Publications by authors named "B Gwen Windham"

138 Publications

Reflection on modern methods: shared-parameter models for longitudinal studies with missing data.

Int J Epidemiol 2021 Jun 11. Epub 2021 Jun 11.

Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.

A primary goal of longitudinal studies is to examine trends over time. Reported results from these studies often depend on strong, unverifiable assumptions about the missing data. Whereas the risk of substantial bias from missing data is widely known, analyses exploring missing-data influences are commonly done either ad hoc or not at all. This article outlines one of the three primary recognized approaches for examining missing-data effects that could be more widely used, i.e. the shared-parameter model (SPM), and explains its purpose, use, limitations and extensions. We additionally provide synthetic data and reproducible research code for running SPMs in SAS, Stata and R programming languages to facilitate their use in practice and for teaching purposes in epidemiology, biostatistics, data science and related fields. Our goals are to increase understanding and use of these methods by providing introductions to the concepts and access to helpful tools.
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http://dx.doi.org/10.1093/ije/dyab086DOI Listing
June 2021

Association between Circulating Protein C Levels and Incident Dementia: The Atherosclerosis Risk in Communities Study.

Neuroepidemiology 2021 Jun 2:1-10. Epub 2021 Jun 2.

Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA.

Introduction: Hemostasis depends on the delicate balance between coagulants and anticoagulants. Higher levels of circulating coagulants have been associated with higher risk of cerebral infarctions and dementia. In contrast, higher levels of circulating protein C, an endogenous anticoagulant, have been associated with lower risk of cerebral infarctions, and the association between protein C levels and the risk of dementia is unknown. The goal of this study was to evaluate the association of circulating protein C levels in midlife and late life with incident dementia.

Methods: Circulating protein C levels were measured using blood samples collected at the midlife baseline (1987-1989) and the late-life baseline (2011-2013) among 14,462 and 3,614 participants, respectively, in the Atherosclerosis Risk in Communities study. Protein C levels were measured using enzyme-linked immunosorbent assay at midlife and a modified aptamer-based assay at late life. Participants were followed up to 2013 from midlife and up to 2017 from late life. Incident dementia was ascertained during the follow-up periods using in-person cognitive and functional assessment, informant interviews, and International Classification of Diseases codes at hospitalization discharge and on death certificates. Cause-specific Cox regression models were used to evaluate the association between quintiles of circulating protein C and incident dementia.

Results: From midlife (mean age of 54), 1,389 incident dementia events were observed over a median follow-up of 23 years. From late life (mean age of 75), 353 incident dementia events were observed over a median follow-up of 4.9 years. At both midlife and late life, circulating protein C had an inverse association with incident dementia after adjusting for demographic, vascular, and hemostatic risk factors, incident stroke as time-dependent covariate, and incorporating stabilized weights based on propensity scores (quintile 5 vs. quintile 1 as the reference, midlife hazard ratio 0.80, 95% confidence interval 0.66-0.96, p value for trend 0.04; late-life hazard ratio 0.84, 95% confidence interval: 0.55-1.28, p value for trend 0.04).

Discussion/conclusion: Circulating protein C has an inverse association with incident dementia independent of established risk factors, including stroke. Our results suggest studying anticoagulants in addition to coagulants can increase our understanding on the relationship between hemostasis and dementia.
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http://dx.doi.org/10.1159/000516287DOI Listing
June 2021

American Diabetes Association Framework for Glycemic Control in Older Adults: Implications for Risk of Hospitalization and Mortality.

Diabetes Care 2021 May 18. Epub 2021 May 18.

Department of Epidemiology and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, MD.

Objective: The 2021 American Diabetes Association (ADA) guidelines recommend different A1C targets in older adults that are based on comorbid health status. We assessed risk of mortality and hospitalizations in older adults with diabetes across glycemic control (A1C <7%, 7 to <8%, ≥8%) and ADA-defined health status (healthy, complex/intermediate, very complex/poor) categories.

Research Design And Methods: Prospective cohort analysis of older adults aged 66-90 years with diagnosed diabetes in the Atherosclerosis Risk in Communities (ARIC) study.

Results: In the 1,841 participants (56% women, 29% Black), 32% were classified as healthy, 42% as complex/intermediate, and 27% as very complex/poor health. Over a median 6-year follow-up, there were 409 (22%) deaths and 4,130 hospitalizations (median [25th-75th percentile] 1 per person [0-3]). In the very complex/poor category, individuals with A1C ≥8% (vs. <7%) had higher mortality risk (hazard ratio 1.76 [95% CI 1.15-2.71]), even after adjustment for glucose-lowering medication use. Within the very complex/poor health category, individuals with A1C ≥8% (vs. <7%) had more hospitalizations (incidence rate ratio [IRR] 1.41 [95% CI 1.03-1.94]). In the complex/intermediate group, individuals with A1C ≥8% (vs. <7%) had more hospitalizations, even with adjustment for glucose-lowering medication use (IRR 1.64 [1.21-2.24]). Results were similar, but imprecise, when the analysis was restricted to insulin or sulfonylurea users ( = 663).

Conclusions: There were substantial differences in mortality and hospitalizations across ADA health status categories, but older adults with A1C <7% were not at elevated risk, regardless of health status. Our results support the 2021 ADA guidelines and indicate that <7% is a reasonable treatment goal in some older adults with diabetes.
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http://dx.doi.org/10.2337/dc20-3045DOI Listing
May 2021

Atrial Fibrillation and Ischemic Stroke with the Amyloidogenic V122I Transthyretin Variant among Black Americans.

J Am Coll Cardiol 2021 Apr 19. Epub 2021 Apr 19.

Division of Cardiology, Department of Medicine, Brigham and Women's Hospital, Boston, MA. Electronic address:

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http://dx.doi.org/10.1016/j.jacc.2021.04.042DOI Listing
April 2021

Longitudinal associations of blood pressure with aortic stiffness and pulsatility: the Atherosclerosis Risk in Communities Study.

J Hypertens 2021 05;39(5):987-993

Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.

Objective: To characterize the longitudinal relationships between blood pressure measured over 24 years and arterial stiffness in late life measured as pulse wave velocity (PWV).

Methods: Carotid--femoral (cf) and femoral--ankle (fa) PWV were measured in 4166 adults at the visit 5 Atherosclerosis Risk in Communities study cohort examination (2011-2013). Participants were categorized into tertiles of PWV measurements. Blood pressure measurements were made at baseline (1987-1989), three subsequent triennial examinations, and visit 5.

Results: Partial correlation coefficients between visit 5 cfPWV and SBP ranged from 0.13 for visit 1 SBP to 0.32 for visit 5 SBP. For visit 5 faPWV, correlations were ∼0 for visits 1 to 4 SBP, but was 0.20 for visit 5 SBP. Over 24 years of follow-up, those with higher average SBP were more likely to fall in the middle and upper tertiles of visit 5 cfPWV. Average pulse pressure and mean arterial pressure over 24 years had similar but weaker associations with cfPWV tertiles. DBP had no clear association with cfPWV. Blood pressure measurements were positively associated with faPWV tertiles only cross-sectionally at visit 5.

Conclusion: Adult life-course measures of SBP, more so than mean arterial and pulse pressure, were associated with later life central arterial stiffness. By contrast, only contemporaneous measures of blood pressure were associated with peripheral arterial stiffness. Although arterial stiffness was only measured at later life, these results are consistent with the notion that elevated blood pressure over time is involved in the pathogenesis of arterial stiffening.
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http://dx.doi.org/10.1097/HJH.0000000000002731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086051PMC
May 2021