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BACKGROUND: Few studies have examined accelerometer-measured physical activity and incident breast cancer (BC). Thus, this study examined associations between accelerometer-measured vector magnitude counts per 15 seconds (VM/15s) and average daily minutes of light physical activity (LPA), moderate-to-vigorous PA (MVPA), and total PA (TPA) and BC risk among women in the Women’s Health Accelerometry Collaboration (WHAC). METHODS: The WHAC comprised 21,089 postmenopausal women (15,375 from the Women’s Health Study [WHS]; 5714 from the Women’s Health Initiative Objective Physical Activity and Cardiovascular Health Study [OPACH]). Women wore an ActiGraph GT3X+ on the hip for ≥4 days and were followed for 7.4 average years to identify physician-adjudicated in situ (n = 94) or invasive (n = 546) BCs. Multivariable stratified Cox regression estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for tertiles of physical activity measures in association with incident BC overall and by cohort. Effect measure modification was examined by age, race/ethnicity, and body mass index (BMI). RESULTS: In covariate-adjusted models, the highest (vs. lowest) tertiles of VM/15s, TPA, LPA, and MVPA were associated with BC HRs of 0.80 (95% CI, 0.64–0.99), 0.84 (95% CI, 0.69–1.02), 0.89 (95% CI, 0.73–1.08), and 0.81 (95% CI, 0.64–1.01), respectively. Further adjustment for BMI or physical function attenuated these associations. Associations were more pronounced among OPACH than WHS women for VM/15s, MVPA, and TPA; younger than older women for MVPA; and women with BMI ≥30 than

Purpose: The purpose of this study was to develop 60-s epoch accelerometer intensity cut points for vertical axis count and vector magnitude (VM) output from hip-worn triaxial accelerometers among women 60–91 years old. We also compared these cut points against cut points derived by multiplying 15-s epoch cut points by four. Methods: Two hundred apparently healthy women wore an ActiGraph GT3X+ accelerometer on their hip while performing a variety of laboratory-based activities that were sedentary (watching television and assembling a puzzle), low light (washing/drying dishes), high light (laundry and dust mopping), or moderate-to-vigorous physical activity (400-m walk) intensity. Oxygen uptake was measured using an Oxycon portable calorimeter. Sedentary behavior and physical activity intensity cut points for vertical axis and VM counts were derived for 60-s epochs from receiver operating characteristic and by multiplying the 15-s cut points by four; both were compared with oxygen uptake. Results: The median age was 74.5 years (interquartile range 70–83). The 60-s epoch cut points for vertical counts were 0 sedentary, 1–73 low light, 74–578 high light, and ≥579 moderate-to-vigorous physical activity. The 60-s epoch cut points for VM were 0–88 sedentary, 89–663 low light, 664–1,730 high light, and ≥1,731 moderate-to-vigorous physical activity. For both sets of cut points, the receiver operating characteristic approach yielded more accurate estimates than the multiplication approach. Conclusion: The derived 60-s epoch cut points for vertical counts and VM can be applied to epidemiologic studies to define sedentary behavior and physical activity intensities in older adult populations.

Maximal oxygen uptake (V˙O2max) is the criterion measure of cardiorespiratory fitness (CRF). Lower CRF is a strong predictor of poor health outcomes, including all-cause mortality. Since V˙O2max testing is resource intensive, several non-exercise based V˙O2max prediction equations have been published. We assess these equations' ability to predict measured V˙O2max, recalibrate these equations, and quantify the association of measured and predicted V˙O2max with all-cause mortality.Baltimore Longitudinal Study of Aging participants with valid V˙O2max tests were included (n = 1,080). Using published V˙O2max prediction equations, we calculated predicted V˙O2max and present performance metrics before and after recalibration (deriving new regression estimates by regressing measured V˙O2max on BLSA covariates). Cox proportional hazards models were fit to quantify associations of measured, predicted, and recalibration-predicted values of V˙O2max with mortality.Mean age and V˙O2max were 69.0 ± 10.4 years and 21.6 ± 5.9 mL·kg-1·min-1, respectively. The prediction equations yielded root mean squared error values ranging from 4.2-20.4 mL·kg-1·min-1. After recalibration, these values decreased to 3.9-4.2 mL·kg-1·min-1. Adjusting for all covariates, all-cause mortality risk was 66% lower for the highest quartile of measured V˙O2max relative to the lowest. Predicted V˙O2max variables yielded similar estimates in unadjusted models but were not robust to adjustment.Measured V˙O2max is an extremely strong predictor of all-cause mortality. Several published V˙O2max prediction equations yielded: (1) reasonable performance metrics relative to measured V˙O2max,especially when recalibrated, (2) all-cause mortality hazard ratios similar to those of measured V˙O2max, especially when recalibrated, yet (3) were not robust to adjustment for basic demographic covariates likely because these were used in the equation for predicted V˙O2max.

