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Direct oral anticoagulants (DOACs; rivaroxaban, apixaban) and warfarin are approved for venous thromboembolism (VTE) treatment. Few direct comparisons of DOACs on risk of mortality among VTE patients exist, and for patients with concomitant conditions (e.g., kidney and liver disease) clinical guidelines are unclear. We evaluated 6-month all-cause mortality by anticoagulant prescribed for primary treatment of VTE. Using Medicare 20% sample data, we created a propensity score matched analytic dataset of 47,860 beneficiaries with non-cancer incident VTE. We used Cox regression to estimate adjusted hazard ratios (HRs) of OACs with 6-month mortality, and tested interactions by liver/kidney disease. There were 3,422 deaths over 6 months of follow-up. In adjusted models, patients prescribed rivaroxaban [HR: 0.82 (95% CI: 0.76-0.90)] had lower rates of mortality versus warfarin. There was no association comparing apixaban to warfarin [HR: 0.96 (95% CI: 0.87-1.07)]. In head-to-head comparisons of apixaban versus rivaroxaban the HR was 1.14 (95% CI: 1.01-1.28)]. Findings were similar among patients with liver and kidney disease. Overall, risk of death was similar by OAC prescribed. Though it is possible residual confounding remained, there was some suggestion of lower risk with rivaroxaban than warfarin. DOACs appear safe among VTE patients with concomitant kidney or liver disease., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Numerous studies have shown inverse associations between serum magnesium (Mg) and risk of cardiovascular disease (CVD), but studies of dietary Mg have not been consistent., Aim: To examine the association of a Mg-rich diet score with risks of CVD, coronary heart disease (CHD), and ischemic stroke in the Atherosclerosis Risk in Communities (ARIC) study., Methods: There were 15,022 Black and White adults without prevalent CVD at baseline (1987-89) included in this analysis. Diet was assessed at two visits 6 years apart using an interviewer-administered 66-item food frequency questionnaire. A Mg-rich diet score was created that included servings of whole grain products, nuts, vegetables, fruit, legumes, coffee, and tea. Cox proportional hazard regression evaluated associations of incident CVD, CHD and stroke across quintiles of Mg-rich diet score, adjusting for demographics, lifestyle factors, and clinical characteristics., Results: Over >30 years of follow-up, there were 3,531 incident CVD events (2,562 CHD, 1,332 ischemic stroke). Participants who consumed more Mg-rich foods were older, female, White, had lower blood pressure, fewer were not current smokers, and more reported being physically active. A Mg-rich diet was inversely associated with incident CVD (HRQ5 vs Q1=0.87, 95%CI: 0.77-0.98, ptrend=0.02) CHD (HRQ5 vs Q1=0.82, 95%CI: 0.71-0.95, ptrend=0.01); however, the diet-stroke association was null (HRQ5 vs Q1=1.00, 95%CI: 0.82-1.22, ptrend=0.97)., Conclusions: Consuming a diet including Mg-rich foods, such as whole grains, nuts, vegetables, fruits, legumes, coffee and tea, is associated with lower risk of CVD and CHD, but not ischemic stroke., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Stroke is a leading cause of death in the United States across all race/ethnicity and sex groups, though disparities exist. We investigated the potential for primary prevention of total first stroke for Americans aged 20 and older, stratified by sex and race/ethnicity. Specifically, we calculated population attributable fractions (PAF) of first stroke for 7 potentially modifiable risk factors: smoking, physical inactivity, poor diet, obesity, hypertension, diabetes, and atrial fibrillation. PAFs are a function of (1) the relative risk of first stroke for people with the exposure and (2) the prevalence of the risk factor in the population. Relative risks came from recent meta-analyses and sex-race/ethnicity-specific prevalence estimates came from the 2015-2018 NHANES or Multi-Ethnic Study of Atherosclerosis (for atrial fibrillation only). Approximately 1/3 (35.7% [CI: 21.6%-49.0%]) for women, 32.7% [CI: 19.2%-45.1%] for men) of strokes were attributable to the 7 risk factors we considered. A 20% proportional reduction in stroke risk factors would result in approximately 37,000 fewer strokes annually in the United States. The estimated PAF was highest for non-Hispanic Black women (39.3% [CI: 24.8%-52.3%]) and lowest for non-Hispanic Asian men (25.5% [CI: 14.6%-36.2%]). For most groups, obesity and hypertension were the largest contributors to stroke rates., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Study Objective: Sleep apnea is associated with unexplained epilepsy in older adults in small studies. We sought to determine the relationship between sleep apnea and additional sleep characteristics and late-onset epilepsy (LOE), adjusting for comorbidities, using data from the large, prospective Atherosclerosis Risk in Communities (ARIC) Study cohort., Methods: We used Medicare claims to identify cases of LOE in ARIC participants. We used polysomnography data from 1309 ARIC participants who also participated in the Sleep Heart Health Study in 1995-1998, and demographic and comorbidity data from ARIC. Later risk of LOE was evaluated using survival analysis with a competing risk of death. We also used survival analysis in 2672 ARIC participants to identify the association between self-reported obstructive sleep apnea (2011-2013), and the risk of subsequent LOE., Results: Late-midlife oxygen desaturation to less than 80% during sleep was associated with subsequent development of LOE, adjusted subhazard ratio 3.28 (1.18-9.08), but the apnea-hypopnea index was not related. Participant report of diagnosis of sleep apnea in 2011-2013 was also associated with subsequent LOE, adjusted subhazard ratio 2.59 (1.24-5.39)., Conclusions: Sleep apnea and oxygen saturation nadir during sleep are associated with LOE, independently of hypertension and other comorbidities. These potentially modifiable risk factors could have large clinical implications for LOE., (© The Author(s) 2023. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: ACC/AHA guidelines caution against the use of antihypertensive therapy in the setting of low standing systolic BP (SBP) < 110 mm Hg due to unclear benefits., Methods: The Atherosclerosis Risk in Communities (ARIC) Study measured supine and standing SBP in adults aged 45-64 years between 1987 and 1989. We used Cox regression to evaluate the associations of low standing SBP (<110 mm Hg) with risk of falls, syncope, coronary heart disease (CHD), and mortality through December 31, 2019. Falls and syncope were ascertained by hospitalization and outpatient claims; CHD events were adjudicated. Associations were examined overall and in strata of hypertension stage, 10-year atherosclerotic cardiovascular disease (ASCVD) risk, age, and sex., Results: Among 12,467 adults followed a median of 24 years (mean age at enrollment 54.1 ± 5.8 years, 55% women, 26% Black adults), 3,000 (24%) had a standing SBP < 110 mm Hg. A standing SBP < 110 mm Hg compared to standing SBP ≥ 110 mm Hg was not significantly associated with falls or syncope, and was associated with a lower risk of CHD events and mortality with HRs of 1.02 (95% CI 0.94, 1.11), 1.02 (0.93, 1.11), 0.88 (0.80, 0.97), and 0.91 (0.86, 0.97), respectively. There were no clinically meaningful differences when stratified by hypertension stage, 10-year ASCVD risk, age, and sex., Conclusions: In this community-based population, low standing SBP was common and not significantly associated with falls or syncope, but was associated with a lower risk of CHD and mortality. These findings do not support screening for low standing BP as a risk factor for adverse events., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We examined the associations between lung function and incident dementia and cognitive decline in 12,688 participants in the ARIC Study who provided lung function measurements in 1990-1992. Cognitive tests were administered up to 7 times, and dementia was ascertained through 2019. We used shared parameter models to jointly fit proportional hazard models and linear mixed-effect models to estimate lung-function-associated dementia rate and cognitive change, respectively. Higher forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were associated with reduced dementia (n = 2,452 persons developed dementia); hazard ratios per 1-L increase in FEV1 and FVC were 0.79 (95% confidence interval (CI): 0.71, 0.89) and 0.81 (95% CI: 0.74, 0.89), respectively. Each 1-L increase in FEV1 and FVC was associated with a 0.08-standard deviation (SD) (95% CI: 0.05, 0.12) and a 0.05-SD (95% CI: 0.02, 0.07) attenuation of 30-year cognitive decline, respectively. A 1% increase in FEV1/FVC ratio was associated with 0.008-SD (95% CI: 0.004, 0.012) less cognitive decline. We observed statistical interaction between FEV1 and FVC, suggesting that cognitive declines depended on values of specific FEV1 and FVC (as compared with FEV1, FVC, or FEV1/FVC ratio models that suggested linear incremental associations). Our findings may have important implications for reducing the burden of cognitive decline that is attributable to environmental exposures and associated lung function impairment., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Study Objectives: Multiple sleep characteristics are informative of health, sleep characteristics cluster, and sleep health can be described as a composite of positive sleep attributes. We assessed the association between a sleep score reflecting multiple sleep dimensions, and mortality. We tested the hypothesis that more favorable sleep (higher sleep scores) is associated with lower mortality., Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) is a racially and ethnically-diverse multi-site, prospective cohort study of US adults. Sleep was measured using unattended polysomnography, 7-day wrist actigraphy, and validated questionnaires (2010-2013). 1726 participants were followed for a median of 6.9 years (Q1-Q3, 6.4-7.4 years) until death (171 deaths) or last contact. Survival models were used to estimate the association between the exposure of sleep scores and the outcome of all-cause mortality, adjusting for socio-demographics, lifestyle, and medical comorbidities; follow-up analyses examined associations between individual metrics and mortality. The exposure, a sleep score, was constructed by an empirically-based Principal Components Analysis on 13 sleep metrics, selected a priori., Results: After adjusting for multiple confounders, a 1 standard deviation (sd) higher sleep score was associated with 25% lower hazard of mortality (Hazard Ratio [HR]: 0.75; 95% Confidence interval: [0.65, 0.87]). The largest drivers of this association were: night-to-night sleep regularity, total sleep time, and the Apnea-Hypopnea Index., Conclusion: More favorable sleep across multiple characteristics, operationalized by a sleep score, is associated with lower risk of death in a diverse US cohort of adults. Results suggest that interventions that address multiple dimensions may provide novel approaches for improving health., (© The Author(s) 2023. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Fibroblast growth factor 23 (FGF23) concentration increases in response to declining kidney function to preserve normal phosphate concentrations. However, the etiological association of change in FGF23 concentration with mortality has not been examined in the general population., Design and Methods: We analyzed 5458 participants of the Atherosclerosis Risk in Communities Study who had intact FGF23 and estimated glomerular filtration rate (eGFR) assessed during midlife (visit 3, 1993-1995, mean age: 58 years) and late life (visit 5, 2011-2013, 76 years) to examine the association of FGF23 change over 18 years from mid-life to late life with the subsequent risk of mortality in late life using Cox regression models., Results: The median 18-year change in intact FGF23 was +17.3 pg/mL. During a median follow-up of 7.2 years following visit 5, 1176 participants died. In multivariable Cox models, elevated mortality was seen in the highest quartile of FGF23 change (ΔFGF23: ≥31.3 pg/mL) (adjusted hazard ratio (aHR): 1.61 (95%CI: 1.36-1.90), or 1.37 (1.15-1.64) after additionally adjusting for eGFR change, compared with the lowest quartile (≤6.4 pg/mL)). When both FGF23 change and FGF23 in late life were simultaneously entered into the Cox model, FGF23 in late life, but not FGF23 change, was an independent predictor of mortality; however, we observed a high correlation between FGF23 change from midlife to late life and FGF23 in late life (r = 0.77)., Conclusions: Serum intact FGF23 change from midlife to late life was associated with subsequent risk of mortality independent of decline in kidney function. Our findings further support the implications of FGF23 beyond its association with kidney function.

