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Objective: Extensive studies on health-related quality of life (HRQOL) in idiopathic inflammatory myopathies (IIM) are lacking. Our objective was to document HRQOL and to identify factors associated with a reduced HRQOL in IIM patients. Methods: A total of 1,715 patients (median age 49.9, 70% female, 87% Caucasian) who met probable or definite Bohan and Peter or Griggs criteria for myositis were included from the MYOVISION registry. HRQOL was ascertained via the SF-12v2® Health Survey questionnaire. HRQOL physical and mental component summary scores (PCS and MCS, respectively) in relation to different patient and disease characteristics were compared to scores from the matched normative data from the U.S. general population and rheumatoid arthritis (RA) patients. Bivariate and multiple linear regression analyses were performed to assess the association between HRQOL and patient and disease parameters. Results: The mean summary scores of the SF-12v2® were significantly lower in IIM as compared to the normative and RA populations. A diagnosis of inclusion body myositis, older age, patient-reported negative effect of disease on work, presence of another concurrent autoimmune disease, polypharmacy, and IIM-associated lung disease and joint involvement were all significantly associated with lower PCS. Lower MCS were associated with joint involvement and a negative effect on work. Conclusion: In this large study of patient-reported outcomes in IIM, an association was found between multiple disease characteristics and reduced HRQOL, mostly in the physical domain. In the United States, HRQOL in IIM patients was lower compared to the general population and to RA patients. This article is protected by copyright. All rights reserved.

Objective Dermatomyositis (DM) has been associated with geospatial differences in ultraviolet (UV) radiation, but the role of individual determinants of UV exposure prior to diagnosis is unknown. Methods We analyzed questionnaire data from 1350 adults in a U.S. national myositis registry (638 with DM, 422 polymyositis [PM], and 290 inclusion body myositis [IBM] diagnosed at ages 18-65 years), examining the likelihood of DM compared with PM and IBM diagnosis, in relation to self-reported sunburn history and job- and hobby-related sun exposures in the year prior to diagnosis. We estimated odds ratios (OR) and 95% confidence intervals (CI) using logistic regression adjusted for age, skin tone, and sex, to determine the association of individual UV exposures with DM diagnosis. We also evaluated the proportion of DM by maximum daily ambient UV exposure, based on UV-B erythemal irradiances for participant residence the year prior to diagnosis. Results DM was associated with sunburn in the year before diagnosis (two or more sunburns, OR=1.77; 95%CI 1.28, 2.43 vs. PM/IBM; one sunburn OR=1.44; 95%CI 1.06, 1.95) and with having elevated job- or hobby-related sun exposure (high OR=1.64; 95%CI 1.08, 2.49 or moderate exposure OR=1.35; 95%CI 1.02, 1.78 vs. low or no exposure). Ambient UV intensity was associated with DM in females (beta=3.97, P=0.046), but not overall. Conclusion Our findings suggest that high or moderate personal exposure to intense sunlight is associated with developing DM compared with other types of myositis. Prospective research on UV exposure as a modifiable risk factor for DM is warranted. This article is protected by copyright. All rights reserved.

Background: Potential associations between background environmental chemical exposures and autoimmunity are understudied. Objectives: Our exploratory study investigated exposure to individual environmental chemicals and selected mixtures in relation to the presence of antinuclear antibodies (ANA), a widely used biomarker of autoimmunity, in a representative sample of the U.S. population. Methods: This cross-sectional analysis used data on 4,340 participants from the National Health and Nutrition Examination Survey (1999–2004), of whom 14% were ANA positive, to explore associations between ANA and concentrations of dioxins, dibenzofurans, polychlorinated biphenyls, organochlorines, organophosphates, phenols, metals, and other environmental exposures and metabolites measured in participants’ serum, whole blood, or urine. For dioxin-like compounds with toxic equivalency factors, we developed and applied a new statistical approach to study selected mixtures. Lognormal models and censored-data methods produced estimates of chemical associations with ANA in males, nulliparous females, and parous females; these estimates were adjusted for confounders and accommodated concentrations below detectable levels. Results: Several associations between chemical concentration and ANA positivity were observed, but only the association in males exposed to triclosan remained statistically significant after correcting for multiple comparisons (mean concentration ratio = 2.8; 95% CI: 1.8, 4.5; p < 0.00001). Conclusions: These data suggest that background levels of most xenobiotic exposures typical in the U.S. population are not strongly associated with ANA. Future studies should ideally reduce exposure misclassification by including prospective measurement of the chemicals of concern and should track changes in ANA and other autoantibodies over time. Citation: Dinse GE, Jusko TA, Whitt IZ, Co CA, Parks CG, Satoh M, Chan EKL, Rose KM, Walker NJ, Birnbaum LS, Zeldin DC, Weinberg CR, Miller FW. 2016. Associations between selected xenobiotics and antinuclear antibodies in the National Health and Nutrition Examination Survey, 1999–2004. Environ Health Perspect 124:426–436; http://dx.doi.org/10.1289/ehp.1409345

Inter-individual variability in blood pressure (BP) is influenced by both genetic and non-genetic factors including socioeconomic and psychosocial stressors. A deeper understanding of the gene-by-socioeconomic/psychosocial factor interactions on BP may help to identify individuals that are genetically susceptible to high BP in specific social contexts. In this study, we used a genomic region-based method for longitudinal analysis, Longitudinal Gene-Environment-Wide Interaction Studies (LGEWIS), to evaluate the effects of interactions between known socioeconomic/psychosocial and genetic risk factors on systolic and diastolic BP in four large epidemiologic cohorts of European and/or African ancestry. After correction for multiple testing, two interactions were significantly associated with diastolic BP. In European ancestry participants, outward/trait anger score had a significant interaction with the C10orf107 genomic region (p = 0.0019). In African ancestry participants, depressive symptom score had a significant interaction with the HFE genomic region (p = 0.0048). This study provides a foundation for using genomic region-based longitudinal analysis to identify subgroups of the population that may be at greater risk of elevated BP due to the combined influence of genetic and socioeconomic/psychosocial risk factors.

Background: Autoantibodies are of growing interest in cancer research as potential biomarkers; yet, the determinants of autoimmunity are not well understood. Antinuclear antibodies (ANA) are common in the general population and are more prevalent in women and older adults. Here, we examined the relationship of ANA with reproductive and hormonal factors in a representative sample of U.S. women. Methods: We analyzed data on reproductive history and exogenous hormone use in relation to serum ANA in 2,037 females ages 12 years and older from the National Health and Nutrition Examination Survey (NHANES; 1999–2004). Estimated ANA prevalences were adjusted for sampling weights. Prevalence ORs (POR) and 95% confidence intervals (CI) were adjusted for age, race, and poverty–income ratio, and models were stratified by menopause status. Results: In premenopausal women ages 20 years and older, ANA prevalence was associated with parity (P < 0.001; parous vs. nulliparous POR = 2.0; 95% CI, 1.2–3.4), but in parous women, ANA did not vary by number of births, age at first birth, years since last birth, or breastfeeding. In postmenopausal women, ANA prevalence was associated with an older age at menarche (P = 0.019; age 16–20 vs. 10–12 years POR = 3.0; 95% CI, 1.6–5.9), but not with parity. Oral contraceptives and estrogen therapy were not associated with a higher ANA prevalence. Conclusions: Childbearing (having had one or more births) may explain age-associated elevations in ANA prevalence seen in premenopausal women. Impact: These findings highlight the importance of considering reproductive history in studies of autoimmunity and cancer in women. Cancer Epidemiol Biomarkers Prev; 23(11); 2492–502. ©2014 AACR.