Purpose: Traditional summary metrics provided by accelerometer device manufacturers, known as counts, are proprietary and manufacturer specific, making it difficult to compare studies using different devices. Alternative summary metrics based on raw accelerometry data have been introduced in recent years. However, they were often not calibrated on ground truth measures of activity-related energy expenditure for direct translation into continuous activity intensity levels. Our purpose is to calibrate, derive, and validate thresholds among women 60 years and older based on a recently proposed transparent raw data-based accelerometer activity index (AAI) and to demonstrate its application in association with cardiometabolic risk factors. Methods: We first built calibration equations for estimating metabolic equivalents continuously using AAI and personal characteristics using internal calibration data (N = 199). We then derived AAI cutpoints to classify epochs into sedentary behavior and physical activity intensity categories. The AAI cutpoints were applied to 4,655 data units in the main study. We then utilized linear models to investigate associations of AAI sedentary behavior and physical activity intensity with cardiometabolic risk factors. Results: We found that AAI demonstrated great predictive accuracy for estimating metabolic equivalents (R2 = .74). AAI-Based physical activity measures were associated in the expected directions with body mass index, blood glucose, and high-density lipoprotein cholesterol. Conclusion: The calibration framework for AAI and the cutpoints derived for women older than 60 years can be applied to ongoing epidemiologic studies to more accurately define sedentary behavior and physical activity intensity exposures, which could improve accuracy of estimated associations with health outcomes.

Little is known about the relationships between annual visit-to-visit blood pressure variability and heart failure subphenotypes. The aim of this analysis was to examine the association between blood pressure variability and incident heart failure with preserved and reduced ejection fraction.Data from 23,918 postmenopausal women enrolled in the Women's Health Initiative Hormone Therapy Trials were analyzed. Blood pressure was measured at baseline (1993‒1998) and then annually through 2005. Variability was defined as the SD of the mean blood pressure across visits or the SD of the participant's regression line for blood pressure across visits. The outcome was the first heart failure hospitalization. Heart failure ascertainment and adjudications were through March 31, 2018.During a mean follow-up of 15.8 years, 913 incident cases of heart failure with preserved ejection fraction and 421 cases of heart failure with reduced ejection fraction were identified. In fully adjusted models, including mean longitudinal systolic and diastolic blood pressure and time-varying coronary events interim to heart failure hospitalization, women in the highest versus in the lowest quartile of SD of the mean systolic blood pressure were at a statistically significantly higher risk of heart failure with preserved ejection fraction (hazard ratio [95% CI]=1.61 [1.12, 2.31]) but not of heart failure with reduced ejection fraction (1.18 [0.70,1.96]). Conversely, the hazard ratio (95% CI) for the highest versus lowest quartile of SD of the mean diastolic blood pressure was 1.56 (0.89, 2.74) for heart failure with reduced ejection fraction and 1.19 (0.85,1.65) for heart failure with preserved ejection fraction. Results attenuated for SD of the participant's regression line when additionally adjusted for the temporal trend of systolic and diastolic blood pressure.Greater systolic blood pressure variability was associated with a higher risk of heart failure with preserved ejection fraction independent of mean blood pressure and coronary events interim to heart failure hospitalization.