Study Objectives: To quantify the gender-specific associations between insomnia symptoms and subclinical atherosclerosis, measured by coronary artery calcium (CAC) scores, which has strong predictive value for incident cardiovascular disease., Methods: We analyzed data from 1,429 participants in the Multi-Ethnic Study of Atherosclerosis (MESA). Participants completed standardized questionnaires and underwent polysomnography (PSG) and 7-day actigraphy. Insomnia symptoms were defined as: self-reported trouble falling, staying or returning to sleep, early-morning awakenings, or hypnotic use, for ≥5 nights/week. MESA assessed CAC using computed tomography. We employed multivariable linear regression to model the probability of CAC >0 overall and to model the linear continuous effect among those with nonzero CAC., Results: Our sample was a mean age of 68.1 ± 9.1 years, 53.9% female, and 36.2% white, 28.0% black, 24.2% Hispanic, and 11.5% Chinese-American. Insomnia symptoms were present in 49.7% of men and 47.2% of women. In multivariable-adjusted analyses, insomnia symptoms was associated with an 18% higher prevalence of CAC (PR 1.18, 95% CI 1.04, 1.33) among females, but no association was observed among males (PR 1.00, 95% CI 0.91, 1.08). There was no evidence that the association between insomnia symptoms and prevalence of CAC >0 differed by objective sleep duration status (by single-night PSG or multi-night actigraphy) in females or males., Conclusions: We found that among women, insomnia symptoms were associated with an 18% higher prevalence of CAC compared to no insomnia. Insomnia symptoms were not associated with CAC prevalence in men. Additionally, there was no evidence that the association between insomnia symptoms and CAC score >0 differed by objective short sleep duration status., (© Sleep Research Society 2021. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Few studies have investigated the association of magnesium levels with incident peripheral artery disease (PAD) despite emerging evidence of magnesium contributing to vascular calcification. Moreover, no data are available on whether the magnesium-PAD relationship is independent of or modified by kidney function., Methods: A cohort of 11 839 participants free of PAD in the Atherosclerosis Risk in Communities Study at Visit 2 (1990-92) was studied. We investigated the association of serum magnesium and other bone-mineral metabolism markers [calcium, phosphorus, intact parathyroid hormone (iPTH) and intact fibroblast growth factor-23] with incident PAD using multivariable Cox proportional hazards regression., Results: Over a median of 23 years, there were 471 cases of incident PAD. The hazard ratio for incident PAD in Quartile 1 (<1.5 mEq/L) versus Quartile 4 (>1.7 mEq/L) of magnesium was 1.96 (95% confidence interval 1.40-2.74) after adjustment for potential confounders. Lower magnesium levels were associated with greater incidence of PAD, particularly in those with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 (n = 11 606). In contrast, the association was largely flat in those with eGFR <60 mL/min/1.73 m2 (n = 233) with P-for-interaction 0.03. Among bone-mineral metabolism markers, only higher iPTH showed an interaction with kidney function (P-for-interaction 0.01) and iPTH >65 pg/mL was significantly related to PAD only in those with eGFR <60 mL/min/1.73 m2., Conclusions: Lower magnesium was independently associated with incident PAD, but this association was significantly weaker in those with reduced kidney function. In contrast, higher iPTH levels were particularly related to PAD risk in this clinical population., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

