Publications by authors named "Maria M Brooks"

106 Publications

Cardiovascular risk and midlife cognitive decline in the Study of Women's Health Across the Nation.

Alzheimers Dement 2021 Mar 12. Epub 2021 Mar 12.

Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Introduction: Cardiovascular risk factors in midlife have been linked to late life risk for Alzheimer's disease and related dementias (ADRD). The relation of vascular risk factors on cognitive decline within midlife has been less studied.

Methods: Using data from the Study of Women's Health Across the Nation, we examined associations of midlife hypertension, elevated lipid levels, diabetes, fasting glucose, central adiposity, and Framingham heart age with rates of cognitive decline in women who completed multiple cognitive assessments of processing speed, and working and verbal memory during midlife.

Results: Diabetes, elevated fasting glucose, central obesity, and heart age greater than chronological age were associated with rate of decline in processing speed during midlife. Vascular risk factors were not related to rate of decline in working or verbal memory.

Discussion: Midlife may be a critical period for intervening on cardiovascular risk factors to prevent or delay later life cognitive impairment and ADRD.
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http://dx.doi.org/10.1002/alz.12300DOI Listing
March 2021

Abdominal visceral adipose tissue over the menopause transition and carotid atherosclerosis: the SWAN heart study.

Menopause 2021 Mar 1. Epub 2021 Mar 1.

Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA Department of Medicine, University of Pittsburgh, Pittsburgh, PA Department of Preventive Medicine, Rush University, Chicago, IL Department of Medicine, Rush University, Chicago, IL.

Objectives: To characterize abdominal visceral adipose tissue (VAT) trajectory relative to the final menstrual period (FMP), and to test whether menopause-related VAT accumulation is associated with greater average, common carotid artery intima-media thickness (cIMT) and/or internal carotid artery intima-media thickness (ICA-IMT).

Methods: Participants were 362 women (at baseline: age was (mean ± SD) 51.1 ± 2.8 y; 61% White, 39% Black) with no cardiovascular disease from the Study of Women's Health Across the Nation Heart study. Women had up to two measurements of VAT and cIMT over time. Splines revealed a nonlinear trajectory of VAT with two inflection points demarcating three time segments: segment 1: >2 years before FMP; segment 2: 2 years before FMP to FMP; and segment 3: after FMP. Piecewise-linear random-effects models estimated changes in VAT. Random-effects models tested associations of menopause-related VAT with each cIMT measure separately. Estimates were adjusted for age at FMP, body mass index, and sociodemographic, lifestyle, and cardiovascular disease risk factors.

Results: VAT increased significantly by 8.2% (95% CI: 4.1%-12.5%) and 5.8% (3.7%-7.9%) per year in segments 2 and 3, respectively, with no significant change in VAT within segment 1. VAT predicted greater ICA-IMT in segment 2, such that a 20% greater VAT was associated with a 2.0% (0.8%-3.1%) greater ICA-IMT. VAT was not an independent predictor of ICA-IMT in the other segments or of the other cIMT measures after adjusting for covariates.

Conclusions: Women experience an accelerated increase in VAT starting 2 years before menopause. This menopause-related increase in VAT is associated with greater risk of subclinical atherosclerosis in the internal carotid artery.

Video Summary:http://links.lww.com/MENO/A722.
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http://dx.doi.org/10.1097/GME.0000000000001755DOI Listing
March 2021

Symptom clusters predict risk of metabolic-syndrome and diabetes in midlife: the Study of Women's Health Across the Nation.

Ann Epidemiol 2021 Feb 22;58:48-55. Epub 2021 Feb 22.

Epidemiologic Science, School of Public Health, University of Michigan, Ann Arbor, MI; Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI.

Purpose: Women's cardio-metabolic risk increases in midlife. Previous work relating menopause symptoms to diabetes/Metabolic Syndrome (MetS) does not consider the adverse impact of multiple concurrent physical and psychological symptoms in midlife.

Methods: Data are from 3097 participants in the Study of Women's Health Across the Nation, a cohort of midlife women followed for over 20 years. Baseline latent symptom classes (LSC) were derived from 58 questions assessing physical, psychological and menopausal symptoms. Six identified LSCs ranged from 1 (most symptoms present at high severity) to 6 (few symptoms present at low severity). Accelerated failure time models estimated time to onset of type 2 diabetes and MetS for each LSC.

Results: Women with multiple high/moderate severity symptoms had an earlier onset of diabetes (13.2%, 14.1% and 20.8% earlier onset in LSCs 1, 2, 3, respectively) and MetS (15.5%, 13.0% and 19.7% earlier onset in LSCs 1, 2, 3, respectively) than women with few/low severity symptoms.

Conclusions: Having multiple concurrent moderate to high intensity physical and psychological symptoms in midlife are associated with early onset of diabetes and MetS. Monitoring and subsequent intervention on a broad range of symptoms in midlife may significantly mitigate cardio-metabolic risk during this critical life stage.
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http://dx.doi.org/10.1016/j.annepidem.2021.02.011DOI Listing
February 2021

Death and Myocardial Infarction Following Initial Revascularization Versus Optimal Medical Therapy in Chronic Coronary Syndromes With Myocardial Ischemia: A Systematic Review and Meta-Analysis of Contemporary Randomized Controlled Trials.

J Am Heart Assoc 2021 Jan 14;10(2):e019114. Epub 2021 Jan 14.

Department of Medicine Washington University School of Medicine St. Louis MO.

Background In chronic coronary syndromes, myocardial ischemia is associated with a greater risk of death and nonfatal myocardial infarction (MI). We sought to compare the effect of initial revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) plus optimal medical therapy (OMT) with OMT alone in patients with chronic coronary syndrome and myocardial ischemia on long-term death and nonfatal MI. Methods and Results Ovid Medline, Embase, Scopus, and Cochrane Library databases were searched for randomized controlled trials of PCI or CABG plus OMT versus OMT alone for patients with chronic coronary syndromes. Studies were screened and data were extracted independently by 2 authors. Random-effects models were used to generate pooled treatment effects. The search yielded 7 randomized controlled trials that randomized 10 797 patients. Median follow-up was 5 years. Death occurred in 640 of the 5413 patients (11.8%) randomized to revascularization and in 647 of the 5384 patients (12%) randomized to OMT (odds ratio [OR], 0.97; 95% CI, 0.86-1.09; =0.60). Nonfatal MI was reported in 554 of 5413 patients (10.2%) in the revascularization arms compared with 627 of 5384 patients (11.6%) in the OMT arms (OR, 0.75; 95% CI, 0.57-0.99; =0.04). In subgroup analysis, nonfatal MI was significantly reduced by CABG (OR, 0.35; 95% CI, 0.21-0.59; <0.001) but was not reduced by PCI (OR, 0.92; 95% CI, 0.75-1.13; =0.43) (-interaction <0.001). Conclusions In patients with chronic coronary syndromes and myocardial ischemia, initial revascularization with PCI or CABG plus OMT did not reduce long-term mortality compared with OMT alone. CABG plus OMT reduced nonfatal MI compared with OMT alone, whereas PCI did not.
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http://dx.doi.org/10.1161/JAHA.120.019114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955292PMC
January 2021

Social Role Stress, Reward, and the American Heart Association Life's Simple 7 in Midlife Women: The Study of Women's Health Across the Nation.

J Am Heart Assoc 2020 12 11;9(24):e017489. Epub 2020 Dec 11.

Department of Epidemiology University of Pittsburgh Graduate School of Public Health Pittsburgh PA.