PurposeThis study estimated associations between neighborhood socioeconomic status (NSES), walkability, green space, and incident falls among postmenopausal women and evaluated modifiers of these associations, including study arm, race and ethnicity, baseline household income, baseline walking, age at enrollment, baseline low physical functioning, baseline fall history, climate region, and urban-rural residence.MethodsThe Women's Health Initiative recruited a national sample of postmenopausal women (50-79years) across 40 U.S. clinical centers and conducted yearly assessments from 1993 to 2005 (n=161,808). Women reporting a history of hip fracture or walking limitations were excluded, yielding a final sample of 157,583 participants. Falling was reported annually. NSES (income/wealth, education, occupation), walkability (population density, diversity of land cover, nearby high-traffic roadways), and green space (exposure to vegetation) were calculated annually and categorized into tertiles (low, intermediate, high). Generalized estimating equations assessed longitudinal relationships.ResultsNSES was associated with falling before adjustment (high vs. low, odds ratio,1.01; 95% confidence interval, 1.00-1.01). Walkability was significantly associated with falls after adjustment (high vs. low, odds ratio,0.99; 95% confidence interval, 0.98-0.99). Green space was not associated with falling before or after adjustment. Study arm, race and ethnicity, household income, age, low physical functioning, fall history, and climate region modified the relationship between NSES and falling. Race and ethnicity, age, fall history, and climate region modified relationships between walkability and green space and falling.ConclusionsOur results did not show strong associations of NSES, walkability, or green space with falling. Future research should incorporate granular environmental measures that may directly relate to physical activity and outdoor engagement.

Background: Despite a large body of literature evaluating the association between recreational physical activity and epithelial ovarian cancer (EOC) risk, the extant evidence is inconclusive, and little is known about the independent association between recreational physical inactivity and EOC risk. We conducted a pooled analysis of nine studies from the Ovarian Cancer Association Consortium to investigate the association between chronic recreational physical inactivity and EOC risk.Methods: In accordance with the 2008 Physical Activity Guidelines for Americans, women reporting no regular, weekly recreational physical activity were classified as inactive. Multivariable logistic regression was utilized to estimate the ORs and 95% confidence intervals (CI) for the association between inactivity and EOC risk overall and by subgroups based upon histotype, menopausal status, race, and body mass index.Results: The current analysis included data from 8,309 EOC patients and 12,612 controls. We observed a significant positive association between inactivity and EOC risk (OR = 1.34; 95% CI, 1.14–1.57), and similar associations were observed for each histotype.Conclusions: In this large pooled analysis examining the association between recreational physical inactivity and EOC risk, we observed consistent evidence of an association between chronic inactivity and all EOC histotypes.Impact: These data add to the growing body of evidence suggesting that inactivity is an independent risk factor for cancer. If the apparent association between inactivity and EOC risk is substantiated, additional work via targeted interventions should be pursued to characterize the dose of activity required to mitigate the risk of this highly fatal disease. Cancer Epidemiol Biomarkers Prev; 25(7); 1114–24. ©2016 AACR.

Supplemental Table S1. Pooled Odds Ratios and 95% Confidence Intervals Representing the Association Between Physical Inactivity and Epithelial Ovarian Cancer by Menopause Status. Supplemental Table S2. Age-Adjusted And Multivariable-Adjusted Pooled Odds Ratios And 95% Confidence Intervals (CI) Representing The Association Between Physical Inactivity And Epithelial Ovarian Cancer By Race. Supplemental Table S3. Pooled odds ratios and 95% confidence intervals representing the association between physical inactivity and epithelial ovarian cancer by standard BMI classification. Supplemental Table S4. Pooled odds ratios and 95% confidence intervals representing the association between physical inactivity and epithelial ovarian cancer by dichotomous BMI classification

Introduction: Sedentary behavior (SB) is a recognized mortality and CVD risk factor. Most studies with accelerometry classified SB using cut-points, which do not capture postural transitions as accurately as thigh-worn devices. The recently published convolutional neural network hip accelerometer posture (CHAP) algorithm more accurately classifies sitting than cut-point methods. Hypothesis: Higher amounts of CHAP-classified sitting time (ST) and mean sitting bout duration (MSBD) are associated with higher all-cause (ACM) and CVD mortality risk. Methods: Older women (n=6,056; mean age=79±7; 34% Black, 17% Hispanic) in the Objective Physical Activity and Cardiovascular Health (OPACH) study without prior MI or stroke wore accelerometers for 7 days in May 2012-April 2014 and were followed through February 19, 2022 for mortality. The CHAP algorithm has been shown to have higher sensitivity (97.1% vs 88.2%) and specificity (88.6% vs 59.7%) for classifying sitting compared to the 100 counts/minute cut-point. Cox models estimated hazard ratios (HR) and 95% confidence intervals (CI) for ACM and CVD mortality adjusting for age, race/ethnicity, education, alcohol, smoking, multimorbidity, self-rated health, physical functioning, HDL, triglycerides, SBP, and log hs-CRP. Results: There were 1,808 deaths and 651 CVD deaths over a median follow-up of 8.4 years. The HR (95% CI; P-trend) comparing women in the highest ST quartile (>11.6 hr/day) to those in the lowest (15 minutes) to those in the lowest ( Conclusions: ST and MSBD were positively associated with ACM and CVD mortality risk, supporting interventions aimed at reducing both ST and MSBD.

