Publications by authors named "Andrea LaCroix"

408 Publications

Community-Dwelling Older Adults and Physical Activity Recommendations: Patterns of Aerobic, Strengthening, and Balance Activities.

J Aging Phys Act 2021 Oct 15:1-13. Epub 2021 Oct 15.

Department of Rehabilitation and Movement Science, The University of Vermont, Burlington, VT,USA.

Though it is known that most older adults do not meet the recommended physical activity (PA) guidelines, little is known regarding their participation in balance activities or the full guidelines. Therefore, we sought to describe PA patterns among 1,352 community-dwelling older adult participants of the Adult Changes in Thought study, a longitudinal cohort study exploring dementia-related risk factors. We used a modified version of the Community Healthy Activities Model Program for Seniors questionnaire to explore PA performed and classify participants as meeting or not meeting the full guidelines or any component of the guidelines. Logistic regression was used to identify factors associated with meeting PA guidelines. Despite performing 10 hr of weekly PA, only 11% of participants met the full guidelines. Older age, greater body mass index, needing assistance with instrumental daily activities, and heart disease were associated with decreased odds of meeting PA guidelines. These results can guide interventions that address PA among older adults.
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http://dx.doi.org/10.1123/japa.2021-0194DOI Listing
October 2021

Accelerometer-Measured Daily Steps, Physical Function, and Subsequent Fall Risk in Older Women: The Objective Physical Activity and Cardiovascular Disease in Older Women Study.

J Aging Phys Act 2021 Oct 9:1-11. Epub 2021 Oct 9.

Herbert Wertheim School of Public Health and Longevity Science, UC San Diego School of Medicine, San Diego, CA,USA.

Steps per day were measured by accelerometer for 7 days among 5,545 women aged 63-97 years between 2012 and 2014. Incident falls were ascertained from daily fall calendars for 13 months. Median steps per day were 3,216. There were 5,473 falls recorded over 61,564 fall calendar-months. The adjusted incidence rate ratio comparing women in the highest versus lowest step quartiles was 0.71 (95% confidence interval [0.54, 0.95]; ptrend across quartiles = .01). After further adjustment for physical function using the Short Physical Performance Battery, the incidence rate ratio was 0.86 ([0.64, 1.16]; ptrend = .27). Mediation analysis estimated that 63.7% of the association may be mediated by physical function (p = .03). In conclusion, higher steps per day were related to lower incident falls primarily through their beneficial association with physical functioning. Interventions that improve physical function, including those that involve stepping, could reduce falls in older adults.
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http://dx.doi.org/10.1123/japa.2021-0159DOI Listing
October 2021

Nonparametric parameters of 24-hour rest-activity rhythms and long-term cognitive decline and incident cognitive impairment in older men.

J Gerontol A Biol Sci Med Sci 2021 Sep 24. Epub 2021 Sep 24.

Research Institute, California Pacific Medical Center, San Francisco, CA.

Altered 24-hour rest-activity rhythms may be associated with cognitive impairment in older adults, but evidence from prospective studies is limited. Non-parametric methods were used to assess actigraphy-based activity patterns in 2,496 older men. Incident cognitive impairment was assessed four times over 12 years using the Modified Mini Mental State Examination (3MS) and Trails B tests, self-reported medication use, and clinical diagnosis. The highest quartile (vs. the lowest) of intradaily variability and the lowest quartiles (vs. the highest) of interdaily stability and relative amplitude were associated with incident cognitive impairment ((Hazard ratio (95% confidence interval): 1.82 (1.31, 2.53)), 1.36 (0.99, 1.86), and 1.85 (1.33, 2.56), respectively). A larger increase in intradaily variability over 7.5 years was associated with a greater subsequent decline in 3MS scores but not in Trails B performance. In conclusion, less stable and more variable rest-activity rhythms may represent early biomarkers of cognitive impairment in older men.
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http://dx.doi.org/10.1093/gerona/glab275DOI Listing
September 2021

The short physical performance battery and incident heart failure among older women: the OPACH study.

Am J Prev Cardiol 2021 Dec 20;8:100247. Epub 2021 Aug 20.

Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, University at Buffalo, SUNY, Buffalo, NY, USA.

Objective: Reduced functional capacity is a hallmark of early pre-clinical stages of heart failure (HF). The Short Physical Performance Battery (SPPB) is a valid measure of lower extremity physical function, has relatively low implementation burden, and is associated with cardiovascular disease and mortality. However, the SPPB-HF association is understudied in older women among whom HF burden is high.

Methods: Women ( = 5325; mean age 79 ± 7 years; 34% Black, 18% Hispanic, and 49% White) without prior HF completed the SPPB consisting of standing balance, strength, and walking tests that were summarized as a composite score from 0 (lowest) to 12 (highest), categorized as very low (0-3), low (4-6), medium (7-9), or high (10-12). Participants were followed for up to 8 years for incident HF (306 cases identified). Cox proportional hazards regression estimated hazard ratios (HR) adjusting for age, race/ethnicity, education, smoking, alcohol, diabetes, hypertension, COPD, osteoarthritis, depression, BMI, systolic blood pressure, lipids, glucose, and accelerometer-measured moderate-vigorous physical activity (MVPA) and sedentary time.

Results: Incident HF cases (crude rate per 1000 person-years) in the four SPPB categories (very low to high) were 34 (26.0), 79 (14.5), 128 (9.3), and 65 (5.6). Corresponding multivariable-adjusted HRs (95% CIs) were 2.22 (1.34-3.66), 1.63 (1.11-2.38), 1.39 (1.00-1.94), and 1.00 (referent; -trend<0.001). Higher HF risk was associated with lower SPPB in women with major modifiable HF risk factors including obesity (HR per 3-unit SPPB decrement: present HR = 1.41, absent HR = 1.41), hypertension (present HR = 1.45, absent HR = 1.30), diabetes (present HR = 1.32, absent HR = 1.44), and lower accelerometer-measured MVPA (<45 min/day HR = 1.29, ≥45 min/day HR = 1.60); all -interaction>0.10.

Conclusion: Lower SPPB scores were associated with greater risk of incident HF in older women even after accounting for differences in HF risk factors and objectively measured PA. Implementing the SPPB in clinical settings could potentially enhance individual-level HF risk assessment, which should be further explored.
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http://dx.doi.org/10.1016/j.ajpc.2021.100247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8441145PMC
December 2021

Biomarkers of kidney function and cognitive ability: A Mendelian randomization study.

J Neurol Sci 2021 Sep 14;430:118071. Epub 2021 Sep 14.

Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, 9500 Gilman Dr, La Jolla, CA, USA.

Background: Estimated glomerular filtration rate (eGFR), albuminuria and serum uric acid (SUA) are markers of kidney function that have been associated with cognitive ability. However, whether these associations are causal is unclear.

Methods: We performed one-sample Mendelian randomization (MR) to estimate the effects of kidney function markers on cognitive performance using data from the UK Biobank. Polygenic scores for SUA, urine albumin to creatinine ratio (ACR), estimated glomerular filtration rate based on serum creatinine (eGFRcre) and serum cystatin C (eGFRcys) were used as instrumental variables, and cognitive function outcomes included tests of verbal-numeric reasoning, reaction time, visual memory, and numeric memory.

