Familial transmission of stroke and myocardial infarction (MI) is partially mediated by transmission of cerebrovascular and cardiovascular risk factors. We examined relationships between family risk of stroke and MI with risk factors for these phenotypes.
Cross-sectional association between the stratified log-rank family score (SLFS) for stroke and MI with prevalent risk factors was assessed in the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort.
Individuals in the 4th quartile of SLFS scores for stroke were more likely to have prevalent risk factors including hypertension (OR: 1.43; 95% CI: [1.30, 1.58]), left ventricular hypertrophy (OR 1.42; 95% CI: [1.16, 1.42]), diabetes (OR: 1.26; 95% CI: [1.12, 1.43]) and atrial fibrillation (OR 1.23; 95% CI: [1.03, 1.45]) compared to individuals in the 1st quartile. Likewise, individuals in the 4th quartile of SLFS scores for MI were more likely to have prevalent risk factors including hypertension (OR 1.57; 95% CI: [1.27, 1.94]) and diabetes (OR 1.29; 95% CI: [1.12, 1.43]) than the 1st quartile. In contrast to stroke, the family risk score for MI was associated with dyslipidemia (OR 1.38; 95% CI: [1.23, 1.55]) and overweight/obesity (OR 1.22; 95% CI: [1.10, 1.37]).
Family risk of stroke and MI are strongly associated with the majority of risk factors associated with each disease. Family history and genetic studies separating nonspecific contributions of intermediate phenotypes from specific contributions to the disease phenotype may lead to more thorough understanding of transmission for these complex disorders.
stroke; myocardial infarction; cohort studies; family risk; REGARDS
Studies of the effect of air pollution on cognitive health are often limited to populations living near cities that have air monitoring stations. Little is known about whether the estimates from such studies can be generalized to the U.S. population, or whether the relationship differs between urban and rural areas. To address these questions, we used a satellite-derived estimate of fine particulate matter (PM2.5) concentration to determine whether PM2.5 was associated with incident cognitive impairment in a geographically diverse, biracial US cohort of men and women (n = 20,150). A 1-year mean baseline PM2.5 concentration was estimated for each participant, and cognitive status at the most recent follow-up was assessed over the telephone using the Six-Item Screener (SIS) in a subsample that was cognitively intact at baseline. Logistic regression was used to determine whether PM2.5 was related to the odds of incident cognitive impairment. A 10 µg/m3 increase in PM2.5 concentration was not reliably associated with an increased odds of incident impairment, after adjusting for temperature, season, incident stroke, and length of follow-up [OR (95% CI): 1.26 (0.97, 1.64)]. The odds ratio was attenuated towards 1 after adding demographic covariates, behavioral factors, and known comorbidities of cognitive impairment. A 10 µg/m3 increase in PM2.5 concentration was slightly associated with incident impairment in urban areas (1.40 [1.06–1.85]), but this relationship was also attenuated after including additional covariates in the model. Evidence is lacking that the effect of PM2.5 on incident cognitive impairment is robust in a heterogeneous US cohort, even in urban areas.
Background and Purpose
When planning clinical trials, decisions regarding sample size are often based on educated guesses of parameters, that may in fact prove to be over- or underestimates. For example, after initiation of the SPS3 study, published data indicated that the recurrent stroke rates might be lower than initially planned for the study. Failure to account for this could result in an under-powered study. Thus, we performed a sample size re-estimation, and describe the experience herein.
We evaluated different scenarios based on a re-estimated overall event rate, including increasing the sample size and increasing the follow-up time, to determine their impact on both Type I error and the power to detect the initially planned treatment difference.
We found that by increasing the sample size from 2500 to 3000 and by following the patients for one year after the end of recruitment, we would maintain our planned Type I error rate, and increase the power to detect the prespecified clinically meaningful difference to between 67% and 87%, depending on the rate of recruitment.
We successfully implemented this unplanned design modification in the SPS3 study, in order to allow for sufficient power to detect the planned treatment differences.
Clinical Trials Registration Information
Clinical Trials Registration - http://clinicaltrials.gov/show/NCT00059306. Unique identifier: NCT00059306
sample size re-estimation; SPS3; randomized clinical trial
To assess risk factors associated with seeking care for stroke symptoms.
Using data from the population-based national cohort study (REasons for Geographic And Racial Differences in Stroke) conducted January 25, 2003–February 28, 2007 (N = 23,664), we assessed care-seeking behavior among 3,668 participants who reported a physician diagnosis of stroke/transient ischemic attack (n = 647) or stroke symptoms (n = 3,021) during follow-up. Care seeking was defined as seeking medical attention after stroke symptoms or a physician diagnosis.