Background: The risk of secondary cardiovascular events associated with proton pump inhibitor (PPI) use and their interaction with thienopyridine antiplatelets such as clopidogrel is well established. Recent evidence from in-vitro and animal studies suggests PPIs may impact cardiovascular disease (CVD) irrespective of antiplatelet use. However, whether PPI use is associated with primary cardiovascular events in humans remains uncertain. Methods: Systematic searches were conducted in the MEDLINE and EMBASE databases from their inception to September 2022. Inclusion criteria included studies that examined participants free from cardiovascular disease at baseline who were followed over time to assess any of the following outcomes according to PPI use: incident myocardial infarction (MI), incident ischemic stroke (IS), or CVD mortality. Hazard ratios (HR) and their 95% confidence intervals (CI) were abstracted, combined estimates and heterogeneity (I 2 ) were calculated using the random-effects model in RevMan 5.4 software. Results: A total of 15 observational studies met the inclusion criteria, 2,272,479 participants were studied for MI, 2,689,943 for IS, and 1,591,428 for CVD mortality. The mean age of participants ranged from 49.3 to 82.2 years. Compared to non-use, PPI use was associated with 30% higher risk of incident MI (HR: 1.30, 95%CI: 1.10-1.53, I 2 =91%) and 15% higher risk of CVD mortality (HR: 1.15, 95%CI: 1.05-1.26, I 2 =56%). However, there was no statistically significant association with incident IS (HR: 1.05, 95%CI: 0.91-1.22, I 2 =96%). Conclusion: The meta-analysis results from published studies suggests PPI use is associated with higher risk of incident MI and CVD mortality. However, these findings should be interpreted with caution given the considerable heterogeneity among published studies and the possibility of residual confounding. More studies are needed to address these limitations and determine the validity of these associations.

Background: Accumulating evidence suggests that participating in physical activity (PA) following heart failure (HF) diagnosis is associated with better prognosis, including lower mortality risk. Few studies have focused on this relationship in postmenopausal women, in whom HF burden is high. Methods: The present study, conducted in the Women’s Health Initiative, included 2,181 postmenopausal women (mean age 68 years; 85% white, 10% black, 3% Hispanic at enrollment in 1993-1998) who were diagnosed postbaseline with incident hospitalized acute HF and had at least one self-reported PA assessment before and after (mean age 73 at latter assessment) HF diagnosis. Total recreational PA was summarized in metabolic equivalent (MET) hours per week. Women were followed for all-cause mortality from their post-HF PA assessment through March 2014. Cox regression with age as the time scale was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for mortality associated with PA categories (before/after HF): Inactive ( Results: There were 1,047 (48%) deaths during a mean follow-up of 12 years. Crude mortality rates per 1,000 person-years [number of deaths] across the above PA groups were 42.4 [533], 42.1 [206], 36.9 [94], and 34.7 [214]. After adjusting for age (timescale), race and ethnicity, and WHI study component, HRs (95% CI) for mortality across the PA groups were 1.00 (referent), 0.94 (0.79, 1.10), 0.80 (0.64, 1.01), and 0.60 (0.51, 0.71). Further adjustment for baseline education, BMI, physical function, smoking, menopausal hormone use, history of diabetes, hypertension, myocardial infarction, stroke, coronary revascularization, atrial fibrillation, and incident myocardial infarction during follow-up prior to HF diagnosis attenuated these associations but did not eliminate statistical significance for the Active/Active group: 1.00 (referent), 1.04 (0.87, 1.24), 0.87 (0.69, 1.10), 0.74 (0.62, 0.89). A similar pattern of results was evident when cardiovascular mortality was the study outcome. Conclusions: Maintaining PA levels following hospitalization for acute HF was associated with lower all-cause mortality in older postmenopausal women, an understudied population in this regard. Among women whose PA following HF diagnosis was higher than their pre-HF PA level, there was a trend for lower mortality although this did not achieve statistical significance. Studies are needed to determine whether PA is associated with prognosis in HF subtypes, such as HF with preserved ejection which is a prevalent HF subtype in older women.