Results: We found no evidence of a causal effect of genetically determined SUA, eGFRcre or eGFRcys on cognitive function outcomes. There was no association between a polygenic score for ACR and verbal-numeric reasoning or numeric memory. However, there was suggestive evidence of a relationship between genetically increased ACR and slower reaction time and worse visual memory. ACR was no longer significantly associated with visual memory in analyses using an unweighted polygenic score and in analyses stratified by sex and age category. Pleiotropy adjusted estimates were directionally consistent with those of the principal analysis but overlapped with the null.

Conclusions: This MR study does not support causal effects of SUA, eGFRcre or eGFRcys on cognitive performance. Genetically increased ACR was associated with slower processing speed and visual memory, but results need confirmation in independent samples.
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http://dx.doi.org/10.1016/j.jns.2021.118071DOI Listing
September 2021

Association of Endogenous Pregnenolone, Progesterone, and Related Metabolites with Risk of Endometrial and Ovarian Cancers in Postmenopausal Women: The B∼FIT Cohort.

Cancer Epidemiol Biomarkers Prev 2021 Aug 31. Epub 2021 Aug 31.

School of Public Health, University of Maryland, College Park, Maryland.

Background: Postmenopausal pregnenolone and/or progesterone levels in relation to endometrial and ovarian cancer risks have been infrequently evaluated. To address this, we utilized a sensitive and reliable assay to quantify prediagnostic levels of seven markers related to endogenous hormone metabolism.

Methods: Hormones were quantified in baseline serum collected from postmenopausal women in a cohort study nested within the Breast and Bone Follow-up to the Fracture Intervention Trial (B∼FIT). Women using exogenous hormones at baseline (1992-1993) were excluded. Incident endometrial ( = 65) and ovarian ( = 67) cancers were diagnosed during 12 follow-up years and compared with a subcohort of 345 women (no hysterectomy) and 413 women (no oophorectomy), respectively. Cox models with robust variance were used to estimate cancer risk.

Results: Circulating progesterone levels were not associated with endometrial [tertile (T)3 vs. T1 HR (95% confidence interval): 1.87 (0.85-4.11); = 0.17] or ovarian cancer risk [1.16 (0.58-2.33); 0.73]. Increasing levels of the progesterone-to-estradiol ratio were inversely associated with endometrial cancer risk [T3 vs. T1: 0.29 (0.09-0.95); 0.03]. Increasing levels of 17-hydroxypregnenolone were inversely associated with endometrial cancer risk [0.40 (0.18-0.91); 0.03] and positively associated with ovarian cancer risk [3.11 (1.39-6.93); 0.01].

Conclusions: Using sensitive and reliable assays, this study provides novel data that endogenous progesterone levels are not strongly associated with incident endometrial or ovarian cancer risks. 17-hydroxypregnenolone was positively associated with ovarian cancer and inversely associated with endometrial cancer.

Impact: While our results require replication in large studies, they provide further support of the hormonal etiology of endometrial and ovarian cancers.
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http://dx.doi.org/10.1158/1055-9965.EPI-21-0669DOI Listing
August 2021

Application of Convolutional Neural Network Algorithms for Advancing Sedentary and Activity Bout Classification.

J Meas Phys Behav 2021 Jun 25;4(2):102-110. Epub 2021 Feb 25.

The Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA, USA.

Background: Machine learning has been used for classification of physical behavior bouts from hip-worn accelerometers; however, this research has been limited due to the challenges of directly observing and coding human behavior "in the wild." Deep learning algorithms, such as convolutional neural networks (CNNs), may offer better representation of data than other machine learning algorithms without the need for engineered features and may be better suited to dealing with free-living data. The purpose of this study was to develop a modeling pipeline for evaluation of a CNN model on a free-living data set and compare CNN inputs and results with the commonly used machine learning random forest and logistic regression algorithms.

Method: Twenty-eight free-living women wore an ActiGraph GT3X+accelerometer on their right hip for 7 days. A concurrently worn thigh-mounted activPAL device captured ground truth activity labels. The authors evaluated logistic regression, random forest, and CNN models for classifying sitting, standing, and stepping bouts. The authors also assessed the benefit of performing feature engineering for this task.

Results: The CNN classifier performed best (average balanced accuracy for bout classification of sitting, standing, and stepping was 84%) compared with the other methods (56% for logistic regression and 76% for random forest), even without performing any feature engineering.

Conclusion: Using the recent advancements in deep neural networks, the authors showed that a CNN model can outperform other methods even without feature engineering. This has important implications for both the model's ability to deal with the complexity of free-living data and its potential transferability to new populations.
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http://dx.doi.org/10.1123/jmpb.2020-0016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8389343PMC
June 2021

Validity of Two Awake Wear-Time Classification Algorithms for activPAL in Youth, Adults, and Older Adults.

J Meas Phys Behav 2021 22;4(2):151-162. Epub 2021 Apr 22.

University of California, San Diego.

Background: The authors assessed agreement between participant diaries and two automated algorithms applied to activPAL (PAL Technologies Ltd, Glasgow, United Kingdom) data for classifying awake wear time in three age groups.

Methods: Study 1 involved 20 youth and 23 adults who, by protocol, removed the activPAL occasionally to create nonwear periods. Study 2 involved 744 older adults who wore the activPAL continuously. Both studies involved multiple assessment days. In-bed, out-of-bed, and nonwear times were recorded in the participant diaries. The CREA (in PAL processing suite) and ProcessingPAL (secondary application) algorithms estimated out-of-bed wear time. Second- and day-level agreement between the algorithms and diary was investigated, as were associations of sedentary variables with self-rated health.

Results: The overall accuracy for classifying out-of-bed wear time as compared with the diary was 89.7% (Study 1) to 95% (Study 2) for CREA and 89.4% (Study 1) to 93% (Study 2) for ProcessingPAL. Over 90% of the nonwear time occurring in nonwear periods >165 min was detected by both algorithms, while <11% occurring in periods ≤165 min was detected. For the daily variables, the mean absolute errors for each algorithm were generally within 0-15% of the diary mean. Most Spearman correlations were very large (≥.81). The mean absolute errors and correlations were less favorable for days on which any nonwear time had occurred. The associations between sedentary variables and self-rated health were similar across processing methods.

Conclusion: The automated awake wear-time classification algorithms performed similarly to the diary information on days without short (≤2.5-2.75 hr) nonwear periods. Because both diary and algorithm data can have inaccuracies, best practices likely involve integrating diary and algorithm output.
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http://dx.doi.org/10.1123/jmpb.2020-0045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386818PMC
April 2021

Association of Epigenetic Age Acceleration with Incident Mild Cognitive Impairment and Dementia Among Older Women.

J Gerontol A Biol Sci Med Sci 2021 Aug 21. Epub 2021 Aug 21.

Herbert Wertheim School of Public Health and Human Longevity Science, University of California, San Diego, La Jolla, CA, USA.

Background: Epigenetic age acceleration (AgeAccel), which indicates faster biological aging relative to chronological age, has been associated with lower cognitive function. However, the association of AgeAccel with mild cognitive impairment (MCI) or dementia is not well-understood. We examined associations of four AgeAccel measures with incident MCI and dementia.

