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Papers by Charles Eaton

Journal of Women's Health, 2019

Background: Postmenopausal women represent the highest population-based burden of cardiovascular ... more Background: Postmenopausal women represent the highest population-based burden of cardiovascular disease, including sudden cardiac death (SCD). Our understanding of the etiology and risk factors contributing to fatal coronary heart disease (CHD) and SCD, particularly among women, is limited. This study examines the association between dietary magnesium intake and fatal CHD and SCD. Materials and Methods: We examined 153,569 postmenopausal women who participated in the Women's Health Initiative recruited between 1993 and 1998. Magnesium intake at baseline was assessed using a validated food frequency questionnaire, adjusting for energy via the residual method. Fatal CHD and SCD were identified over an average follow-up of 10.5 years. Results: For every standard deviation increase in magnesium intake, there was statistically significant risk reduction, after adjustment for confounders, of 7% for fatal CHD (hazard ratio [HR] 0.93, 95% confidence interval [CI] 0.89-0.97), and 18% risk reduction for SCD (HR 0.82, 95% CI 0.58-1.15) the latter of which did not reach statistical significance. In age-adjusted quartile analysis, women with the lowest magnesium intake (189 mg/day) had the greatest risk for fatal CHD (HR 1.54, 95% CI 1.40-1.69) and SCD (HR 1.70, 95% CI 0.94-3.07). This association was attenuated in the fully adjusted model, with HRs of 1.19 (95% CI 1.06-1.34) for CHD and 1.24 (95% CI 0.58-2.65) for SCD for the lowest quartile of magnesium intake. Conclusions: This study provides evidence of a potential inverse association between dietary magnesium and fatal CHD and a trend of magnesium with SCD in postmenopausal women. Future studies should confirm this association and consider clinical trials to test whether magnesium supplementation could reduce fatal CHD in high-risk individuals.

Journal of Clinical and Translational Science, 2018

OBJECTIVES/SPECIFIC AIMS: The aim of this study is to determine whether quantitative measures of ... more OBJECTIVES/SPECIFIC AIMS: The aim of this study is to determine whether quantitative measures of knee structures including effusion, bone marrow lesions, cartilage, and meniscal damage can improve upon an existing model of demographic and clinical characteristics to classify accelerated knee osteoarthritis (AKOA). METHODS/STUDY POPULATION: We conducted a case-control study using data from baseline and four annual follow-up visits from the osteoarthritis initiative. Participants had no radiographic knee osteoarthritis (KOA) at baseline. AKOA is defined as progressing from no KOA to advance-stage KOA in at least 1 knee within 48 months. AKOA knees were matched 1:1 based on sex to (1) participants who did not develop KOA within 48 months and (2) participants who developed KOA but not AKOA. Analyses were person based. Classification and regression tree analysis was used to determine the important variables and percent of variance explained. RESULTS/ANTICIPATED RESULTS: A previous classi...

The Journal of Rheumatology, 2018

Objective.We examined the longterm effectiveness of corticosteroid or hyaluronic acid injections ... more Objective.We examined the longterm effectiveness of corticosteroid or hyaluronic acid injections in relieving symptoms among persons with knee osteoarthritis (OA).Methods.Using Osteoarthritis Initiative data, a new-user design was applied to identify participants initiating corticosteroid or hyaluronic acid injections (n = 412). Knee symptoms (pain, stiffness, function) were measured using The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). We used marginal structural models adjusting for time-varying confounders to estimate the effect on symptoms of newly initiated injection use compared to nonusers over 2 years of followup.Results.Among 412 participants initiating injections, 77.2% used corticosteroid injections and 22.8% used hyaluronic acid injections. About 18.9% had additional injection use after initiation, but switching between injection types was common. Compared to nonusers, on average, participants initiating a corticosteroid injection experienced ...

The Journal of rheumatology, 2018

To examine the association between leisure-time physical activity (PA) and survival to age 85 wit... more To examine the association between leisure-time physical activity (PA) and survival to age 85 with mobility limitation or death before age 85 after total knee (TKR) or total hip replacement (THR) for osteoarthritis (OA). This was a prospective study among participants from the Women's Health Initiative (WHI), recruited 1993-1998 (baseline age 65-79 yrs) and followed through 2012. Medicare claims data were linked to WHI data to determine TKR (n = 1986) and THR (n = 1034). Self-reported PA was collected before total joint replacement (TJR). Women who were physically inactive before THR had the highest risk of mobility limitation at age 85 (OR 2.36, 95% CI 1.30-4.26) compared with women who had the highest amount of PA [> 17.42 metabolic equivalent of task (MET)-hrs/week]. Women who reported no moderate to vigorous PA (MVPA) before THR had the strongest risk of mobility limitation (OR 2.00, 95% CI 1.24-3.22) compared with women with the highest level of MPVA (≥ 15 MET-hrs/week)....