BackgroundTo investigate the association between walking pace and the risk of heart failure (HF) and HF sub-types.MethodsWe examined associations of self-reported walking pace with risk of incident HF and HF subtypes of preserved (HFpEF) and reduced (HFrEF) ejection fractions, among 25,183 postmenopausal women, ages 50-79 years. At enrollment into the Women's Health Initiative cohort in 1993-1998, this subset of women was free of HF, cancer, or the inability to walk one block, with self-reported information on walking pace and walking duration. Multivariable Cox regression was used to examine associations of walking pace (casual 3 mph) with incident HF. We also examined the joint association of walking pace and duration with incident HF.ResultsThere were 1455 incident adjudicated acute decompensated HF hospitalization cases during a median of 16.9 years of follow-up. There was a strong inverse association between walking pace and overall risk of HF (HR=0.73, 95% CI [0.65, 0.83] for average vs. casual walking; HR=0.66, 95%CI [0.56, 0.78] for fast vs. casual walking). There were similar associations of walking pace with HFpEF (HR=0.73, 95%CI [0.62, 0.86] average vs. casual; HR=0.63, 95%CI [0.50, 0.80] for fast vs. casual) and with HFrEF (HR=0.72, 95%CI [0.57, 0.91] for average vs. casual; HR=0.74, 95%CI [0.54, 0.99] for fast vs. casual). The risk of HF associated with fast walking with less than 1h/week walking duration was comparable with the risk of HF among casual and average walkers with more than 2h/week walking duration.ConclusionWalking pace was inversely associated with risks of overall HF, HFpEF, and HFrEF in postmenopausal women. Whether interventions to increase the walking pace in older adults will reduce HF risk and whether fast pace will compensate for the short duration of walking warrants further study.

Background Prospective evidence on associations between diet quality indices and lung cancer risk is limited, particularly among older women. Objectives We investigated associations between 4 diet quality indices [Healthy Eating Index-2015 (HEI-2015), Alternate Healthy Eating Index 2010 (AHEI-2010), alternate Mediterranean Diet (aMED), and Dietary Approaches to Stop Hypertension (DASH)] and lung cancer incidence and mortality in the Women's Health Initiative Observational Study. Methods Postmenopausal women aged 50-79 y at baseline (1993-1998) self reported their diet intake and information on relevant covariates. We used Cox proportional hazards regression models to estimate HRs and 95% CIs after controlling for age, smoking, and other relevant covariates. Results During ∼17 y of follow-up among 86,090 participants, 1491 lung cancer cases and 1393 lung cancer deaths were documented. Dietary indices were not associated with overall lung cancer incidence but were protective against squamous cell carcinoma (12.8% of total lung cancer) cases (HEI-2015: HR: 0.85; 95% CI: 0.76, 0.96; AHEI-2010: HR: 0.87; 95% CI: 0.78, 0.98; aMED: HR: 0.90; 95% CI: 0.81, 0.99; DASH: HR: 0.87; 95% CI: 0.77, 0.98). Among the indices, only HEI-2015 showed an inverse trend (P-trend = 0.02) with overall lung cancer mortality. Smoking status or participant age at baseline did not modify the association between dietary indices and lung cancer incidence or mortality. Conclusions After comprehensive control of smoking exposure, we found that diet quality was not associated with overall lung cancer among postmenopausal women. However, a high-quality diet was inversely related to incident lung cancer of the squamous cell subtype. Future studies in populations with diverse age, smoking history, and dietary intake may further elucidate the relation between diet quality indices and lung cancer, especially by histological subtype.