Overall, 58.5% of participants (2,146/3,668) sought medical care. In multivariable models, higher income was associated with greater likelihood of seeking care ( p = 0.02): participants with income of ≥$75,000 had odds 1.43 times (95% confidence interval [CI], 1.02–2.02) greater than those with income of less than $20,000. Diabetes and previous heart disease were associated with increased care seeking: odds ratio (OR) of 1.23 (95% CI, 1.04 –1.47) and OR of 1.26 (95% CI, 1.06– 1.49), respectively. Participants with previous stroke symptoms but no stroke history were less likely to seek care than those with stroke history or without previous symptoms (OR, 0.80; 95% CI, 0.67– 0.96). Past smoking was associated with lower likelihood (OR, 0.71; 95% CI, 0.59–0.85; p = 0.0003) of seeking care relative to nonsmokers.
Only approximately half of participants with stroke symptoms sought care. This is despite the encouragement of advocacy groups to seek prompt attention for stroke symptoms. Our results highlight the importance of identifying characteristics associated with care-seeking behavior. Recognizing factors that contribute to delays provides opportunities to enhance education on the importance of seeking care for stroke symptoms.
Background and Purpose
Diabetes and hypertension impart approximately the same increased relative risk for stroke, although hypertension has a larger population-attributable risk because of its higher population prevalence. With a growing epidemic of obesity and associated increasing prevalence of diabetes that disproportionately impacts the southeastern Stroke Belt states, any potential contribution of diabetes to the geographic disparity in stroke mortality will only increase.
Racial and geographic differences in diabetes prevalence and diabetes awareness, treatment, and control were assessed in the REasons for Geographic And Racial Differences in Stroke study, a national population-based cohort of black and white participants older than 45 years of age. At the time of this report, 21 959 had been enrolled.
The odds of diabetes were significantly increased in both white and black residents of the stroke buckle (OR, 1.26; [1.10, 1.44]; OR, 1.45 [1.26, 1.66], respectively) and Stroke Belt (OR, 1.22; [1.09, 1.36]; OR, 1.13 [1.02, 1.26]) compared to the rest of the United States. In the buckle, regional differences were not fully mediated and remained significant when controlling for socioeconomic status and risk factors. Addition of hypertension to the models did not reduce the magnitude of the associations. There were no significant differences by region with regard to awareness, treatment, or control for either race.
These analyses support a possible role of regional variation in the prevalence of diabetes as, in part, an explanation for the regional variation in stroke mortality but fail to support the potential for a contribution of regional differences in diabetes management.
diabetes; geography; racial differences
The contribution of albuminuria to the increased risk of incident end-stage renal disease (ESRD) in individuals with a family history of ESRD has not been well studied.
Prospective cohort study.
Study Setting & Participants
We analyzed data for family history of ESRD collected from 19,409 participants of the Renal REGARDS (Reasons for Geographic and Racial Differences in Stroke) cohort study.
Family history of ESRD was ascertained by asking “Has anyone in your immediate family ever been told that he or she had kidney failure? This would be someone who is on or had been on dialysis or someone who had a kidney transplant.”
Incidence rate for ESRD.
Morning urine albumin-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR). Incident cases of ESRD were identified through the US Renal Data System.
A family history of ESRD was reported by 11.1% of participants. Mean eGFRs for those with and without a family history of ESRD were 87.5 ± 22.2 (SD) and 86.5 ± 19.3 mL/min/1.73 m2, respectively (P = 0.05) and the respective geometric mean ACRs were 12.2 and 9.7 mg/g (P < 0.001). ESRD incidence rates for those with and without a family history of ESRD were 244.3 and 106.1/100,000 person-years, respectively. After adjusting for age, sex, and race, the ESRD HR for those with versus those without a family history of ESRD was 2.13 (95% CI, 1.18-3.83). Adjustment for comorbid conditions and socioeconomic status attenuated this association (HR, 1.82; 95% CI, 1.00-3.28), and further adjustment for baseline eGFR and ACR completely attenuated the association between family history of ESRD and incident ESRD (HR, 1.12; 95% CI, 0.69-1.80).
The report of a family history of ESRD was not validated.
Family history of ESRD is common in older Americans and the increased risk of ESRD associated with a family history reflects lower GFR, higher albuminuria, and comorbid conditions.
Race; albuminuria; end-stage renal disease; chronic kidney disease
Stroke symptoms are common among people without a history of stroke or transient ischemic attack; however, it is unknown if particular attention should be focused on specific symptoms for subgroups of patients.