Acute stroke patients require immediate medical attention. Therefore, American Stroke Association guidelines recommend that for suspected stroke cases, emergency medical services (EMS) personnel spend less than 15 minutes on-scene at least 90% of the time. However, not all EMS providers include specific scene time limits in their stroke patient care protocols.We sought to determine whether having a protocol with a specific scene time limit was associated with less time EMS spent on scene. Methods. Stroke protocols from the 100 EMS systems in North Carolina were collected and abstracted for scene time instructions. Suspected stroke events occurring in 2009 were analyzed using data from the North Carolina Prehospital Medical Information System. Scene time was defined as the time from EMS arrival at the scene to departure with the patient. Quantile regression was used to estimate how the 90th percentile of the scene time distribution varied by systems with protocol instructions limiting scene time, adjusting for system patient volume and metropolitan status.In 2009, 23 EMS systems in North Carolina had no instructions regarding scene time; 73 had general instructions to minimize scene time; and 4 had a specific limit for scene time (i.e., 10 or 15 min). Among 9,723 eligible suspected stroke events, mean scene time was 15.9 minutes (standard deviation 6.9 min) and median scene time was 15.0 minutes (90th percentile 24.3 min). In adjusted quantile regression models, the estimated reduction in the 90th percentile scene time, comparing protocols with a specific time limit to no instructions, was 2.2 minutes (95% confidence interval 1.3, 3.1 min). The difference in 90th percentile scene time between general and absent instructions was not statistically different (0.7 min [95% confidence interval -0.1, 1.4 min]).Protocols with specific scene time limits were associated with EMS crews spending less time at the scene while general instructions were not. These findings suggest EMS systems can modestly improve scene times for stroke by specifying a time limit in their protocols.

Objective To examine the survival benefit of multiple medical therapies in a large, community-based population of validated myocardial infarction (MI) events. Design Retrospective observational cohort study. Setting Population-based sample of 30 986 definite or probable MIs in residents of four US communities aged 35–74 years randomly sampled between 1987 and 2008 as part of the Atherosclerosis Risk in Communities Surveillance Study. Interventions None. Main outcome measures All-cause mortality 30, 90 and 365 days after discharge. Results We used unadjusted and propensity score (PS) adjusted models to examine the relationship between medical therapy use and mortality. In unadjusted models, each medication and procedure was inversely associated with 30-day mortality. After PS adjustment, the crude survival benefits were attenuated for all therapies except for intravenous tissue plasminogen activator therapy (IV-tPA) and stent use. After inclusion of other therapies received during the event in regression models, risk ratio effect estimates (RR; (95% CI)) were attenuated for aspirin (0.66; (0.58 to 0.76) to 0.91 (0.80 to 1.03)), non-aspirin antiplatelets (0.74; (0.59 to 0.92) to 0.92 (0.72 to 1.18)), IV-tPA (0.50; (0.41 to 0.62) to 0.65 (0.52 to 0.80)) and stents (0.53 (0.40 to 0.69) to 0.68 (0.49 to 0.94)). Effect estimates remained stable for all other therapies and were similar for 90- and 365-day mortality endpoints. Conclusions We observed inverse associations between receipt of six medications and procedures for MI and all-cause mortality at 30, 90 and 365 days after adjustment for PS. The mortality benefits observed in this population-based setting are consistent with those reported in clinical trials.

Background: Industrial swine operations emit odorant chemicals including ammonia, hydrogen sulfide (H2S), and volatile organic compounds. Malodor and pollutant concentrations have been associated with self-reported stress and altered mood in prior studies. Objectives: We conducted a repeated-measures study of air pollution, stress, and blood pressure in neighbors of swine operations. Methods: For approximately 2 weeks, 101 nonsmoking adult volunteers living near industrial swine operations in 16 neighborhoods in eastern North Carolina sat outdoors for 10 min twice daily at preselected times. Afterward, they reported levels of hog odor on a 9-point scale and measured their blood pressure twice using an automated oscillometric device. During the same 2- to 3-week period, we measured ambient levels of H2S and PM10 at a central location in each neighborhood. Associations between systolic and diastolic blood pressure (SBP and DBP, respectively) and pollutant measures were estimated using fixed-effects (conditional) linear regression with adjustment for time of day. Results: PM10 showed little association with blood pressure. DBP [β (SE)] increased 0.23 (0.08) mmHg per unit of reported hog odor during the 10 min outdoors and 0.12 (0.08) mmHg per 1-ppb increase of H2S concentration in the same hour. SBP increased 0.10 (0.12) mmHg per odor unit and 0.29 (0.12) mmHg per 1-ppb increase of H2S in the same hour. Reported stress was strongly associated with BP; adjustment for stress reduced the odor–DBP association, but the H2S–SBP association changed little. Conclusions: Like noise and other repetitive environmental stressors, malodors may be associated with acute blood pressure increases that could contribute to development of chronic hypertension.

Autoantibodies to cellular constituents are the serologic hallmarks of autoimmunity and are frequently seen in systemic autoimmune diseases, including systemic lupus erythematosus (SLE), scleroderma, and polymyositis/dermatomyositis (1). They also are detected in patients with organ-specific autoimmune diseases, such as autoimmune thyroiditis and hepatitis (1), certain infections and neoplasms (2), and in some individuals without diagnosed disease (2, 3). The most common autoantibodies are antinuclear antibodies (ANA), which are traditionally assessed by indirect immunofluorescence and include antibodies to both nuclear and cytoplasmic components (4). The cellular staining patterns and specific autoantibodies detected in those with ANA are clinically useful as they are strongly associated with particular autoimmune diseases, such as the nucleolar staining patterns that are often seen in scleroderma and anti-Sm autoantibodies that are included in SLE classification criteria (1). A variety of methods have been used to estimate ANA prevalence in selected populations, including blood donors (5, 6), hospital workers (6, 7), healthy volunteers (3, 8), or residents in small areas (9, 10), leading to a wide range of prevalence estimates (from 1.1% to 20%), which are difficult to compare. Factors associated with ANA production are largely unknown with the exception of some reports suggesting higher prevalence of ANA in females (8, 10–13) and older individuals (12, 14–16). A proportion of the ANA-positive population is thought to represent the preclinical stage of autoimmune diseases based on observations that autoantibodies are usually produced prior to clinical manifestations of disease (17). Thus, defining the prevalence and types of ANA, as well as characterizing factors associated with their production, may provide insight into the etiology of autoimmune diseases, which are thought to be increasing in frequency but are more difficult to characterize and study than ANA at the population level (18). Therefore, we evaluated serum samples from the United States (U.S.) National Health and Nutrition Examination Survey (NHANES) from 1999–2004 to estimate ANA prevalence, cellular patterns and specific autoantibody reactivities, and to identify sociodemographic and biobehavioral factors associated with their production. We specifically assessed selected systemic autoimmune disease risk factors including smoking (19) and alcohol use (20). We also evaluated C-reactive protein (21) and obesity, the former being a marker and the latter an underlying cause of chronic inflammation (22) and a growing public health concern.

Background— Among patients with heart failure (HF), early readmission or death and repeat hospitalizations may be indicators of poor disease management or more severe disease. Methods and Results— We assessed the association of neighborhood median household income (nINC) and Medicaid status with rehospitalization or death in the Atherosclerosis Risk in Communities cohort study (1987 to 2004) after an incident HF hospitalization in the context of individual socioeconomic status and evaluated the relationship for modification by demographic and comorbidity factors. We used generalized linear Poisson mixed models to estimate rehospitalization rate ratios and 95% CIs and Cox regression to estimate hazard ratios (HRs) and 95% CIs of rehospitalization or death. In models controlling for race and study community, sex, age at HF diagnosis, body mass index, hypertension, educational attainment, alcohol use, and smoking, patients with a high burden of comorbidity who were living in low-nINC areas at baseline had an elevated hazard of all-cause rehospitalization (HR, 1.40; 95% CI, 1.10 to 1.77), death (HR, 1.36; 95% CI, 1.02 to 1.80), and rehospitalization or death (HR, 1.36; 95% CI, 1.08 to 1.70) as well as increased rates of hospitalization compared to those with a high burden of comorbidity living in high-nINC areas. Medicaid recipients with a low level of comorbidity had an increased hazard of all-cause rehospitalization (HR, 1.19; 95% CI, 1.05 to 1.36) and rehospitalization or death (HR, 1.21; 95% CI, 1.07 to 1.37) and a higher rate of repeat hospitalizations compared to non-Medicaid recipients. Conclusions— Comorbidity burden appears to influence the association among nINC, Medicaid status, and rehospitalization and death in patients with HF.