Background Most women occupy multiple social roles during midlife. Perceived stress and rewards from these roles may influence health behaviors and risk factors. This study examined whether social role stress and reward were associated with the American Heart Association Life's Simple 7 in a cohort of midlife women in the United States. Methods and Results Women (n=2764) rated how stressful and rewarding they perceived their social roles during cohort follow-up (age range, 42-61 years). Body mass index, blood pressure, glucose, cholesterol, physical activity, diet, and smoking were assessed multiple times. All components were collected at the fifth study visit for 1694 women (mean age, 51 years). Adjusted linear and logistic regression models were used in analyses of the number of ideal components and the odds of achieving the ideal level of each component, respectively. Longitudinal analyses using all available data from follow-up visits were conducted. At the fifth visit, more stressful and less rewarding social roles were associated with fewer ideal cardiovascular factors. Higher average stress was associated with lower odds of any component of a healthy diet and an ideal blood pressure. Higher rewards were associated with greater odds of ideal physical activity and nonsmoking. Longitudinal analyses produced consistent results; moreover, there was a significant relationship between greater stress and lower odds of ideal glucose and body mass index. Conclusions Perceived stress and rewards from social roles may influence cardiovascular risk factors in midlife women. Considering social role qualities may be important for improving health behaviors and risk factors in midlife women.
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http://dx.doi.org/10.1161/JAHA.120.017489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955397PMC
December 2020

Gestational Weight Gain and Long-term Maternal Obesity Risk: A Multiple-Bias Analysis.

Epidemiology 2021 Mar;32(2):248-258

From the Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA.

Background: Lifecourse research provides an important framework for chronic disease epidemiology. However, data collection to observe health characteristics over long periods is vulnerable to systematic error and statistical bias. We present a multiple-bias analysis using real-world data to estimate associations between excessive gestational weight gain and mid-life obesity, accounting for confounding, selection, and misclassification biases.

Methods: Participants were from the multiethnic Study of Women's Health Across the Nation. Obesity was defined by waist circumference measured in 1996-1997 when women were age 42-53. Gestational weight gain was measured retrospectively by self-recall and was missing for over 40% of participants. We estimated relative risk (RR) and 95% confidence intervals (CI) of obesity at mid-life for presence versus absence of excessive gestational weight gain in any pregnancy. We imputed missing data via multiple imputation and used weighted regression to account for misclassification.

Results: Among the 2,339 women in this analysis, 937 (40%) experienced obesity in mid-life. In complete case analysis, women with excessive gestational weight gain had an estimated 39% greater risk of obesity (RR = 1.4, CI = 1.1, 1.7), covariate-adjusted. Imputing data, then weighting estimates at the guidepost values of sensitivity = 80% and specificity = 75%, increased the RR (95% CI) for obesity to 2.3 (2.0, 2.6). Only models assuming a 20-point difference in specificity between those with and without obesity decreased the RR.

Conclusions: The inference of a positive association between excessive gestational weight gain and mid-life obesity is robust to methods accounting for selection and misclassification bias.
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http://dx.doi.org/10.1097/EDE.0000000000001310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855686PMC
March 2021

The design of a Bayesian platform trial to prevent and eradicate inhibitors in patients with hemophilia.

Blood Adv 2020 11;4(21):5433-5441

Division of Hematology/Oncology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA; and.

Among individuals with the rare congenital bleeding disorder hemophilia A, the major challenge is inhibitor formation, which is associated with significant morbidity and cost. Yet, as the optimal approach to prevent and eradicate inhibitors is not known, we are at equipoise. Because classic trial design is not practical in a rare disease setting, we designed 2 48-week randomized trials comparing ELOCTATE and emicizumab to prevent and eradicate inhibitors. To achieve statistical efficiency, we incorporated historic data (Bayesian priors) on inhibitor formation to allow preferential randomization to emicizumab, piecewise exponential survival models to determine mean and 95% confidence interval for inhibitor formation in each arm, and simulations to determine the best model design to optimize power. To achieve administrative efficiency, the trials will be performed with the same sites, staff, visit frequency, blood sampling, laboratories, and laboratory assays, with streamlined enrollment so patients developing inhibitors in the first trial may be enrolled on the second trial. The primary end point is the probability of inhibitor formation or inhibitor eradication, respectively. The design indicates early stopping rules for overwhelming evidence of superiority of the emicizumab arms. Simulations indicate that, with 66 subjects, the Prevention Trial will have 84% power to detect noninferiority of emicizumab to ELOCTATE with a margin of 10% if emicizumab is truly 10% superior to ELOCTATE; with 90 subjects, the Eradication Trial will have 80% power to detect 15% superiority of ELOCTATE immune tolerance induction with vs without emicizumab. Thus, a platform design provides statistical and administrative efficiency to conduct INHIBIT trials.
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http://dx.doi.org/10.1182/bloodadvances.2020002789DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656929PMC
November 2020

Influence of LDL-Cholesterol Lowering on Cardiovascular Outcomes in Patients With Diabetes Mellitus Undergoing Coronary Revascularization.

J Am Coll Cardiol 2020 11;76(19):2197-2207

Icahn School of Medicine at Mount Sinai, New York, New York; Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.

Background: Elevated low-density lipoprotein cholesterol (LDL-C) is associated with increased cardiovascular events, especially in high-risk populations.

Objectives: This study sought to evaluate the influence of LDL-C on the incidence of cardiovascular events either following a coronary revascularization procedure (percutaneous coronary intervention [PCI] or coronary artery bypass grafting [CABG]) or optimal medical therapy alone in patients with established coronary heart disease and type 2 diabetes (T2DM).

Methods: Patient-level pooled analysis of 3 randomized clinical trials was undertaken. Patients with T2DM were categorized according to the levels of LDL-C at 1 year following randomization. The primary endpoint was major adverse cardiac or cerebrovascular events ([MACCE] the composite of all-cause mortality, nonfatal myocardial infarction, and nonfatal stroke).

Results: A total of 4,050 patients were followed for a median of 3.9 years after the index 1-year assessment. Patients whose 1-year LDL-C remained ≥100 mg/dl experienced higher 4-year cumulative risk of MACCE (17.2% vs. 13.3% vs. 13.1% for LDL-C between 70 and <100 mg/dl and LDL-C <70 mg/dl, respectively; p = 0.016). When compared with optimal medical therapy alone, patients with PCI experienced a MACCE reduction only if 1-year LDL-C was <70 mg/dl (hazard ratio: 0.61; 95% confidence interval: 0.40 to 0.91; p = 0.016), whereas CABG was associated with improved outcomes across all 1-year LDL-C strata. In patients with 1-year LDL-C ≥70 mg/dl, patients undergoing CABG had significantly lower MACCE rates as compared with PCI.

Conclusions: In patients with coronary heart disease with T2DM, lower LDL-C at 1 year is associated with improved long-term MACCE outcome in those eligible for either PCI or CABG. When compared with optimal medical therapy alone, PCI was associated with MACCE reductions only in those who achieved an LDL-C <70 mg/dl.
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http://dx.doi.org/10.1016/j.jacc.2020.09.536DOI Listing
November 2020

Identifying women who share patterns of reproductive hormones, vasomotor symptoms, and sleep maintenance problems across the menopause transition: group-based multi-trajectory modeling in the Study of Women's Health Across the Nation.

Menopause 2020 10 5;28(2):126-134. Epub 2020 Oct 5.

Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA.

