and function and the success of AF ablation in patient subgroups in whom clinical benefit from ablation varies, and potential platforms to advance clinical research in this area. This report also considers the potential value and challenges of a sham ablation randomized trial. Prioritized research opportunities are identified and highlighted to empower relevant stakeholders to collaborate in designing and conducting effective, cost-efficient, and transformative research to optimize the use and outcomes of AF ablation.

Background: Most heart failure (HF) risk scores have been derived from cohorts of stable HF patients and may not incorporate up to date treatment regimens or deep phenotype characterization that change baseline risk over the short- and long-term follow-up period. We undertook the current analysis of participants in the GUIDE-IT (Guiding Evidence-Based Therapy Using Biomarker Intensified Treatment) trial to address these limitations., Methods and Results: The GUIDE-IT study randomized 894 high-risk patients with HF and reduced ejection fraction (≤ 40%) to biomarker-guided treatment strategy vs. usual care. We performed risk modelling using Cox proportional hazards models and analysed the relationship between 35 baseline clinical factors and the primary composite endpoint of cardiovascular (CV) death or HF hospitalization, the secondary endpoint of all-cause mortality, and the exploratory endpoint of 90-day HF hospitalization or death. Prognostic relationships for continuous variables were examined and key predictors were identified using a backward variable selection process. Predictive models and risk scores were developed. Over a median follow-up of 15 months, the cumulative number of HF hospitalizations and CV deaths was 328 out of 894 patients (Kaplan-Meier event rate 34.5% at 12 months). Frequency of all-cause deaths was 143 out of 894 patients (Kaplan-Meier event rate 12.2% at 12 months). Outcomes for the primary and secondary endpoints between strategy arms of the study were similar. The most important predictor that was present in all three models was the baseline natriuretic peptide level. Hispanic ethnicity, low sodium and high heart rate were present in two of the three models. Other important predictors included the presence or absence of a device, New York Heart Association class, HF duration, black race, co-morbidities (sleep apnoea, elevated creatinine, ischaemic heart disease), low blood pressure, and a high congestion score., Conclusion: Risk models using readily available clinical information are able to accurately predict short- and long-term CV events and may be useful in optimizing care and enriching patients for clinical trials., Clinical Trial Registration: ClinicalTrials.gov ID number NCT01685840., (© 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiology.)

Background: Patients with heart failure (HF) who live in rural areas have less access to cardiac services than patients in urban areas. We conducted a randomized, clinical trial to determine the impact of an educational intervention on the composite end point of HF rehospitalization and cardiac death in this population., Methods and Results: Patients (n=602; age, 66±13 years; 41% female; 51% with systolic HF) were randomized to 1 of 3 groups: control (usual care), Fluid Watchers LITE, or Fluid Watchers PLUS. Both intervention groups included a face-to-face education session delivered by a nurse focusing on self-care. The LITE group received 2 follow-up phone calls, whereas the PLUS group received biweekly calls (mean, 5.3±3.6; range, 1-19) until the nurse judged the patient to be adequately trained. Over 2 years of follow-up, 35% of patients (n=211) experienced cardiac death or hospitalization for HF, with no difference among the 3 groups in the proportion who experienced the combined clinical outcome (P=0.06). Although patients in the LITE group had reduced cardiac mortality compared with patients in the control group over the 2 years of follow-up (7.5% and 17.7%, respectively; P=0.003), there was no significant difference in cardiac mortality between patients in the PLUS group and the control group., Conclusions: A face-to-face education intervention did not significantly decrease the combined end point of cardiac death or hospitalization for HF. Increasing the number of contacts between the patient and nurse did not significantly improve outcome., Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT00415545., (© 2014 American Heart Association, Inc.)

An HIE model developed in Florida leverages local and regional networks and offers a flexible, scalable framework that aligns them with national health IT and exchange priorities.