Using baseline data from 26,792 REasons for Geographic and Racial Differences in Stroke (REGARDS) participants without a history of transient ischemic attack or stroke, we assessed the association between age, sex, race, current smoking, hypertension and diabetes and the six stroke symptoms in the Questionnaire for Verifying Stroke-Free Status.
The mean age of participants was 64.4 ± 9.4 years, 40.7% were black and 55.2% women. After multivariable adjustment, older persons more often reported an inability to understand (odds ratio [OR] = 1.16 per 10 years older age, 95% confidence interval [CI]: 1.07–1.25) and unilateral vision loss (OR=1.09, 95% CI: 1.01–1.18) and less often reported numbness (OR=0.83, 95% CI: 0.79–0.87) and weakness (OR=0.85, 95% CI: 0.80–0.90). Women reported difficulty communicating more often than men (OR=1.36, 95% CI: 1.19–1.56). The OR for blacks compared to whites for each of the six stroke symptoms was increased, markedly so for unilateral numbness (OR=1.97, 95% CI: 1.81–2.16), unilateral weakness (OR=1.96, 95% CI: 1.76–2.18) and inability to understand (OR=1.87, 95% CI: 1.61–2.18). Current smoking, hypertension, and diabetes were associated with higher ORs for each stroke symptom.
The association of risk factors with six individual stroke symptoms studied was not uniform, suggesting the need to emphasize individual stroke symptoms in stroke awareness campaigns when targeting populations defined by risk.
individual stroke symptoms; stroke symptoms; risk factors
Significant and persistent racial and income disparities in birth outcomes exist in the US. The analyses in this manuscript examine whether adverse birth outcome time trends and associations between area-level variables and adverse birth outcomes differ by urban–rural status.
Alabama births records were merged with ZIP code-level census measures of race, poverty, and rurality. B-splines were used to determine long-term preterm birth (PTB) and low birth weight (LBW) trends by rurality. Logistic regression models were used to examine differences in the relationships between ZIP code-level percent poverty or percent African-American with either PTB or LBW. Interactions with rurality were examined.
Population dense areas had higher adverse birth outcome rates compared to other regions. For LBW, the disparity between population dense and other regions increased during the 1991–2005 time period, and the magnitude of the disparity was maintained through 2010. Overall PTB and LBW rates have decreased since 2006, except within isolated rural regions. The addition of individual-level socioeconomic or race risk factors greatly attenuated these geographical disparities, but isolated rural regions maintained increased odds of adverse birth outcomes. ZIP code-level percent poverty and percent African American both had significant relationships with adverse birth outcomes. Poverty associations remained significant in the most population-dense regions when models were adjusted for individual-level risk factors.
Population dense urban areas have heightened rates of adverse birth outcomes. High-poverty African American areas have higher odds of adverse birth outcomes in urban versus rural regions. These results suggest there are urban-specific social or environmental factors increasing risk for adverse birth outcomes in underserved communities. On the other hand, trends in PTBs and LBWs suggest interventions that have decreased adverse birth outcomes elsewhere may not be reaching isolated rural areas.
Health status disparities; Low birth weight; Premature birth; Rural health; Urban health
To examine the association between prolongation of heart rate–corrected QT interval (QTc) with incident stroke.
Unlike cardiovascular morbidity and mortality, little is known about the relationship between QTc and risk of stroke.
A total of 27,411 participants aged ≥ 45 years without prior stroke from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study were included in this analysis. QTc was calculated using Framingham formula (QTcFram). Stroke cases were identified and adjudicated during up to 8.2 years of follow-up (median 5.1 years).
The risk of incident stroke in study participants with prolonged QTcFram was almost three times the risk in those with normal QTcFram [HR (95% CI): 2.88 (2.12, 3.92), p<0.0001]. After adjustment for demographics (age, race, sex), traditional stroke risk factors (antihypertensive medication use, systolic blood pressure, current smoking, diabetes, left ventricular hypertrophy, atrial fibrillation, prior cardiovascular disease), warfarin use, aspirin use, QRS duration and use of QT-prolonging drugs, the risk of stroke remained significantly high [HR (95% CI): 1.67 (1.16, 2.41), p=0.0061)], and was consistent across several subgroups of REGARDS participants. Similar results were obtained when the risk of stroke was estimated per 1-standard deviation increase in QTcFram, [HR (95% CI): 1.12 (1.03, 1.21), p=0.0053 in multivariable-adjusted model], and when other QTc correction formulas including Hodge’s, Bazett’s and Fridericia’s were used.
QTc prolongation is associated with a significantly increased risk of incident stroke independent of traditional stroke risk factors. Examining the risk of stroke associated with QT-prolonging drugs may be warranted.