Objective: To identify groups of women who share levels and patterns of change in follicle-stimulating hormone (FSH), self-reported sleep maintenance problems, and frequent vasomotor symptoms (VMS) up to 10 years before and after their final menstrual period and to evaluate their premenopausal characteristics.

Method: Group-based multi-trajectory modeling grouped 1,407 women from the Study of Women's Health Across the Nation who had an observed natural menopause and did not use hormone therapy, based on repeated measures of FSH, sleep maintenance problems, and frequent VMS relative to final menstrual period. Multivariable analyses assessed race/ethnicity, body mass index, smoking, and depressive symptoms as predictors of group membership.

Results: Women formed five distinct groups: (1) low symptoms (low VMS/sleep problems)/high FSH rise (N = 552; 39.2%); (2) moderate VMS and sleep problems/low FSH rise (N = 169; 12.0%); (3) dominant sleep problems (lower VMS/high sleep problems)/high FSH rise (N = 203; 14.4%); (4) dominant VMS (high VMS/lower sleep problems)/high FSH rise (N = 297; 21.1%)); and (5) high symptoms (high VMS/high sleep problems)/intermediate FSH rise (N = 186; 13.2%)). Multivariate analyses showed that race/ethnicity, premenopausal body mass index and depressive symptoms, and increasing depressive symptoms during the early phase of the transition predicted group membership.

Conclusions: Women can be classified based on shared levels and patterns of FSH, sleep maintenance problems, and frequent VMS across the menopause transition. Either VMS or sleep maintenance problems can be dominant in the face of high FSH. Experiencing one menopause-related symptom or hormone profile does not automatically imply that another is also being experienced.
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http://dx.doi.org/10.1097/GME.0000000000001663DOI Listing
October 2020

Population-attributable fraction of risk factors for severe maternal morbidity.

Am J Obstet Gynecol MFM 2020 02 22;2(1):100066. Epub 2019 Nov 22.

Department of Obstetrics, Gynecology, and Reproductive Sciences, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.

Background: Severe maternal morbidity is an important proxy for maternal mortality. Population attributable fraction is the proportion of a disease that is attributable to a given risk factor and can be used to estimate the reduction in the disease that would be anticipated if a risk factor was reduced or eliminated.

Objective: We sought to determine the population-attributable fraction (PAF) of potentially modifiable risk factors for severe maternal morbidity.

Study Design: We used a retrospective cohort of 86,260 delivery hospitalizations from Magee-Womens Hospital, Pittsburgh, PA for this analysis (2003-2012). Severe maternal morbidity was defined as any of the following: Centers for Disease Control and Prevention International Classification of Diseases 9 Revision diagnosis and procedure codes for the identification of maternal morbidity; prolonged postpartum length of stay (defined as >3 standard deviations beyond the mean length of stay: >3 days for vaginal deliveries and >5 days for Cesarean deliveries); or maternal intensive care unit admission. We used multivariable logistic regression with generalized estimating equations to estimate the association of prepregnancy overweight or obesity, maternal age ≥35 years, preexisting hypertension, preexisting diabetes, excessive gestational weight gain, smoking, education, and marital status with severe maternal morbidity. We then calculated the PAF for each risk factor. We also examined the impact of modest reductions and elimination of risk factors on the PAF of severe maternal morbidity.

Results: The overall rate of severe maternal morbidity was 2.0%. Overweight and obesity, maternal age ≥35 years, preexisting hypertension, excessive gestational weight gain, and lack of a college degree had PAF ranging from 4.5% to 13%. If all risk factors were eliminated, 36% of cases could have been prevented. Modest reductions in the prevalence of excessive BMI and advanced maternal age had minimal impact on preventing severe maternal morbidity. Smoking during pregnancy and marital status were not associated with severe maternal morbidity.

Conclusions: Our data suggest maternal morbidity can be reduced by modifying common, individual-level risk factors. Nevertheless, the majority of cases were not attributable to the patient level risk factors we examined. These data support the need for large studies of patient-, provider-, system- and population-level factors to identify high-impact interventions to reduce maternal morbidity.
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http://dx.doi.org/10.1016/j.ajogmf.2019.100066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7450808PMC
February 2020

Vasomotor symptoms and lipids/lipoprotein subclass metrics in midlife women: Does level of endogenous estradiol matter? The SWAN HDL Ancillary Study.

J Clin Lipidol 2020 Sep - Oct;14(5):685-694.e2. Epub 2020 Jul 8.

Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address:

Background: A greater frequency of vasomotor symptoms (VMSs) has been associated with higher low-density lipoprotein cholesterol (LDL-C), but the association with high-density lipoprotein cholesterol (HDL-C) remains unclear. Endogenous estradiol (E2) levels are associated with both VMS and lipid levels and thus may confound such associations.

Objectives: To assess the relationship of VMS frequency with HDL-C, LDL-C, and lipoprotein concentrations (HDL and LDL particles [HDL-P; LDL-P]) and lipoprotein sizes in midlife women and to evaluate whether these associations are explained by E2.

Methods: Participants were from the Study of Women's Health Across the Nation (SWAN) HDL ancillary study who had both nuclear magnetic resonance (NMR) spectroscopy lipoprotein subclass metrics and self-reported frequency of VMS measured 2-5 times over the menopause transition. VMS frequency was categorized into none, 1-5 days (infrequent), or ≥6 days (frequent) within the past 2 weeks.

Results: We evaluated 522 women [at baseline: mean age 50.3 (SD: 2.8) years; infrequent VMS: 29.8%, frequent VMS: 16.5%]. Adjusting for potential confounders except E2, frequent VMS was associated with smaller HDL size [β(SE): -0.06 (0.03); P = .04] and higher concentrations of LDL-C [β(SE): 3.58 (1.77); P = .04] and intermediate LDL-P [β(SE): 0.09 (0.05); P = .04] than no VMS. These associations were largely explained by E2, all P's > .05.

Conclusions: Frequent VMSs were associated with smaller HDL size and higher concentrations of LDL-C and intermediate LDL-P. These associations were explained by endogenous E2. Whether treating frequent VMS with exogenous E2 could simultaneously improve lipids/lipoproteins profile should be assessed in future studies.
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http://dx.doi.org/10.1016/j.jacl.2020.07.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642056PMC
July 2020

Excessive gestational weight gain is associated with severe maternal morbidity.

Ann Epidemiol 2020 10 26;50:52-56.e1. Epub 2020 Jun 26.

Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA; Department of Obstetrics, Gynecology, and Reproductive Sciences, School of Medicine, University of Pittsburgh, Pittsburgh, PA; Magee-Womens Research Institute, Pittsburgh, PA. Electronic address:

Purpose: We determined the association between gestational weight gain and severe maternal morbidity.

Methods: We used data on 84,241 delivery hospitalizations at Magee-Womens Hospital, Pittsburgh, PA (2003-2012). Total gestational weight gain (kilogram) was converted to gestational age-standardized z-scores. We defined severe maternal morbidity as having ≥1 of the 21 Centers for Disease Control diagnosis or procedure codes for severe maternal morbidity identification, intensive care unit admission, or extended postpartum stay. We used multivariable logistic regression to determine the association between weight gain and severe maternal morbidity after confounder adjustment.

Results: High gestational weight gain z-scores were associated with an increased risk of severe maternal morbidity. Compared with z-score 0 SD (equivalent to 16 kg at 40 weeks in a normal-weight woman), risk differences (95% confidence intervals) for z-scores -2 SD (7 kg), -1 SD (11 kg), +1 SD (23 kg), and +2 SD (31 kg) were 1.5 (-0.71, 3.7), 0.056 (-0.81, 0.93), 3.4 (1.7, 5.0), and 8.6 (4.0, 13) per 1000 deliveries. The results did not vary by gestational age at delivery or prepregnancy body mass index.