Objective: To examine the association between prevalent cerebral abnormalities identified on MRI and cognitive functioning in a predominantly middle-aged, population-based study cohort., Methods: Cerebral MRI was performed on 1,538 individuals (aged 55 to 72) from the Atherosclerosis Risk in Communities (ARIC) cohort, with no history of stroke or TIA, at study sites in Forsyth County, NC, and Jackson, MS. White matter hyperintensities (WMHs), ventricular size, and sulcal size were graded by trained neuroradiologists on a semiquantitative, 10-point scale. Cognitive functioning was assessed using the Delayed Word Recall Test (DWRT), Digit Symbol Substitution Test (DSST), and Word Fluency Test (WFT)., Results: High ventricular grade was independently associated with significantly lower scores on the DWRT and DSST and greater risk (odds ratio [OR] 2.32, 95% confidence interval [CI] 1.51 to 3.56) of impaired scores (i.e., < or =10th percentile) on the DWRT. High sulcal grade was associated with a modest decrement in scores on the DWRT. The presence of coexisting high grade WMHs and silent infarcts was independently associated with lower scores on all cognitive tests and greater risk of impaired functioning on the DSST (OR 2.91, 95% CI: 1.23 to 6.89) and WFT (OR 2.28, 95% CI 1.03 to 5.08). The presence of two or more high-grade abnormalities was associated with increased risk of impaired functioning on all cognitive tests (DWRT: OR 2.23, 95% CI 1.40 to 3.55; DSST: OR 2.06, 95% CI 1.13 to 3.76; WFT: OR 2.07, 95% CI 1.23 to 3.49) independent of multiple covariates and silent infarcts., Conclusion: Common changes in brain morphology are associated with diminished cognitive functioning in middle-aged and young-elderly individuals.

Objectives: We evaluated self-perceived access to health care in a cohort of Medicare beneficiaries., Methods: We identified patterns of use and barriers to health care from self-administered questionnaires collected during the 1993-1994 annual examination of the Cardiovascular Health Study., Results: The questionnaires were completed by 4889 (91.1%) participants, with a mean age of 76.0 years. The most common barriers to seeing a physician were the doctor's lack of responsiveness to patient concerns, medical bills, transportation, and street safety. Low income, no supplemental insurance, older age, and female gender were independently related to perceptions of barriers. Race was not significant after adjustment for other factors., Conclusions: Psychological and physical barriers affect access to care among the elderly; these may be influenced by poverty more than by race.

Previous observational studies conducted predominantly in white men before 1988 estimated that 20% to 40% of myocardial infarctions (MIs) are unrecognized. Recent data on the proportion of MIs that are unrecognized, especially in women and African-Americans, are largely unavailable. Participants in the Atherosclerosis Risk in Communities (ARIC) study were men and women, aged 45 to 65 years, who were free of clinically recognized coronary heart disease and electrocardiographic evidence of MI at baseline (n = 12,843). Three follow-up clinic examinations were conducted approximately 3, 6, and 9 years after baseline, and included a 12-lead electrocardiogram at rest. Electrocardiographic evidence of infarction was defined as the appearance between the baseline and subsequent examinations of a major Q wave or a minor Q wave with ischemic ST-T changes. Clinically recognized (hospitalized) MI events were also identified and validated. Incident unrecognized MI was defined as electrocardiographic evidence of MI before, or in the absence of, a clinically recognized MI during the follow-up period. Of 508 MIs, 20% were unrecognized (95% confidence interval 16% to 23%), with African-Americans having a slightly higher percentage (23%) than whites (19%). The percentage of unrecognized MIs in men and women was similar. The percentage of unrecognized MIs in the ARIC sample between 1987 and 1998 was slightly lower than previous estimates from other populations.

Background and Purpose: Although patterns of stroke occurrence and mortality have been well studied, few epidemiological data are available regarding the clinical characteristics of stroke events., Methods: We evaluated hospitalized stroke events reported in the Atherosclerosis Risk in Communities (ARIC) Study to describe the clinical characteristics of incident stroke. Confirmed stroke cases (n=474) were evaluated for stroke symptoms (headache, vertigo, gait disturbance, convulsions) and stroke signs (hemianopia, diplopia, speech deficits, paresis, paresthesia/sensory deficits) and their univariate associations with race, sex, and stroke subtype., Results: Over 9.2 years of follow-up, 402 (85%) ischemic and 72 (15%) hemorrhagic strokes occurred. Frequency of stroke symptoms (95% CIs) were as follows: headache (27.4%; 23.4% to 31.4%), gait disturbance (10.8%; 7.9% to 13.6%), convulsions (4.4%; 2.6% to 6.3%), and vertigo (2.1%; 0.8% to 3.4%). Speech deficits occurred in 24.0% (20.2% to 27.9%), hemianopia in 14.6% (11.4% to 17.7%), and diplopia in 5.5% (3.4% to 7.5%) of cases. Most cases involved paresis (81.6%; 78.1% to 85.1%), while fewer cases experienced sensory deficits (44.5%; 40.0% to 49.0%). Blacks were more likely than whites to experience paresis (85.4% versus 78.2%; P=0.044). Men were more likely than women to experience a gait disturbance (14.4% versus 6.7%; P=0.007). Persons with hemorrhagic strokes had a higher proportion of headaches (55.6% versus 22.4%; P=0.001) and convulsions (11.1% versus 3.2%; P=0.003) than those with ischemic events, while speech and sensory deficits were more common in ischemic strokes (26.1% versus 12.5%, P=0.013, and 49.0% versus 19.4%, P=0.001, respectively)., Conclusions: We present epidemiological data concerning the clinical characteristics of incident stroke in a population-based cohort. Although minor differences by race, sex, and stroke subtype were observed, data from additional follow-up are required to confirm observed variations.