Exposure to military combat has been associated with myriad adverse health effects. Mechanisms are not well understood, but may include negative emotional states. The authors investigated the relationship between combat and trait anger and vital exhaustion among 5,347 middle-aged male participants in the Atherosclerosis Risk in Communities Study. Combat was significantly associated with trait anger, although results were limited to men of the Korean and Vietnam War eras. Among men of the Korean War era, combat- and noncombat veterans, compared to their nonveteran counterparts, reported more trait anger. Compared to their noncombat and nonveteran counterparts, Vietnam War era combat veterans reported more trait anger. Noncombat veterans from the World War II and Vietnam War eras reported lower vital exhaustion compared to nonveterans. Anger proneness may be a mechanism through which combat stress is associated with adverse health outcomes.

BACKGROUND: Bedroom allergen exposures contribute to allergic disease morbidity because people spend considerable time in bedrooms, having close contact with allergen reservoirs. OBJECTIVE: We investigated participant and housing characteristics, including sociodemographic, regional and climatic factors, associated with bedroom allergen exposures in a nationally representative sample of the US population. METHODS: Data were obtained from National Health and Nutrition Examination Survey (NHANES) 2005–2006. Information on participant and housing characteristics was collected by questionnaire and environmental assessments. Concentrations of 8 indoor allergens (Alt a 1, Bla g 1, Can f 1, Fel d 1, Der f 1, Der p 1, Mus m 1, and Rat n 1) in dust vacuumed from nearly 7,000 bedrooms were measured by immunoassays. Exposure levels were classified as elevated based on percentile (75(th)/90(th)) cut-offs. We estimated the burden of exposure to multiple allergens and used multivariable logistic regression to identify independent predictors for each allergen and household allergen burden. RESULTS: Almost all participants (>99%) had at least one and 74.2% had 3–6 allergens detected. Over 2/3 of participants (72.9%) had at least one allergen and 18.2% had ≥3 allergens exceeding elevated levels. Although exposure variability showed significant racial/ethnic and regional differences, high exposure burden to multiple allergens was most consistently associated with the presence of pets and pests, living in mobile homes/trailers, older and rental homes, and in non-metropolitan areas. CONCLUSIONS: Exposure to multiple allergens is common. Despite highly variable exposures, bedroom allergen burden is strongly associated with the presence of pets and pests. CLINICAL IMPLICATIONS: In the general US population, exposure to indoor allergens varies by sociodemographic and housing characteristics; however, exposure patterns show sociodemographic differences when compared to sensitization patterns.

Background Studies of the cardiovascular consequences of combat stress are few and inconclusive. Objective The association between combat exposure and subclinical atherosclerosis at Atherosclerosis Risk in Communities (ARIC) Study visits 1 (1987–1989) and 2 (1990–1992) was assessed among 5347 men from four U.S. communities. Methods Measured an average of 36 years after military entry, carotid intima-media thickness (CIMT) and carotid plaque among non-combat veterans ( n = 2127) were compared with non-veterans ( n = 2042) and veterans reporting combat experience ( n = 1178). Results Compared to non-combat veterans, non-veterans (risk difference (RD): 10.61; 95% confidence interval (CI): 0.81, 20.41) and combat veterans (RD: 12.79; 95% CI: 0.72, 24.86) had higher age-adjusted mean CIMT. Differences remained for combat veterans after adjustment for race, father's education and age at service entry but not years of service and for non-veterans after adjustment for race but not father's education. No differences in carotid plaque were noted. Conclusion Results do not suggest that combat has a long-term detrimental effect on subclinical atherosclerosis among men.

Purpose To investigate the association of employment status with coronary heart disease (CHD) and ischemic stroke among middle-aged women. Methods Proportional hazards regression was used to assess the association of employment status, incident CHD, and incident ischemic stroke among 7,058 women, ages 45–64 years at baseline (1987–1989), from the Atherosclerosis Risk in Communities Study. Results After adjusting for age and race-field center, women employed outside the home had a decreased risk of CHD (hazard ratio [HR], 0.70; 95% confidence interval [95% CI], 0.56–0.86) and ischemic stroke (HR, 0.62; 95% CI, 0.47–0.84) compared with homemakers. Differences in cardiovascular disease risk factors partially accounted for the association of employment status and CHD (HR, 0.79; 95% CI, 0.63–0.99) and stroke (HR, 0.79; 95% CI, 0.58–1.08). Also, modest differences were noted when the results were stratified by education, with employed women having a lower risk of CHD (HR, 0.65; 95% CI, 0.45–0.93) than homemakers among those with less than a high school education. Conclusions Women employed outside of the home had a lower risk of CHD and stroke compared with homemakers and, for CHD, this association was stronger among women with less than a high school education. These findings suggest additional research into the varied occupational experiences of women, socioeconomic status, and health is warranted.

The objective of this study was to examine the association of individual socioeconomic status (iSES) and neighborhood SES (nSES) on the prevalence of metabolic syndrome (MetS) in the Atherosclerosis Risk in Communities Study (1987-1999).Participants included 2932 black and 9777 white men and women aged 45 to 64 years without diabetes at baseline. Total combined family income for the past 12 months and six census tract socioeconomic measures combined into a composite index were used to quantify iSES and nSES, respectively. Poisson regression was used to assess associations of the joint contribution of iSES and nSES on the MetS, stratified by gender and race and adjusting for multiple covariates. For analyses that included nSES, hierarchical modeling techniques were used.Using 2005 Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults criteria, MetS was identified in 40% of black women, 30% of white women, 28% of black men, and 35% of white men. Among black and white men, there was no association between MetS and iSES or nSES. In contrast, after adjustment for risk factors, black and white women with low (L)-iSES and medium (M)-iSES were more likely to have MetS than those with high (H)-iSES. Similar but weaker patterns were noted for L-nSES and M-nSES.In summary, both iSES and nSES were independently associated with an increased prevalence of MetS among women but not men. Efforts aimed at understanding the causes of these gender differences may offer insight into avenues for reducing the prevalence of the MetS and its chronic disease sequelae.

Background For people living close to busy roads, traffic is a major source of air pollution. Few prospective data have been published on the effects of long-term exposure to traffic on the incidence of coronary heart disease (CHD). Objectives In this article, we examined the association between long-term traffic exposure and incidence of fatal and nonfatal CHD in a population-based prospective cohort study. Methods We studied 13,309 middle-age men and women in the Atherosclerosis Risk in Communities study, without previous CHD at enrollment, from 1987 to 1989 in four U.S. communities. Geographic information system–mapped traffic density and distance to major roads served as measures of traffic exposure. We examined the association between traffic exposure and incident CHD using proportional hazards regression models, with adjustment for background air pollution and a wide range of individual cardiovascular risk factors. Results Over an average of 13 years of follow-up, 976 subjects developed CHD. Relative to those in the lowest quartile of traffic density, the adjusted hazard ratio (HR) in the highest quartile was 1.32 [95% confidence interval (CI), 1.06–1.65; p-value for trend across quartiles = 0.042]. When we treated traffic density as a continuous variable, the adjusted HR per one unit increase of log-transformed density was 1.03 (95% CI, 1.01–1.05; p = 0.006). For residents living within 300 m of major roads compared with those living farther away, the adjusted HR was 1.12 (95% CI, 0.95–1.32; p = 0.189). We found little evidence of effect modification for sex, smoking status, obesity, low-density lipoprotein cholesterol level, hypertension, age, or education. Conclusion Higher long-term exposure to traffic is associated with incidence of CHD, independent of other risk factors. These prospective data support an effect of traffic-related air pollution on the development of CHD in middle-age persons.

Objective: To examine the association between cumulative life course and adult socioeconomic status (SES) and adult levels of inflammatory risk markers (fibrinogen, white blood cell count (WBC), C-reactive protein (CRP), von Willebrand factor (vWF) and an overall inflammatory score). Design: Retrospective cohort study. Setting: 12 681 white and African-American participants in the Atherosclerosis Risk in Communities (ARIC) study and two ancillary studies. Methods: Participants provided information on SES and place of residence in childhood and young (30–40 years) and mature (45+) adulthood. Residences were linked to census data for neighbourhood SES information. Multiple imputation (MI) was used for missing data. Linear regression and adjusted geometric means were used to estimate the effects of SES on inflammatory risk marker levels. Results: Graded, statistically significant associations were observed between greater cumulative life-course exposure to low education and social class and elevated levels of fibrinogen and WBC among white participants. Stronger graded, statistically significant associations were observed between low adult education, social class and neighbourhood SES and elevated inflammatory levels. Associations were weaker and less consistent in African-Americans. Covariate adjustment attenuated results but many associations remained strong. Conclusions: Our results suggest that cumulative exposure to adverse SES conditions across the life course and low adult SES are associated with an elevated systemic inflammatory burden in adulthood. Chronic systemic inflammation may be one pathway linking low life-course SES and elevated cardiovascular disease risk.