Conclusions: The increased risk of severe maternal morbidity with high pregnancy weight gain may allow scientists to understand and prevent this serious condition.
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http://dx.doi.org/10.1016/j.annepidem.2020.06.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541767PMC
October 2020

Life Course Changes in Cardiometabolic Risk Factors Associated With Preterm Delivery: The 30-Year CARDIA Study.

J Am Heart Assoc 2020 08 22;9(15):e015900. Epub 2020 Jul 22.

Department of Epidemiology University of Pittsburgh Graduate School of Public Health Pittsburgh PA.

Background Women who deliver preterm infants (<37 weeks) have excess cardiovascular risk; however, it is unclear whether the unfavorable changes in the cardiometabolic profile associated with preterm delivery initiate before, during, or after childbearing. Methods and Results We identified 1306 women (51% Black) with births between baseline (1985-1986) and year 30 in the CARDIA (Coronary Artery Risk Development in Young Adults) study. We compared life course changes in blood pressure, body mass index, waist circumference, and lipids in women with preterm deliveries (n=318) with those with all term deliveries (n=988), using piecewise linear mixed-effects models. Specifically, we evaluated group differences in rates of change before and after the childbearing period and change in level across the childbearing period. After adjusting for the covariates, women with preterm deliveries had a higher change in diastolic blood pressure across the childbearing period than those with all term deliveries (1.59 versus -0.73 mm Hg, <0.01); the rates of change did not differ by group, both prechildbearing and postchildbearing. Women with preterm deliveries had a larger body mass index increase across the childbearing period (1.66 versus 1.22 kg/m, =0.03) compared with those with all term deliveries, followed by a steeper increase after the childbearing period (0.22 versus 0.17 kg/m per year, =0.02). Conclusions Preterm delivery was associated with unfavorable patterns of change in diastolic blood pressure and adiposity that originate during the childbearing years and persist or exacerbate later in life. These adverse changes may contribute to the elevated cardiovascular risk among women with preterm delivery.
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http://dx.doi.org/10.1161/JAHA.119.015900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792274PMC
August 2020

Comparison of Oral Anticoagulant Use and Stroke Risk Among Older Adults Newly-Diagnosed Atrial Fibrillation Living in Urban-Versus-Rural Areas.

Am J Cardiol 2020 09 17;130:64-69. Epub 2020 Jun 17.

Center for Pharmaceutical Policy and Prescribing, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Pharmacy and Therapeutics, University of Pittsburgh, Pittsburgh, Pennsylvania. Electronic address:

We aimed to assess the association between urban/rural residence and the risk of ischemic stroke in individuals with newly diagnosed atrial fibrillation (AF), and to quantify the role of oral anticoagulation (OAC) initiation in the variation in stroke risk between urban and rural residents with AF. Using 5% random samples of Medicare claims, we identified fee-for-service beneficiaries who were diagnosed with AF between January 2014 and December 2015. Beneficiaries were followed for 1 year since their AF diagnosis, and were categorized according to their initiation of OAC within the year. We used the Rural-Urban Continuum Codes to define urban (levels 1 to 3) and rural (levels 4 to 9) areas. We applied marginal structural models to examine to what extent the difference in stroke risk between rural and urban areas were attributable to the difference in OAC initiation. In the year of AF diagnosis, 52% of those residing in urban areas and 56% residing in rural areas initiated an OAC (p <0.001). Urban residence, compared with rural residence, was associated with a 22% (hazard ratio and 95% confidence interval: 1.22 [1.13, 1.31]) increased risk of stroke. The hazard ratio attributed to urban residence decreased to 1.14 (1.01, 1.30) after accounting for the mediating role of lack of OAC initiation. Lack of OAC initiation explained 34% of the increased stroke risk observed in urban areas. In conclusion, urban residents with newly diagnosed AF were less likely to initiate OAC than rural counterparts, which explained one third of the increased risk of stroke observed in urban areas.
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http://dx.doi.org/10.1016/j.amjcard.2020.06.015DOI Listing
September 2020

Temporal Acute Serum Estradiol and Tumor Necrosis Factor-α Associations and Risk of Death after Severe Traumatic Brain Injury.

J Neurotrauma 2020 10 24;37(20):2198-2210. Epub 2020 Jun 24.

Department of Physical Medicine and Rehabilitation, University of Pittsburgh, Pittsburgh, Pennsylvania.

Severe traumatic brain injury (TBI) activates a robust systemic response that involves inflammatory and other factors, including estradiol (E2), associated with increased deaths. Tumor necrosis factor-alpha (TNFα) is a significant mediator of systemic shock, and it is an extra-gonadal transcription factor for E2 production. The study objectives were to test the hypotheses: (1) a positive feedback relationship exists between acute serum TNFα and E2; and (2) acute concentrations of E2 and TNFα are prognostic indicators of death after severe TBI. This prospective cohort study included N = 157 adults with severe TBI. Serum samples were collected for the first five days post-injury. The TNFα and E2 levels were averaged into two time epochs: first 72 h (T1) and second 72 h post-injury (T2). A cross-lag panel analysis conducted between T1 and T2 TNFα and E2 levels showed significant cross-lag effects: T1 TNFα and T1 E2 were related to T2 E2 and T2 TNFα, respectively. Cox proportional hazards multi variable regression models determined that increases in T1 E2 (hazard ratio [HR] = 1.79, 95% confidence interval [CI]: 1.15, 2.81), but not T2 E2 (HR = 0.91, 95% CI: 0.56, 1.47), were associated with increased risk of death. Increased T2 TNFα (HR = 2.47, 95% CI: 1.35, 4.53), and T1 TNFα (HR = 1.47, 95% CI: 0.99, 2.19), to a lesser degree, were associated with increased risk of death. Relationships of death with T2 TNFα and T1 E2 were mediated partially by cardiovascular, hepatic, and renal dysfunction. Both E2 and TNFα are systemic, reciprocally related biomarkers that may be indicative of systemic compromise and increased risk of death after severe TBI.
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http://dx.doi.org/10.1089/neu.2019.6577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7580589PMC
October 2020

Real-World Direct Comparison of the Effectiveness and Safety of Apixaban, Dabigatran, Rivaroxaban, and Warfarin in Medicare Beneficiaries With Atrial Fibrillation.

Am J Cardiol 2020 07 10;126:29-36. Epub 2020 Apr 10.

Department of Pharmacy and Therapeutics, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania.

It remains unknown whether the comparative effectiveness of direct oral anticoagulants (DOACs) and warfarin differs between atrial fibrillation patients with and without a history of stroke or transient ischemic attack (TIA). Using 2012 to 2014 Medicare claims data, we identified patients newly diagnosed with AF in 2013 to 2014 who initiated apixaban, dabigatran, rivaroxaban, or warfarin. We categorized patients based on a history of stroke or TIA. We constructed Cox proportional hazard models that included indicator variables for treatment groups, a history of stroke or TIA, and the interaction between them, and controlled for demographics and clinical characteristics. DOACs were generally more effective than warfarin in stroke prevention; however, there were important differences between subgroups defined by a history of ischemic stroke. In particular, the superiority of dabigatran compared with warfarin in ischemic stroke prevention was more pronounced in patients with a history of stroke or TIA (hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.48 to 0.85) than in patients with no history of stroke or TIA (HR 0.94; 95% CI 0.75 to 1.16; p value for interaction = 0.034). There was no difference in the risk of stroke between apixaban, dabigatran, and rivaroxaban in patients with no history of stroke or TIA. However, in patients with a history of stroke or TIA, the risk of stroke was lower with dabigatran (HR 0.64; 95% CI 0.48 to 0.85) and rivaroxaban (HR 0.70; 95% CI 0.56 to 0.87), compared with apixaban (p value for both interactions <0.05). In conclusion, the comparative effectiveness of DOACs differs substantially between patients with and without a history of stroke or TIA; specifically, apixaban is less effective in patients with a history of stroke or TIA.
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http://dx.doi.org/10.1016/j.amjcard.2020.03.034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275920PMC
July 2020

Life-course impact of child maltreatment on midlife health-related quality of life in women: longitudinal mediation analysis for potential pathways.