PURPOSE: Robert (“Bob”) Genco was a member of the research team that established the Buffalo Osteoporosis and Periodontal Disease (OsteoPerio) study. Here we detail the scientific discoveries emanating from this enduring collaboration. STUDY COHORTS: OsteoPerio is ancillary to the Women’s Health Initiative Observational Study (WHI-OS). WHI-OS is a longitudinal study of 93,000 postmenopausal women aged 50–79 enrolled at 40 U.S. centers (enrolled 1993–1998). OsteoPerio enrolled 1342 women 3 years later (1997–2001) from the Buffalo WHI-OS participants to study the association of osteoporosis and periodontal disease. OsteoPerio has 5-year (N=1026) and 17-year (N=518) follow-up examinations. PARTICIPANTS: In addition to information on health status from the WHI-OS, OsteoPerio further included comprehensive oral examinations assessing probing pocket depth, clinical attachment loss, gingival bleeding, alveolar crestal height, and DMFT. Systemic bone density (measured by DXA), blood, saliva and plaque also were collected at all three visits. SUMMARY: Findings from these studies are summarized here.

Background The D3-creatine (D3Cr) dilution method provides a direct measure of skeletal muscle. The aim of this study was to compare the association of D3Cr muscle mass with lean body mass (LBM) measured by dual-energy x-ray absorptiometry (DXA) and examine its relation with physical function in postmenopausal women. Methods Seventy-four community-dwelling women (mean age 82.3 ± 5.4) participated in this pilot study from the Buffalo, New York clinical site of the Women’s Health Initiative (WHI). Participants attended a clinic visit which included anthropometric measures, blood draw, DXA scan, measures of physical function, and initiated the D3Cr protocol. Physical function was evaluated using hand grip strength, short physical performance battery (SPPB), and RAND-36 physical function scale. Descriptive statistics and logistic regression models were used to examine the associations of D3Cr muscle mass with functional outcomes. Results D3-creatine muscle mass was moderately correlated with DXA LBM (r = 0.50) and DXA appendicular lean mass (ALM) (r = 0.50). Individuals with high D3Cr muscle mass (%) had higher physical function compared to individuals with low muscle mass (%), indicated by high scores on SPPB (odds ratio [OR] = 5.24; 95% confidence interval [CI]: 1.40, 19.58). We observed stronger relationships between high D3Cr and physical function than either DXA LBM (OR = 3.40; 95% CI: 0.88, 13.11) or DXA ALM (OR = 4.15; 95% CI: 1.10, 15.68) and physical function. Conclusions Our findings provide strong preliminary data for the associations of D3Cr muscle mass with measures of physical function in older women. These findings support and extend prior work on D3Cr muscle mass in older men.

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.

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

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 (n = 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); Ptrend = 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); Ptrend = 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]; P = 0.01); the HR for replacing 30 min of light PA with MVPA was 0.85 (95% CI 0.73–0.98); P = 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.

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' 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.

BACKGROUND The aim of this study was to quantify the association between subgingival microbiota and periodontal disease progression in older women, for which limited published data exist. METHODS A total of 1016 postmenopausal women, aged 53 to 81 years, completed baseline (1997 to 2001) and 5-year (2002 to 2006) dental exams that included probing depth, clinical attachment level, gingival bleeding, and radiographic alveolar crestal height (ACH). Baseline microbiota were measured in subgingival plaque using 16S rRNA sequencing. Associations between 52 microbiota we previously found statistically significantly associated with clinical periodontal disease at baseline, were examined with disease progression. The traditional Socransky microbiota complexes also were evaluated. Side-by-side radiograph comparisons were used to define progression as ≥2 teeth with ≥1 mm ACH loss or ≥1 new tooth loss to periodontitis. The association between baseline centered log(2) ratio transformed microbial relative abundances and 5-year periodontal disease progression was measured with generalized linear models. RESULTS Of 36 microbiota we previously showed were elevated in moderate/severe disease at baseline, 24 had statistically significantly higher baseline mean relative abundance in progressing compared with non-progressing women (P

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.