Arthritis care & research, Jan 3, 2017

To investigate associations of body mass index (BMI), waist circumference (WC), and waist-hip rat... more To investigate associations of body mass index (BMI), waist circumference (WC), and waist-hip ratio (WHR) with survival to age 85 with mobility limitation or death before age 85 among older women with total knee (TKR) or total hip (THR) replacement for osteoarthritis. This was a prospective study of women (aged 65-79 years at baseline) from the Women's Health Initiative recruited during 1993-1998 and followed through 2012. Women's Health Initiative data were linked to Medicare claims data to determine TKR (n=1,867) and THR (n=944) for osteoarthritis. Women were followed for up to 18 years after undergoing THR or TKR to determine mobility status at age 85. Compared with normal-weight women, overweight, obese I, and obese II women with THR had significantly increased risk of survival to age 85 with mobility limitation (P for linear trend <0.001), with the strongest risk among obese II women (OR = 4.37; 95% CI = 1.96-9.74). Obese II women with THR also had increased risk of ...

Clinical rheumatology, 2017

We evaluated the relationship of systolic blood pressure, diastolic blood pressure, pulse pressur... more We evaluated the relationship of systolic blood pressure, diastolic blood pressure, pulse pressure, and treatment with antihypertensives with knee osteoarthritis incidence in a US cohort. We performed a longitudinal study (2004-2010) nested within the Osteoarthritis Initiative Study including only individuals without knee osteoarthritis at baseline. Systolic blood pressure, diastolic blood pressure, and pulse pressure were assessed at baseline, 12-, 24-, and 36-month visits. Knee radiographs at baseline, 12-, 24-, 36- and 48-month visits defined radiographic osteoarthritis, Kellgren and Lawrence grade ≥2. We performed logistic regression, adjusting for age, sex, body mass index, NSAID use, number of antihypertensive medications, diabetic medications, and cholesterol medications. One thousand nine hundred and thirty people (6040 observations) were included. Annual incidence rates of radiographic osteoarthritis by systolic blood pressure quartiles (lowest to highest) were 2.1, 3.4, 3....

American journal of epidemiology, Jan 27, 2016

To our knowledge, no study has investigated the association of long-term exposure to traffic poll... more To our knowledge, no study has investigated the association of long-term exposure to traffic pollution with markers of atherosclerosis in 4 vascular beds simultaneously in an all-African-American cohort. Among participants in the Jackson Heart Study (Jackson, Mississippi; baseline mean age = 55.5 (standard deviation, 12.7) years), we used linear regression to estimate percent differences in carotid intima-media thickness (CIMT) at baseline (2004) and used modified Poisson regression (robust error variance) to estimate prevalence ratios for peripheral artery disease (PAD), coronary artery calcification (CAC), and abdominal aortic calcification (AAC) at the first follow-up visit (2005-2008) for persons living less than 150 m (versus more than 300 m) from major roadways, adjusting for confounders. Living less than 150 m from such roadways was associated with a significant 6.67% (95% confidence interval: 1.28, 12.35) increase in CIMT (4,800 participants). PAD prevalence among persons li...

Epidemiology, 2017

Background-Several recent papers have called into question the deleterious effects of high animal... more Background-Several recent papers have called into question the deleterious effects of high animal fat diets due to mixed results from epidemiologic studies and the lack of clinical trial evidence in meta-analyses of dietary intervention trials. We were interested in examining the theoretical effects of substituting plant-based fats from different types of margarine for animal based fat from butter on the risk of atherosclerosis-related cardiovascular disease (CVD). Methods-We prospectively studied 71,410 women, aged 50-79 years, and evaluated their risk for clinical myocardial infarction (MI), total coronary heart disease (CHD), ischemic stroke and atherosclerosis-related CVD with an average of 13.2 years of follow-up. Butter and margarine intakes were obtained at baseline and Year 3 by means of a validated food frequency questionnaire. Cox proportional hazards regression using a cumulative average diet method was used to estimate the theoretical effect of substituting 1 teaspoon/day of three types of margarine for the same amount of butter. Results-Substituting butter or stick margarine with tub margarine was associated with lower risk of MI (HRs=0.95 and 0.91). Subgroup analyses, which evaluated these substitutions among participants with a single source of spreadable fat, showed stronger associations for MI (HRs=0.92 and 0.87). Outcomes of total CHD, ischemic stroke, and atherosclerosis-related CVD showed wide confidence intervals but the same trends as the MI results.