QTc; stroke; electrocardiogram; QT-prolonging drugs; REGARDS
While black-white and regional disparities in U.S. stroke mortality rates are well documented, the contribution of disparities in stroke incidence is unknown. We provide national estimates of stroke incidence by race and region, contrasting these to publicly available stroke mortality data.
This analysis included 27,744 men and women without prevalent stroke (40.4% black), aged ≥45 years from the REasons for Geographic And Racial Differences in Stroke (REGARDS) national cohort study, enrolled 2003–2007. Incident stroke was defined as first occurrence of stroke over 4.4 years of follow-up. Age-sex–adjusted stroke mortality rates were calculated using data from the Centers for Disease Control and Prevention (CDC) Wide-Ranging Online Data for Epidemiological Research (WONDER) System.
There were 460 incident strokes over 113,469 person-years of follow-up. Relative to the rest of the United States, incidence rate ratios (IRRs) of stroke in the southeastern stroke belt and stroke buckle were 1.06 (95% confidence interval [CI], 0.87–1.29) and 1.19 (95% CI, 0.96–1.47), respectively. The age-sex–adjusted black/white IRRblack was 1.51 (95% CI, 1.26–1.81), but for ages 45–54 years the IRRblack was 4.02 (95% CI, 1.23–13.11) while for ages 85+ it was 0.86 (95% CI, 0.33–2.20). Generally, the IRRsblack were less than the mortality rate ratios (MRRs) across age groups; however, only in ages 55–64 years and 65–74 years did the 95% CIs of IRRsblack not include the MRRblack. The MRRs for regions were within 95% CIs for IRRs.
National patterns of black-white and regional differences in stroke incidence are similar to those for stroke mortality; however, the magnitude of differences in incidence appear smaller.
Background and Purpose
Black/white disparities in stroke incidence are well-documented, but few studies have assessed the contributions to the disparity. Here we assess the contribution of “traditional” risk factors.
25,714 black and white men and women, aged 45+ and stroke-free at baseline were followed for an average of 4.4 years to detect stroke. Mediation analysis employing proportional hazards analysis assessed the contribution of “traditional” risk factors to racial disparities.
At age 45, incident stroke risk was 2.90 (95% CI: 1.72 – 4.89) times more likely in blacks than whites, and 1.66 (95% CI: 1.34 – 2.07) times at age 65. Adjustment for risk factors attenuated these excesses by 40% and 45%, respectively, resulting in relative risks of 2.14 (95% CI: 1.25 – 3.67) and 1.35 (95% CI: 1.08 – 1.71). Approximately one-half of this mediation is attributable to systolic blood pressure. Further adjustment for socioeconomic factors resulted in total mediation of 47% and 53% to relative risks of 2.01 (95% CI: 1.16 – 3.47) and 1.30 (1.03 – 1.65) respectively.
Between ages 45 to 65 years, approximately half of the racial disparity in stroke risk is attributable to traditional risk factors (primarily systolic blood pressure) and socioeconomic factors, suggesting a critical need to understand the disparity in the development of these traditional risk factors. Because half of the excess stroke risk in blacks is not attributable to traditional risk factors and socioeconomic factors, differential racial susceptibility to risk factors, residual confounding or non-traditional risk factors may also play a role.
stroke; risk factors; hypertension; diabetes; mediation analysis
Background and Purpose
Previously in the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort, we found 18% of the stroke/TIA-free study population reported ≥ 1 stroke symptom (SS) at baseline. We sought to evaluate the additional impact of these stroke symptoms (SS) on risk for subsequent stroke.
REGARDS recruited 30,239 U.S. blacks and whites, aged 45+ in 2003–7, who are being followed every 6 months for events. All stroke events are physician-verified; those with prior diagnosed stroke or TIA are excluded from this analysis. At baseline, participants were asked six questions regarding stroke symptoms. Measured stroke risk factors were components of the Framingham Stroke Risk Score (FSRS).
After excluding those with prior stroke or missing data, there were 24,412 participants in this analysis, with a median follow-up of 4.4 years. Participants were 39% black, 55% female, and had median age of 64 years. There were 381 physician-verified stroke events. The FSRS explained 72.0% of stroke risk; individual components explained between 0.2% (LVH) and 5.7% (age + race) of stroke risk. After adjustment for FSRS factors, SS were significantly related to stroke risk: for each SS reported, the risk of stroke increased by 21% per symptom.