Several serum inflammatory biomarkers have been associated with blood pressure and hypertension prevalence in cross-sectional studies. Few of these associations have been evaluated prospectively. We examined associations for 10 serum inflammatory biomarkers with incident hypertension among 471 postmenopausal women (mean age = 65) in the Buffalo OsteoPerio Study. Concentrations of C-reactive protein, interleukin (IL)-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, monocyte chemoattractant protein (MCP)-1, adiponectin, and leptin were measured using multiplexed sandwich immunoassays on fasting serum samples collected at baseline (1997-2001). Incident hypertension (195 cases) was defined as physician-diagnosed hypertension and treatment with medication identified on annual mailed health surveys during follow-up (mean 10 years). Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) between log-transformed biomarkers (per 1-SD) and hypertension. When adjusted for age, leptin was significantly associated with hypertension risk (HR = 1.55, 95% CI: 1.04, 2.29), however, the association was attenuated and not significant after adjustment for demographic and lifestyle factors, including BMI. Significant (P < 0.10) interactions were observed for smoking (never, ever) with CRP (HR: never, 1.31; ever, 0.91; P = 0.06) and MCP-1 (HR: never, 0.59; ever, 5.11; P = 0.004); for BMI (

This study investigated the association between menopausal hormone therapy (HT) use and the subgingival microbiome, for which published information is limited.This cross-sectional study included 1270 postmenopausal women, aged 53-81 years, who completed clinical examinations. Detailed information on HT use (type, delivery mode, duration) was obtained from questionnaires. HT use was categorized into three groups (never, former, current). 16S rRNA sequencing was performed on subgingival plaque samples obtained during dental examinations. Operational taxonomic units were centered log2-ratio (CLR) transformed to account for the compositional data structure. Analysis of variance was used to compare mean microbial relative abundances across HT categories with Benjamini-Hochberg correction.Significantly higher alpha diversity (Shannon Index) and beta diversity (Aitchison distance) was observed in never compared with current HT users (p 0.05, each). Of the total 245 microbial taxa identified, 18 taxa differed significantly among the three HT groups, 11 of which were higher in current users and seven of which were lower in current users as compared with never users (p 0.05, each). Differences in relative abundance between never and current HT users were materially unchanged after adjustment for age, body mass index, and oral hygiene.Relative abundance of several subgingival bacteria differed significantly between never and current HT users in a cohort of postmenopausal women. Additional studies are needed to determine the extent that these relationships might account for the previously reported inverse association between HT use and periodontal disease in older women.

Cardiovascular disease surveillance involves quantifying the evolving population‐level burden of cardiovascular outcomes and risk factors as a data‐driven initial step followed by the implementation of interventional strategies designed to alleviate this burden in the target population. Despite widespread acknowledgement of its potential value, a national surveillance system dedicated specifically to cardiovascular disease does not currently exist in the United States. Routinely collected health care data such as from electronic health records (EHRs) are a possible means of achieving national surveillance. Accordingly, this article elaborates on some key strengths and limitations of using EHR data for establishing a national cardiovascular disease surveillance system. Key strengths discussed include the: (1) ubiquity of EHRs and consequent ability to create a more “national” surveillance system, (2) existence of a common data infrastructure underlying the health care enterprise with respect to data domains and the nomenclature by which these data are expressed, (3) longitudinal length and detail that define EHR data when individuals repeatedly patronize a health care organization, and (4) breadth of outcomes capable of being surveilled with EHRs. Key limitations discussed include the: (1) incomplete ascertainment of health information related to health care–seeking behavior and the disconnect of health care data generated at separate health care organizations, (2) suspect data quality resulting from the default information‐gathering processes within the clinical enterprise, (3) questionable ability to surveil patients through EHRs in the absence of documented interactions, and (4) the challenge in interpreting temporal trends in health metrics, which can be obscured by changing clinical and administrative processes.

Background Oral microbiota are thought to influence blood pressure (BP) regulation. However, epidemiological data supporting this hypothesis are limited. We examined associations between oral microbiota, BP, and incident hypertension in postmenopausal women. Methods and Results Baseline (1997–2001) examinations were completed on 1215 women (mean age, 63 years) during which subgingival plaque was collected, BP was measured, and medical and lifestyle histories and medication inventory were obtained. Microbiome composition of subgingival plaque was measured using 16S ribosomal RNA gene amplicon sequencing. Baseline measured BP was defined as normotensive (systolic P P Conclusions Specific oral bacteria are associated with baseline BP status and risk of hypertension development among postmenopausal women. Research to confirm these observations and elucidate mechanisms is needed.