Methods: This prospective analysis included 578 older women from the Women's Health Initiative Memory Study selected for a case-cohort study of coronary heart disease (CHD). Women were free of CHD and cognitive impairment at baseline. Associations of AgeAccel measures (intrinsic AgeAccel [IEAA], extrinsic AgeAccel [EEAA], AgeAccelPheno, and AgeAccelGrim) with risks for incident adjudicated diagnoses of MCI and dementia overall and stratified by incident CHD status were evaluated.

Results: IEAA was not significantly associated with MCI (HR 1.23; 95% CI 0.99-1.53), dementia (HR 1.10; 95% CI 0.88-1.38), or cognitive impairment (HR 1.18; 95% CI 0.99-1.40). In stratified analysis by incident CHD status, there was a 39% (HR 1.39; 95% CI 1.07-1.81) significantly higher risk of MCI for every 5-year increase in IEAA among women who developed CHD during follow-up. Other AgeAccel measures were not significantly associated with MCI or dementia.

Conclusion: IEAA was not significantly associated with cognitive impairment overall but was associated with impairment among women who developed CHD. Larger studies designed to examine associations of AgeAccel with cognitive impairment are needed, including exploration of whether associations are stronger in the setting of underlying vascular pathologies.
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http://dx.doi.org/10.1093/gerona/glab245DOI Listing
August 2021

Associations Between Perceived Neighborhood Walkability and Device-Based Physical Activity and Sedentary Behavior Patterns in Older Adults.

J Aging Phys Act 2021 Aug 13:1-9. Epub 2021 Aug 13.

Neighborhood walkability has been associated with self-reported sedentary behavior (SB) and self-reported and objective physical activity. However, self-reported measures of SB are inaccurate and can lead to biased estimates, and few studies have examined how associations differ by gender and age. The authors examined the relationships between perceived neighborhood walkability measured with the Physical Activity Neighborhood Environment Scale (scored 1.0-4.0) and device-based SB and physical activity in a cohort of community-dwelling older adults (N = 1,077). The authors fit linear regression models adjusting for device wear time, demographics, self-rated health, and accounting for probability of participation. The Higher Physical Activity Neighborhood Environment Scale was associated with higher steps (+676 steps/point on the Physical Activity Neighborhood Environment Scale, p = .001) and sit-to-stand transitions (+2.4 transitions/point, p = .018). Though not statistically significant, stratified analyses suggest an attenuation of effect for those aged 85 years and older and for women. Consistent with previous literature, neighborhood walkability was associated with more steps, though not with physical activity time. The neighborhood environment may also influence SB.
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http://dx.doi.org/10.1123/japa.2020-0387DOI Listing
August 2021

Markers of Kidney Function and Longitudinal Cognitive Ability Among Older Community-Dwelling Adults: The Rancho Bernardo Study.

J Alzheimers Dis 2021 ;83(1):319-331

Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA, USA.

Background: Reduced kidney function has been associated with cognitive decline. Most studies have examined a single marker of kidney function and have limited duration of follow-up.

Objective: This study evaluated associations between markers of kidney function (urine albumin, estimated glomerular filtration rate [eGFR], and hyperuricemia) with cognitive performance over time.

Methods: This is a longitudinal study of 1,634 community-dwelling adults (mean age = 71.7 years), with kidney function markers and cognitive ability measured at baseline (1992-1996) and at up to five additional time points with a maximum of 23.4 years (mean = 8.1 years) of follow-up. Associations between kidney function and cognitive performance were assessed using linear mixed effects models. Testing for interaction by sex was conducted.

Results: Albuminuria (urine albumin-to-creatinine ratio [ACR]≥30 mg/g) was associated with steeper annual declines in global cognitive function (MMSE, β= -0.12, p = 0.003), executive function (Trails B, β= 4.50, p < 0.0001) and episodic memory (Buschke total recall, β= -0.62, p = 0.02) scores in men. Results were similar when cognitive test scores were regressed on latent trajectory classes of ACR. In men, hyperuricemia (serum uric acid [SUA]≥6.8 mg/dl for men and SUA≥6.0 mg/dl for women) was associated with lower baseline MMSE (β= -0.70, p = 0.009) scores but not with MMSE change over time. No such associations were detected in women. There were no significant associations between eGFR and cognitive performance for either sex.

Conclusion: In older men, albuminuria is an independent predictor of subsequent cognitive decline. More investigations are needed to explain the observed sex differences and the potential relationship between hyperuricemia and poorer global cognition.
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http://dx.doi.org/10.3233/JAD-201605DOI Listing
January 2021

Recruitment of a multi-site randomized controlled trial of aerobic exercise for older adults with amnestic mild cognitive impairment: The EXERT trial.

Alzheimers Dement 2021 Jul 23. Epub 2021 Jul 23.

Department of Internal Medicine-Geriatrics, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.

Introduction: Effective strategies to recruit older adults with mild cognitive impairment (MCI) into nonpharmacological intervention trials are lacking.

Methods: Recruitment for EXERT, a multisite randomized controlled 18-month trial examining the effects of aerobic exercise on cognitive trajectory in adults with amnestic MCI, involved a diverse portfolio of strategies to enroll 296 participants.

Results: Recruitment occurred September 2016 through March 2020 and was initially slow. After mass mailings of 490,323 age- and geo-targeted infographic postcards and brochures, recruitment rates increased substantially, peaking at 16 randomizations/month in early 2020. Mass mailings accounted for 52% of randomized participants, whereas 25% were recruited from memory clinic rosters, electronic health records, and national and local registries. Other sources included news broadcasts, public service announcements (PSA), local advertising, and community presentations.

Discussion: Age- and geo-targeted mass mailing of infographic materials was the most effective approach in recruiting older adults with amnestic MCI into an 18-month exercise trial.
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http://dx.doi.org/10.1002/alz.12401DOI Listing
July 2021

After the initial fracture in postmenopausal women, where do subsequent fractures occur?

EClinicalMedicine 2021 May 5;35:100826. Epub 2021 May 5.

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

Background: The locations of subsequent fractures after initial fracture in postmenopausal women are poorly characterized.

Methods: We conducted a prospective analysis of subsequent fractures after initial fracture in Women's Health Initiative (1993-2018) participants who provided follow-up (mean 15.4 years, SD 6.2 years) data ( = 157,282 participants; baseline age 50-79; 47,458 participants with incident fracture). Cox proportional hazards models were adjusted for age, race/ethnicity, body mass index, and other covariates.

Findings: The risk of each type of subsequent fracture was increased after each type of initial fracture. Incident lower arm/wrist fracture was associated with significantly elevated risks of subsequent fractures at the upper arm/shoulder, upper leg, knee, lower leg/ankle, hip/pelvis, and spine (adjusted hazard ratios [aHRs] ranging 2·63-5·68). The risk of hip fracture was increased after initial lower arm or wrist fracture (aHR 4·80, 95% CI 4·29-5·36), initial upper arm or shoulder fracture (aHR 5·06, 95% CI 4·39-5·82), initial upper leg fracture (aHR 5·11, 95% CI 3·91-6·67), initial knee fracture (aHR 5·03, 95% CI 4·20-6·03), initial lower leg/ankle fracture (aHR 4·10, 95% CI 3·58-4·68), and initial spine fracture (aHR 6·69, 95% CI 5·95-7·53). Associations were significant in all age groups, even women aged 50-59 years. Risks of subsequent fracture were more pronounced among non-Hispanic Black, Hispanic/Latina, and Asian/Pacific Islander than among non-Hispanic White women.