Among participants without self-reported stroke or TIA, prior SS are highly predictive of future stroke events. Compared to FSRS factors, the impact of SS on the prediction of future stroke was almost as large as the impact of smoking and hypertension, and larger than the impact of diabetes and heart disease.
Acute Stroke; Aphasia; Ischemia; Risk Factors; TIA; Transient Ischemic Attack
Background and Purpose
We compared the associations of self-reported atrial fibrillation (SR-AF) and electrocardiogram-detected AF (ECG-AF) with incident stroke in the REGARDS study.
27,109 participants aged ≥45 years without prior stroke were included in this analysis. Stroke cases were identified and adjudicated during an average of 4.4 years of follow-up. Cox proportional hazards analysis was used to calculate hazard ratios of SR-AF, ECG-AF, and AF detected by either method with incident stroke. We also examined the predictive ability of the Framingham Stroke Risk Score (FSRS) where the component AF was defined by different methods.
After adjustment for components of the FSRS, SR-AF, ECG-AF, and AF by either method were predictive of incident stroke [HR (95% CI): 1.41 (1.05,1.88), 1.90 (1.10,3.27), 1.53 and (1.16,2.01), respectively]. When self-report, ECG or either method, separately, were considered as the method of AF ascertainment in the FSRS, the Hazard ratios per 1% increase in the FSRS were identical across AF ascertainment methods [1.04 (1.03,1.04); 1.04 (1.04,1.05); 1.04 (1.03,1.04) respectively].
SR-AF is a strong predictor of stroke that can be used interchangeably or in combination with ECG-AF in stroke risk prediction models.
Atrial fibrillation; self-report; Electrocardiogram
Little is known about post-stroke depression in patients with lacunar stroke due to cerebral small vessel disease. Our objectives were to describe the prevalence of depression, its correlates and to examine the course of depression over time in a cohort of patients with lacunar stroke, the majority of whom had mild functional disability.
Depression was determined in participants in the international Secondary Prevention of Small Subcortical Strokes (SPS3) trial which is testing antiplatelet therapies and targets of blood pressure control in patients with lacunar strokes and assessing stroke recurrence and cognitive decline. Depression was evaluated using the Patient Health Questionnaire. Multivariable logistic regression models were fitted to examine the relationship between the covariates of interest and depression. Generalized estimating equations were used to examine the likelihood of depression over time, while accounting for the multiple measurements within each subject.
The prevalence of depression in 2,477 participants at approximately 4 months after stroke was 19%. Older age (OR 0.97; 95% CI 0.96–0.99), male gender (OR 0.62; 95% CI 0.48–0.80) and less cognitive impairment (OR 0.99; 95% CI 0.98–1.00) were independently associated with a lower risk of depression. Functional disability (OR 1.8; 95% CI 1.3–2.4), living with a spouse/family (OR 1.6; 95% CI 1.1–2.3) and risk factors for stroke (OR 1.2; 95% CI 1.0–1.3) were each independently associated with a higher risk of depression. Longitudinal modeling indicated that the likelihood of depression decreased by 1.12 times (95% CI 1.06–1.17) for each 1-year increase in time.
One fifth of those in the SPS3 trial cohort reported depression that is sustained over time. Although this is lower than the prevalence reported for stroke in general, these results underscore the importance of early screening for post-stroke depression, treatment and follow-up to minimize the negative consequences associated with depression.
Lacunar stroke; Depression after stroke; Predictors of outcome; Longitudinal study; Secondary Prevention of Small Subcortical Strokes study
Longitudinal cohort studies normally identify and adjudicate incident events detected during follow-up by retrieving medical records. There are several reasons why the adjudication process may not be successfully completed for a suspected event including the inability to retrieve medical records from hospitals and an insufficient time between the suspected event and data analysis. These “incomplete adjudications” are normally assumed not to be events, an approach which may be associated with loss of precision and introduction of bias. In this article, the authors evaluate the use of multiple imputation methods designed to include incomplete adjudications in analysis. Using data from the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study, 2008−2009, they demonstrate that this approach may increase precision and reduce bias in estimates of the relations between risk factors and incident events.
cohort studies; imputation; longitudinal studies; missing data
There are racial and geographic disparities in stroke mortality, with higher rates among African Americans (AAs) and those living in the southeastern US (‘stroke belt’). Racial and geographic differences in dyslipidemia prevalence, awareness, treatment and control may, in part, account for the observed disparities in stroke mortality.
Reasons for Geographic and Racial Differences in Stroke (REGARDS) is a national observational study of community-dwelling black and white participants aged 45 and older, with oversampling from the stroke belt. As of January 15, 2007, 26,122 participants were enrolled and a fasting lipid panel was available of 21,068. Awareness, treatment and control of dyslipidemia were estimated overall and compared across race-sex-region strata.