Journal of Clinical Lipidology, 2016

Objective-To identify patterns of use and predictors of non-adherence to lipid lowering therapy (... more Objective-To identify patterns of use and predictors of non-adherence to lipid lowering therapy (LLT) in commercially insured children ages 8 to 20, and the high-risk subgroup with known dyslipidemia. Design, Setting and Participants-Commercially insured patients with a new dispensing for a LLT were included. Non-adherence was defined as a gap of ≥90 days between the last dispensing plus the medication days-supply and the next dispensing or censoring. Descriptive statistics characterize the patterns of LLT (statin, non-statin, statin combination and non-statin combination) adherence, adding, and class or specific drug switching. Kaplan-Meier curves and multivariable Cox proportional hazard models were used to identify time to, and predictors of, non-adherence for the cohort and the dyslipidemia subgroup.

Clinical rheumatology, Jan 16, 2016

We described a definition of end-stage knee osteoarthritis (esKOA) and evaluated its association ... more We described a definition of end-stage knee osteoarthritis (esKOA) and evaluated its association with health outcomes and osteoarthritis risk factors. We included Osteoarthritis Initiative participants with or at risk for knee osteoarthritis who had complete baseline data. We defined esKOA by adapting a validated appropriateness algorithm for total knee replacement based on data from baseline and the first four follow-up visits. We performed person-based analyses, including both knees from all participants. Participants met the definition of esKOA at the visit at which ≥1 knee reached the esKOA criteria. We assessed differences in individual characteristics between groups at baseline and over time and tested if incident esKOA (outcome) was associated with osteoarthritis risk factors (e.g., age, maximum adult weight, and quadriceps strength). The cohort consisted of 3916 participants with mean age of 61 (SD = 9) years and mean body mass index of 28.4 (4.7) kg/m(2); 59 % were female a...

Diabetes Care, 2015

OBJECTIVE In 2010, the American Diabetes Association (ADA) added hemoglobin A1c (A1C) to the guid... more OBJECTIVE In 2010, the American Diabetes Association (ADA) added hemoglobin A1c (A1C) to the guidelines for diagnosing type 2 diabetes. However, existing models for predicting diabetes risk were developed prior to the widespread adoption of A1C. Thus, it remains unknown how well existing diabetes risk prediction models predict incident diabetes defined according to the ADA 2010 guidelines. Accordingly, we examined the performance of an existing diabetes prediction model applied to a cohort of African American (AA) and white adults from the Coronary Artery Risk Development Study in Young Adults (CARDIA). RESEARCH DESIGN AND METHODS We evaluated the performance of the Atherosclerosis Risk in Communities (ARIC) diabetes risk prediction model among 2,456 participants in CARDIA free of diabetes at the 2005–2006 exam and followed for 5 years. We evaluated model discrimination, calibration, and integrated discrimination improvement with incident diabetes defined by ADA 2010 guidelines befo...

Arthritis & rheumatology (Hoboken, N.J.), 2015

The purpose of this study was to estimate the effectiveness of the combination of glucosamine and... more The purpose of this study was to estimate the effectiveness of the combination of glucosamine and chondroitin in relieving knee symptoms and slowing disease progression among patients with knee osteoarthritis (OA). The 4-year followup data from the Osteoarthritis Initiative data set were analyzed. We used a "new-user" design, for which only participants who were not using glucosamine/chondroitin at baseline were included in the analyses (n = 1,625). Cumulative exposure was calculated as the number of visits when participants reported use of glucosamine/chondroitin. Knee symptoms were measured with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and structural progression was determined by measuring the joint space width (JSW). To control for the time-varying confounders that might be influenced by previous treatments, we used marginal structural models to estimate the effects on OA of using glucosamine/chondroitin for 3 years, 2 years, and 1 yea...