We examined associations of individual- and neighborhood-level life-course (LC) socioeconomic status (SES) with incident dementia in the Atherosclerosis Risk in Communities cohort. Individual- and neighborhood-level SES were assessed at 3 life epochs (childhood, young adulthood, midlife) via questionnaire (2001-2002) and summarized into LC-SES scores. Dementia was ascertained through 2013 using cognitive exams, telephone interviews, and hospital and death certificate codes. Cox regression was used to estimate hazard ratios of dementia by LC-SES scores in race-specific models. The analyses included data from 12,599 participants (25% Black) in the United States, with a mean age of 54 years and median follow-up of 24 years. Each standard-deviation greater individual LC-SES score was associated with a 14% (hazard ratio (HR) = 0.86, 95% confidence interval (CI): 0.81, 0.92) lower risk of dementia in White and 21% (HR = 0.79, 95% CI: 0.71, 0.87) lower risk in Black participants. Education was removed from the individual LC-SES score and adjusted for separately to assess economic factors of LC-SES. A standard-deviation greater individual LC-SES score, without education, was associated with a 10% (HR = 0.90, 95% CI: 0.84, 0.97) lower dementia risk in White and 15% (HR = 0.85, 95% CI: 0.76, 0.96) lower risk in Black participants. Neighborhood LC-SES was not associated with dementia. We found that individual LC-SES is a risk factor for dementia, whereas neighborhood LC-SES was not associated., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Study Objectives: To examine the associations of sleep measures with hemoglobin A1c (HbA1c) among individuals with and without type 2 diabetes., Methods: Data were from 2049 Multi-Ethnic Study of Atherosclerosis participants taking part in a sleep ancillary study. Cross-sectional linear regression models examined associations of actigraphy estimates of sleep (sleep duration, variability, and maintenance efficiency) and polysomnography measures (obstructive sleep apnea [OSA] and hypoxemia) with HbA1c, stratified by diabetes status. Primary models were adjusted for demographics, lifestyle behaviors, and obesity., Results: Among individuals with diabetes (20 per cent population), those who slept <5 hr/night had greater HbA1c than those who slept 7-8 hr/night (7.44 vs. 6.98 per cent, ptrend = 0.04), with no attenuation of associations after adjusting for OSA/hypoxemia. In women with diabetes, but not men, those in the lowest quartile of sleep maintenance efficiency had greater HbA1c than those in the highest quartile of sleep maintenance efficiency (7.60 vs. 6.97 per cent, ptrend < 0.01). Among those without diabetes, individuals with severe OSA or in the highest quartile of hypoxemia had significantly greater HbA1c than those without OSA or who were in the lowest quartile of hypoxemia (5.76 vs. 5.66 per cent, ptrend = 0.01; 5.75 vs. 5.66 per cent, ptrend < 0.01, respectively). Associations did not meaningfully differ by race/ethnicity., Conclusions: Among individuals with diabetes, HbA1c was significantly higher in men and women with short sleep duration and in women with poor sleep maintenance efficiency, suggesting a role for behavioral sleep interventions in the management of diabetes. Among individuals without diabetes, untreated severe OSA/hypoxemia may adversely influence HbA1c.

Study Objectives: To investigate the prevalence of concurrent periodic limb movements during sleep (PLMS) and restless leg syndrome (RLS), as well as the prevalence of PLMS and RLS separately. Additionally, we document these prevalences by age, race/ethnicity, sex, and obesity status., Methods: Cross-sectional data from 2041 Multi-Ethnic Study of Atherosclerosis (MESA) Sleep ancillary study participants were used. PLMS (>15 periodic limb movements per hour of sleep) was measured by polysomnography. RLS symptoms were assessed using the 2009 International Restless Legs Syndrome Study Group clinical criteria., Results: The prevalence of RLS with PLMS was 6.7%, RLS alone 16.1%, and PLMS alone 21.2%. RLS with PLMS was prevalent in 7.0% of whites, 4.9% of blacks, 10.1% of Hispanics, and 3.3% of Chinese-Americans. In adjusted models, odds of RLS with PLMS was higher for those older than 67 years versus those younger (odds ratio [OR] [95% confidence interval [CI]] = 1.62 [1.09-2.40]). Relative to white participants, the prevalence of RLS with PLMS tended to be lower among blacks (0.56 [0.32-0.96]). The prevalence of concurrent RLS and PLMS did not statistically differ by sex or obesity status. RLS alone was more common in women., Conclusions: Approximately 7% of our sample had RLS with PLMS ("electro-clinical RLS"). This condition was more common among older individuals, did not vary by sex, and was less common among blacks. The findings provide some of the first information about the prevalence of concurrent RLS and PLMS in a community-based sample and show distinct sex and race associations for RLS versus electro-clinical RLS.

Study Objectives: To identify systematic biases across groups in objectively and subjectively measured sleep duration., Methods: We investigated concordance of self-reported habitual sleep duration compared with actigraphy- and single-night in-home polysomnography (PSG) across white, black, Hispanic, and Chinese participants in the Multi-Ethnic Study of Atherosclerosis., Results: Among 1910 adults, self-reported sleep duration, determined by differences between bed and wake times, was overestimated in all racial groups compared with PSG and actigraphy. Compared with whites (ρ = 0.45), correlations were significantly lower only in blacks (ρ = 0.28). Self-reporting bias for total sleep time compared with wrist actigraphy was 66 min (95% confidence interval [CI]: 61-71) for whites, 58 min (95% CI: 48-69) for blacks, 66 min (95% CI: 57-74) for Hispanics, and 60 min (95% CI: 49-70) for Chinese adults. Compared with PSG, self-reporting bias in whites at 73 min (95% CI: 67-79) was higher than in blacks (54 min [95% CI: 42-65]) and Chinese (49 min [95% CI: 37-61]) but not different from Hispanics (67 min [95% CI: 56-78]). Slight agreement/concordance was observed between self-reported and actigraphy-based total sleep time (kw = 0.14 for whites, 0.10 for blacks, 0.17 for Hispanics, and 0.11 for Chinese) and PSG (kw = 0.08 for whites, 0.04 for blacks, 0.05 for Hispanics, and 0.01 for Chinese) across race/ethnicity., Conclusions: Self-reported sleep duration overestimated objectively measured sleep across all races, and compared with PSG, overestimation is significantly greater in whites compared with blacks. Larger reporting bias reduces the ability to identify significant associations between sleep duration and health among blacks compared with whites. Sleep measurement property differences should be considered when comparing sleep indices across racial/ethnic groups.