This study examined the association between vascular headaches and retinal microvascular disease.We investigated the cross-sectional association between headaches (migraine/other headaches with aura, migraine without aura, other headaches without aura, no headaches) and retinal microvascular signs (retinopathy, focal arteriolar narrowing, arteriovenous nicking; arteriolar and venular calibers) among middle-aged African American and white men and women from the third examination of the Atherosclerosis Risk in Communities Study (1993 through 1995).After controlling for age, gender, race, study center, and cardiovascular risk factors, we determined that persons with headaches were more likely to have retinopathy than those without a history of headaches (odds ratio [OR] = 1.38, 95% CI = 0.96 to 1.99 for migraine/other headaches with aura; OR = 1.49, 95% CI = 1.05 to 2.12 for migraine without aura; and OR = 1.28, 95% CI = 0.99 to 1.65 for other headaches). Associations with migraine were stronger among the subset of participants without a history of diabetes or hypertension (OR = 1.79, 95% CI = 1.09 to 2.95 for migraine/other headaches with aura; and OR = 1.74, 95% CI = 1.11 to 2.71 for migraine without aura). Headaches were not associated with focal arteriolar narrowing or arteriovenous nicking. Persons with headaches tended to have smaller mean arteriolar and venular calibers; however, these associations did not tend to persist among those without hypertension or diabetes.Middle-aged persons with migraine and other headaches were more likely to have retinopathy signs, supporting the hypothesis that neurovascular dysfunction may underlie vascular headaches.

Background: Associations between childhood and adult socioeconomic status (SES) and adult levels of inflammatory markers (C-reactive protein [CRP], fibrinogen, white blood cell count [WBC], and von Willebrand factor [vWF]) were examined in the Atherosclerosis Risk in Communities (ARIC) Study cohort. Methods: A total of 12,681 white and African-American participants provided information on SES (via education and social class) and place of residence in childhood and adulthood. Residences were linked to census data for neighborhood SES information. Multiple imputation was used to impute missing data. Hierarchical and linear regression were used to estimate the effects of SES and possible mediation by adult cardiovascular disease (CVD) risk factors. Findings: Low childhood social class and education were associated with elevated levels of CRP, fibrinogen, WBC, and vWF (increments of 17%, 2%, 4% and 3% for lowest versus highest education in childhood, respectively) among whites. Findings were less consistent among African-Americans. Adult SES was more strongly associated with inflammation than childhood SES. Individual-level SES measures were more consistently associated with inflammation than neighborhood-level measures. Fibrinogen and WBC showed the most consistent associations with SES; the largest changes in inflammation by SES were observed for CRP. Covariate adjustment strongly attenuated these associations. Mediation of the SES-inflammation associations by BMI, smoking and HDL cholesterol (HDL-C) are suggested by these data. Conclusion: Low individual- and neighborhood-level SES in childhood and adulthood are associated with modest increments in adult inflammatory burden. These associations may operate through the influence of low SES on traditional CVD risk factors, especially BMI, smoking and HDL-C.

Inhaled endotoxin induces airway inflammation and is an established risk factor for asthma. The 2005-2006 National Health and Nutrition Examination Survey included measures of endotoxin and allergens in homes as well as specific IgE to inhalant allergens.To understand the relationships between endotoxin exposure, asthma outcomes, and sensitization status for 15 aeroallergens in a nationally representative sample.Participants were administered questionnaires in their homes. Reservoir dust was vacuum sampled to generate composite bedding and bedroom floor samples. We analyzed 7,450 National Health and Nutrition Examination Survey dust and quality assurance samples for their endotoxin content using extreme quality assurance measures. Data for 6,963 subjects were available, making this the largest study of endotoxin exposure to date. Log-transformed endotoxin concentrations were analyzed using logistic models and forward stepwise linear regression. Analyses were weighted to provide national prevalence estimates and unbiased variances.Endotoxin exposure was significantly associated with wheeze in the past 12 months, wheeze during exercise, doctor and/or emergency room visits for wheeze, and use of prescription medications for wheeze. Models adjusted for age, sex, race and/or ethnicity, and poverty-to-income ratio and stratified by allergy status showed that these relationships were not dependent upon sensitization status but were worsened among those living in poverty. Significant predictors of higher endotoxin exposures were lower family income; Hispanic ethnicity; participant age; dog(s), cat(s), cockroaches, and/or smoker(s) in the home; and carpeted floors.In this U.S. nationwide representative sample, higher endotoxin exposure was significantly associated with measures of wheeze, with no observed protective effect regardless of sensitization status.

Background— An association between orthostatic hypotension (OH) and mortality has been reported, but studies are limited to older adults or high-risk populations. Methods and Results— We investigated the association between OH (a decrease of 20 mm Hg in systolic blood pressure or a decrease of 10 mm Hg in diastolic blood pressure on standing) and 13-year mortality among middle-aged black and white men and women from the Atherosclerosis Risk in Communities Study (1987–1989). At baseline, 674 participants (5%) had OH. All-cause mortality was higher among those with (13.7%) than without (4.2%) OH. After we controlled for ethnicity, gender, and age, the hazard ratio (HR) for OH for all-cause mortality was 2.4 (95% confidence interval [CI], 2.1 to 2.8). Adjustment for risk factors for cardiovascular disease and mortality and selected health conditions at baseline attenuated but did not completely explain this association (HR=1.7; 95% CI, 1.4 to 2.0). This association persisted among subsets that (1) excluded those who died within the first 2 years of follow-up and (2) were limited to those without coronary heart disease, cancer, stroke, diabetes, hypertension, or fair/poor perceived health status at baseline. In analyses by causes of death, a significant increased hazard of death among those with versus without OH persisted after adjustment for risk factors for cardiovascular disease (HR=2.0; 95% CI, 1.6 to 2.7) and other deaths (HR=2.1; 95% CI, 1.6 to 2.8) but not for cancer (odds ratio=1.1; 95% CI, 0.8 to 1.6). Conclusions— OH predicts mortality in middle-aged adults. This association is only partly explained by traditional risk factors for cardiovascular disease and overall mortality.

Objective: To evaluate the occurrence of stroke/TIA symptoms and ischemic stroke events among those with a lifetime history of migraine or other headaches with some migraine features in a biracial cohort of older adults. Methods: Participants were 12,750 African-American and white men and women from the Atherosclerosis Risk in Communities Study (1993 to 1995). The participants were queried about their lifetime headache history and characterized using modified International Headache Society diagnostic criteria. Stroke/TIA symptoms were classified using a computerized diagnostic algorithm, and ischemic stroke events were identified and validated using medical records. Multivariate logistic regression was used to assess the relationship between headache types and stroke/TIA symptoms and ischemic stroke events. Results: Migraine with aura was strongly associated with stroke symptoms (odds ratio [OR] 5.46, 95% CI: 3.64 to 8.18), TIA symptoms (OR 4.28, 95% CI: 3.02 to 6.08), and verified ischemic stroke events (OR 2.81, 95% CI: 1.60 to 4.92). Similarly, other headaches with aura were significantly associated with stroke symptoms (OR 3.68, 95% CI: 2.26 to 5.99) and TIA symptoms (OR 4.53, 95% CI: 3.08 to 6.67). In contrast, the associations for migraine without aura and other headaches without aura were not as consistent or robust. Conclusions: Migraines and other headaches, particularly those accompanied by aura, were associated with an increased occurrence of stroke/TIA symptoms and ischemic stroke events.