Ann Epidemiol 2020 03 18;43:58-65. Epub 2020 Jan 18.

Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA; Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA.

Purpose: We examined (1) if child maltreatment (CM) is associated with lower health-related quality of life (HRQoL) and fewer quality-adjusted life years (QALY) over a 9-year follow-up of midlife women and (2) if adulthood psychosocial mediators could explain these associations.

Methods: Women (n = 342) completed the Childhood Trauma Questionnaire. Longitudinal HRQoL and QALY outcomes measured at five study visits include 36-item Short-Form Health Survey mental component score and physical component score and the Short Form-6 Dimension health index. Aims 1 and 2 were investigated by generalized estimating equations and sequential structural nested mean models, respectively.

Results: Twenty percent reported 2+ CM types. Compared with women without CM, women who experienced 2+ CM types reported 5- and 4-points lower scores in mental component score and physical component score, respectively, and 28 fewer healthy days per year in QALY. Low optimism, sleep problems, and low social support each explained greater than 10% of the relationship between 2+ CM and HRQoL and QALY over time.

Conclusions: CM is a life-course social determinant of HRQoL and QALY throughout midlife, particularly in women who experienced 2+ CM types. Several mediators are modifiable and could be targets of interventions to mitigate the negative impact of CM on midlife HRQoL and QALY in women.
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http://dx.doi.org/10.1016/j.annepidem.2020.01.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7153694PMC
March 2020

Latent Classes of Adherence to Oral Anticoagulation Therapy Among Patients With a New Diagnosis of Atrial Fibrillation.

JAMA Netw Open 2020 02 5;3(2):e1921357. Epub 2020 Feb 5.

Department of Pharmacy and Therapeutics, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania.

Importance: Less than half of US patients with a diagnosis of atrial fibrillation (AF) receive oral anticoagulation.

Objectives: To identify patients with similar patterns of adherence to regimens of warfarin and direct oral anticoagulants (DOACs) in the first year after AF diagnosis and to evaluate associations between patient characteristics and membership in latent classes of adherence.

Design, Setting, And Participants: This retrospective cohort study used 2013 to 2016 Medicare claims data to identify 7491 patients with a new diagnosis of AF in 2014 to 2015 who initiated warfarin after AF diagnosis and 9478 patients with a new diagnosis of AF in 2014 to 2015 who initiated DOAC treatment after AF diagnosis, for a total of 16 969 Medicare beneficiaries. Participants were followed up for 12 months after AF diagnosis. Statistical analysis was performed from February 1 to November 30, 2018.

Exposures: Treatment with warfarin or DOAC after AF diagnosis.

Main Outcomes And Measures: The main outcome was the proportion of days that patients received warfarin or DOAC, measured in 30-day intervals after AF diagnosis. Independent variables included patient demographic characteristics, socioeconomic status, region of residence, and clinical characteristics. Latent class mixed models were used to identify latent classes of warfarin and DOAC adherence, and polytomous logistic regression was used to assess the association between patient characteristics and membership in each latent class.

Results: Among the 7491 patients receiving warfarin (4348 women), the mean (SD) age was 76.0 (10.0) years; among the 9478 patients receiving DOAC (5496 women), the mean (SD) age was 77.0 (8.5) years. Four latent classes of patients were identified based on warfarin adherence: late initiators (980 [13%]), early initiators who discontinued therapy at months 1 to 3 (1297 [17%]) or at months 5 to 10 (735 [10%]), and continuously adherent patients (4479 [60%]). Four latent classes of patients were also identified based on DOAC adherence: patients who initiated DOAC in months 1 to 5 (1368 [14%]) or months 6 to 11 (800 [8%]), patients with suboptimal and decreasing adherence (2267 [24%]), and continuously adherent patients (5043 [53%]). Membership in latent classes of warfarin adherence was significantly associated with sex, eligibility for Medicaid and income subsidy, region of residence, CHA2DS2-VASc (cardiac failure or dysfunction, hypertension, age 65-74 [1 point] or ≥75 years [2 points], diabetes, and stroke, transient ischemic attack or thromboembolism [2 points]-vascular disease, and sex category [female]) risk score, and HAS-BLED (hypertension, abnormal renal and liver function, stroke, bleeding, labile international normalized ratio, elderly, and drugs or alcohol) score. Membership in latent classes of DOAC adherence was significantly associated with race/ethnicity, region of residence, HAS-BLED score, and use of antiarrhythmic medications.

Conclusions And Relevance: This study found that, among patients who initiated anticoagulation therapy, 40% of those who initiated warfarin therapy and 47% of those who initiated DOAC treatment did not continuously adhere to therapy in the first year after AF diagnosis. Identifying longitudinal patterns of warfarin and DOAC adherence and the factors associated with them provides suggestions for the design of targeted strategies to mitigate suboptimal oral anticoagulation use.
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http://dx.doi.org/10.1001/jamanetworkopen.2019.21357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081375PMC
February 2020

Association of Overweight and Obesity Development Between Pregnancies With Stillbirth and Infant Mortality in a Cohort of Multiparous Women.

Obstet Gynecol 2020 03;135(3):634-643

Department of Epidemiology, Graduate School of Public Health, and the Department of Obstetrics, Gynecology, and Reproductive Sciences, School of Medicine, University of Pittsburgh, and the Magee-Womens Research Institute, Pittsburgh, Pennsylvania.

Objective: To identify the association of newly developed prepregnancy overweight and obesity with stillbirth and infant mortality.

Methods: We studied subsequent pregnancies of mothers who were normal weight at fertilization of their first identified pregnancy, from a population-based cohort that linked birth registry with death records in Pennsylvania, 2003-2013. Women with newly developed prepregnancy overweight and obesity were defined as those whose body mass index (BMI) before second pregnancy was between 25 and 29.9 or 30 or higher, respectively. Our main outcomes of interest were stillbirth (intrauterine death at 20 weeks of gestation or greater), infant mortality (less than 365 days after birth), neonatal death (less than 28 days after birth) and postneonatal death (29-365 days after birth). Associations of both prepregnancy BMI categories and continuous BMI with each outcome were estimated by nonparametric targeted minimum loss-based estimation and inverse-probability weighted dose-response curves, respectively, adjusting for race-ethnicity, smoking, and other confounders (eg, age, education).