Context: Vitamin D inadequacy is common in the adult population of the United States. Although the genetic determinants underlying vitamin D inadequacy have been studied in people of European ancestry, less is known about populations with Hispanic or African ancestry., Objective: The Trans-Ethnic Evaluation of Vitamin D (TRANSCEN-D) genomewide association study (GWAS) consortium was assembled to replicate genetic associations with 25-hydroxyvitamin D [25(OH)D] concentrations from the Study of Underlying Genetic Determinants of Vitamin D and Highly Related Traits (SUNLIGHT) meta-analyses of European ancestry and to identify genetic variants related to vitamin D concentrations in African and Hispanic ancestries., Design: Ancestry-specific (Hispanic and African) and transethnic (Hispanic, African, and European) meta-analyses were performed with Meta-Analysis Helper software (METAL)., Patients or Other Participants: In total, 8541 African American and 3485 Hispanic American (from North America) participants from 12 cohorts and 16,124 European participants from SUNLIGHT were included in the study., Main Outcome Measures: Blood concentrations of 25(OH)D were measured for all participants., Results: Ancestry-specific analyses in African and Hispanic Americans replicated single nucleotide polymorphisms (SNPs) in GC (2 and 4 SNPs, respectively). An SNP (rs79666294) near the KIF4B gene was identified in the African American cohort. Transethnic evaluation replicated GC and DHCR7 region SNPs. Additionally, the transethnic analyses revealed SNPs rs719700 and rs1410656 near the ANO6/ARID2 and HTR2A genes, respectively., Conclusions: Ancestry-specific and transethnic GWASs of 25(OH)D confirmed findings in GC and DHCR7 for African and Hispanic American samples and revealed findings near KIF4B, ANO6/ARID2, and HTR2A. The biological mechanisms that link these regions with 25(OH)D metabolism warrant further investigation.

Vitamin D is a fat-soluble vitamin that is synthesized in the skin with exposure to sunlight or is ingested from dietary supplements or food. There has been a dramatic increase in research on vitamin D, linking it with health outcomes as varied as reproductive function, infection, cardiovascular disease, and cancer. The study of vitamin D has generated much excitement, partly because there is an ideal intervention: Low levels may be common and can be remedied with widely available supplements. Determination of vitamin D status is complex and has advanced dramatically in the past 5 years. In this paper, we begin by describing important considerations for measurement of total 25-hydroxyvitamin D (25(OH)D), the biomarker traditionally assessed in epidemiologic studies. While 25(OH)D remains the most commonly measured biomarker, emerging evidence suggests that other related analytes may contribute to the characterization of an individual's vitamin D status (e.g., vitamin D-binding protein, bioavailable and free 25(OH)D, the C-3 epimer of 25(OH)D, 1,25-dihydroxyvitamin D, and 24,25-dihydroxyvitamin D). The measurement of these analytes is also complex, and there are important considerations for deciding whether their measurement is warranted in new research studies. Herein we discuss these issues and provide the reader with an up-to-date synthesis of research on vitamin D measurement options and considerations.

Context: Mineral and bone disorders (MBDs) might be relevant in the etiology of infection., Objective: To determine whether MBD biomarkers were associated with the incidence of hospitalization with infection. We also assessed the cross-sectional association between MBD biomarker levels and kidney function., Design, Setting, Participants: Community-based cohort study of 11,218 participants with an estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73m2 in the Atherosclerosis Risk in Communities study. We assessed the cross-sectional associations of five MBD markers-fibroblast growth factor 23 (FGF23), 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), calcium corrected for hypoalbuminemia, and phosphorus-with eGFR from 1990 to 1992 and their longitudinal associations with incident hospitalization with infection in 1990 to 2013., Main Outcome: Incident hospitalization with infection., Results: In age-, sex-, and race-adjusted models, lower eGFRs were significantly associated with greater levels of FGF23, PTH, and corrected calcium but not 25(OH)D or phosphorus. During follow-up, 5078 hospitalizations with infection occurred. In fully adjusted Cox models, with the second quartile as the reference, the hazard ratio (HR) was significantly greater in the highest quartile of FGF23 [HR, 1.12; 95% confidence interval (CI), 1.03 to 1.21], PTH (HR, 1.09; 95% CI, 1.01 to 1.18), and corrected calcium (HR, 1.11; 95% CI, 1.03 to 1.20), and lowest quartile for 25(OH)D (HR, 1.11; 95% CI, 1.03 to 1.21). The association with phosphorus was significant only when the outcome was restricted to primary diagnosis of infection. These findings were consistent across subgroups of age, sex, race, and eGFR (<60 vs ≥60 mL/min/1.73 m2)., Conclusions: MBD biomarkers were associated with eGFR and the subsequent risk of infection, supporting MBD involvement in the etiology of infection., (Copyright © 2017 Endocrine Society)

Context: Cardiovascular outcomes in mild thyroid dysfunction (treatment controversial) and moderate or severe dysfunction (treatment standard) remain uncertain., Objective: To examine cross-sectional and prospective associations of thyroid function with cardiovascular risk factors and events., Design: In the Atherosclerosis Risk in Communities Study, we measured concentrations of thyrotropin, free thyroxine, and total triiodothyronine (T3) in stored serum samples originally collected in 1990-1992. We used multivariable linear regression to assess cross-sectional associations of thyroid function with cardiovascular risk factors and Cox regression to assess prospective associations with cardiovascular events. Follow-up occurred through 31 December 2014., Setting: General community., Participants: Black and white men and women from the United States, without prior myocardial infarction (MI), stroke, or heart failure., Main Outcomes and Measures: Cross-sectional outcomes were blood pressure, glycemic markers, and blood lipids. Prospective outcomes were adjudicated fatal and nonfatal MI and stroke., Results: Among 11,359 participants (57 ± 6 years, 58% women), thyroid function was more strongly associated with blood lipids than blood pressure or glycemic measures. Mean adjusted differences in low-density lipoprotein cholesterol were +15.1 (95% confidence interval: 10.5 to 19.7) and +3.2 (0.0 to 6.4) mg/dL in those with moderate/severe and mild chemical hypothyroidism, relative to euthyroidism; an opposite pattern was seen in hyperthyroidism. Similar differences were seen in triglycerides and non-high-density lipoprotein cholesterol. With a 22.5-year median follow-up, 1102 MIs and 838 strokes occurred, with similar outcomes among baseline thyroid function groups and by T3 concentrations., Conclusions: Hypothyroidism is associated with hyperlipidemia, but the magnitude is small in mild chemical hypothyroidism, and cardiovascular outcomes are similar between thyroid function groups., (Copyright © 2017 Endocrine Society)