There were 55% of the participants with dyslipidemia and no racial differences in prevalence. Adjusting for demographic and established stroke risk factors, AAs had a lower prevalence (OR 0.74; 95% CI: 0.66, 0.77) and were less likely to be aware (0.69; 0.61, 0.78), treated (0.77; 0.67, 0.89) and controlled (0.67; 0.58, 0.77) than whites. There was lower control outside of the stroke belt (0.87; 0.76, 0.99).
Racial, but not geographic, differences in dyslipidemia management may play a role in the excess stroke burden in the Southeast.
Cholesterol; Risk factors; Risk factor management; Racial differences; Stroke prevention
Obesity management requires understanding of the mortality risks associated with different adiposity measures.
Setting and Participants
5,805 adults with BMI ≥ 18.5 and stage 1–4 CKD defined by a spot urine albumin-creatinine ratio ≥ 30 mg/g and/or an estimated glomerular filtration rate < 60 ml/min/1.73 m2 enrolled in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study
Body mass index (BMI) in kg/m2 categorized as 18.5–24.9, 25.0–29.9, 30.0–34.9, 35.0–39.9 and ≥ 40 kg/m2 and waist circumference categorized as < 80, 80–87.9, 88–97.9, 98–107.9, and ≥ 108 cm in women and < 94, 94–101.9, 102–111.9, 112–121.9, and ≥122 cm in men.
All cause mortality
BMI and WC were measured using a standardized protocol during the home visit.
A total of 686 deaths (11.8%) occurred during a median follow-up of 4 years. Compared to the referent BMI category 25–29.9 kg/m2, hazard ratios for mortality were 1.27 (95% CI, 0.96–1.69) for BMI < 25 kg/m2, and 0.84 (95% CI, 0.62–1.13), 0.81 (0.52–1.26) and 0.95 (95% CI, 0.54–1.65) for BMI categories 30–34.9, 35–39.9 and ≥ 40 kg/m2, respectively, after adjustment for covariates including waist circumference. In contrast, after adjustment for covariates including BMI, higher mortality rates were noted for all waist circumference categories compared to the referent (< 80 cm in women and < 94 cm in men) with hazard ratios 1.04 (95% CI, 0.77–1.41) for waist circumference 80–87.9 in women and 94–101.9 in men, 1.29 (95% CI, 0.92–1.81) for waist circumference 88–97.9 in women and 102–111.9 in men, 1.72 (95% CI, 1.12–2.62) for waist circumference 98–107.9 in women and 112–121.9 in men, and 2.09 (95% CI, 1.26–3.46) for waist circumference ≥ 108 in women and ≥ 122 in men.
BMI and waist circumference measured at baseline only.
waist circumference should be considered in conjunction with BMI when assessing mortality risk associated with obesity in adults with CKD.
Obesity; waist circumference; mortality; chronic kidney disease
To determine whether incidence of impaired cognitive screening status is higher in the southern Stroke Belt region of the United States than in the remaining U.S.
A national cohort of adults ≥ age 45 was recruited by the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study from 2003–2007. Participants’ global cognitive status was assessed annually by telephone with the Six-item Screener (SIS) and every two years with fluency and recall tasks. Participants who reported no stroke history and who were cognitively intact at enrollment (SIS > 4 of 6) were included (N = 23,913, including 56% women, 38% African Americans and 62% European Americans, 56% Stroke Belt residents and 44% from the remaining contiguous United States and the District of Columbia). Regional differences in incident cognitive impairment (SIS score ≤ 4) were adjusted for age, sex, race, education, and time between first and last assessments.
1,937 participants (8.1%) declined to an SIS score ≤ 4 at their most recent assessment, over a mean of 4.1 (± 1.6) years. Residents of the Stroke Belt had greater adjusted odds of incident cognitive impairment than non-Belt residents (OR = 1.18; 95% CI 1.07 – 1.30). All demographic factors and time independently predicted impairment.
Regional disparities in cognitive decline mirror regional disparities in stroke mortality, suggesting shared risk factors for these adverse outcomes. Efforts to promote cerebrovascular and cognitive health should be directed to the Stroke Belt.
This paper documents individual asthma action plan presence and quick relief medication (albuterol) availability for elementary students enrolled in five Alabama school systems.