Objective: Barriers to the use of emergency medical services (EMS) and patient delay in seeking care can limit the receipt or effectiveness of reperfusion therapies and the availability of prehospital emergency cardiac care. The Rapid Early Action for Coronary Treatment (REACT) trial was designed to determine the impact of a community intervention on use of EMS among demographic and clinical subgroups of patients with suspected acute cardiac ischemia., Methods: A randomized controlled community trial was conducted in 20 pair-matched communities in the United States. One community from each pair received an 18-month, multicomponent community education program. Data were collected at 44 participating hospitals during a four-month baseline period and throughout the 18-month trial, using medical record abstracts to collect information on mode of transport to the hospital and other sociodemographic and clinical variables. Eligible patients were persons aged > or = 30 years presenting with chest pain or discomfort to emergency departments (EDs) who were admitted and discharged with a cardiac-related diagnoses (ICD 410-414, 427-429, 440, 786.9)., Results: The net change in the odds of EMS use was an increase of 34% in intervention compared with control communities [adjusted odds ratio (OR) 1.34, 95% CI 1.07-1.67]. We observed greater increases in the odds of EMS use among patients who had chronic or other cardiac diagnoses (adjusted OR 1.53, 95% CI 1.18-1.99, and adjusted OR 1.52, 95% CI 1.17-1.97, respectively) than in those diagnosed as having acute ischemia (adjusted OR 1.14, 95% CI 0.91-1.44). We observed greater increases in odds of EMS ulse in those who were retired (adjusted OR 1.62, 95% CI 1.29-2.04) or had systolic blood pressure (SBP) at or below 160 mm Hg upon presentation to the ED (adjusted OR 1.55, 95% CI 1.26-1.91 for SBP 100-160 mm Hg; 1.61, 95% CI 0.88-2.97 for SBP <100 mm Hg)., Conclusions: The REACT trial demonstrated a significant impact on the use of EMS among patients admitted to the hospital for suspected acute myocardial infarction, with greater increases among patients with chronic or other cardiac ICD-9 discharge diagnoses, those presenting with lower SBP, and retired persons.

Purpose: Retinal microvascular characteristics, as graded from retinal photography, have been shown to predict stroke. We evaluated the reliability of retinal photographic grading in the Atherosclerosis Risk in Communities Study., Design: Cohort study., Methods: Retinal photographs were taken of all subjects who attended the third Atherosclerosis Risk in Communities Study examination (1993 to 1995). These were graded using standardized protocols. Focal retinal characteristics were graded using a "light box" system. Generalized retinal arteriolar narrowing was quantified from computer-assisted measurements of digitized photographs. Two sub-studies were conducted to investigate the reliability of these grading methods. In the Individual Variability Study, selected subjects (n = 206) had two retinal photographs taken on one day, and a further one or two photographs taken 3 weeks later. In the Grader Variability Study, a stratified random sample of photographs had repeat retinal grading (n = 495 photographs for light box grading; n = 276 photographs for computer-assisted grading)., Results: Reliability of the computer-assisted quantification of generalized retinal arteriolar narrowing was high in both studies (reliability coefficients 0.64 to 0.69 for Individual Variability Study, and 0.79 to 0.83 for the Grader Variability Study). There was more variability for focal abnormalities graded using the light box system. Variability for Individual Variability Study (same individuals, repeat photographs) tended to be greater than for the Grader Variability Study (same photographs, repeat gradings)., Conclusion: Retinal microvascular characteristics, especially computer-assisted quantification of generalized retinal arteriolar narrowing, can be ascertained reliably by standardized photographic grading methods, supporting the validity of their associations with cardiovascular disease. However, these characteristics appear to vary somewhat between eyes and over time in a single individual.