Results: A cohort of 212,889 women were included for infant mortality analysis (192,941 women for stillbirth analysis). The crude rate of stillbirth and infant mortality in these final analytic cohorts were 3.3 per 1,000 pregnancies and 2.9 per 1,000 live births, respectively. Compared with women who stayed at a normal weight in their second pregnancies, those becoming overweight had 1.4 (95% CI 0.6-2.1) excess stillbirths per 1,000 pregnancies. Those becoming obese had 3.6 (95% CI 1.3-5.9) excess stillbirths per 1,000 pregnancies and 2.4 (95% CI 0.4-4.4) excess neonatal deaths per 1,000 live births. There was a dose-response relationship between prepregnancy BMI increases of more than 2 units and increased risk of stillbirth and infant mortality. In addition, BMI increases were associated with higher risks of infant mortality among women with shorter interpregnancy intervals (less than 18 months) compared with longer intervals.

Conclusion: Transitioning from normal weight to overweight or obese between pregnancies was associated with an increased risk of stillbirth and neonatal mortality.
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http://dx.doi.org/10.1097/AOG.0000000000003677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7147965PMC
March 2020

Heart fat and carotid artery atherosclerosis progression in recently menopausal women: impact of menopausal hormone therapy: The KEEPS trial.

Menopause 2020 03;27(3):255-262

Los Angeles Biomedical Research Institute, Torrance, CA.

Objective: Heart fat deposition has been linked to atherosclerosis, and both accelerate after menopause. Hormone therapy (HT) may differentially slow heart fat deposition and progression of atherosclerosis, depending on the specific HT agent or its route of administration. Our objective was to evaluate the effects of different HT agents, oral and transdermal, on associations between heart fat accumulation and atherosclerosis progression, measured by carotid intima-media thickness (CIMT), in recently menopausal women from the Kronos Early Estrogen Prevention Study (KEEPS) trial.

Methods: KEEPS was a randomized, placebo-controlled trial of the effects of 0.45 mg/d oral conjugated equine estrogens (o-CEE) or 50 mcg/d transdermal 17β-estradiol (t-E2), compared with placebo, on 48 months progression of CIMT. Epicardial adipose tissue (EAT) and paracardial adipose tissue (PAT) volumes were quantified by computed tomography.

Results: In all, 467 women (mean age [SD] 52.7 [2.5]; 78.2% White; 30% on o-CEE, 30.8% t-E2, 39.2% placebo) with heart fat volumes and CIMT at baseline and 48 months were included. EAT and PAT changes were not associated with CIMT progression; however, the assigned treatment significantly modified the association between PAT (but not EAT) change and CIMT progression. In the o-CEE group, adjusted CIMT progression was 12.66 μm (95% confidence interval [CI] 1.80, 23.52) lower than in t-E2 group (P = 0.02), and 10.09 μm (95% CI 0.79, 19.39) lower than in placebo group (P = 0.03), as per 1-SD increase in PAT.

Conclusion: Compared with t-E2, o-CEE appears to slow down the adverse effect of increasing PAT on progression of atherosclerosis. Whether this beneficial association is specific to CEE or to the oral route of CEE administration is unclear and should be assessed further.
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http://dx.doi.org/10.1097/GME.0000000000001472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113029PMC
March 2020

Visualization tool of variable selection in bias-variance tradeoff for inverse probability weights.

Ann Epidemiol 2020 01 13;41:56-59. Epub 2019 Dec 13.

Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA. Electronic address:

Purpose: Inversed probability weighted (IPW) estimators are commonly used to adjust for time-fixed or time-varying confounders. However, in high-dimensional settings, including all identified confounders may result in unstable weights leading to higher variance. We aimed to develop a visualization tool demonstrating the impact of each confounder on the bias and variance of IPW estimates, as well as the propensity score overlap.

Methods: A SAS macro was developed for this visualization tool and we demonstrate how this tool can be used to identify potentially problematic confounders of the association of statin use after myocardial infarction on one-year mortality in a plasmode simulation study using a cohort of 39,792 patients from the UK (1998-2012).

Results: Through the tool's output, we can identify problematic confounders (two instrumental variables) and important confounders by comparing the estimated psuedo MSE with that from the fully adjusted model and propensity score overlap plot.

Conclusion: Our results suggest that the analytic impact of all confounders should be considered carefully when fitting IPW estimators.
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http://dx.doi.org/10.1016/j.annepidem.2019.12.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864095PMC
January 2020

Arterial Stiffness Accelerates Within 1 Year of the Final Menstrual Period: The SWAN Heart Study.

Arterioscler Thromb Vasc Biol 2020 04 23;40(4):1001-1008. Epub 2020 Jan 23.

From the Department of Epidemiology, Graduate School of Public Health (S.S., M.M.B., E.B.-M., S.R.E.), University of Pittsburgh, PA.

Objective: Menopause may augment age-dependent increases in arterial stiffness, with black women having greater progression in midlife compared with white women. We sought to determine whether and when women experience changes in arterial stiffness relative to the final menstrual period (FMP) and whether these changes differ between black and white midlife women. Approach and Results: We evaluated 339 participants from the SWAN (Study of Women's Health Across the Nation) Heart Ancillary study (Study of Women's Health Across the Nation). Women had ≤2 carotid-femoral pulse-wave velocity (cfPWV) exams over a mean±SD of 2.3±0.5 years of follow-up. Annual percentage changes in cfPWV were estimated in 3 time segments relative to FMP and compared using piecewise linear mixed-effects models. At baseline, women were 51.1±2.8 years of age and 36% black. Annual percentage change (95% CI) in cfPWV varied by time segments: 0.9% (-0.6% to 2.3%) for >1 year before FMP, 7.5% (4.1% to 11.1%) within 1 year of FMP, and -1.0% (-2.8% to 0.8%) for >1 year after FMP. Annual percentage change in cfPWV within 1 year of FMP was significantly greater than the other 2 time segments; <0.05 for both comparisons. Adjusting for concurrent cardiovascular disease risk factors explained part of the change estimates but did not eliminate the difference. Black women had greater increase in cfPWV compared with white women in the first segment; for interaction, 0.04.

Conclusions: The interval within 1 year of FMP is a critical period for women when vascular functional alterations occur. These findings underscore the importance of more intensive lifestyle modifications in women transitioning through menopause.
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http://dx.doi.org/10.1161/ATVBAHA.119.313622DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101253PMC
April 2020

Mediation analysis for estimating cardioprotection of longitudinal RAS inhibition beyond lowering blood pressure and albuminuria in type 1 diabetes.

Ann Epidemiol 2020 01 6;41:7-13.e1. Epub 2019 Dec 6.

Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA.

Purpose: We assessed the extent of cardiovascular benefit of renin-angiotensin system (RAS) inhibition beyond lowering blood pressure (BP) and albuminuria in type 1 diabetes (T1D).

Methods: This cohort study included 605 T1D participants from the Pittsburgh Epidemiology of Diabetes Complications study without baseline coronary artery disease (CAD). Participant follow-up extended through 25 years. We implemented marginal structural models to estimate total effect of and controlled direct effect by isolating the role of BP or albuminuria in mediating the relation between RAS inhibitors and CAD.

Results: Total effect of longitudinal RAS inhibition treatment was associated with 38% decreased CAD risk (HR [95% CI]: 0.62 [0.23, 1.77]). The controlled direct effect of RAS inhibition was a 27% risk reduction (HR: 0.73 [0.20, 2.59]) when isolating the role of BP and 26% risk reduction (HR: 0.74 [0.16, 3.35]) when isolating the role of albuminuria. The mediation proportion for each 10 mm Hg systolic BP and each 1 log unit of albumin excretion rate were 34% and 37%, respectively.

