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- [Show abstract] [Hide abstract] ABSTRACT: Inhaled endotoxin induces airway inflammation and is an established risk factor for asthma. The 2005-2006 National Health and Nutrition Examination Survey (NHANES) included measures of endotoxin and allergens in homes and specific IgE to inhalant allergens. To understand the relationship 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 7450 NHANES dust and quality assurance samples for their endotoxin content using extreme quality assurance measures. Data for 6963 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/emergency room visits for wheeze, and use of prescription medications for wheeze. Models adjusted for age, gender, race/ethnicity and poverty 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 or smoker(s) in the home; and carpeted floor. In this US nationwide representative sample, higher endotoxin exposure was significantly associated with measures of wheeze with no observed protective effect regardless of sensitization status.
- [Show abstract] [Hide abstract] ABSTRACT: Potential associations between background environmental chemical exposures and autoimmunity are understudied. 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. This cross-sectional analysis used data on 4340 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 that were adjusted for confounders and accommodated concentrations below detectable levels. 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% confidence interval = 1.8,4.5; p < 10(-5)). 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 track changes in ANA and other autoantibodies over time.
- [Show abstract] [Hide abstract] ABSTRACT: Background and Objective Cotinine is considered a “gold standard” biomarker for smoking. However, some researchers propose alternative biomarkers, such as 2,5-dimethylfuran (2DF), and others question the value of measuring biomarkers at all. We evaluated the impact of combining self-reported smoking and each of two smoking biomarkers on smoking prevalence and the estimated association between smoking and wheezing. Methods We analyzed data from 2,228 National Health and Nutrition Survey (2005-2006) participants with self-reported current smoking data and two serum smoking biomarkers (cotinine and 2,5-dimethylfuran). Cut-points for defining smoking were > 3.08 ng/mL for cotinine and 0.014 ng/mL for 2DF. Smoking prevalence was estimated using self-report alone and then augmented with biomarker data. We compared odds ratios for wheeze in the past year associated with each smoking measure adjusted for age, gender, and education. Results 502 (23%) participants reported being current smokers. Inclusion of self-reported nonsmokers positive for smoking by cotinine increased smoking prevalence to 29%, while consideration of 2DF increased the prevalence to 24%. In adjusted models, self-reported smokers were more likely to report wheeze than nonsmokers (OR=2.45, 95% CI=1.87-3.20). The association did not change when adding 2DF to the definition (OR=2.45, 95% CI=1.89-3.19) and was modestly attenuated when adding cotinine (OR=2.32, 95% CI=1.80-3.01). Conclusions Of the two biomarkers examined, only cotinine modified smoking prevalence and effect estimates in a model of the effects of smoking on wheeze. Variation across measures could reflect underreporting, inappropriate biomarker cut-points, or differences in biomarker sensitivity. Measurement of cotinine and sensitivity analyses to estimate misclassification bias may be most beneficial in studies of populations that tend to under-report current smoking status.
- [Show abstract] [Hide abstract] ABSTRACT: 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.
- [Show abstract] [Hide abstract] ABSTRACT: 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.
- [Show abstract] [Hide abstract] ABSTRACT: 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 and older from the National Health and Nutrition Examination Survey (NHANES; 1999-2004). Estimated ANA prevalences were adjusted for sampling weights. Prevalence odds ratios (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 and older, ANA prevalence was associated with parity (p<0.001; parous versus 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 versus 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.
- [Show abstract] [Hide abstract] ABSTRACT: 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.
- [Show abstract] [Hide abstract] ABSTRACT: 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. Socioeconomic 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.