Previous analysis in the Hypertension Genetic Epidemiology Network (HyperGEN) of the National Heart Lung and Blood Institute (NHLBI) Family Blood Pressure Program, a multicenter study of genetic and environmental factors related to hypertension, indicated regions of linkage for blood pressure traits together with several coincident regions for phenotypically correlated traits, including systolic blood pressure (SBP) response to a postural challenge and body mass index (BMI). Motivated by these findings and by our desire to better understand the physiology of these traits, we conducted bivariate linkage analysis of postural SBP change and BMI. Sibships in HyperGEN were recruited from 5 field centers in Massachusetts, North Carolina, Minnesota, Utah, and Alabama. All available affected siblings, their parents, and selected nonmedicated offspring were recruited. Among 1636 whites and 1747 blacks, we performed a maximum likelihood bivariate genome scan for quantitative trait loci influencing postural SBP change and BMI, similarly adjusted for race, study center, sex, age, and age-by-sex interactions. Genome scans were performed using SOLAR (version 2.0) and race-specific marker allele frequencies derived from founders. The maximum genome-wide logarithm of odds (LOD) score of 3.2 was detected on chromosome 13 at 24 cM. This marker (D13S493) lies within 20 cM of a marker previously linked to BMI in the Family Heart Study and is substantially higher than the univariate linkage for each trait (LOD scores for BMI and postural SBP change were 2.4 and 0.9, respectively). These findings suggest that a gene(s) on chromosome 13q jointly regulates the SBP response to postural change and BMI.

The association between the blood pressure response to a change from the supine to the standing position and the 6-year incidence of hypertension was studied in a bi-ethnic, middle-aged cohort of 6951 normotensive men and women free of coronary heart disease at baseline. Postural change in systolic blood pressure (SBP) was categorized into deciles, and the middle four deciles served as the referent (no change) group. In unadjusted analyses, the incidence of hypertension was higher among both those with SBP increases and decreases relative to those in the referent group. Associations were modestly attenuated after controlling for age, ethnicity, and gender and cardiovascular disease risk factors. However, after adjustment for baseline, seated SBP, a modest association with incident hypertension persisted only for SBP decreases. Orthostatic hypotension (upon standing) was associated with incident hypertension and isolated systolic hypertension and, unexpectedly, this increased risk was highest among those with the lowest levels of baseline, resting SBP.

Objective: To evaluate adiponectin and leptin levels in older men and women with migraine. Methods: Fasting total and high molecular weight (HMW) adiponectin and leptin levels were evaluated in a case–cohort study of nondiabetic older migraine and nonmigraine control participants from the ongoing, longitudinal, general population, Atherosclerosis Risk in Communities Study at visit 1 (1987–1989). A standardized headache questionnaire was completed at visit 3 (1993–1995). Logistic regression models adjusted for age, sex, race, center, body mass index, and fasting glucose were used to evaluate the association of each adipocytokine with migraine. Results: Of the 981 participants, the mean age at baseline was 52.8 years (SE 0.3); 131 fulfilled migraine criteria. Crude, mean total adiponectin levels were greater in men and women with migraine (8.1 µg/mL, SE 0.5) as compared to those without migraine (7.0 µg/mL, SE 0.2) ( p = 0.031). After adjustments, the odds of migraine were increased by 88% with each SD increase in total adiponectin in men (odds ratio [OR] 1.86; 95% confidence interval [CI] 1.15, 3.01; p = 0.011), but not in women (OR 1.05; 95% CI 0.80, 1.37; p = 0.728; p interaction = 0.029). Similar results were demonstrated for HMW adiponectin. Crude and adjusted leptin levels were not associated with migraine. Conclusions: Although crude, total adiponectin levels were higher in older men and women with migraine than controls, after adjustments, the prevalence of migraine was significantly associated with total adiponectin only in older men, suggesting the association may be confounded or absent in older women. Leptin was not associated with migraine in older men or women.

Background No previous studies have examined the interplay among socioeconomic status, sex, and race with the risk of atrial fibrillation ( AF ). Methods and Results We prospectively followed 14 352 persons (25% black, 75% white, 55% women, mean age 54 years) who were free of AF and participating in the Atherosclerosis Risk in Communities ( ARIC ) study. S ocioeconomic status was assessed at baseline (1987–1989) through educational level and total family income. Incident AF through 2009 was ascertained from electrocardiograms, hospitalizations, and death certificates. Cox regression was used to estimate hazard ratios and 95% CIs of AF for education and family income. Interactions were tested between socioeconomic status and age, race, or sex. Over a median follow‐up of 20.6 years, 1794 AF cases occurred. Lower family income was associated with higher AF risk ( hazard ratio 1.45, 95% CI 1.27 to 1.67 in those with income less than $25 000 per year compared with those with $50 000 or more per year). The association between education and AF risk varied by sex ( P =0.01), with the lowest education group associated with higher AF risk in women ( hazard ratio 1.88, 95% CI 1.55 to 2.28) but not in men ( hazard ratio 1.15, 95% CI 0.97 to 1.36) compared with the highest education group. Adjustment for cardiovascular risk factors attenuated the associations. There were no interactions with race or age. Blacks had lower AF risk than whites in all income and education groups. Conclusions Lower family income was associated with a higher AF risk overall, whereas the impact of education on AF risk was present only in women. Differences in socioeconomic status do not explain the lower risk of AF in blacks compared with whites.

Background and Purpose: Having a small social network and lack of social support have been associated with incident coronary heart disease, but little is known about their association with incident stroke. Thus, we assessed the association of a small social network and lack of social support with risk of incident stroke and evaluated whether the relation was mediated by vital exhaustion and inflammation. Methods: The Atherosclerosis Risk in Communities (ARIC) Study measured social network and social support in 13,686 men and women (mean, 57 ± 5.7 years, 56% female, 24% black; 76% white) initially free of stroke. The 10-item Lubben Social Network Scale and 16-item Interpersonal Support Evaluation List-Short Form were used to assess social network size and social support, respectively. Results: Over a median follow-up of 18.6-years, 905 incident strokes occurred. Relative to participants with a large social network, those with a small social network had a higher risk of stroke [HR (95% CI): 1.43 (1.03-2.00)] after adjustment for demographic and socioeconomic characteristics and marital status ( Table ). Further adjustment for other potential confounders attenuated the association slightly. Vital exhaustion, but not inflammation, partly mediated the association between a small social network and stroke. Social support was unrelated to incident stroke. Conclusions: In this sample of US community-dwelling men and women, having a small social network was associated with excess risk of incident stroke. As with other cardiovascular conditions, having a small social network appears to be associated with modestly increased risk of incident stroke.

Background and Purpose— Having a small social network and lack of social support have been associated with incident coronary heart disease; however, epidemiological evidence for incident stroke is limited. We assessed the longitudinal association of a small social network and lack of social support with risk of incident stroke and evaluated whether the association was partly mediated by vital exhaustion and inflammation. Methods— The Atherosclerosis Risk in Communities study measured social network and social support in 13 686 men and women (mean, 57 years; 56% women; 24% black; 76% white) without a history of stroke. Social network was assessed by the 10-item Lubben Social Network Scale and social support by a 16-item Interpersonal Support Evaluation List-Short Form. Results— During a median follow-up of 18.6 years, 905 incident strokes occurred. Relative to participants with a large social network, those with a small social network had a higher risk of stroke (hazard ratio [95% confidence interval], 1.44 [1.02–2.04]) after adjustment for demographics, socioeconomic variables, marital status, behavioral risk factors, and major stroke risk factors. Vital exhaustion, but not inflammation, partly mediated the association between a small social network and incident stroke. Social support was unrelated to incident stroke. Conclusions— In this sample of US community-dwelling men and women, having a small social network was associated with excess risk of incident stroke. As with other cardiovascular conditions, having a small social network may be associated with a modestly increased risk of incident stroke.