Experiences of discrimination are associated with increased risk of adverse health outcomes; however, it is unknown whether discrimination is related to incident type 2 diabetes mellitus (diabetes). We investigated the associations of major experiences of discrimination (unfair treatment in 6 situations) and everyday discrimination (frequency of day-to-day experiences of unfair treatment) with incident diabetes among 5,310 participants from the Multi-Ethnic Study of Atherosclerosis, enrolled in 2000-2002. Using Cox proportional hazards models, we estimated hazard ratios and confidence intervals, adjusting for demographic factors, depressive symptoms, stress, smoking, alcohol, physical activity, diet, waist circumference, and body mass index. Over a median follow-up of 9.4 years, 654 diabetes cases were accrued. Major experiences of discrimination were associated with greater risk of incident diabetes when modeled continuously (for each additional experience of discrimination, hazard ratio = 1.09, 95% confidence interval: 1.01, 1.17) or categorically (for ≥2 experiences vs. 0, hazard ratio = 1.34, 95% confidence interval: 1.08, 1.66). Similar patterns were observed when evaluating discrimination attributed to race/ethnicity or to a combination of other sources. Everyday discrimination was not associated with incident diabetes. In conclusion, major experiences of discrimination were associated with increased risk of incident diabetes, independent of obesity or behavioral and psychosocial factors. Future research is needed to explore the mechanisms of the discrimination-diabetes relationship., (© The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Context: Low 25-hydroxyvitamin D [25(OH)D] is associated with coronary heart disease (CHD) in people who are white and Chinese but not black or Hispanic. Vitamin D binding globulin (VDBG) avidly binds 25(OH)D, reducing its bioavailability, and differs in isoform and concentration by race., Objective: Evaluate associations of VDBG with CHD and whether accounting for VDBG or estimating bioavailable 25(OH)D explains the heterogeneity of the association of 25(OH)D with CHD., Design and Setting: We conducted a case-cohort study within the Multi-Ethnic Study of Atherosclerosis. Participants with an incident CHD event over 12 years of follow-up (n = 538) and a randomly assigned subcohort (n = 999) were included. We measured baseline 25(OH)D, VDBG, and isoforms using mass spectrometry and estimated bioavailable 25(OH)D from published equations., Results: VDBG was associated with an increased risk of CHD [hazard ratio, 1.77 (95% confidence interval, 1.46 to 2.14) per standard deviation increment, P < 0.0001], without evidence of heterogeneity by race or isoform (each P for interaction > 0.1). Low total 25(OH)D was differentially associated with CHD events, by race, with or without adjustment for VDBG (P for interaction = 0.04 or 0.05, respectively). Associations of 25(OH)D with CHD were strengthened with adjustment for VDBG among participants who were white or Chinese, and bioavailable 25(OH)D was associated with CHD events only among white participants., Conclusions: High VDBG concentration was associated with CHD events in all racial and ethnic groups. Incorporation of VDBG strengthened existing associations of 25(OH)D with CHD but did not explain racial heterogeneity in associations of 25(OH)D with CHD., (Copyright © 2017 Endocrine Society)

Introduction: Cigarette smoking, various metabolic and lipid-related factors and hypertension are well-recognized cardiovascular disease (CVD) risk factors. Since smoking affects many of these factors, use of a single imprecise smoking metric, for example, ever or never smoked, may allow residual confounding and explain inconsistencies in current assessments of interactions., Methods: Using a comprehensive model in pack-years and cigarettes/day for the complex smoking-related relative risk (RR) of CVD to reduce residual confounding, we evaluated interactions with non-tobacco risk factors, including additive (non-synergistic) and multiplicative (synergistic) forms. Data were from the prospective Atherosclerosis Risk in Communities (ARIC) Study from four areas of the United States recruited in 1987-1989 with follow-up through 2008. Analyses included 14 127 participants, 207 693 person-years and 2857 CVD events., Results: Analyses revealed distinct interactions with smoking: including statistical consistency with additive (body mass index [BMI], waist to hip ratio [WHR], diabetes mellitus [DM], glucose, insulin, high density lipoproteins [HDL] and HDL(2)); and multiplicative (hypertension, total cholesterol [TC], low density lipoproteins [LDLs], apolipoprotein B [apoB], TC to HDL ratio and HDL(3)) associations, as well as indeterminate (apolipoprotein A-I [apoA-I] and triglycerides) associations., Conclusions: The forms of the interactions were revealing but require confirmation. Improved understanding of joint associations may help clarify the public health burden of smoking for CVD, links between etiologic factors and biological mechanisms, and the consequences of joint exposures, whereby synergistic associations highlight joint effects and non-synergistic associations suggest distinct contributions., Implications: Joint associations for cigarette smoking and non-tobacco risk factors were distinct, revealing synergistic/multiplicative (hypertension, TC, LDL, apoB, TC/HDL, HDL(3)), non-synergistic/additive (BMI, WHR, DM, glucose, insulin, HDL, HDL(2)) and indeterminate (apoA-I and TRIG) associations. If confirmed, these results may help better define the public health burden of smoking on CVD risk and identify links between etiologic factors and biologic mechanisms, where synergistic associations highlight joint impacts and non-synergistic associations suggest distinct contributions from each factor., (Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Context: Physical activity (PA) is associated with 25-hydroxyvitamin D [25(OH)D] levels. Both are associated with atherosclerotic cardiovascular disease (ASCVD), but their joint association with ASCVD risk is unknown., Objective: To examine the relationship between PA and 25(OH)D, and assess effect modification of 25(OH)D and PA with ASCVD., Design: Cross-sectional and prospective study., Setting: Community-dwelling cohort., Participants: A total of 10,342 participants free of ASCVD, with moderate- to vigorous-intensity PA assessed (1987 to 1989) and categorized per American Heart Association (AHA) guidelines (recommended, intermediate, or poor)., Main Outcome Measures: Serum 25(OH)D levels (1990 to 1992) and ASCVD events (i.e., incident myocardial infarction, fatal coronary disease, or stroke) through 2013., Results: Participants had mean age of 54 years, and were 57% women, 21% black, 30% 25(OH)D deficient [<20 ng/mL (<50 nmol/L)], and <40% meeting AHA-recommended PA. PA was linearly associated with 25(OH)D levels in whites. Whites meeting recommended PA were 37% less likely to have 25(OH)D deficiency [relative risk, 0.63 (95% confidence interval [CI], 0.56, 0.71)]; there was no significant association in blacks. Over 19.3 years of follow-up, 1800 incident ASCVD events occurred. Recommended PA was associated with reduced ASCVD risk [hazard ratio [HR], 0.78 (95% CI, 0.65, 0.93) and 0.76 (95% CI, 0.62, 0.93)] among participants with intermediate [20 to <30 ng/mL (50 to <75 nmol/L)] and optimal [≥30 ng/mL (≥75 nmol/L)] 25(OH)D, respectively, but not among those with deficient 25(OH)D (P for interaction = 0.04)., Conclusion: PA is linearly associated with higher 25(OH)D levels in whites. PA and 25(OH)D may have synergistic beneficial effects on ASCVD risk., (Copyright © 2017 by the Endocrine Society)