Interpretation: Increased risk of subsequent fracture is observed for all fracture types across all ages. Women who experience any of these fractures should be targeted for interventions to prevent subsequent fractures.

Funding: National Institutes of Health HHSN268201600018C,HHSN268201600001C, HHSN268201600002C, HHSN268201600003C, and HHSN268201600004C.
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http://dx.doi.org/10.1016/j.eclinm.2021.100826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176125PMC
May 2021

Risk of Subsequent Fractures in Postmenopausal Women After Nontraumatic vs Traumatic Fractures.

JAMA Intern Med 2021 Aug;181(8):1055-1063

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

Importance: The burden of fractures among postmenopausal women is high. Although nontraumatic fractures are strong risk factors for future fracture, current clinical guidelines do not address traumatic fractures.

Objective: To determine how future fracture risk varies according to whether an initial fracture is traumatic or nontraumatic.

Design, Setting, And Participants: We conducted a prospective observational study using data from the Women's Health Initiative Study (WHI) (enrollment, September 1994-December 1998; data analysis, September 2020 to March 2021), which enrolled postmenopausal women aged 50 to 79 years at baseline at 40 US clinical centers. The WHI Clinical Trials and WHI Bone Density Substudy, conducted at 3 of the clinical centers, asked participants to report the mechanism of incident fractures. Of 75 335 participants, information regarding incident fracture and covariates was available for 66 874 participants (88.8%), who comprised the analytic sample of this study. Mean (SD) follow-up was 8.1 (1.6) years.

Interventions: None.

Main Outcomes And Measures: Incident clinical fractures were self-reported at least annually and confirmed using medical records. Participants reported the mechanism of incident fracture as traumatic or nontraumatic.

Results: Among the 66 874 participants in the analytic sample (mean [SD] age, 63.1 [7.0] years and 65.3 [7.2] years among women without and with clinical fracture, respectively), 7142 participants (10.7%) experienced incident fracture during the study follow-up period. The adjusted hazard ratio (aHR) of subsequent fracture after initial fracture was 1.49 (95% CI, 1.38-1.61). Among women whose initial fracture was traumatic, the association between initial fracture and subsequent fracture was significantly increased (aHR, 1.25; 95% CI, 1.06-1.48). Among women whose initial fracture was nontraumatic, the association between initial fracture and subsequent fracture was also increased (aHR, 1.52; 95% CI, 1.37-1.68). Confidence intervals for associations between initial fracture and subsequent fracture were overlapping for traumatic and nontraumatic initial fracture strata.

Conclusions And Relevance: In this cohort study, among postmenopausal women older than 50 years, fracture was associated with a greater risk of subsequent fracture regardless of whether the fracture was traumatic or nontraumatic. These findings suggest that clinical osteoporosis assessment should include high-trauma as well as low-trauma fractures.
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http://dx.doi.org/10.1001/jamainternmed.2021.2617DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185628PMC
August 2021

Results From the United States Chronic Thromboembolic Pulmonary Hypertension Registry: Enrollment Characteristics and 1-Year Follow-up.

Chest 2021 Jun 4. Epub 2021 Jun 4.

Temple University Hospital, Philadelphia, PA.

Background: The United States Chronic Thromboembolic Pulmonary Hypertension Registry (US-CTEPH-R) was designed to characterize the demographic characteristics, evaluation, clinical course, and outcomes of surgical and nonsurgical therapies for patients with chronic thromboembolic pulmonary hypertension.

Research Question: What are the differences in baseline characteristics and 1-year outcomes between operated and nonoperated subjects?

Study Design And Methods: This study describes a multicenter, prospective, longitudinal, observational registry of patients newly diagnosed (< 6 months) with CTEPH. Inclusion criteria required a mean pulmonary artery pressure ≥ 25 mm Hg according to right heart catheterization and radiologic confirmation of CTEPH. Between 2015 and 2018, a total of 750 patients were enrolled and followed up biannually until 2019.

Results: Most patients with CTEPH (87.9%) reported a history of acute pulmonary embolism. CTEPH diagnosis delays were frequent (median, 10 months), and most patients reported World Health Organization functional class 3 status at enrollment with a median mean pulmonary artery pressure of 44 mm Hg. The registry cohort was subdivided into Operable patients undergoing pulmonary thromboendarterectomy (PTE) surgery (n = 566), Operable patients who did not undergo surgery (n = 88), and those who were Inoperable (n = 96). Inoperable patients were older than Operated patients; less likely to be obese; have a DVT history, non-type O blood group, or thrombophilia; and more likely to have COPD or a history of cancer. PTE resulted in a median pulmonary vascular resistance decline from 6.9 to 2.6 Wood units (P < .001) with a 3.9% in-hospital mortality. At 1-year follow-up, Operated patients were less likely treated with oxygen, diuretics, or pulmonary hypertension-targeted therapy compared with Inoperable patients. A larger percentage of Operated patients were World Health Organization functional class 1 or 2 at 1 year (82.9%) compared with the Inoperable (48.2%) and Operable/No Surgery (56%) groups (P < .001).

Interpretation: Differences exist in the clinical characteristics between patients who exhibited operable CTEPH and those who were inoperable, with the most favorable 1-year outcomes in those who underwent PTE surgery.

Clinical Trial Registration: ClinicalTrials.gov; No.: NCT02429284; URL: www.clinicaltrials.gov.
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http://dx.doi.org/10.1016/j.chest.2021.05.052DOI Listing
June 2021

The CNN Hip Accelerometer Posture (CHAP) Method for Classifying Sitting Patterns from Hip Accelerometers: A Validation Study.

Med Sci Sports Exerc 2021 Nov;53(11):2445-2454

Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA.

Introduction: Sitting patterns predict several healthy aging outcomes. These patterns can potentially be measured using hip-worn accelerometers, but current methods are limited by an inability to detect postural transitions. To overcome these limitations, we developed the Convolutional Neural Network Hip Accelerometer Posture (CHAP) classification method.

Methods: CHAP was developed on 709 older adults who wore an ActiGraph GT3X+ accelerometer on the hip, with ground-truth sit/stand labels derived from concurrently worn thigh-worn activPAL inclinometers for up to 7 d. The CHAP method was compared with traditional cut-point methods of sitting pattern classification as well as a previous machine-learned algorithm (two-level behavior classification).

Results: For minute-level sitting versus nonsitting classification, CHAP performed better (93% agreement with activPAL) than did other methods (74%-83% agreement). CHAP also outperformed other methods in its sensitivity to detecting sit-to-stand transitions: cut-point (73%), TLBC (26%), and CHAP (83%). CHAP's positive predictive value of capturing sit-to-stand transitions was also superior to other methods: cut-point (30%), TLBC (71%), and CHAP (83%). Day-level sitting pattern metrics, such as mean sitting bout duration, derived from CHAP did not differ significantly from activPAL, whereas other methods did: activPAL (15.4 min of mean sitting bout duration), CHAP (15.7 min), cut-point (9.4 min), and TLBC (49.4 min).