Patients and Methods
Data were obtained during baseline data collection (fall 2005) of a school-based supervised asthma medication trial. All students attended 1 of 36 participating elementary schools across five school systems in Jefferson County, Alabama. In addition, they had to have physician-diagnosed asthma requiring daily controller medication. Each school system had its own superintendent and elected school board. Asthma action plan presence and albuterol availability was confirmed by study personnel. Asthma action plans had to contain daily and acute asthma management instructions. Predictors of asthma action plan presence and albuterol availability were also investigated. Associations between albuterol availability and self-reported characteristics including health care utilization prior to study enrollment and outcomes during the study baseline period were also investigated.
Enrolled students had a mean (SD) age of 11.0 (2.1) years, 91% were African American, and 79% had moderate persistent asthma. No student had a complete asthma action plan on file and only 14% had albuterol physically available at school. Albuterol availability was not predicted by gender, race, insurance status, second-hand smoke exposure, need for pre-exercise albuterol, asthma severity, or self-reported health care utilization prior to study enrollment. Albuterol availability did not predict school absences, red/yellow peak flow recordings, or medication adherence during the study's baseline period.
Despite policies permitting students to possess albuterol, few elementary students across five independent school systems in Alabama actually had it readily available at school.
There is growing interest in determining the degree of anemia, which is clinically significant. The goal of this study was to determine the association between hemoglobin concentration and cognitive impairment in a large sample of U.S. adults.
We used cross-sectional data from 19,701 adults participating in the REasons for Geographic And Racial Differences in Stroke study. Cognitive impairment was defined as a score of 4 or less on the six-item screener. Hemoglobin was analyzed in 1 g/dL increments relative to the World Health Organization (WHO) threshold (<13 g/dL for men and <12 g/dL for women).
The mean hemoglobin concentration was 13.7 ± 1.5 g/dL. The prevalence of cognitive impairment increased from 4.3% among individuals with a hemoglobin >3 g/dL above the WHO threshold to 16.8% for those with a hemoglobin ≥2 g/dL below the WHO threshold. After adjustment for demographics, chronic health conditions, health status, and inflammation, the association between reduced hemoglobin and cognitive impairment was attenuated and no longer significant, including among those with hemoglobin ≥2 g/dL below the WHO threshold (odds ratio 1.39, 95% confidence interval = 0.94–2.04). A test for linear trend was of borderline significance (p value = .06). For 94% of the sample within 2 g/dL of the WHO threshold, there was no relationship between hemoglobin concentration and the odds of cognitive impairment. The associations did not differ by sex and race.
Within a large sample of community-dwelling adults, there was no significant association between hemoglobin concentration and cognitive impairment after multivariable adjustment.
Hemoglobin; Anemia; Cognitive impairment
Chronic kidney disease (CKD) and albuminuria are associated with increased risk of all-cause mortality.
Prospective observational cohort study
Setting and Participants
17,393 participants (mean age, 64.3 ± 9.6 years) in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) Study.
Estimated glomerular filtration rate (eGFR), urinary albumin-creatinine ratio (ACR).
All-cause mortality (710 deaths); median duration of follow-up: 3.6 years.
Measurements and Analysis
Categories of eGFR (90– <120, 60–<90, 45–<60, 30–<45, and 15–<30 mL/min/1.73 m2) and urinary ACR (<10 mg/g or normal, 10–<30 mg/g or high normal, 30–300 mg/g or high, and >300 mg/g or very high). Cox’s proportional hazards models were adjusted for demographic factors, cardiovascular covariates, and hemoglobin.
The background all-cause mortality rate for participants with normal ACR, eGFR of 90–<120 mL/min/1.73 m2 and no CHD was 4.3 deaths/1,000 person-years. Higher ACR was associated with an increased multivariable adjusted hazard ratio for all-cause mortality within each eGFR category. Reduced eGFR was associated with higher adjusted hazard ratio for all-cause mortality for participants with high normal (P value = 0.01) and high (P value <0.001) ACR values, but not for those with normal or very high ACR values.
Only one laboratory assessment for serum creatinine and ACR was available
Increased albuminuria was an independent risk factor for all-cause mortality. Reduced eGFR was associated with increased mortality risk among those with high normal and high ACR. The mortality rate was low in the normal ACR group and increased in the very high ACR group but did not vary with eGFR in these groups.
Complex diseases often aggregate within families and using the history of family members’ disease can potentially increase the accuracy of the risk assessment and allow clinicians to better target on high risk individuals. However, available family risk scores do not reflect the age of disease onset, gender and family structures simultaneously. In this paper, we propose an alternative approach for a family risk score, the stratified log-rank family score (SLFS), which incorporates the age of disease onset of family members, gender differences and the relationship among family members. Via simulation, we demonstrate that the new SLFS is more closely associated with the true family risk for the disease and more robust to family sizes than two existing methods. We apply our proposed method and the two existing methods to a study of stroke and heart disease. The results show that assessing family history can improve the prediction of disease risks and the SLFS has strongest positive associations with both myocardial infarction and stroke.
family history; family risk; family history score; age of onset; heart disease
Stroke mortality rates differ by race and region, and smoking and exposure to secondhand smoke are associated with stroke. We evaluated regional and racial differences in current smoking and secondhand smoke exposure among participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study.