Background: Quantifying the variability of biomarkers is important, as high within-person variability can lead to misclassification of individuals. Short-term variability of important markers of vitamin D metabolism is relatively unknown., Methods: A repeatability study was conducted in 160 Atherosclerosis Risk in Communities study participants (60% female, 28% black, mean age 76 years). Fasting serum was drawn at 2 time points, a median of 6 (range 3-13) weeks apart. Vitamin D binding protein (VDBP) and 25-hydroxyvitamin D [25(OH)D] were measured by LC-MS, fibroblast growth factor (FGF23) and parathyroid hormone (PTH) by enzyme-linked immunoassay, and calcium and phosphorus by Roche Cobas 6000. Free and bioavailable 25(OH)D were calculated. We calculated the within-person CV (CV W ), intraclass correlation coefficient (ICC), Spearman rank correlation coefficient (r), and percent reclassified., Results: The CV W was lowest for calcium (2.0%), albumin (3.6%), 25(OH)D (6.9%), VDBP (7.0%) and phosphorus (7.6%); intermediate for free 25(OH)D (9.0%) and bioavailable 25(OH)D (9.9%); and highest for PTH (16.7%) and FGF23 (17.8%). Reclassification was highest for PTH, VDBP, and phosphorus (all 7.5%). The ICC and r were highest (≥0.80) for 25(OH)D, free 25(OH)D, bioavailable 25(OH)D and PTH, but somewhat lower (approximately 0.60-0.75) for the other biomarkers., Conclusions: Six-week short-term variability, as assessed by CV W , was quite low for VDBP, calcium and phosphorus, but fairly high for FGF23 and PTH. As such, multiple measurements of FGF23 and PTH may be needed to minimize misclassification. These results provide insight into the extent of potential misclassification of vitamin D markers in research and clinical settings., (© 2016 American Association for Clinical Chemistry.)

Study Objectives: To investigate the cross-sectional relationship between objectively measured sleep characteristics and multiple indices of adiposity in racially/ethnically diverse older adults within the MESA Sleep study (n = 2,146)., Methods: 7-day actigraphy was used to assess sleep duration, sleep efficiency, and night-to-night variability. Body mass index (BMI), waist circumference, and total body fat were modeled continuously and according to obesity cut-points. Models were adjusted for demographic, socioeconomic, and behavioral variables., Results: Participants who slept less than 6 hours a night had significantly higher BMI, waist circumference, and body fat relative to those who slept 7-8 hours. Those who slept less than 5 hours had a 16% higher prevalence of general obesity (BMI ≥ 30 vs. < 25 kg/m(2)) (95% [CI]: 0.08-0.24) and a 9% higher prevalence of abdominal obesity (waist circumference: women ≥ 88 centimeters, men ≥ 102 centimeters; 95% CI: 0.03-0.16) compared to those who slept 7-8 hours. Results were similar for sleep efficiency and night-to-night sleep variability., Conclusions: Among an older multi-ethnic cohort, we found robust associations across multiple indices of sleep and adiposity. Targeting sleep characteristics may be of benefit in obesity interventions, but more research is needed to rule out reverse causality., (© 2016 Associated Professional Sleep Societies, LLC.)

Aims: To assess the prospective association between circulating 25-hydroxyvitamin D [25(OH)D] and atrial fibrillation (AF) risk., Methods and Results: We studied 12 303 participants from the Atherosclerosis Risk in Communities study without baseline AF (1990-92). Baseline serum total 25(OH)D was measured using mass spectrometry. Incident AF cases were identified from electrocardiograms, hospital discharge codes, and death certificates through 2012. We estimated hazard ratios (HRs) and 95% confidence intervals (95% CIs) of AF across clinical categories of serum 25(OH)D concentrations with multivariable Cox models, and tested interactions by age, race, and sex. We meta-analysed our results with those from published prospective studies that reported associations between 25(OH)D and AF risk. During a median follow-up of 21 years, we identified 1866 AF events. In multivariable models, deficient 25(OH)D status (<20 ng/mL), compared with optimal levels (≥30 ng/mL), was not associated with AF risk (HR, 95% CI: 1.10, 0.96-1.26). A significant interaction of 25(OH)D concentrations with age (P = 0.01), but not with race or sex (P > 0.40), was identified, with higher risk of AF among those with deficient 25(OH)D status in younger (HR, 95% CI: 1.35, 1.05-1.73) but not older individuals (HR, 95% CI: 1.02, 0.86-1.21). A meta-analysis of these results and four prospective studies did not support a clinically relevant association of circulating 25(OH)D with AF risk [pooled HR, 95%CI: 1.04, 1.00-1.08, per 1 SD lower 25(OH)D]., Conclusion: Low serum 25(OH)D was not associated with incident AF in a community-based cohort and in a meta-analysis of prospective studies. A possible association in younger individuals warrants further investigation., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Background: Although venous stasis is a risk factor for venous thromboembolism (VTE) and orthostatic hypotension (OH) can cause venous stasis, to our knowledge no study has examined the relationship between OH and VTE risk. We sought to quantify the association between OH and VTE (deep vein thrombosis or pulmonary embolism) using data from 2 large, prospective cohort studies: the Cardiovascular Health Study (CHS) and the Atherosclerosis Risk in Communities (ARIC) Study. We hypothesized that OH was positively associated with incident VTE., Methods: We measured OH-defined as a drop in systolic blood pressure (SBP) of at least 20 mm Hg or diastolic blood pressure (DBP) of at least 10 mm Hg within 3 minutes of standing-in participants aged 45-64 years in ARIC (n = 12,480) and ≥65 years in CHS (n = 5,027) at baseline visits (1987-1989 in ARIC; 1989-1990 and 1992-1993 in CHS), and followed participants for incident VTE (n = 568 in ARIC through 2011 and n = 148 in CHS through 2001). We calculated adjusted hazard ratios (HRs) and their 95% confidence intervals (CIs) for incident VTE in relation to OH status., Results: In CHS, there was a positive association between OH status and incident VTE (HR for VTE = 1.74 (95% CI: 1.20-2.51)). In contrast, there was no association between OH and VTE in the ARIC study (HR for VTE = 0.97 (95% CI: 0.70-1.33))., Conclusions: Community-dwelling older adults with OH had a moderately increased risk of VTE. These results were not seen in a population-based middle-aged cohort., (© American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Study Objectives: Prospective data evaluating abnormal sleep quality and quantity with cognitive decline are limited because most studies used subjective data and/or had short follow-up. We hypothesized that, over 15 y of follow-up, participants with objectively measured obstructive sleep apnea (OSA) and other indices of poor sleep quantity and quality would experience greater decline in cognitive functioning than participants with normal sleep patterns., Methods: ARIC participants (n = 966; mean age 61 y, 55% women) with in-home polysomnography (1996-1998) and repeated cognitive testing were followed for 15 y. Three cognitive tests (Delayed Word Recall, Word Fluency, and Digit Symbol Substitution) were administered at two time points (1996-1998 and 2011-2013). Ten additional cognitive tests were administered at the 2011-2013 neurocognitive examination. OSA was modeled using established clinical OSA severity categories. Multivariable linear regression was used to explore associations of OSA and other sleep indices with change in cognitive tests between the two assessments., Results: A median of 14.9 y (max: 17.3) passed between the two cognitive assessments. OSA category and additional indices of sleep (other measures of hypoxemia and disordered breathing, sleep fragmentation, sleep duration) were not associated with change in any cognitive test. Analyses of OSA severity categories and 10 cognitive tests administered only in 2011-2013 also showed little evidence of an association., Conclusions: Overall, abnormal sleep quality and quantity at midlife was not related to cognitive decline and later-life cognition. The effect of adverse sleep quality and quantity on cognitive decline among the elderly remains to be determined., (© 2016 Associated Professional Sleep Societies, LLC.)