- [Show abstract] [Hide abstract] ABSTRACT: Background Low birth weight (LBW) has been associated with an increased risk of cardiovascular disease (CVD). A previous study, however, found higher risk of atrial fibrillation (AF) in individuals with higher birth weight (BW). To further understand this apparent paradox, we examined the relationship between AF and BW in the Atherosclerosis Risk in Communities (ARIC) cohort. Methods The analysis included 10,132 individuals free of AF at baseline (1996–1998), who provided BW information, were not born premature, and were not a twin. Self-reported BW was categorized as low (<2.5 kg), medium (2.5-4 kg), and high (>4.0 kg). AF incidence was ascertained from hospital discharge codes and death certificates. We used multivariable Cox proportional hazard models to determine the hazard ratios (HR) and 95% confidence intervals (CI) of AF across BW groups. Results During an average follow-up of 10.3 years, we identified 882 incident AF cases. LBW was associated with higher risk of AF. Compared to individuals in the medium BW category, the HR (95% CI) of AF was 1.33 (0.99, 1.78) for LBW and 1.00 (0.81, 1.24) for high BW after adjusting for sociodemographic variables (p for trend = 0.29). Additional adjustment for CVD risk factors did not attenuate the associations (HR 1.42, 95% CI 1.06, 1.90 for LBW and HR 0.86, 95% CI 0.69-1.07 for high BW, compared to medium BW, p for trend = 0.01). Conclusion LBW was associated with a higher risk of AF. This association was independent of known predictors of AF and is consistent with that observed for other cardiovascular diseases.
- [Show abstract] [Hide abstract] ABSTRACT: Background/Purpose:The myositis syndromes are rare systemic autoimmune diseases with poorly understood etiologies. We present the demographics, illness features and treatments of patients with juvenile dermatomyositis (JDM) who enrolled in a newly created national registry.Methods:Using a patient database from The Myositis Association and supplemental advertisements, a national registry of myositis patients was established. Between December 2010 and July 2012 questionnaires were mailed to 8847 myositis patients in the US and Canada. The questionnaire queried demographics, clinical features, environmental exposures, and quality of life. Descriptive statistics and multivariable logistic regression analysis were computed using GraphPad Prysm and SAS.Results:1956 patients (22%) returned the questionnaire and consented to participate; 1806 who met probable or definite Bohan and Peter criteria for myositis were included (708 DM, 483 PM, 466 IBM, 139 JDM, 10 JPM); juvenile patients were diagnosed before age 18 years. Of the 139 JDM patients, the median age at diagnosis was 6.9 years and median disease duration at enrollment was 10.3 years. Most JDM patients were female (78%) and Non-Hispanic Caucasian (88%), and the remainder were Hispanic (6.5%), Asian (2.9%), multiple races (2.2%), and Black (0.7%). Patients or their parents often completed a graduate degree (23%) or college degree (29%). JDM patients were primarily diagnosed by a pediatric rheumatologist (48%), with adult and pediatric dermatologists (22%), pediatric neurologists and primary care physicians (11% each) diagnosing most of the remaining patients; 67% were under the care of a pediatric rheumatologist. JDM patients frequently had skin rashes as a major manifestation (86%); arthritis (35%) and dysphagia (32%) were also common, whereas lung disease (12%) was less frequent. An additional autoimmune disease was present in 18% of JDM patients, with JIA (8%) and SLE and celiac disease (3% each) the most frequent. There were no recorded associated malignancies. 98% of JDM patients received prednisone therapy. Methotrexate was the most common steroid-sparing agent (84%), followed by hydroxychloroquine (60%), IV pulse solumedrol (54%), IVIG (48%), cyclosporine (19%), rituximab and anti-TNFs (10% each). Predictors of which agents were received varied among medications, but included age, year of JDM diagnosis, gender, and region of country. Pulse solumedrol and cyclosporine were more likely to be used in JDM patients with dysphagia, hydroxychloroquine in patients with skin rashes and less likely in those with fevers, and azathioprine was less likely in patients with arthritis. Of medications utilized, 45% of JDM patients reported responding best to IVIG, 39% responded best to prednisone, 33% to anti-TNFs, and 29% to cyclophosphamide.Conclusion:A nationwide myositis registry has been established and includes a subsample of JDM patients that appears demographically and clinically representative of other US populations. This registry may help identify environmental exposures associated with myositis, elucidate factors associated with quality of life, and serve as an important resource for future clinical investigations.