BMC Pulmonary Medicine, 2014

Background: Evidence suggests that there is an association between chronic obstructive pulmonary ... more Background: Evidence suggests that there is an association between chronic obstructive pulmonary disease (COPD) and coronary heart disease (CHD). An important etiological link between COPD and CHD may be an underlying systemic inflammatory process. Given that COPD patients are at greater risk of cardiovascular mortality, understanding the burden of CHD on COPD patients could permit future risk attenuation. Methods: Longitudinal cohort analyses of the Third National Health and Nutrition Examination Survey from 1988-1994 were performed. 3,681 individuals ≥40 years of age with good quality spirometry data were included. Participants were divided into 5 groups: 1) no COPD, no CHD; 2) COPD without inflammation, no CHD; 3) COPD with inflammation, no CHD; 4) CHD only, and 5) CHD + COPD. A novel "inflammatory" COPD designation included those with COPD and clinical evidence of inflammation (i.e., CRP ≥95.24 nmol/L). Results: The risk for CHD mortality was significant only for the CHD group (HR 5.56, 95% CI 3.24-9.55) and the COPD + CHD group (HR 5.02, 95% CI 2.83-8.90). Similarly, the risk for cardiovascular disease (CVD) mortality was significant only for the CHD group (HR 4.25, 95% CI 2.70-6.69) and the CHD + COPD group (HR 4.12, 95% CI 2.60-6.54) after adjusting for nonmodifiable CHD risk factors (age, gender, race/ethnicity, family history of CHD). After adjusting for modifiable CHD risk factors (diabetes, BMI, physical activity, systolic blood pressure, cholesterol, and smoking), hazard ratios of the two groups remained similar but attenuated. For total mortality, the risk was significant for the four groups: the non-inflammatory COPD group; the COPD with inflammation group, the CHD group, and the COPD + CHD group. Conclusions: Our study did not confirm that inflammatory COPD may be a CHD risk equivalent. However, due to the small size of the "inflammatory" COPD group, further prospective replication and validation is needed. Moreover, given that COPD results from inflammation, the systemic inflammation associated with COPD may have worsened comorbid conditions and may have lead to the increased total mortality found in the COPD with inflammation and COPD + CHD groups which requires further investigation.

Menopause, 2013

Objectives-While joint symptoms are commonly reported after menopause, observational studies exam... more Objectives-While joint symptoms are commonly reported after menopause, observational studies examining exogenous estrogen influence on joint symptoms provide mixed results. Against this background, estrogen alone effects on joint symptoms were examined in post hoc analyses in the Women's Health Initiative randomized, placebo-controlled clinical trial. Methods-10,739 postmenopausal women with prior hysterectomy were randomized to receive daily oral conjugated equine estrogen (0.625 mg/d) or matching placebo. The frequency and severity of joint pain and joint swelling were assessed by questionnaire at entry and year 1 from all participants and in a random 9.9% subsample (n=1062) following years 3 and 6. Logistic regression models were used to compare frequency and severity of symptoms by randomization group. Sensitivity analyses evaluated adherence influence on symptoms. Results-At baseline, joint pain and swelling were closely comparable in the randomization groups (about 77% with joint pain and 40% with joint swelling). After one year, joint pain

Journal of Women's Health, 2011

Objective: To test the hypothesis of a significant association between resting heart rate (RHR) a... more Objective: To test the hypothesis of a significant association between resting heart rate (RHR) and coronary artery calcium (CAC). Methods: This is a cross-sectional study of a subset of women enrolled in the estrogen-alone clinical trial of the Women's Health Initiative (WHI). We used a longitudinal study that enrolled 998 postmenopausal women with a history of hysterectomy between the ages of 50 and 59 at enrollment at 40 different clinical centers. RHR was measured at enrollment and throughout the study, and CAC was determined approximately 7 years after the baseline clinic visit. Results: The mean (standard deviation [SD]) age was 55 (2.8) years. With adjustment for age and ethnicity, a 10unit increment in RHR was significantly associated with CAC (SD 1.18, 95% confidence interval [CI] 1.01-1.38), but this was no longer significant after adjustment for body mass index (BMI), income, education, dyslipidemia, diabetes, smoking, and hypertension (SD 1.06, 95% CI 0.90-1.25). In a fully adjusted multivariable model, however, there was a significant interaction (p = 0.03) between baseline RHR and systolic blood pressure (SBP) for the presence of any CAC. Compared to women with an RHR < 80 beats per minute (BPM) and an SBP < 140 mm Hg, those who had an RHR ‡ 80 BPM and an SBP ‡ 140 mm Hg had 2.66-fold higher odds (1.08-6.57) for the presence of any CAC. Conclusions: Compared to those with normal BP and RHR, postmenopausal, hysterectomized women with an elevated SBP and RHR have a significantly higher odds for the presence of calcified coronary artery disease.

Journal of the American College of Cardiology, 2011

Objective-To estimate the effect of education and income on incident heart failure (HF) hospitali... more Objective-To estimate the effect of education and income on incident heart failure (HF) hospitalization among post-menopausal women. Background-Investigations of socioeconomic status (SES) have focused on outcomes after HF diagnosis, not associations with incident HF. We used data from the Women's Health Initiative Hormone Trials to examine the association between SES levels and incident HF hospitalization. Methods-We included 26,160 healthy, post-menopausal women. Education and income were self-reported. ANOVA, Chi-square tests, and proportional hazards models were used for statistical analysis, with adjustment for demographics, co-morbid conditions, behavioral factors, and hormone and dietary modification assignments.