Background: Vitamin D deficiency is associated with poor bone health and other adverse health outcomes; however, the associations are greatly attenuated in black vs white individuals. One possible explanation for this attenuation is different concentrations of bioavailable vitamin D metabolites in plasma, which are estimated with equations that include the total concentration of vitamin D binding globulin (VDBG) and haplotype-specific dissociation constants., Methods: We developed a method to quantify VDBG with LC-MS/MS that could also identify the haplotypes/isoforms of VDBG present. We validated the method according to recent recommendations for publications of biomarker studies. We determined serum VDBG concentrations in samples from the Atherosclerosis Risk in Communities cohort and compared the results with a widely used monoclonal immunoassay., Results: With 10 μL of serum or plasma, the lower limit of quantification for the assay (<20% CV) was 71 μg/mL. The assay was linear from 62 to 434 μg/mL, with total imprecision of 7.3-9.0% CV at approximately 250 μg/mL. Significant hemolysis interfered with quantification. The identification of isoforms was 97% concordant with genotyping (κ coefficient). Method comparison with immunoassay revealed significant isoform-specific effects in the immunoassay. Mean concentrations (SD) of VDBG by mass spectrometry were similar in whites and blacks [262 (25) vs 266 (35) μg/mL, respectively; P = 0.43]., Conclusions: Validated mass spectrometric methods for the quantification of proteins in human samples can provide additional information beyond immunoassay. Counter to prior observations by immunoassay, VDBG concentrations did not vary by race., (© 2015 American Association for Clinical Chemistry.)

Context: A single measurement of 25-hydroxyvitamin D (25 [OH] D) may not accurately reflect long-term vitamin D status. Little is known about change in 25(OH)D levels over time, particularly among blacks., Objective: The objective of the study was to determine the longitudinal changes in 25(OH)D levels among Atherosclerosis Risk in Communities (ARIC) study participants., Design: This was a longitudinal study., Setting: The study was conducted in the general community., Participants: A total of 9890 white and 3222 black participants at visit 2 (1990-1992), 888 whites and 876 blacks at visit 3 (1993-1994), and 472 blacks at the brain visit (2004-2006) participated in the study., Main Outcome Measure: The 25(OH)D levels were measured, and regression models were used to assess the associations between clinical factors and longitudinal changes in 25(OH)D., Results: Vitamin D deficiency (<50 nmol/L [<20 ng/mL]) was seen in 23% and 25% of whites at visits 2 and 3, and in 61%, 70%, and 47% of blacks at visits 2, 3, and the brain visit, respectively. The 25(OH)D levels were correlated between visits 2 and 3 (3 y interval) among whites (r = 0.73) and blacks (r = 0.66). Among blacks, the correlation between visit 2 and the brain visit (14 y interval) was 0.33. Overall, increases in 25(OH)D levels over time was associated with male gender, use of vitamin D supplements, greater physical activity, and higher high-density lipoprotein-cholesterol (P < .001). Decreases in 25(OH)D levels over time were associated with current smoking, higher body mass index, higher education, diabetes, and hypertension (all P < .05)., Conclusions: Among US blacks and whites, 25(OH)D levels remained relatively stable over time. Certain modifiable lifestyle factors were associated with change in 25(OH)D levels over time.

Perceived discrimination is positively related to cardiovascular disease (CVD) risk factors; its relationship with incident CVD is unknown. Using data from the Multi-Ethnic Study of Atherosclerosis, a population-based multiethnic cohort study of 6,508 adults aged 45-84 years who were initially free of clinical CVD, we examined lifetime discrimination (experiences of unfair treatment in 6 life domains) and everyday discrimination (frequency of day-to-day occurrences of perceived unfair treatment) in relation to incident CVD. During a median 10.1 years of follow-up (2000-2011), 604 incident events occurred. Persons reporting lifetime discrimination in ≥2 domains (versus none) had increased CVD risk, after adjustment for race/ethnicity and sociodemographic factors, behaviors, and traditional CVD risk factors (hazard ratio (HR) = 1.36, 95% confidence interval (CI): 1.09, 1.70) and after control for chronic stress and depressive symptoms (HR = 1.28, 95% CI: 1.01, 1.60). Reported discrimination in 1 domain was unrelated to CVD (HR = 1.05, 95% CI: 0.86, 1.30). There were no differences by race/ethnicity, age, or sex. In contrast, everyday discrimination interacted with sex (P = 0.03). Stratified models showed increased risk only among men (for each 1-standard deviation increase in score, adjusted HR = 1.14, 95% CI: 1.03, 1.27); controlling for chronic stress and depressive symptoms slightly reduced this association (HR = 1.11, 95% CI: 0.99, 1.25). This study suggests that perceived discrimination is adversely related to CVD risk in middle-aged and older adults., (© The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: There is limited research on racial/ethnic variation in sleep disturbances. This study aimed to quantify the distributions of objectively measured sleep disordered breathing (SDB), short sleep duration, poor sleep quality, and self-reported sleep disturbances (e.g., insomnia) across racial/ethnic groups., Design: Cross-sectional study., Setting: Six US communities., Participants: Racially/ethnically diverse men and women aged 54-93 y in the Multi-Ethnic Study of Atherosclerosis Sleep Cohort (n = 2,230)., Interventions: N/A., Measurements and Results: Information from polysomnography-measured SDB, actigraphy-measured sleep duration and quality, and self-reported daytime sleepiness were obtained between 2010 and 2013. Overall, 15.0% of individuals had severe SDB (apnea-hypopnea index [AHI] ≥ 30); 30.9% short sleep duration (< 6 h); 6.5% poor sleep quality (sleep efficiency < 85%); and 13.9% had daytime sleepiness. Compared with Whites, Blacks had higher odds of sleep apnea syndrome (AHI ≥ 5 plus sleepiness) (sex-, age-, and study site-adjusted odds ratio [OR] = 1.78, 95% confidence interval [CI]: 1.20, 2.63), short sleep (OR = 4.95, 95% CI: 3.56, 6.90), poor sleep quality (OR = 1.57, 95% CI: 1.00, 2.48), and daytime sleepiness (OR = 1.89, 95% CI: 1.38, 2.60). Hispanics and Chinese had higher odds of SDB and short sleep than Whites. Among non-obese individuals, Chinese had the highest odds of SDB compared to Whites. Only 7.4% to 16.2% of individuals with an AHI ≥ 15 reported a prior diagnosis of sleep apnea., Conclusions: Sleep disturbances are prevalent among middle-aged and older adults, and vary by race/ethnicity, sex, and obesity status. The high prevalence of sleep disturbances and undiagnosed sleep apnea among racial/ethnic minorities may contribute to health disparities., (© 2015 Associated Professional Sleep Societies, LLC.)