Background Allergic sensitization is an important risk factor for the development of atopic disease. The National Health and Nutrition Examination Survey (NHANES) 2005-2006 provides the most comprehensive information on IgE-mediated sensitization in the general US population. Objective We investigated clustering, sociodemographic, and regional patterns of allergic sensitization and examined risk factors associated with IgE-mediated sensitization. Methods Data for this cross-sectional analysis were obtained from NHANES 2005-2006. Participants aged 1 year or older (n = 9440) were tested for serum specific IgEs (sIgEs) to inhalant and food allergens; participants 6 years or older were tested for 19 sIgEs, and children aged 1 to 5 years were tested for 9 sIgEs. Serum samples were analyzed by using the ImmunoCAP System. Information on demographics and participants' characteristics was collected by means of questionnaire. Results Of the study population aged 6 years and older, 44.6% had detectable sIgEs, whereas 36.2% of children aged 1 to 5 years were sensitized to 1 or more allergens. Allergen-specific IgEs clustered into 7 groups that might have largely reflected biological cross-reactivity. Although sensitization to individual allergens and allergen types showed regional variation, the overall prevalence of sensitization did not differ across census regions, except in early childhood. In multivariate modeling young age, male sex, non-Hispanic black race/ethnicity, geographic location (census region), and reported pet avoidance measures were most consistently associated with IgE-mediated sensitization. Conclusions The overall prevalence of allergic sensitization does not vary across US census regions, except in early life, although allergen-specific sensitization differs based on sociodemographic and regional factors. Biological cross-reactivity might be an important but not the sole contributor to the clustering of allergen-specific IgEs.

Background and Purpose —The association between orthostatic hypotension (OH) and stroke has rarely been investigated in longitudinal studies. The purpose of the present study was to determine whether OH predicts ischemic stroke in a middle-aged, biethnic population after adjustment for known stroke risk factors. Diastolic, systolic, and consensus OH were evaluated for baseline associations and for the ability to predict stroke. Methods —In 11 707 persons from the Atherosclerosis Risk in Communities (ARIC) cohort who were free of stroke and overt heart disease at baseline, Cox proportional hazards analyses modeled the association between OH at baseline and incident ischemic stroke over 7.9 years of follow-up. OH was defined as a systolic blood pressure drop ≥20 mm Hg (systolic OH), a diastolic blood pressure drop ≥10 mm Hg (diastolic OH), or a drop in either (consensus OH) when a person changed from a supine to standing position. Results —OH was predictive of ischemic stroke, even after adjustment for numerous stroke risk factors (consensus OH: hazard ratio, 2.0; 95% CI, 1.2 to 3.2). While the baseline characteristics associated with OH varied depending on the type of OH, all types of OH had a similar risk of stroke. Conclusions —OH is an easily obtained measurement that may help to identify middle-aged persons at risk for stroke.

Mutations in the low density lipoprotein receptor (LDLR) result in ineffective clearance of serum low density lipoprotein (LDL) cholesterol and contribute to premature atherosclerosis and cardiovascular disease (CVD) in familial hypercholesterolemia [1]. Several mutations of the LDLR have been described, affecting exons, splicing sites and the promoter region (summarized in [2]). Mutations in genes of other proteins involved in LDL uptake and metabolism (ApoB and LDL receptor adaptor protein – LDLRAP1) and in LDLR intracellular recycling (propoprotein convertase subtilisin/kexin type 9 serine protease, PCSK9) have also been implicated in familial hypercholesterolemia [2]. More recently, PCSK9 mutations associated with reduced serum LDL cholesterol were associated with a lower risk of coronary heart disease (CHD) in the Atherosclerosis Risk in Communities (ARIC) study [3].

PURPOSE: This study examined the cross-sectional and prospective associations between employment status and hypertension among middle-aged, African-American (AA) and European-American (EA) women participating in the Atherosclerosis Risk in Communities Study. METHODS: Employed women and homemakers from the baseline examination (1987–89) were included in the cross-sectional study ( n = 7351). Associations between employment and the incidence of hypertension ascertained at visit 2 (1990–92) were determined among those who at baseline, had low-normal blood pressure (not hypertensive and systolic blood pressure (SBP) ⩽ 120 mm Hg systolic and diastolic blood pressure (DBP) ⩽ 80 mm Hg ( n = 3194). Logistic regression analysis was used to examine the association between employment status and hypertension by ethnicity, taking into account covariates. RESULTS: At baseline, employed women were less likely to be hypertensive (SBP ⩾ 140 mm Hg or DBP ⩾ 90 mm Hg or current use of antihypertensive drugs) than were homemakers (prevalence odds ratio (POR) = 0.70; 95% confidence interval (CI) = 0.62–0.79), controlling for age, body mass index, and education. Among the subgroup who had low-normal blood pressure at baseline, employed women were less likely to develop hypertension during the three-year time period than were homemakers (odds ratio (OR) = 0.68; 95% CI = 0.44–1.05). The inverse association was stronger among AA (RR = 0.37; 95% CI = 0.16–0.88) than EA (OR = 0.83; 95% CI = 0.50–1.38) women. CONCLUSIONS: These findings suggest that the inverse association between hypertension and employment status is not due to a healthy worker effect, and that employment may confer protection against incident hypertension in women.

The association between extent of employment and hypertension was examined among 3,824 women participants of the Second National Health and Nutrition Examination Survey. Women in three employment groups (full-time, part-time, and short-term) were compared to homemakers. In covariate-adjusted, logistic regression models, women employed full-time had a somewhat lower, but not significantly different, prevalence of hypertension (OR = 0.8, 95% CI = 0.7, 1.1), whereas both part-time (OR = 0.6, 95% CI = 0.4, 0.7) and short-term (OR = 0.5, 95% CI = 0.4, 0.7) workers had significantly lower prevalences. Associations did not tend to vary by age, ethnicity, or occupation. Employment does not appear to increase the risk of hypertension in women; in fact, moderate levels were associated with lower risk.

ROSE, KATHRYN M, BETH NEWMAN, ELIZABETH J. MAYER-DAVIS, JOSEPH V. SELBY. Genetic and behavioral determinants of waist-hip ratio and waist circumference in women twins. Obes Res. 1998;6:383–392. Objectives: This study examines genetic and behavioral determinants of waist-hip ratio (WHR) and waist circumference among women twins. Research Methods and Procedures: Six hundred eighty participants from the second examination of the Kaiser-Permanente Women Twins Study (1989 to 1990) were included. Women ranged in age from 31 to 90 years, and included 59% monozygotic and 41% dizygotic twins. Heritabilities of WHR and waist circumference were estimated (range = 0 to 1) using three different statistical methods. Linear regression models that adjusted for the lack of independence within twin pairs were used to assess associations between behavioral variables, WHR, and waist circumference. Results: Age and body mass index-adjusted heritability estimates ranged from 0.36 to 0.61 for WHR and 0.72 to 0.82 for waist circumference. When considered individually, after adjusting for age and body mass index, all behavioral characteristics, except calorie-adjusted fat intake, were significantly (p

PURPOSE: The association between employment status and high blood pressure in women was examined at two time periods to determine if associations between employment status and high blood pressure varied by time period or by age, race, education, marital status, or parental status. METHODS: Women participants from the National Health Examination Survey (1960) and the Second National Health and Nutrition Survey (1976–1980) between the ages of 25 and 64 and currently employed or keeping house were included. Logistic regression analysis was used to examine the cross-sectional association between employment status and high blood pressure in each survey, taking into account potential effect modifiers and covariates. RESULTS: In 1960 employment was associated with a slight, but not statistically significant, elevation in odds of high blood pressure. In 1976–1980, it was associated with a modest but significant reduction in odds of high blood pressure. Variations in associations occurred by marital status (protective associations were limited to unmarried women) and race (associations were of stronger magnitude among African-American women). CONCLUSIONS: The employment status-high blood pressure relationship shifted across surveys Changes in the composition of the employed and nonemployed groups account for at least part of the varying relationships.

Measurement error/misclassification is commonplace in research when variable(s) cannot be measured accurately. A number of statistical methods have been developed to tackle this problem in a variety of settings and contexts. However, relatively few methods are available to handle misclassified categorical exposure variable(s) in the Cox proportional hazards regression model. In this article, we aim to review and compare different methods to handle this problem—naive methods, regression calibration, pooled estimation, multiple imputation, corrected score estimation, and MC-SIMEX—by simulation. These methods are also applied to a life course study with recalled data and historical records. In practice, the issue of measurement error/misclassification should be accounted for in design and analysis, whenever possible. Also, in the analysis, it could be more ideal to implement more than one correction method for estimation and inference, with proper understanding of underlying assumptions.