Conclusion: Our findings suggest that BP regulation and albuminuria reduction can only partially explain cardiovascular benefit of RAS inhibition on CAD in T1D, supporting the assertion that RAS inhibitors provide additional cardioprotection beyond lowering BP and albuminuria.
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http://dx.doi.org/10.1016/j.annepidem.2019.12.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7024023PMC
January 2020

Effects of hospital-acquired pneumonia on long-term recovery and hospital resource utilization following moderate to severe traumatic brain injury.

J Trauma Acute Care Surg 2020 04;88(4):491-500

From the Department of Epidemiology (R.G.K., M.M.B., A.F.), Department of Physical Medicine and Rehabilitation (R.G.K., M.R.K., A.K.W.), and Department of Surgery (M.R.K., J.S.), University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Physical Medicine and Rehabilitation (S.B.J.), and Department of Rehabilitation Counseling (S.B.J.), UT Southwestern, Dallas, Texas; Department of Epidemiology (M.M.B), University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Rehabilitation Medicine (K.D.-O.'C.), and Department of Neurology (K.D.-O.'C.), Icahn School of Medicine at Mount Sinai, New York, New York; Department of Internal Medicine Epidemiology Division (M.J.P.), University of Utah, Salt Lake City, Utah; Clinical and Translational Science Institute (A.K.W.), Center for Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania, and Safar Center for Resuscitation Research (A.K.W.), University of Pittsburgh, Pittsburgh, Pennsylvania.

Background: Individuals with traumatic brain injury (TBI) have extended inpatient hospital stays that include prolonged mechanical ventilation, increasing risk for infections, including pneumonia. Studies show the negative short-term effects of hospital-acquired pneumonia (HAP) on hospital-based outcomes; however, little is known of its long-term effects.

Methods: A prospective cohort study was conducted. National Trauma Databank and Traumatic Brain Injury Model Systems were merged to derive a cohort of 3,717 adults with moderate-to-severe TBI. Exposure data were gathered from the National Trauma Databank, and outcomes were gathered from the Traumatic Brain Injury Model Systems. The primary outcome was the Glasgow Outcome Scale-Extended (GOS-E), which was collected at 1, 2, and 5 years postinjury. The GOS-E was categorized as favorable (>5) or unfavorable (≤5) outcomes. A generalized estimating equation model was fitted estimating the effects of HAP on GOS-E over the first 5 years post-TBI, adjusting for age, race, ventilation status, brain injury severity, injury severity score, thoracic Abbreviated Injury Scale score of 3 or greater, mechanism of injury, intraventricular hemorrhage, and subarachnoid hemorrhage.

Results: Individuals with HAP had a 34% (odds ratio, 1.34; 95% confidence interval, 1.15-1.56) increased odds for unfavorable GOS-E over the first 5 years post-TBI compared with individuals without HAP, after adjustment for covariates. There was a significant interaction between HAP and follow-up, such that the effect of HAP on GOS-E declined over time. Sensitivity analyses that weighted for nonresponse bias and adjusted for differences across trauma facilities did not appreciably change the results. Individuals with HAP spent 10.1 days longer in acute care and 4.8 days longer in inpatient rehabilitation and had less efficient functional improvement during inpatient rehabilitation.

Conclusion: Individuals with HAP during acute hospitalization have worse long-term prognosis and greater hospital resource utilization. Preventing HAP may be cost-effective and improve long-term recovery for individuals with TBI. Future studies should compare the effectiveness of different prophylaxis methods to prevent HAP.

Level Of Evidence: Prospective cohort study, level III.
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http://dx.doi.org/10.1097/TA.0000000000002562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7802881PMC
April 2020

Effects of Hormone Therapy on Heart Fat and Coronary Artery Calcification Progression: Secondary Analysis From the KEEPS Trial.

J Am Heart Assoc 2019 08 1;8(15):e012763. Epub 2019 Aug 1.

Los Angeles Biomedical Research Institute Torrance CA.

Background Heart fats (epicardial and paracardial adipose tissue [PAT]) are greater after menopause. Endogenous estrogen may regulate these fat depots. We evaluated the differential effects of hormone therapy formulations on heart fat accumulations and their associations with coronary artery calcification (CAC) progression in recently menopausal women from KEEPS (Kronos Early Estrogen Prevention Study). Methods and Results KEEPS was a multicenter, randomized, placebo-controlled trial of the effects of 0.45 mg/d oral conjugated equine estrogens and 50 µg/d transdermal 17β-estradiol, compared with placebo, on 48-month progression of subclinical atherosclerosis among 727 early menopausal women. CAC progression was defined if baseline CAC score was 0 and 48-month CAC score was >0 or if baseline CAC score was >0 and <100 and annualized change in CAC score was ≥10. Of 727 KEEPS participants, 474 (mean age: 52.7 [SD: 2.6]; 78.1% white) had computed tomography-based heart fat and CAC measures at both baseline and 48 months. Compared with women on placebo, women on oral conjugated equine estrogens were less likely to have any increase in epicardial adipose tissue (odds ratio for oral conjugated equine estrogens versus placebo: 0.62 [95% CI, 0.40-0.97]; =0.03). PAT did not change in any group. Changes in epicardial adipose tissue and PAT did not differ by treatment group. CAC increased in 14% of participants. The assigned treatment modified the association between PAT changes and CAC progression (=0.02) such that PAT increases were associated with CAC increases only in the transdermal 17β-estradiol group. Conclusions In recently menopausal women, oral conjugated equine estrogens may slow epicardial adipose tissue accumulation, whereas transdermal 17β-estradiol may increase progression of CAC associated with PAT accumulation. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00154180.
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http://dx.doi.org/10.1161/JAHA.119.012763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6761637PMC
August 2019

The menopause transition and women's health at midlife: a progress report from the Study of Women's Health Across the Nation (SWAN).

Menopause 2019 10;26(10):1213-1227

Department of Epidemiology, Graduate School of Public Health University of Pittsburgh, Pittsburgh, PA.

Objective: Our initial understanding of the menopause transition (MT) has been framed by clinical samples of women seeking treatment rather than by population-based studies. The Study of Women's Health Across the Nation (SWAN) initiated in 1996 with an overall goal to define the MT, to characterize its biological and psychosocial antecedents and sequelae in an ethnically and racially diverse sample of midlife women.

Methods: This review summarizes the central findings of SWAN to date that can inform women and their healthcare providers about the impact of the MT and midlife aging on overall health and well-being.

Results: SWAN characterized changes in reproductive axis and menstrual cycle patterns that informed the development of the reproductive aging staging system Staging of Reproductive Aging Workshop+10; MT-related symptoms and mental health (vasomotor symptoms, sleep complaints, psychological symptoms, cognitive performance, and urogenital and sexual health); and physiological systems and functions (cardiovascular and cardiometabolic health, bone health, physical function performance) that are influenced by the MT. SWAN demonstrated substantial interrelations among these changes and significant racial/ethnic differences in the rate and magnitude of change in multiple health indictors in midlife women. The findings point to midlife as a critical stage for adopting healthy behavior and preventive strategies.

Conclusions: Over the past 23 years, SWAN has advanced our understanding of the impact of the MT and midlife aging on health and well-being in women. SWAN will be instrumental to determine whether MT-related changes during midlife are related to unfavorable health and well-being in early old age.
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http://dx.doi.org/10.1097/GME.0000000000001424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6784846PMC
October 2019

Adherence to Anticoagulation and Risk of Stroke Among Medicare Beneficiaries Newly Diagnosed with Atrial Fibrillation.

Am J Cardiovasc Drugs 2020 Apr;20(2):199-207

Division of General Internal Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.