Despite reportedly having less tobacco exposure compared with whites, African Americans account for a disproportionate number of smoking-related deaths. The purpose of this study was to compare the prospective associations between smoking and cardiovascular risk in whites and African Americans. Smoking status was obtained on 14,200 participants from the Atherosclerosis Risk in Communities Study. Incidence of cardiovascular disease (CVD) was ascertained from 1987 through 2007. Adjusted Cox proportional hazard models were used to estimate the CVD incidence associated with smoking behavior. Over 17 years' follow-up, there were 2,777 cardiovascular events. In men, compared with never smoking, current smoking was independently associated with 67% (95% confidence interval (CI): 43, 95) and 72% (95% CI: 30, 126) greater risk of CVD in whites and African Americans, respectively. In women, the smoking-related cardiovascular risk was higher: 136% (95% CI: 88, 196) and 169% (95% CI: 126, 219) in African-American and white women, respectively. Early age at smoking initiation was independently associated with increased risk among all participants irrespective of race. Smoking cessation during follow-up was equally beneficial in both whites and African Americans. African Americans who smoke incur a similar level of cardiovascular risk as white smokers and would derive the same benefits from quitting as whites.

Recently, there has been interest in determining whether diet is associated with the risk of venous thromboembolism. The article by Varraso et al. (Am J Epidemiol. 2012;175(2):114-126) published in this issue of the Journal is an important contribution to this literature. In this commentary, the author discusses the findings of Varraso et al. within the context of the existing literature and posits epidemiologic explanations for why investigators might have failed to identify strong associations between diet and venous thromboembolism.

Functional biomarkers like large artery elasticity (LAE) and small artery elasticity (SAE) may predict cardiovascular disease (CVD) events beyond blood pressure. The authors examined the prognostic value of LAE and SAE for clinical CVD events among 6,235 Multi-Ethnic Study of Atherosclerosis participants who were initially aged 45-84 years and without symptomatic CVD. LAE and SAE were derived from diastolic pulse contour analysis. During a median 5.8 years of follow-up between 2000 and 2008, 454 adjudicated CVD events occurred, including 256 cases of coronary heart disease (CHD), 93 strokes, and 126 heart failures (multiple diagnoses were possible). After adjustment for age, race/ethnicity, sex, clinic, height, heart rate, body mass index, systolic and diastolic blood pressure, use of antihypertensive and cholesterol-lowering medications, smoking, total cholesterol, high density lipoprotein cholesterol, triglycerides, diabetes, and high-sensitivity C-reactive protein, the hazard ratio for any CVD per standard-deviation increase in SAE was 0.71 (95% confidence interval: 0.61, 0.83; P < 0.0001). The lowest (stiffest) SAE quartile had a hazard ratio of 2.28 (95% confidence interval: 1.55, 3.36) versus the highest (most elastic) quartile. The net reclassification index, conditional on base risk, was 0.11. SAE was significantly associated with future CHD, stroke, and heart failure. After adjustment, LAE was not significantly related to CVD. In asymptomatic participants free of overt CVD, lower SAE added prognostic information for CVD, CHD, stroke, and heart failure events.

Background: The incidence of venous thromboembolism (VTE) is increased with severe kidney disease, but whether less-severe chronic kidney disease (CKD) increases the risk of VTE is less certain., Methods: We studied this in a prospective cohort of 10 700 whites and African Americans, aged 53-75 years, attending Visit 4 (1996-98) of the Atherosclerosis Risk in Communities Study. Estimated glomerular filtration rate (eGFR) values were estimated from prediction equations based on serum creatinine (eGFR(creat)) or cystatin C (eGFR(cys)). Normal kidney function was defined as eGFR ≥90 ml/min/1.73 m(2), mildly decreased kidney function as eGFR between 60 and 89 ml/min/1.73 m(2) and Stage 3 to 4 CKD as eGFR between 15 and 59 ml/min/1.73 m(2). VTE occurrence (n = 228) was ascertained over a median of 8.3 years., Results: For eGFR(cys), the age-, race- and sex-adjusted hazard ratios of total VTE were 1.0, 1.40 and 1.94 (P trend = 0.003) for normal kidney function, mildly impaired kidney function and Stage 3 to 4 CKD, respectively. These respective hazard ratios were moderately attenuated to 1.0, 1.26 and 1.60 (P trend = 0.04) with adjustment for hormone replacement therapy, diabetes and body mass index. Associations between CKD based on eGFR(cys) and VTE were slightly stronger for idiopathic VTE than for secondary VTE. In contrast, CKD based on eGFR(creat) was not associated with total VTE occurrence., Conclusions: Stage 3 to 4 CKD, based on eGFR(cys) but not eGFR(creat), was associated with an approximately 1.6-fold increased risk of VTE.

This study examined how adiposity influences racial/ethnic differences in diabetes incidence by exploring whether relations between anthropometric measures and incident diabetes vary by race/ethnicity. Data from the Multi-Ethnic Study of Atherosclerosis initiated in 2000 (n = 5,446 US men and women aged 45-84 years) were analyzed by using proportional hazards and Poisson regression. The diabetes incidence rate was 2/100 person-years (n = 479 cases). Interactions were present between race and anthropometry (P-interaction((race x body mass index)) = 0.002). The slope of incident diabetes per anthropometric unit was greatest for Chinese, less for whites and Hispanics, and still less for blacks. For small waist, risk of incident diabetes was <1/100 person-years for all racial/ethnic groups. At intermediate waist levels, Chinese had the highest and whites the lowest rates of incident diabetes. At the respective 95th percentiles of waist circumference, risk of incident diabetes per 100 person-years was 3.9 for Chinese (104 cm), 3.5 for whites (121 cm), 5.0 for blacks (125 cm), and 5.3 for Hispanics (121 cm). Adiposity influenced relative diabetes occurrence across racial/ethnic groups, in that Chinese had a steeper diabetes risk per unit of adiposity. However, the generally low level of adiposity in Chinese led to a relatively low diabetes occurrence.

The authors used data from the Multi-Ethnic Study of Atherosclerosis and latent trajectory class modeling to determine patterns of neighborhood poverty over 20 years (1980-2000 residential history questionnaires were geocoded and linked to US Census data). Using these patterns, the authors examined 1) whether trajectories of neighborhood poverty were associated with differences in the amount of subclinical atherosclerosis (common carotid intimal-media thickness) and 2) associated risk factors (body mass index, hypertension, diabetes, current smoking) at baseline (January 2000-August 2002). The authors found evidence of 5 stable trajectory groups with differing levels of neighborhood poverty ( approximately 6%, 12%, 20%, 30%, and 45%) and 1 group with 29% poverty in 1980 and approximately 11% in 2000. Mostly for women, higher cumulative neighborhood poverty was generally significantly associated with worse cardiovascular outcomes. Trends generally persisted after adjustment for adulthood socioeconomic position and race/ethnicity, although they were no longer statistically significant. Among women who had moved during the 20 years, the long-term measure had stronger associations with outcomes (except smoking) than a single, contemporaneous measure. Results indicate that cumulative 20-year exposure to neighborhood poverty is associated with greater cardiovascular risk for women. In residentially mobile populations, single-point-in-time measures underestimate long-term effects.