Conclusion: CHAP was the most accurate method for classifying sit-to-stand transitions and sitting patterns from free-living hip-worn accelerometer data in older adults. This promotes enhanced analysis of older adult movement data, resulting in more accurate measures of sitting patterns and opening the door for large-scale cohort studies into the effects of sitting patterns on healthy aging outcomes.
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http://dx.doi.org/10.1249/MSS.0000000000002705DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8516667PMC
November 2021

Interrupting Sitting Time in Postmenopausal Women: Protocol for the Rise for Health Randomized Controlled Trial.

JMIR Res Protoc 2021 May 13;10(5):e28684. Epub 2021 May 13.

Kaiser Permanente Washington Health Research Institute, Seattle, WA, United States.

Background: Many older adults spend the majority of their waking hours sitting, which increases their risk of chronic diseases. Given the challenges that many older adults face when engaging in moderate-to-vigorous physical activity, understanding the health benefits of decreasing sitting time and increasing the number of sit-to-stand transitions is needed to address this growing public health concern.

Objective: The aim of this 3-arm randomized controlled trial is to investigate how changes in sitting time and brief sit-to-stand transitions impact biomarkers of healthy aging and physical, emotional, and cognitive functioning compared with a healthy attention control arm.

Methods: Sedentary and postmenopausal women (N=405) will be recruited and randomly assigned to 1 of the 3 study conditions for 3 months: healthy living attention control (Healthy Living), reduce sitting time (Reduce Sitting), and increase sit-to-stand transitions (Increase Transitions). Assessments conducted at baseline and 3 months included fasting blood draw, blood pressure, anthropometric measurements, physical functioning, cognitive testing, and 7 days of a thigh-worn accelerometer (activPAL) and a hip-worn accelerometer (ActiGraph). Blood-based biomarkers of healthy aging included those associated with glycemic control (glycated hemoglobin, fasting plasma insulin and glucose, and homeostatic model assessment of insulin resistance).

Results: Recruitment began in May 2018. The intervention is ongoing, with data collection expected to continue through the end of 2022.

Conclusions: The Rise for Health study is designed to test whether 2 different approaches to interrupting sitting time can improve healthy aging in postmenopausal women. Results from this study may inform the development of sedentary behavior guidelines and interventions to reduce sitting time in older adults.

Trial Registration: ClinicalTrials.gov NCT03473145; https://clinicaltrials.gov/ct2/show/NCT03473145.

International Registered Report Identifier (irrid): DERR1-10.2196/28684.
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http://dx.doi.org/10.2196/28684DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160808PMC
May 2021

The United States Chronic Thromboembolic Pulmonary Hypertension Registry: Protocol for a Prospective, Longitudinal Study.

JMIR Res Protoc 2021 May 25;10(5):e25397. Epub 2021 May 25.

Division of Cardiology, Temple University, Philadelphia, PA, United States.

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare sequela of acute pulmonary embolism that is treatable when recognized. Awareness of this disease has increased with recent advancements in therapeutic options, but delays in diagnosis remain common, and diagnostic and treatment guidelines are often not followed. Data gathered from international registries have improved our understanding of CTEPH, but these data may not be applicable to the US population owing to differences in demographics and medical practice patterns.

Objective: The US CTEPH Registry (US-CTEPH-R) was developed to provide essential information to better understand the demographics, risk factors, evaluation, and treatment of CTEPH in the United States, as well as the short- and long-term outcomes of surgical and nonsurgical therapies in the modern treatment era.

Methods: Thirty sites throughout the United States enrolled 750 subjects in this prospective, longitudinal, observational registry of patients newly diagnosed with CTEPH. Enrollment criteria included a mean pulmonary artery pressure ≥25 mmHg by right heart catheterization and radiologic confirmation of CTEPH by a multidisciplinary adjudication committee. Following enrollment, subjects were followed biannually until the conclusion of the study. Quality of life surveys were administered at enrollment and biannually, and all other testing was at the discretion of the treating clinician. Details regarding surgical therapy, balloon pulmonary angioplasty, and medical therapy were collected at enrollment and at follow-up, as well as information related to health care utilization and survival.

Results: Data from this registry will improve understanding of the demographics, risk factors, and treatment patterns of patients with CTEPH, and the longitudinal impact of therapies on quality of life, health care utilization, and survival.

Conclusions: This manuscript details the methodology and design of the first large, prospective, longitudinal registry of patients with CTEPH in the United States.

Trial Registration: ClinicalTrials.gov NCT02429284; https://www.clinicaltrials.gov/ct2/show/NCT02429284.

International Registered Report Identifier (irrid): DERR1-10.2196/25397.
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http://dx.doi.org/10.2196/25397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188310PMC
May 2021

Endogenous Progestogens and Colorectal Cancer Risk among Postmenopausal Women.

Cancer Epidemiol Biomarkers Prev 2021 06 7;30(6):1100-1105. Epub 2021 Apr 7.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.

Background: The role of progestogens in colorectal cancer development is poorly characterized. To address this, our group developed a highly sensitive assay to measure concentrations of seven markers of endogenous progestogen metabolism among postmenopausal women.

Methods: The markers were measured in baseline serum collected from postmenopausal women in a case-cohort study within the breast and bone follow-up to the fracture intervention trial (B∼FIT). We followed women not using exogenous hormones at baseline (1992-1993) for up to 12 years: 187 women with incident colorectal cancer diagnosed during follow-up and a subcohort of 495 women selected on strata of age and clinical center. We used adjusted Cox regression models with robust variance to estimate risk for colorectal cancer [hazard ratios (HR), 95% confidence intervals (CI)].

Results: High concentrations of pregnenolone and progesterone were not associated with colorectal cancer [quintile(Q)5 versus Q1: pregnenolone HR, 0.71, 95% CI, 0.40-1.25; progesterone HR, 1.25; 95% CI, 0.71-2.22]. A trend of increasing risk was suggested, but statistically imprecise across quintiles of 17-hydroxypregnenolone (Q2 to Q5 HRs, 0.75-1.44; , 0.06).

Conclusions: We used sensitive and reliable assays to measure multiple circulating markers of progestogen metabolism. Progestogens were generally unassociated with colorectal cancer risk in postmenopausal women.

Impact: Our findings are consistent with most prior research on circulating endogenous sex hormones, which taken together suggest that sex hormones may not be major drivers of colorectal carcinogenesis in postmenopausal women.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-1568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172440PMC
June 2021

Associations between physical function and device-based measures of physical activity and sedentary behavior patterns in older adults: moving beyond moderate-to-vigorous intensity physical activity.

BMC Geriatr 2021 03 31;21(1):216. Epub 2021 Mar 31.

Kaiser Permanente Washington Health Research Institute, 1730 Minor Ave, Suite 1600, Seattle, WA, 98101, USA.

Background: Research supports that moderate-to-vigorous intensity physical activity (MVPA) is key to prolonged health and function. Among older adults, substantial changes to MVPA may be infeasible, thus a growing literature suggests a shift in focus to whole-day activity patterns.