Introduction: The objective of this study was to compare the risk of stroke in atrial fibrillation (AF) with adherent use of oral anticoagulation (OAC), non-adherent use, and non-use of OAC.

Methods: Using 2013-2016 Medicare claims data, we identified patients newly diagnosed with AF in 2014-2015 and collected prescriptions filled for OAC in the 12 months after AF diagnosis (n = 39,272). We categorized participants each day into three time-dependent exposures: adherent use (≥ 80% of the previous 30 days covered with OAC), non-adherent use (0-80% covered with OAC), and non-use (0%). We constructed Cox proportional hazards models to estimate the association between time-dependent exposures and time to stroke, adjusting for demographics and clinical characteristics.

Results: The sample included 39,272 patients. Study participants spent 35.0% of the follow-up period in the adherent use exposure category, 10.9% in the non-adherent category, and 54.0% in the non-use category. OAC adherent use [hazard ratio (HR) 0.62; 95% confidence interval (CI) 0.52-0.74] and non-adherent use (HR 0.74; 95% CI 0.57-0.95) were associated with lower hazards of stroke than non-use. Adherent use of DOAC (HR 0.54; 95% CI 0.42-0.69) and warfarin (HR 0.70; 95% CI 0.56-0.89) was associated with lower risk of stroke than non-use, but the risk of stroke did not statistically differ between DOAC and warfarin adherent use (HR 0.77; 95% CI 0.56-1.04).

Discussion: Although adherence to OAC reduces stroke risk by nearly 40%, newly diagnosed AF patients in Medicare adhere to OAC on average only one third of the first year after AF diagnosis.
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http://dx.doi.org/10.1007/s40256-019-00371-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073283PMC
April 2020

Social Role-Related Stress and Social Role-Related Reward as Related to Subsequent Subclinical Cardiovascular Disease in a Longitudinal Study of Midlife Women: The Study of Women's Health Across the Nation.

Psychosom Med 2019 Nov/Dec;81(9):821-832

From the Department of Epidemiology (Stewart, Barinas-Mitchell, Matthews, El Khoudary, Brooks), University of Pittsburgh Graduate School of Public Health; Department of Psychiatry (Matthews), University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Department of Medicine (Magnani), University of Pittsburgh, Pittsburgh, PA; and Division of Cardiovascular Medicine (Jackson), University of Alabama Birmingham, Birmingham, Alabama.

Objective: The purpose of this study was to determine if midlife social role quality, defined by the stress and rewards associated with four social roles, is related to later-life subclinical cardiovascular disease (SCVD) in a cohort of women transitioning through menopause.

Methods: The Study of Women's Health Across the Nation (SWAN) is a longitudinal cohort study of midlife women. Stress and reward from four social roles (spouse, parent, employee, caregiver) were assessed at seven early visits. Later-life SCVD was assessed via carotid ultrasound and brachial-ankle pulse wave velocity at two later visits. We tested whether ever reporting an "extremely" or "quite a bit" stressful role was related to SCVD. We also tested whether cumulative stress and reward, as well as baseline and change in stress and reward were related to SCVD, adjusting for demographics and cardiovascular risk factors.

Results: Among 1602 women, reporting a stressful role during midlife (between ages 47 and 52 years) was associated with later-life (age 61 years) carotid intima-media thickness, which was 21 μm thicker than never reporting a stressful role. No significant relationships between stressful roles and other SCVD measures were identified. Cumulative and baseline change models of stress and reward were not related to SCVD.

Conclusion: A stressful social role in midlife was associated with greater atherosclerotic burden in later-life in a cohort of women transitioning through menopause. Social role rewards were unrelated to better later-life SCVD. These findings extend the knowledge of stress and cardiovascular disease in women by using measures of stress and reward for multiple social roles over the years of midlife.
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http://dx.doi.org/10.1097/PSY.0000000000000733DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832794PMC
August 2020

Optimal Blood Pressure Thresholds for Minimal Coronary Artery Disease Risk in Type 1 Diabetes.

Diabetes Care 2019 09 27;42(9):1692-1699. Epub 2019 Jun 27.

Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA.

Objective: We aimed to determine optimal blood pressure (BP) thresholds for minimizing coronary artery disease (CAD) risk in people with childhood-onset type 1 diabetes.

Research Design And Methods: The Pittsburgh Epidemiology of Diabetes Complications (EDC) Study participants without known CAD at baseline ( = 605) were included and followed for 25 years. The associations of time-weighted BP measures (systolic BP [SBP], diastolic BP [DBP], and mean arterial pressure) with incident CAD were examined by using Cox models. Areas under the receiver operating characteristic curve (AUC) were summarized by different cut points of time-weighted BPs. Risk stratification analyses were then performed on the basis of BP (<120/80 vs. ≥120/80 mmHg) and HbA (<8% vs. ≥8%).

Results: Baseline mean age was 27 years. Half of the cohort were women and 98% were white. A dose-gradient association was observed for categorized time-weighted BPs and CAD. According to AUC, the optimal cut point for SBP was 120 mmHg and for DBP was 80 mmHg. BP ≥120/80 mmHg was associated with a 1.9 times (95% CI 1.4, 2.6) greater risk of developing CAD than that for BP <120/80 mmHg. Participants with good control of both BP and HbA had BP <120/80 mmHg and HbA <8%. Those with only high BP (hazard ratio [HR] 2.0 [95% CI 1.1, 3.9]) carried a similar risk of developing CAD as those with only high HbA (HR 1.6 [95% CI 0.97, 2.8]).

Conclusions: The optimal BP threshold associated with minimal CAD risk is 120/80 mmHg in young adults with childhood-onset type 1 diabetes.
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http://dx.doi.org/10.2337/dc19-0480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6702601PMC
September 2019

Prognostic Significance of Pulse Pressure and Other Blood Pressure Components for Coronary Artery Disease in Type 1 Diabetes.

Am J Hypertens 2019 10;32(11):1075-1081

Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Background: To compare in individuals with type 1 diabetes the prediction of incident coronary artery disease (CAD) by components of resting blood pressure-systolic, diastolic, pulse pressure, and mean arterial pressure.

Methods: In 605 participants without known CAD at baseline and followed sequentially for 25 years, we used Cox modeling built for each blood pressure component associated with incident CAD, overall and stratified by age (<35 and ≥35 years) or hemoglobin A1c (HbA1c) (<9% and ≥9%).

Results: Baseline mean age and diabetes duration were 27 and 19 years, respectively. We observed an early asymptote and then fall in diastolic blood pressure in their late 30s and early 40s in this group of type 1 diabetes individuals, followed by an early rise of pulse pressure. Adjusted hazard ratios (HR) (95% con) for CAD associated with 1 SD pressure increase were 1.35 (1.17, 1.56) for systolic pressure; 1.30 (1.12, 1.51) for diastolic pressure; 1.20 (1.03, 1.39) for pulse pressure; and 1.35 (1.17, 1.56) for mean arterial pressure. Pulse pressure emerged as a strong predictor of CAD at age ≥ 35 years (HR: 1.49 [1.15, 1.94]) and for HbA1c ≥ 9% (HR: 1.32 [1.01, 1.72]).

Conclusions: Individuals with type 1 diabetes may manifest early vascular aging by an early decline in diastolic blood pressure and rise in pulse pressure, the latter parameter becoming a comparable to systolic blood pressure in predictor incident CAD in those aged over 35 years and those with poor glycemic control.
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http://dx.doi.org/10.1093/ajh/hpz099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6794945PMC
October 2019