Introduction Prior assessments of emergency medical services (EMS) stroke capacity found deficiencies in education and training, use of protocols and screening tools, and planning for the transport of patients. A 2001 survey of North Carolina EMS providers found many EMS systems lacked basic stroke services. Recent statewide efforts have sought to standardize and improve prehospital stroke care. The objective of this study was to assess EMS stroke care capacity in North Carolina and evaluate statewide changes since 2001. Methods In June 2012, we conducted a web-based survey on stroke education and training and stroke care practices and policies among all EMS systems in North Carolina. We used the McNemar test to assess changes from 2001 to 2012. Results Of 100 EMS systems in North Carolina, 98 responded to our survey. Most systems reported providing stroke education and training (95%) to EMS personnel, using a validated stroke scale or screening tool (96%), and having a hospital prenotification policy (98%). Many were suboptimal in covering basic stroke educational topics (71%), always communicating stroke screen results to the destination hospital (46%), and always using a written destination plan (49%). Among 70 EMS systems for which we had data for 2001 and 2012, we observed significant improvements in education on stroke scales or screening tools (61% to 93%, P < .001) and use of validated stroke scales or screening tools (23% to 96%, P < .001). Conclusion Major improvements in EMS stroke care, especially in prehospital stroke screening, have occurred in North Carolina in the past decade, whereas other practices and policies, including use of destination plans, remain in need of improvement.

Background External common carotid artery (CCA) diameter and intima-media thickness (IMT) are independently associated with incident stroke and other cardiovascular events. Arterial geometry such as large IMT and large diameter may reflect vulnerable plaques and so impact stroke risk. Finally, arterial changes that exist bilaterally may increase stroke risk. Method We studied middle-aged men and women (n=7276) from a prospective observational study who had right (R) and left (L) CCA IMT and external diameters measured via B-mode ultrasound (1987–89) in order to categorize CCA geometry. Using side- and gender-specific IMT and diameter medians, we categorized each measurement as large (≥ median) vs. not large (< median) and defined four geometries: both IMT and diameter were large, only one parameter was large, or neither was large (reference group). Participants were followed for first time stroke through December 31, 1999. We used proportional hazards models to assess associations between right and left CCA geometries with new stroke. We also calculated positive and negative likelihood ratios (+LR and -LR) for CCA bilateral phenotypes as a measure of diagnostic accuracy. Results Presence of both large CCA IMT and large diameter on one side was associated with strong stroke risk even after risk factor adjustment (men: RCCA hazard ratio [HR]=3.7 95% confidence interval [CI]=1.9-7.4; LCCA HR=2.4 95% CI=1.4-4.4; women: RCCA HR=4.0 95% CI=1.5-10.5; LCCA HR=5.7 95% CI=1.7-19.0). Presence of both large IMT and large diameter bilaterally was the strongest predictor of stroke identifying 64% of women and 44% of men who developed strokes. This phenotype showed potential for predicting stroke among individuals (women: +LR=3.1, 95% CI=2.6-3.8; men: +LR=2.3, 95% CI=1.8-2.8). Conclusion Bilateral carotid artery geometries may be useful for stroke risk prediction.

Background: Acute stroke patients require immediate medical attention. Therefore, American Stroke Association guidelines recommend that for suspected stroke cases, emergency medical services (EMS) personnel spend less than 15 minutes (min) on-scene at least 90% of the time. However, not all EMS providers include specific scene time limits in their stroke patient care protocols. We sought to determine whether a protocol with a specific time goal was associated with less time spent at the scene. Methods: Stroke protocols from each of the 100 EMS systems in North Carolina (NC) were collected and abstracted for scene time instructions. Suspected stroke events occurring in 2009 were analyzed using data from the NC Prehospital Medical Information System, a statewide electronic healthcare record used for evaluation of EMS patient care and system performance. Scene time was defined as the time from EMS arrival at the scene to departure with the patient. Quantile regression was used to estimate how the 90th percentile of the scene time distribution varied by the presence of protocol instructions limiting scene time. Models adjusted for system annual patient volume and metropolitan status. Results: In 2009, NC EMS systems varied in their stroke protocols: 23 had no instructions regarding scene time; 73 had general instructions to minimize scene time; and 4 had a specific limit for scene time (i.e. 10 or 15 min). Among 9,723 eligible suspected stroke events, mean scene time was 15.9 min (standard deviation 6.9 min) and median scene time was 15.0 min (interquartile range 11.0-19.5 min). We observed significantly lower 90th percentile scene times in EMS systems with specific time limit instructions (22.0 min) compared to systems without any instructions on scene time (24.6 min). There was no significant difference between 90th percentile scene times in EMS systems with general instructions compared to systems without instructions (25.0 versus 24.6 min). In adjusted quantile regression models, the estimated reduction in the 90th percentile scene time, comparing specific to no instructions, was 2.2 min (95% confidence interval 1.3, 3.1 min). The adjusted difference in 90th percentile scene time between general and absent instructions was not statistically different (0.7 min (95% confidence interval -0.1, 1.4 min)). Conclusion: Specific scene time limits were associated with EMS crews spending less time at the scene while general instructions were not. These findings suggest that EMS stroke protocols that include specific scene time limits are more likely to reduce on-scene times than those with no or only general instructions.

Though several large epidemiologic studies have demonstrated the positive association of anger with coronary heart disease (CHD) onset, a dearth of population-based evidence exists regarding the relationship of anger to the clinical course of CHD among people with established disease. Trait anger is conceptualized as a stable personality trait and defined as the tendency to experience frequent and intense anger. Therefore, it is plausible that the effects of trait anger on CHD are long standing. We assessed the hypothesis that trait anger predicts short-term and long-term risk for recurrent CHD among middle-aged men and women. Participants were 611 black or white men and women, ages 48 - 67, who had a history of CHD at the second clinical examination (1990-1992) of the Atherosclerosis Risk in Communities (ARIC) Study. They were followed for the recurrence of CHD (myocardial infarction or fatal CHD) from 1990 through three different time intervals: 1995, 2003, and 2009 (maximum follow-up = 19.0 years). Trait anger (measured at Visit 2) was assessed using the Spielberger Trait Anger Scale, with scores categorized as high, moderate, and low. Cox proportional hazards regression analyses were adjusted for age, sex, race-center, educational level, waist-to-hip ratio, plasma LDL-and HDL-cholesterol levels, hypertension, diabetes, cigarette smoking status, and pack-years of cigarette smoking. After 3 - 5 years of follow-up, the risk for recurrent CHD among participants with high trait anger was more than twice that of their counterparts with low trait anger (2.24 [95% C.I: 1.14 to 4.40]). After 11 - 13 years, the risk was 80% greater (1.80 [95% C.I: 1.17 to 2.78]) and after 17 - 19 years, it was 70% greater (1.70 [95% C.I: 1.15 to 2.52]). The risk for recurrent CHD was strongest in the first time interval but remained strong and statistically significant through 19 years of follow-up. In conclusion, the experience of frequent and intense anger increases short-term and long-term risk for recurrent CHD in middle-aged men and women.

Objective: Migraine is associated with white matter hyperintensities (WMH) cross-sectionally, but its effect on WMH progression is uncertain. Methods: Participants in the Atherosclerosis Risk in Communities cohort study (n = 10,924) completed a standardized headache questionnaire between 1993 and 1995. A subset of participants (n = 1,028) received 2 MRIs 8 to 12 years apart: once at the time of headache ascertainment, and again from 2004 to 2006. WMH were quantified using both a visually graded score (0–9) and semiautomated volumetric analysis. Linear and logistic regression models adjusted for age, sex, and other vascular risk factors were constructed. Results: Individuals who had migraine without aura were cross-sectionally associated with an 87% greater odds of having a WMH score ≥3 than individuals without headache (adjusted odds ratio = 1.87; 95% confidence interval [CI]: 1.04, 3.37). Participants with migraine had an average of 2.65 cm 3 more WMH than those without headache (95% CI: 0.06, 5.24). However, there was no significant difference in WMH progression over the study period between individuals with and without migraine (1.58 cm 3 more progression for individuals with migraine compared to those without; 95% CI: −0.37, 3.53). Conclusion: Migraine is associated with WMH volume cross-sectionally but not with WMH progression over time. This suggests that the association between migraine and WMH is stable in older age and may be primarily attributable to changes occurring earlier in life, although further work is needed to confirm these findings.