Methods: With data from 795 older adults aged 65-100 in the Adult Changes in Thought Activity Monitoring study, we used linear regression to estimate associations between ActiGraph and activPAL measured activity patterns - including light intensity physical activity, steps, standing, and sedentary behaviors - and physical function as measured by a short Performance-based Physical Function (sPPF) score (range 0-12), a composite score based on three standardized physical performance tasks: gait speed, timed chair stands, and grip strength. We examined whether relationships persisted when controlling for MVPA or differed across age, gender, or quartiles of MVPA.

Results: In models unadjusted for MVPA, a 1-standard deviation (SD) increment of daily sitting (1.9 h more), mean sitting bout duration (8 min longer average), or time spent in sedentary activity (1.6 h more) was associated with ~ 0.3-0.4 points lower mean sPPF score (all p < 0.05). A 1-SD increment in daily steps (~ 3500 more steps) was associated with ~ 0.5 points higher mean sPPF score (95% CI: 0.22 to 0.73). MVPA adjustment attenuated all relationships. The association between physical function and steps was strongest among adults aged 75+; associations of worse function with greater sedentary behavior were more pronounced in participants with the lowest levels of MVPA.

Conclusions: We found associations between function and activity metrics other than MVPA in key subgroups, findings that support research on broader activity patterns and may offer ideas regarding practical intervention opportunities for improving function in older adults.
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http://dx.doi.org/10.1186/s12877-021-02163-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011072PMC
March 2021

Association between postmenopausal vulvovaginal discomfort, vaginal microbiota, and mucosal inflammation.

Am J Obstet Gynecol 2021 08 4;225(2):159.e1-159.e15. Epub 2021 Mar 4.

Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA.

Background: Half of all postmenopausal women report symptoms of vulvar, vaginal, or urinary discomfort with substantial impact on sexual function and quality of life; underlying mechanisms leading to symptoms are poorly understood.

Objective: To examine the possibility that the vaginal microbiota and/or mucosal immune response contributes to the severity of bothersome vaginal symptoms, we conducted a substudy of samples from a randomized trial of vaginal treatment for genitourinary syndrome of menopause to compare these features between women whose symptoms improved and women whose symptoms did not improve.

Study Design: This is a secondary analysis of samples collected in a 12-week randomized trial of treatment with vaginal estradiol or moisturizer vs placebo for moderate-severe postmenopausal symptoms of vaginal discomfort. We randomly selected 20 women in each arm with ≥2-point decrease in most bothersome symptom severity (responders) and 20 matched controls with ≤1-point decrease (nonresponders). At 0, 4, and 12 weeks, we characterized vaginal microbiota (16S ribosomal RNA gene sequencing), vaginal fluid metabolites (broad-based metabolomic profiling), vaginal fluid-soluble immune markers (Meso Scale Discovery), pH, and vaginal maturation index. We compared responders with nonresponders at baseline and across all visits using linear mixed models to evaluate associations with microbiota, metabolites, and immune markers, incorporating visit and participant-specific random effects while controlling for treatment arm.

Results: Here, the mean age of women was 61 years (n=120), and most women (92%) were White. At enrollment, no significant differences were observed between responders and nonresponders in age, most bothersome symptom type or severity, microbiota composition or diversity, Lactobacillus dominance, metabolome, or immune markers. There was a significant decrease in diversity of the vaginal microbiota in both responders and nonresponders (P<.001) over 12 weeks. Although this change did not differ by responder status, diversity was associated with treatment arm: more women in the estradiol arm (63%) had Lactobacillus-dominant, lower diversity bacterial communities than women in the moisturizer (35%) or dual placebo (23%) arms (P=.001) at 12 weeks. The metabolome, vaginal maturation index, and measured immune markers were not associated with responder status over the 12 weeks but varied by treatment arm.

Conclusion: Postmenopausal vaginal symptom severity was not significantly associated with vaginal microbiota or mucosal inflammatory markers in this small study. Women receiving vaginal estradiol experienced greater abundance of lactobacilli and lower vaginal pH at end of treatment.
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http://dx.doi.org/10.1016/j.ajog.2021.02.034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8328873PMC
August 2021

Associations of Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker Use with Colorectal Cancer Risk in the Women's Health Initiative.

Cancer Epidemiol Biomarkers Prev 2021 05 24;30(5):1029-1032. Epub 2021 Feb 24.

Division of Epidemiology, Herbert Wertheim School of Public Health and Human Longevity Science, University of California, San Diego, California.

Background: Use of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) has been postulated to reduce cancer risk by inhibition of tumor progression, vascularization, and metastasis. The renin-angiotensin system is upregulated in colorectal cancers; however, the association of ACEi and ARB use with colorectal cancer risk is not well understood.

Methods: The study population was 142,812 Women's Health Initiative participants free of colorectal cancer who reported on ACEi and ARB use at baseline; 2,216 incident colorectal cancers were diagnosed during 10 years of follow-up. Cox regression models estimated adjusted HRs and 95% confidence intervals for associations relative to nonuse among normotensive women, untreated hypertensive women, and hypertensive women treated with other antihypertensive medications.

Results: HRs among women who used any ACEi or ARB compared with nonuse in the three referent groups ranged between 0.97 and 1.01. Findings were similar for increased ACEi/ARB duration and for medications examined as separate classes or individually.

Conclusions: In this large prospective study of women, no associations of ACEi or ARB use with colorectal cancer risk were observed.

Impact: Choice of drug in the large population of aging women who will be prescribed ACEi and ARB should be made without factoring in any benefit on colorectal cancer risk.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-1401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102324PMC
May 2021

Evaluation of Light Physical Activity Measured by Accelerometry and Mobility Disability During a 6-Year Follow-up in Older Women.

JAMA Netw Open 2021 02 1;4(2):e210005. Epub 2021 Feb 1.

Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla.

Importance: Almost 1 in 4 women older than 65 years is unable to walk 2 to 3 blocks, and mobility disability is a key factor associated with loss of independence. Lack of moderate to vigorous-intensity physical activity is associated with mobility disability, but whether lighter physical activity is associated with mobility disability is unknown.

Objective: To determine the association of light-intensity physical activity and incident mobility disability among older women.

Design, Setting, And Participants: This prospective cohort study included women enrolled in the Objectively Measured Physical Activity and Cardiovascular Health study, an ancillary study of the Women's Health Initiative, between March 2012 and April 2014, with follow-up through March 31, 2018. The Women's Health Initiative was a population-based, multisite study that recruited from 40 clinical sites across the US. Participants in the present analysis included 5735 of 7058 ambulatory, community-dwelling women aged 63 years and older who returned an accelerometer with usable data, were free of mobility disability, and had follow-up data on mobility status. Data were analyzed from August 2018 to May 2019.

Exposures: Light-intensity physical activity, defined as movement requiring energy expenditure between 1.6 and 2.9 metabolic equivalents, captured using an accelerometer over 7 days.

Main Outcomes And Measures: Incident mobility disability, defined as the first self-reported inability to walk 1 block or up a flight of stairs at annual follow-up, and persistent incident mobility disability, defined as incident mobility loss that persisted through the end of follow-up.