Journal of the American College of Cardiology, 2012

Human Genetics, 2013

study. Despite their biological plausibility, we were unable to detect significant SNP × smoking ... more study. Despite their biological plausibility, we were unable to detect significant SNP × smoking interactions. Short report Candidate gene and genome-wide association studies (GWAS) have identified numerous common variants associated with high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). However, examination of possible interactions with environmental factors such as smoking is still lacking (Ordovas et al. 2011). Smoking has been associated Abstract Genome-wide association studies (GWAS) have identified many variants that influence high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and/or triglycerides. However, environmental modifiers, such as smoking, of these known genotype-phenotype associations are just recently emerging in the literature. We have tested for interactions between smoking and 49 GWAS-identified variants in over 41,000 racially/ethnically diverse samples with lipid levels from the Population Architecture Using Genomics and Epidemiology (PAGE)

Human molecular genetics, 2011

The prevalence of hypertension in African Americans (AAs) is higher than in other US groups; yet,... more The prevalence of hypertension in African Americans (AAs) is higher than in other US groups; yet, few have performed genome-wide association studies (GWASs) in AA. Among people of European descent, GWASs have identified genetic variants at 13 loci that are associated with blood pressure. It is unknown if these variants confer susceptibility in people of African ancestry. Here, we examined genome-wide and candidate gene associations with systolic blood pressure (SBP) and diastolic blood pressure (DBP) using the Candidate Gene Association Resource (CARe) consortium consisting of 8591 AAs. Genotypes included genome-wide single-nucleotide polymorphism (SNP) data utilizing the Affymetrix 6.0 array with imputation to 2.5 million HapMap SNPs and candidate gene SNP data utilizing a 50K cardiovascular gene-centric array (ITMAT-Broad-CARe [IBC] array). For Affymetrix data, the strongest signal for DBP was rs10474346 (P= 3.6 × 10(-8)) located near GPR98 and ARRDC3. For SBP, the strongest signa...

Arthritis Research & Therapy, 2013

Introduction: We evaluated the associations between bone marrow lesion (BML) volume change and ch... more Introduction: We evaluated the associations between bone marrow lesion (BML) volume change and changes in periarticular bone mineral density (paBMD) as well as subchondral sclerosis to determine whether BML change is associated with other local bone changes. Methods: The convenience sample comprised participants in the Osteoarthritis Initiative (OAI) with weight-bearing posterior-anterior knee radiographs and magnetic resonance images (MRIs) at the 24-and 48-month visits and dual-energy x-ray absorptiometry (DXA) at the 30-/36-month and 48-month visits. The right knee was assessed unless contraindicated for MRI. We used knee DXA scans to measure medial tibia paBMD and medial/lateral paBMD ratio (M:L paBMD). Knee radiographs were scored for sclerosis (grades 0 to 3) in the medial tibia. Two raters determined BML volume on sagittal fat-suppressed MRI by using a semiautomated segmentation method. To focus on knees with only medial tibia BML changes, knees with lateral tibial BMLs were excluded. Medial tibial BML volume change was classified into three groups: BML regression (lowest quartile of medial tibial BML volume change), no-to-minimal change (middle two quartiles), and BML progression (highest quartile). We used proportional odds logistic regression models to evaluate the association between quartiles of changes in medial paBMD or M:L paBMD ratio, as outcomes, and BML volume change. Results: The sample (n = 308) included 163 (53%) female subjects, 212 (69%) knees with radiographic osteoarthritis, and participants with a mean age of 63.8 ± 9.3 years and mean body mass index of 29.8 ± 4.7 kg/m 2. We found an association between greater increases in medial tibia paBMD and BML regression (OR = 1.7 (95% confidence interval (CI) = 1.1 to 2.8)) and a similar trend for BML progression (OR = 1.6 (95% CI = 1.0 to 2.6]). We also detected associations between greater increase in M:L paBMD and BML regression (OR = 1.6 (95% CI = 1.0 to 2.7]) and BML progression (OR = 1.8 (95% CI = 1.1 to 3.0)), although BML regression had borderline statistical significance. The frequency of sclerosis progression in the medial tibia (n = 14) was greater among knees with BML progression or regression compared with knees without BML change (P = 0.01 and P = 0.04, respectively). Conclusion: BML regression and BML progression are characterized by concurrent increases in paBMD and sclerosis, which are characteristic of increased radiographic osteoarthritis severity. At least during 24 months, BML regression is not representative of improvement in other periarticular bone measures.