Background: Retinal microvascular abnormalities reflect damage from hypertension and other vascular processes. We examined the relation of such abnormalities to incident stroke., Methods: A cohort of 10358 men and women (aged 51 to 72 years) living in four US communities underwent retinal photography and standard grading for retinal microvascular abnormalities. The calibres of all retinal arterioles and venules were measured after digital conversion of the photographs, and a summary arteriole-to-venule ratio (AVR) was calculated as an index of arteriolar narrowing (smaller AVR indicates greater narrowing). Cases of incident stroke admitted to hospital were identified and validated by case record reviews., Findings: Over an average of 3.5 years, 110 participants had incident strokes. After adjustment for age, sex, race, 6-year mean arterial blood pressure, diabetes, and other stroke risk factors, most retinal microvascular characteristics were predictive of incident stroke, with adjusted relative risks of 2.58 (1.59-4.20) for any retinopathy, 3.11 (1.71-5.65) for microaneurysms, 3.08 (1.42-6.68) for soft exudates, 2.55 (1.27-5.14) for blot haemorrhages, 2.26 (1.00-5.12) for flame-shaped haemorrhages, and 1.60 (1.03-2.47) for arteriovenous nicking. The relative risk of stroke increased with decreasing AVR (p=0.03). The associations were similar for ischaemic strokes specifically, and for strokes in individuals with hypertension, either with or without diabetes., Interpretation: Retinal microvascular abnormalities are related to incident stroke. The findings support a microvascular role in the pathogenesis of stroke. They suggest that retinal photography may be useful for cerebrovascular-risk stratification in appropriate populations.

Background: Declining mortality rates of coronary heart disease in the United States could be attributable to declining incidence, declining severity, and/or improvements in treatment., Methods: We examined trends in severity of patients hospitalized for myocardial infarction to characterize its contribution to this decline by using data from the Atherosclerosis Risk in Communities (ARIC) study., Results: No significant change in the proportion having systolic blood pressure <100 mm Hg or an abnormal pulse at presentation was noted. The proportion with ST-segment elevation on the initial electrocardiogram increased 10% per year (P <.001), and the proportion with a diagnostic or evolving diagnostic electrocardiogram abnormality increased 4% per year (P <.01); the proportion that had a new Q-wave infarction develop remained unchanged. The mean peak creatine kinase level decreased 5% per year (P <.001), the proportion with abnormal enzyme levels decreased 10% per year (P <.001), and the proportion that met criteria for definite myocardial infarction decreased 4% per year (P <.05). The proportion that had cardiogenic shock decreased 10.9% per year (P <. 01), but the proportion that had an acute episode of congestive heart failure was stable., Conclusions: With stable hemodynamic indicators, worsening electrocardiographic indicators, and improving enzymatic indicators, these results provide mixed support for decreases in the severity of myocardial infarction.

Background: The use of thrombolytic therapy for patients with myocardial infarction has been limited by patient delay in seeking care. We sought to characterize prehospital delay in patients hospitalized for evaluation of heart attack symptoms., Methods and Results: The Rapid Early Action for Coronary Treatment (REACT) is a multicenter, randomized community trial designed to reduce patient delay. At baseline, data were abstracted from the medical records of 3783 patients hospitalized for evaluation of heart attack symptoms in 20 communities. The median prehospital delay was 2.0 hours; 25% of patients delayed longer than 5.2 hours. In a multivariable analysis, delay time was longer among non-Hispanic blacks than among non-Hispanic whites, longer at older ages, longer among Medicaid-only recipients and shorter among Medicare recipients than among privately insured patients, and shorter among patients who used an ambulance., Conclusions: The observed pattern of differences is consistent with the contention that demographic, cultural, and/or socioeconomic barriers exist that impede rapid care seeking.

Objective: To develop protocols to photograph and evaluate retinal vascular abnormalities in the Atherosclerosis Risk in Communities (ARIC) Study; to test reproducibility of the grading system; and to explore the relationship of these microvascular changes with blood pressure., Design: Population-based, cross-sectional study., Participants: Among 4 examination centers, 11,114 participants (48-73 years of age) at their third triennial examination, after excluding persons with diabetes from this analysis., Methods: One eye of each participant was photographed by technicians with nonmydriatic fundus cameras. Reading center graders evaluated focal arteriolar narrowing, arteriovenous (AV) nicking, and retinopathy by examining slides on a light box and measured diameters of all vessels in a zone surrounding the optic disc on enhanced digitized images. To gauge generalized narrowing, vessel diameters were combined into central arteriolar and venular equivalents with formulas adjusting for branching, and the ratio of equivalents (A/V ratio) was calculated., Main Outcome Measures: Retinal vascular abnormalities, mean arteriolar blood pressure (MABP)., Results: Among 11,114 participants, photographs were obtained of 99%, with quality sufficient to perform retinal evaluations in 81%. In the 9040 subjects with usable photographs, A/V ratio (lower values indicate generalized arteriolar narrowing) ranged from 0.57 to 1.22 (median = 0.84, interquartile range = 0.10), focal arteriolar narrowing was found in 7%, AV nicking in 6%, and retinopathy in 4%. Because of attrition of subjects and limitation of methods, prevalence of abnormality was likely underestimated. Controlling for gender, race, age, and smoking status, these retinal changes were associated with higher blood pressure. For every 10-mmHg increase in MABP, A/V ratio decreased by 0.02 unit (P < 0.0001), focal arteriolar narrowing had an odds ratio (OR) of 2.00 (95% confidence interval [CI] = 1.87-2.14), AV nicking had an OR of 1.25 (95% CI = 1.16-1.34), and retinopathy had an OR of 1.25 (95% CI = 1.15-1.37). For any degree of generalized narrowing, individuals with focal narrowing had MABP approximately 8 mmHg higher than those without (P < 0.0001). Masked replicate assessment of a sample found the following reproducibility: for A/V ratio, correlation coefficient = 0.79 and median absolute difference = 0.03; for focal arteriolar narrowing, kappa = 0.45; for AV nicking, kappa = 0.61; and for retinopathy, kappa = 0.89., Conclusion: Protocols have been developed for nonmydriatic fundus photography and for evaluation of retinal vascular abnormalities. Several microvascular changes were significantly associated with higher blood pressure; follow-up will show whether these are predictive of later cerebrovascular or cardiovascular disease independently of other known risk factors.