- [Show abstract] [Hide abstract] ABSTRACT: Autonomic fluctuations are associated with the initiation and possibly maintenance of atrial fibrillation (AF). However, little is known about the relationship between orthostatic blood pressure change, a common manifestation of autonomic dysfunction, and incident AF. We examined whether supine-to-standing changes in systolic blood pressure (SBP) are associated with incident AF in 12,071 African American and white men and women aged 45-64 years, enrolled in the Atherosclerosis Risks in Communities (ARIC) study. Orthostatic hypotension (OH) was defined as a supine-standing drop in SBP by ≥20 mmHg or diastolic blood pressure by ≥10 mmHg. AF cases were identified based on study scheduled 12-lead ECG, hospital discharge ICD codes, and death certificates through 2009. OH was seen in 603 (5%) at baseline. During an average follow-up of 18.1 years, 1438 (11.9%) study participants developed AF. Incident AF occurred more commonly among those with OH than those without, a rate of 9.3 vs. 6.3 per 1000 person years, (p<0.001). The age, gender, and race adjusted hazard ratio (95%CI) of AF among those with OH compared to those without was 1.62 (1.34, 2.14). This association was attenuated after adjustment for common AF risk factors to HR 1.40 (1.15, 1.71), a strength similar to that of diabetes or hypertension with AF in the same model. A non-linear relationship between orthostatic change in SBP and incident AF was present after multivariable adjustment. OH is associated with higher AF incidence. Whether interventions that decrease OH can reduce AF risk remains unknown.
- [Show abstract] [Hide abstract] ABSTRACT: Measurement error/misclassification is commonplace in research when variable(s) can notbe measured accurately. A number of statistical methods have been developed to tackle this problemin a variety of settings and contexts. However, relatively few methods are available to handlemisclassified categorical exposure variable(s) in the Cox proportional hazards regression model. Inthis paper, we aim to review and compare different methods to handle this problem - naïvemethods, 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 recalleddata and historical records. In practice, the issue of measurement error/misclassification should beaccounted for in design and analysis, whenever possible. Also, in the analysis, it could be moreideal to implement more than one correction method for estimation and inference, with properunderstanding of underlying assumptions.
- [Show abstract] [Hide abstract] ABSTRACT: 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 on-scene at least 90% of the time. However, not all EMS providers include specific scene time limits in their stroke patient care protocols. Objective: 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. Results: 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]). Conclusion: 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.
- [Show abstract] [Hide abstract] ABSTRACT: 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. 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. 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). 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.
- [Show abstract] [Hide abstract] ABSTRACT: Whereas dyslipidemia has been associated with leukocytosis, the relationship between serum cholesterol and other hematopoietic lineages is poorly defined. Erythrocytes and platelets, anucleate cells relegated to nonspecific, diffusional exchange of cholesterol with serum, have been proposed to have a distinct relationship to cholesterol from leukocytes. We examined the relationship between serum cholesterol and circulating erythrocyte/platelet indices in 4,469 adult participants of the National Health and Nutrition Examination Survey (NHANES) 2005-2006. In linear regression analyses, serum non-high density lipoprotein-cholesterol (non-HDL-C) was positively associated with mean erythrocyte number, hematocrit, hemoglobin concentration, platelet count, and platelet crit independently of age, gender, race/ethnicity, smoking, body mass index, serum folate, and C-reactive protein. The magnitude of the relationship was most marked for platelets, with lowest vs. highest non-HDL-C quartile subjects having geometric mean platelet counts of 258,000/μL vs. 281,000/μL, respectively (adjusted model, P<0.001 for trend). These associations persisted in a sensitivity analysis excluding several conditions that affect erythrocyte/platelet and/or serum cholesterol levels, and were also noted in an independent analysis of 5,318 participants from NHANES 2007-2008. As non-HDL-C, erythrocytes, and platelets all impact cardiovascular disease risk, there is a need for advancing understanding of the underlying interactions that govern levels of these three blood components.
- [Show abstract] [Hide abstract] ABSTRACT: Migraine is associated with white matter hyperintensities (WMH) cross-sectionally, but its effect on WMH progression is uncertain. 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. 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). 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.
- [Show abstract] [Hide abstract] ABSTRACT: 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.
- [Show abstract] [Hide abstract] ABSTRACT: 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.
Social & Scientific SystemsSilver Spring, Maryland, United States
Shaw UniversityRaleigh, North Carolina, United States
University of Arkansas at Little RockLittle Rock, Arkansas, United States
Johns Hopkins UniversityBaltimore, Maryland, United States