Results: A total of 5735 participants were included for primary analysis of all incident mobility disability (mean [SD] age, 78.5 [6.6] years [range, 63-97 years]; 2811 [49.0%] White participants). Compared with women in the lowest quartile of light-intensity physical activity, lower risk of incident mobility disability was observed in quartile 2 (multivariable hazard ratio [HR], 0.78; 95% CI, 0.67-0.90), quartile 3 (HR, 0.60; 95% CI, 0.51-0.71), and quartile 4 (HR, 0.60; 95% CI, 0.51-0.71) (P < .001). This beneficial association was stronger for persistent mobility disability in quartile 2 (multivariable HR, 0.72; 95% CI, 0.60-0.85), quartile 3 (HR, 0.55; 95% CI, 0.46-0.67), and quartile 4 (HR, 0.52; 95% CI, 0.42-0.63) (P < .001). Stratified analyses showed the association was stronger among women with a body mass index of less than 30.0 (HR, 0.73; 95% CI, 0.66-0.82) compared with women with a body mass index of 30.0 or higher (HR, 0.91; 95% CI; 0.79-1.04; P = .04 for interaction).

Conclusions And Relevance: In this cohort study, increased time spent in light-intensity physical activity was associated with reduced incident mobility disability. These findings support placing greater emphasis on promoting light-intensity physical activity for preserving mobility in later life.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.0005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903251PMC
February 2021

Women's Health Initiative Strong and Healthy Pragmatic Physical Activity Intervention Trial for Cardiovascular Disease Prevention: Design and Baseline Characteristics.

J Gerontol A Biol Sci Med Sci 2021 03;76(4):725-734

Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.

Background: National guidelines promote physical activity to prevent cardiovascular disease (CVD), yet no randomized controlled trial has tested whether physical activity reduces CVD.

Methods: The Women's Health Initiative (WHI) Strong and Healthy (WHISH) pragmatic trial used a randomized consent design to assign women for whom cardiovascular outcomes were available through WHI data collection (N = 18 985) or linkage to the Centers for Medicare and Medicaid Services (N30 346), to a physical activity intervention or "usual activity" comparison, stratified by ages 68-99 years (in tertiles), U.S. geographic region, and outcomes data source. Women assigned to the intervention could "opt out" after receiving initial physical activity materials. Intervention materials applied evidence-based behavioral science principles to promote current national recommendations for older Americans. The intervention was adapted to participant input regarding preferences, resources, barriers, and motivational drivers and was targeted for 3 categories of women at lower, middle, or higher levels of self-reported physical functioning and physical activity. Physical activity was assessed in both arms through annual questionnaires. The primary outcome is major cardiovascular events, specifically myocardial infarction, stroke, or CVD death; primary safety outcomes are hip fracture and non-CVD death. The trial is monitored annually by an independent Data Safety and Monitoring Board. Final analyses will be based on intention to treat in all randomized participants, regardless of intervention engagement.

Results: The 49 331 randomized participants had a mean baseline age of 79.7 years; 84.3% were White, 9.2% Black, 3.3% Hispanic, 1.9% Asian/Pacific Islander, 0.3% Native American, and 1% were of unknown race/ethnicity. The mean baseline RAND-36 physical function score was 71.6 (± 25.2 SD). There were no differences between Intervention (N = 24 657) and Control (N = 24 674) at baseline for age, race/ethnicity, current smoking (2.5%), use of blood pressure or lipid-lowering medications, body mass index, physical function, physical activity, or prior CVD (10.1%).

Conclusion: The WHISH trial is rigorously testing whether a physical activity intervention reduces major CV events in a large, diverse cohort of older women. Clinical Trials Registration Number: NCT02425345.
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http://dx.doi.org/10.1093/gerona/glaa325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011700PMC
March 2021

Sedentary Behavior and Diabetes Risk Among Women Over the Age of 65 Years: The OPACH Study.

Diabetes Care 2021 02 3;44(2):563-570. Epub 2020 Dec 3.

Department of Family Medicine and Public Health, University of California, San Diego, La Jolla, CA.

Objective: To evaluate whether sedentary time (ST) and/or sedentary behavior patterns are related to incident diabetes in the U.S.'s oldest age-groups.

Research Design And Methods: Women without physician-diagnosed diabetes ( = 4,839, mean ± SD age = 79 ± 7 years) wore accelerometers for ≥4 days and were followed up to 6 years for self-reported newly diagnosed diabetes requiring treatment with medications. Hazard ratios (HRs) for incident diabetes were estimated across quartiles of accelerometer-measured ST and mean bout duration with use of Cox proportional hazards models. We conducted isotemporal substitution analyses using Cox regression and tested associations with risk for diabetes after statistically replacing ST with light physical activity (PA) or moderate-to-vigorous PA (MVPA) and after replacing light PA with MVPA.

Results: During 20,949 person-years, 342 diabetes cases were identified. Women in ST quartile (Q)2, Q3, and Q4 (vs. Q1) had incident diabetes HR 1.20 (95% CI 0.87-1.65), 1.33 (0.97-1.82), and 1.21 (0.86-1.70); = 0.04. Respective HRs following additional adjustment for BMI and MVPA were 1.04 (95% CI 0.74-1.47), 1.04 (0.72-1.50), and 0.85 (0.56-1.29); = 0.90. Fully adjusted isotemporal substitution results indicated that each 30 min of ST replaced with MVPA (but not light PA) was associated with 15% lower risk for diabetes (HR 0.85 [95% CI 0.75-0.96]; = 0.01); the HR for replacing 30 min of light PA with MVPA was 0.85 (95% CI 0.73-0.98); = 0.03. Mean bout duration was not associated with incident diabetes.

Conclusions: Statistically replacing ST or light PA with MVPA was associated with lower diabetes risk in older women. While reducing ST is important for several health outcomes, results indicate that to reduce diabetes risk among older adults, the primary public health focus should be on increasing MVPA.
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http://dx.doi.org/10.2337/dc20-0709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818329PMC
February 2021

Accelerometer-Measured Sedentary Patterns are Associated with Incident Falls in Older Women.

J Am Geriatr Soc 2021 03 30;69(3):718-725. Epub 2020 Nov 30.

Family Medicine and Public Health, University of California, San Diego, California, USA.

Background/objective: Falls cause significant problems for older adults. Sedentary time is associated with lower physical function and could increase the risk for falls.

Design: Prospective study.

Setting: Sites across the United States.

Participants: Older women (N = 5,545, mean age 79 years) from the Women's Health Initiative Objective Physical Activity and Cardiovascular Health study.

Measurements: Accelerometers worn at the hip for up to 1 week collected measures of daily sedentary time and the mean sedentary bout duration, a commonly used metric for sedentary accumulation patterns. For up to 13 months after accelerometer wear, women reported daily whether they had fallen on monthly calendars.

Results: In fully adjusted models, the incident rate ratios (95% confidence interval) for quartiles 1 (lowest), 2, 3, and 4 of sedentary time respectively were 1.0 (ref.), 1.07 (0.93-1.24), 1.07 (0.91-1.25), and 1.14 (0.96-1.35; P-trend = .65) and for mean sedentary bout duration was 1.0 (ref.), 1.05 (0.92-1.21), 1.02 (0.88-1.17), and 1.17 (1.01-1.37; P-trend = .01), respectively. Women with a history of two or more falls had stronger associations between sedentary time and falls incidence compared with women with a history of no or one fall (P for interaction = .046).