Objective: We tested the hypothesis that diabetes, body fat distribution, and (in nondiabetic subjects) fasting insulin levels are positively associated with ischemic stroke incidence in the general population., Research Design and Methods: As part of the Atherosclerosis Risk in Communities (ARIC) Study, we measured diabetes by using fasting glucose criteria, waist and hip circumferences, and fasting insulin levels with a radioimmunoassay in > 12,000 adults aged 45-64 years who had no cardiovascular disease at baseline. We followed them for 6-8 years for ischemic stroke occurrence (n = 191)., Results: After adjustment for age, sex, race, ARIC community, smoking, and education level, the relative risk of ischemic stroke was 3.70 (95% CI 2.7-5.1) for diabetes, 1.74 (1.4-2.2) for a 0.11 increment of waist-to-hip ratio, and 1.19 (1.1-1.3) for a 50-pmol/l increment of fasting insulin among nondiabetic subjects. Ischemic stroke incidence was not statistically significantly associated with BMI (comparably adjusted relative risk = 1.15, 95% CI 0.97-1.36). With adjustment for other stroke risk factors (some of which may mediate the effects of diabetes, fat distribution, and hyperinsulinemia), the relative risks for diabetes, waist-to-hip ratio, and fasting insulin level were 2.22 (95% CI 1.5-3.2), 1.08 (0.8-1.4), and 1.14 (1.01-1.3), respectively., Conclusions: Diabetes is a strong risk factor for ischemic stroke. Aspects of insulin resistance, as reflected by elevated waist-to-hip ratios and elevated fasting insulin levels, may also contribute to a greater risk of ischemic stroke.

Background and Methods: To clarify the determinants of contemporary trends in mortality from coronary heart disease (CHD), we conducted surveillance of hospital admissions for myocardial infarction and of in-hospital and out-of-hospital deaths due to CHD among 35-to-74-year-old residents of four communities of varying size in the United States (a total of 352,481 persons in 1994). Between 1987 and 1994, we estimate that there were 11,869 hospitalizations for myocardial infarction (on the basis of 8572 hospitalizations sampled) and 3407 fatal coronary events (3023 sampled)., Results: The largest average annual decrease in mortality due to CHD occurred among white men (change in mortality, -4.7 percent; 95 percent confidence interval, -2.2 to -7.1 percent), followed by white women (-4.5 percent; 95 percent confidence interval, -0.7 to -8.2 percent), black women (-4.1 percent; 95 percent confidence interval, -10.3 to +2.5 percent), and black men (-2.5 percent; 95 percent confidence interval, -6.9 to +2.2 percent). Overall, in-hospital mortality from CHD fell by 5.1 percent per year, whereas out-of-hospital mortality declined by 3.6 percent per year. There was no evidence of a decline in the incidence of hospitalization for a first myocardial infarction among either men or women; in fact, such hospital admissions increased by 7.4 percent per year (95 percent confidence interval for the change, +0.5 to +14.8 percent) among black women and 2.9 percent per year (95 percent confidence interval, -3.6 to +9.9 percent) among black men. Rates of recurrent myocardial infarction decreased, and survival after myocardial infarction improved., Conclusions: From 1987 to 1994, we observed a stable or slightly increasing incidence of hospitalization for myocardial infarction. Nevertheless, there were significant annual decreases in mortality from CHD. The decline in mortality in the four communities we studied may be due largely to improvements in the treatment and secondary prevention of myocardial infarction.