Heart failure (HF) accounts for 6.5 million hospital days per year. It remains unknown if socioeconomic factors are associated with hospital length of stay (LOS). We analyzed predictors of longer hospital LOS [mean (days), 95% confidence interval (CI)] among participants with incident hospitalized HF (n = 1,300) in the Atherosclerosis Risk in Communities (ARIC) cohort from 1987 to 2005. In a statistical model adjusted for median household income, age, gender, race/study community, education level, hypertension, alcohol use, smoking, Medicaid status, and Charlson comorbidity index score, Medicaid recipients experienced a longer LOS (7.5, 6.3-8.9) compared to non-Medicaid recipients (6.2, 5.7-6.7), and patients with a higher burden of comorbidity had a longer LOS (7.5, 6.4-8.6) compared to patients with a lower burden (6.2, 5.7-6.9). Median household income and education were not associated with longer LOS in multivariable models. Medicaid recipients and patients with more comorbid disease may not have the resources for adequate, comprehensive, out-of-hospital management of HF symptoms, and may require a longer LOS due to the need for more care during the hospitalization because of more severe HF. Data on out-of-hospital management of chronic diseases as well as HF severity are needed to further elucidate the mechanisms leading to longer LOS among subgroups of HF patients.

Declines in case fatality post-myocardial infarction (MI) have been observed over the past 3 decades. Few studies report socioeconomic disparities in survival post-MI.We assessed 1-year case fatality among 9,116 incident MI patients included in the Atherosclerosis Risk in Communities community surveillance from 1992 to 2002. Addresses of hospitalized MI patients were geocoded by a commercial vendor and linked to year 2000 United States Census tract-level neighborhood income (nINC) data. We estimated case fatality odds ratios and 95% CIs with a multinomial logistic model to quantify the association between nINC tertile and case fatality, comparing short- (within 28 days) and long-term (29-365 days) case fatality to no death 1 year post-MI.Overall, 1-year age-adjusted case fatality rates were highest among MI patients living in low-nINC areas, followed by medium- and high-nINC areas, respectively. We found significant odds ratio modification by race (P.10) and formed race-nINC strata with high-nINC whites as the referent group. In multivariable models adjusting for age, gender, study community, and year of MI, low-nINC whites and low- and medium-nINC blacks had higher short-term case fatality than high-nINC whites. Low- and medium-nINC blacks had higher long-term case fatality compared with high-nINC whites.Differences in short- and long-term case fatality by neighborhood socioeconomic factors have not been systematically studied in the United States. Surveillance efforts can be expanded to incorporate measures of the neighborhood context to examine these associations over time.

We appreciate the letter submitted by Grossman et al1 in response to our recent publication on the association of orthostatic hypotension (OH) with incident heart failure (HF) within the Atherosclerosis Risk in Communities cohort.2 Indeed, reverse diurnal blood pressure patterns, including nocturnal nondipping (decrease of nocturnal blood pressure ≤10% from daytime blood pressure) or reverse-dipping (increase of nocturnal blood pressure compared with daytime blood pressure) could explain the association between OH and HF, particularly in those with hypertension. The authors note that in their previous study of 185 patients referred for 24-hour ambulatory blood pressure monitoring either to confirm a hypertension diagnosis or to assess …

Reports from large studies using administrative data sets and event registries have characterized recent temporal trends and treatment patterns for acute myocardial infarction. However, few were population based, and fewer examined differences in patterns of treatment for patients presenting with ST-segment elevation myocardial infarction (STEMI) and non–ST-segment elevation myocardial infarction (NSTEMI). The aim of this study was to examine 22-year trends in the use of 10 medical therapies and procedures by STEMI and NSTEMI classification in 30,986 definite or probable myocardial infarctions in the Atherosclerosis Risk in Communities (ARIC) Community Surveillance Study from 1987 to 2008. Weighted multivariate Poisson regression, controlling for gender, race and center classification, age, and Predicting Risk of Death in Cardiac Disease Tool score, was used to estimate average annual percentage changes in medical therapy use. From 1987 to 2008, 6,106 hospitalized events (19.7%) were classified as STEMIs and 20,302 (65.5%) as NSTEMIs. Among patients with STEMIs, increases were noted in the use of angiotensin-converting enzyme inhibitors (6.4%, 95% confidence interval [CI] 5.7 to 7.2), antiplatelet agents other than aspirin (5.0%, 95% CI 4.0% to 6.0%), lipid-lowering medications (4.5%, 95% CI 3.1% to 5.8%), β blockers (2.7%, 95% CI 2.4% to 3.0%), aspirin (1.2%, 95% CI 1.0% to 1.3%), and heparin (0.8%, 95% CI 0.4% to 1.3%). Among patients with NSTEMIs, the use of angiotensin-converting enzyme inhibitors (5.5%, 95% CI 5.0% to 6.1%), antiplatelet agents other than aspirin (3.7%, 95% CI 2.7% to 4.7%), lipid-lowering medications (3.0%, 95% CI% 1.9 to 4.1%), β blockers (4.2%, 95% CI 3.9% to 4.4%), aspirin (1.9%, 95% CI 1.6% to 2.1%), and heparin (1.7%, 95% CI 1.3% to 2.1%) increased. Among patients with STEMIs, decreases in the use of thrombolytic agents (−7.2%, 95% CI −7.9% to −6.6%) and coronary artery bypass grafting (−2.4%, 95% CI −3.6% to −1.2%) were observed. Similar increases in percutaneous coronary intervention and decreases in the use of thrombolytic agents and coronary artery bypass grafting were noted among all patients. In conclusion, trends of increasing use of evidence-based therapies were found for patients with STEMIs and those with NSTEMIs over the past 22 years.

Heart failure causes significant morbidity and mortality. Distinguishing risk factors for incident heart failure can help identify at-risk individuals. Orthostatic hypotension may be a risk factor for incident heart failure; however, this association has not been fully explored, especially in nonwhite populations. The Atherosclerosis Risk in Communities Study included 12363 adults free of prevalent heart failure with baseline orthostatic measurements. Orthostatic hypotension was defined as a decrease of systolic blood pressure ≥20 mmHg or diastolic blood pressure ≥10 mmHg with position change from supine to standing. Incident heart failure was identified from hospitalization or death certificate disease codes. Over 17.5 years of follow-up, orthostatic hypotension was associated with incident heart failure with multivariable adjustment (hazard ratio: 1.54 [95% CI: 1.30–1.82]). This association was similar across race and sex groups. A stronger association was identified in younger individuals ≤55 years old (hazard ratio: 1.90 [95% CI: 1.41–2.55]) than in older individuals >55 years old (hazard ratio: 1.37 [95% CI: 1.12–1.69]; interaction P =0.034). The association between orthostatic hypotension and incident heart failure persisted with exclusion of those with diabetes mellitus, coronary heart disease, and those on antihypertensives or psychiatric or Parkinson disease medications. However, exclusion of those with hypertension somewhat attenuated the association (hazard ratio: 1.34 [95% CI: 1.00–1.80]). We identified orthostatic hypotension as a predictor of incident heart failure among middle-aged individuals, particularly those 45 to 55 years of age. This association may be partially mediated through hypertension. Orthostatic measures may enhance risk stratification for future heart failure development.

Occupational data are a common source of workplace exposure and socioeconomic information in epidemiologic research. We compared the performance of two occupation coding methods, an automated software and a manual coder, using occupation and industry titles from U.S. historical records.We collected parental occupational data from 1920-40s birth certificates, Census records, and city directories on 3,135 deceased individuals in the Atherosclerosis Risk in Communities (ARIC) study. Unique occupation-industry narratives were assigned codes by a manual coder and the Standardized Occupation and Industry Coding software program. We calculated agreement between coding methods of classification into major Census occupational groups.Automated coding software assigned codes to 71% of occupations and 76% of industries. Of this subset coded by software, 73% of occupation codes and 69% of industry codes matched between automated and manual coding. For major occupational groups, agreement improved to 89% (kappa = 0.86).Automated occupational coding is a cost-efficient alternative to manual coding. However, some manual coding is required to code incomplete information. We found substantial variability between coders in the assignment of occupations although not as large for major groups.