African American and white adults (n = 26,373) aged 45 years or older were recruited during 2003 through 2007. Logistic regression was used to examine the likelihood of current smoking and secondhand smoke exposure by race (African American vs white) and region. We compared the buckle of the stroke belt (the coastal plain region of North Carolina, South Carolina, and Georgia) with the stroke belt (the remainder of North Carolina, South Carolina, and Georgia, plus Alabama, Mississippi, Tennessee, Arkansas, and Louisiana) and compared each of these regions with the remaining contiguous states.
Among whites, no regional differences in current smoking were seen, but among African Americans, the odds of current smoking were 5% lower in the stroke belt, and 24% lower in the stroke buckle than those in the nonbelt region. Similarly, among whites no regional differences in exposure to secondhand smoke were found, whereas among African Americans, the odds of being exposed to secondhand smoke were 14% lower in the stroke buckle than for nonbelt residents.
These data suggest that rates of current smoking and secondhand smoke exposure are not higher in regions that have higher stroke mortality and therefore cannot contribute to geographic disparities; nevertheless, given that 15% of our participants reported current smoking and 16% reported secondhand smoke exposure, continued implementation of tobacco control policies is needed.
Asthma exacerbations are seasonal with the greatest risk in elementary-age students occurring shortly after returning to school following summer break. Recent research suggests that this seasonality in children is primarily related to viral respiratory tract infections. Regular hand washing is the most effective method to prevent the spread of viral respiratory infections; unfortunately, achieving hand washing recommendations in schools is difficult. Therefore, we designed a study to evaluate the effect of hand sanitizer use in elementary schools on exacerbations among children with asthma.
To describe the process of redesigning the trial in response to changes in the safety profile of the hand sanitizer as well as changes in hand hygiene practice in the schools.
The original trial was a randomized, longitudinal, subject-blinded, placebo-controlled, community-based crossover trial. The primary aim was to evaluate the incremental effectiveness of hand sanitizer use in addition to usual hand hygiene practices to decrease asthma exacerbations in elementary-age children. Three events occurred that required major modifications to the original study protocol: (1) safety concerns arose regarding the hand sanitizer’s active ingredient; (2) no substitute placebo hand sanitizer was available; and (3) community preferences changed regarding hand hygiene practices in the schools.
The revised protocol is a randomized, longitudinal, community-based crossover trial. The primary aim is to evaluate the incremental effectiveness of a two-step hand hygiene process (hand hygiene education plus institutionally provided alcohol-based hand sanitizer) versus usual care to decrease asthma exacerbations. Enrollment was completed in May 2009 with 527 students from 30 schools. The intervention began in August 2009 and will continue through May 2011. Study results should be available at the end of 2011.
The changed design does not allow us to directly measure the effectiveness of hand sanitizer use as a supplement to traditional hand washing practices.
The need to balance a rigorous study design with one that is acceptable to the community requires investigators to be actively involved with community collaborators and able to adapt study protocols to fit changing community practices.
There are pronounced disparities among black compared to white Americans for risk of end-stage renal disease. This study examines whether similar relationships exist between poverty and racial disparities in chronic kidney disease (CKD) prevalence.
We studied 22,538 participants in the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort study. We defined individual poverty as family income below USD 15,000 and a neighborhood as poor if 25% or more of the households were below the federal poverty level.
As the estimated glomerular filtration rate (GFR) declined from 50–59 to 10–19 ml/min/ 1.73 m2, the black:white odds ratio (OR) for impaired kidney function increased from 0.74 (95% CI 0.66, 0.84) to 2.96 (95% CI 1.96, 5.57). Controlling for individual income below poverty, community poverty, demographic and comorbid characteristics attenuated the black:white prevalence to an OR of 0.65 (95% CI 0.57, 0.74) among individuals with a GFR of 59–50 ml/min/1.73 m2 and an OR of 2.21 (95% CI 1.25, 3.93) among individuals with a GFR between 10 and 19 ml/min/ 1.73 m2.
Household, but not community poverty, was independently associated with CKD and attenuated but did not fully account for differences in CKD prevalence between whites and blacks.
Chronic kidney disease; Poverty; Racial disparities