Conclusions: Older women in the highest quartile of mean sedentary bout duration had a significantly increased risk of falling. Women with a history of frequent falling may be at higher risk for falling if they have high sedentary time. Interventions testing whether shortening total sedentary time and/or sedentary bouts lowers fall risk are needed to confirm these observational findings.
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http://dx.doi.org/10.1111/jgs.16923DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020891PMC
March 2021

Association of Sedentary Time and Incident Heart Failure Hospitalization in Postmenopausal Women.

Circ Heart Fail 2020 12 24;13(12):e007508. Epub 2020 Nov 24.

Brown University Warren Alpert School of Medicine, and School of Public Health, Providence, RI (C.A.N., C.B.E.).

Background: The 2018 US Physical Activity Guidelines recommend reducing sedentary behavior (SB) for cardiovascular health. SB's role in heart failure (HF) is unclear.

Methods: We studied 80 982 women in the Women's Health Initiative Observational Study, aged 50 to 79 years, who were without known HF and reported ability to walk ≥1 block unassisted at baseline. Mean follow-up was 9 years for physician-adjudicated incident HF hospitalization (1402 cases). SB was assessed repeatedly by questionnaire. Time-varying total SB was categorized according to awake time spent sitting or lying down (≤6.5, 6.6-9.5, >9.5 h/d); sitting time (≤4.5, 4.6-8.5, >8.5 h/d) was also evaluated. Hazard ratios and 95% CI were estimated using Cox regression.

Results: Controlling for age, race/ethnicity, education, income, smoking, alcohol, menopausal hormone therapy, and hysterectomy status, higher HF risk was observed across incremental tertiles of time-varying total SB (hazard ratios [95% CI], 1.00 [referent], 1.15 [1.01-1.31], 1.42 [1.25-1.61], trend <0.001) and sitting time (1.00 [referent], 1.14 [1.01-1.28], 1.54 [1.34-1.78], trend <0.001). The inverse trends remained significant after further controlling for comorbidities including time-varying myocardial infarction and coronary revascularization (hazard ratios: SB, 1.00, 1.11, 1.27; sitting, 1.00, 1.09, 1.37, trend <0.001 each) and for baseline physical activity (hazard ratios: SB 1.00, 1.10, 1.24; sitting 1.00, 1.08, 1.33, trend <0.001 each). Associations with SB exposures were not different according to categories of baseline age, race/ethnicity, body mass index, physical activity, physical functioning, diabetes, hypertension, or coronary heart disease.

Conclusions: SB was associated with increased risk of incident HF hospitalization in postmenopausal women. Targeted efforts to reduce SB could enhance HF prevention in later life.
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.120.007508DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738397PMC
December 2020

The Relationship of Accelerometer-Assessed Standing Time With and Without Ambulation and Mortality: The WHI OPACH Study.

J Gerontol A Biol Sci Med Sci 2021 01;76(1):77-84

Department of Family Medicine and Public Health, University of California San Diego, La Jolla.

Background: Self-reported time spent standing has been associated with lower risk of mortality. No previous studies have examined this association using device-measured standing.

Method: This was a prospective cohort study of 5878 older (median age = 80 years), racial/ethnically diverse, community-dwelling women in the WHI Objective Physical Activity and Cardiovascular Health Study (OPACH). Women wore accelerometers for 1 week and were followed for mortality. The study applied previously validated machine learning algorithms to ActiGraph GT3X+ accelerometer data to separately measure time spent standing with and without ambulation. Cox proportional hazards models were used to estimate mortality risk adjusting for potential confounders. Effect modification by age, body mass index, moderate-to-vigorous physical activity, sedentary time, physical functioning, and race/ethnicity was evaluated.

Results: There were 691 deaths during 26 649 person-years of follow-up through March 31, 2018 (mean follow-up = 4.8 years). In fully adjusted models, all-cause mortality risk was lower among those with more standing without ambulation (quartile [Q] 4 vs Q1 HR = 0.63; 95% CI = 0.49-0.81, p-trend = .003) and more standing with ambulation (Q4 vs Q1 HR = 0.50; 95% CI = 0.35-0.71, p-trend < .001). Associations of standing with ambulation and mortality were stronger among women with above-median sedentary time (HR = 0.51; 95% CI = 0.38-0.68) compared to women with below-median sedentary time (HR = 0.80; 95% CI = 0.59-1.07; p-interaction = .02).

Conclusions: In this prospective study among older women, higher levels of accelerometer-measured standing were associated with lower risks of all-cause mortality. Standing is an achievable approach to interrupting prolonged sedentary time, and if not contraindicated, is a safe and feasible behavior that appears to benefit health in older ages.
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http://dx.doi.org/10.1093/gerona/glaa227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756713PMC
January 2021

A Menopause Strategies-Finding Lasting Answers for Symptoms and Health (MsFLASH) Investigation of Self-Reported Menopausal Palpitation Distress.

J Womens Health (Larchmt) 2021 04 20;30(4):533-538. Epub 2020 Nov 20.

Department of Family Medicine and Public Health, University of California, San Diego, California, USA.

Study to describe the degree of menopausal palpitation distress and its demographic, clinical, symptom, and quality-of-life (QOL) correlates. Analysis of existing, baseline, data from peri- and postmenopausal women, 42 to 62 years of age, who participated in the Menopause Strategies-Finding Lasting Answers for Symptoms and Health (MsFLASH) clinical trials testing interventions for vasomotor symptoms ( = 759). Up to 46.8% of menopausal women report having palpitations, yet the symptom is relatively understudied. Little is known about palpitation distress or its correlates. Degree of distress from "heart racing or pounding" was self-reported over the past two weeks as "not at all," "a little bit," "moderately," "quite a bit," or "extremely." Other measures included self-report forms, clinic-verified body mass index (BMI), vasomotor symptom diaries, and validated symptom and QOL tools. The percentage who reported palpitation distress was 19.6%, 25.2%, and 33.5% in the three trials or 25.0% overall. In multivariate analysis, the odds of reporting palpitation distress was lower in past smokers (odds ratio [OR] = 0.59 [95% confidence interval (CI) 0.38-0.90]) and current smokers (OR = 0.48 [0.27-0.87]) relative to never-smokers and lower with every 5 kg/m higher BMI (OR = 0.82 [0.69-0.98]).The odds of reporting palpitation distress was higher with every five point more severe insomnia (OR = 1.28 [1.05-1.54]), five point worse depressive symptoms (OR = 1.47 [1.11-1.95]), five point worse perceived stress (OR = 1.19 [1.01-1.39]), and one point worse menopausal QOL (OR = 1.29 [1.06-1.57]). Menopausal palpitation distress is common and associated with demographic, clinical, symptom, and QOL factors. Findings can be used for screening in clinical practice and to justify additional research on this understudied symptom.
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http://dx.doi.org/10.1089/jwh.2020.8586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064942PMC
April 2021
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