Background Sedentary behavior is associated with cardiovascular disease, but its association with incident atrial fibrillation is not well studied. Our aim was to measure the association between objectively measured sedentary behavior and incident atrial fibrillation. Methods and Results Sedentary behavior was measured by a triaxial accelerometer worn on a belt for 1 week. Incident atrial fibrillation was ascertained from Medicare claims. The associations between total sedentary time (or patterns of sedentary behavior) and incident atrial fibrillation were assessed using Cox proportional hazards models adjusted for demographic and clinical covariates. Among 2675 participants (mean age, 78.2 years), there were 268 (10.0%) cases of incident atrial fibrillation at a rate of 31 cases per 1000 person‐years. Greater total sedentary time was associated with a higher risk of incident atrial fibrillation after adjustment for age, race and ethnicity, body mass index, education, smoking history, hypertension, diabetes, stroke, heart disease, and other chronic conditions (quartile 4 versus quartile 1: hazard ratio, 1.20, [95% CI, 0.81–1.78]; P for trend=0.05). After adjusting for physical function and self‐rated health, this was no longer statistically significant. Both longer mean sedentary bout duration and more continuous sedentary periods (versus frequent breaks in sedentary time) were also associated with higher risks of incident atrial fibrillation, but these associations were also attenuated with serial adjustment. Conclusions Total sedentary time and prolonged patterns of sedentary accumulation were associated with a higher risk of atrial fibrillation in this prospective study of community‐dwelling older women, but these associations were attenuated by adjustment for physical function and self‐reported health. This suggests that associations between sedentary behavior and atrial fibrillation may be attributable to global measures of overall function and health.

Introduction: The AHA’s Life’s Simple 7 (LS7) includes physical activity (PA) as one of the metrics for assessing cardiovascular health. Using self-reported PA can misclassify those who meet the PA component of the LS7. Using accelerometer-measured PA may improve the utility of the LS7. Our study compares associations of LS7 and incident cardiovascular disease (CVD) associations using both self-reported and accelerometer-measured PA. Methods: Women’s Health Initiative (WHI) participants in the Objective Physical Activity and Cardiovascular Health Study (n=4075; mean±SD age = 79±7) with no history of CVD completed the WHI PA questionnaire (PAQ) and the Community Healthy Activities Model Program for Seniors (CHAMPS) PAQ prior to wearing a hip-worn accelerometer for up to 7 consecutive days. LS7 components (PA, diet, body mass index, smoking, blood pressure, fasting serum total cholesterol and glucose) were scored on a scale of 0-2 using AHA guidelines, resulting in an LS7 summary score ranging from 0-14 with higher scores reflecting more favorable status. Four LS7 summary scores were created using different PA measures: the WHI PAQ, the CHAMPS PAQ, and two accelerometer measures (MVPA min/week and mean steps/day). LS7 scores were analyzed using quartiles (LS7 scores 1-7, 8, 9, 10-14) and hazard ratios (HR) for incident physician-adjudicated CVD were estimated. Results: There were 500 incident CVD events (see Table) over an average 6 years of follow-up. Multivariable HRs (95% CI) comparing women with high (10-14) vs. low (1-7) LS7 scores were: WHI PAQ= 0.81 (0.60-1.09), CHAMPS PAQ= 0.80 (0.61-1.05), accelerometer (MVPA)= 0.61 (0.47-0.79), accelerometer (steps)= 0.65 (0.45-0.94; see Table). Conclusions: PA is just one component of the LS7, yet the LS7-incident CVD associations vary considerably by PA measurement. Accelerometer-measured PA, such as daily steps, improves the accuracy of the LS7 PA component used to classify cardiovascular health and may be feasible for practitioners to implement.

Introduction: The association between physical activity (PA) and incident venous thromboembolism (VTE) is inconsistent and incompletely characterized. Hypothesis: Higher amounts of self-reported total PA will be associated with a lower risk of incident VTE. Methods: Eligible women were Women’s Health Initiative (WHI) Hormone Therapy (HT) trial and Observational Study (OS) participants without prior VTE, able to walk at least one block, with baseline PA data (n=110,631). At multiple timepoints, women reported their current usual frequency and duration of walking and low, moderate, and strenuous intensity recreational PA, which were used to estimate energy expended. VTE, including deep vein thrombosis and pulmonary embolism, were validated in the WHI-HT and self-reported in the WHI-OS. Multivariable-adjusted (Table) Cox Proportional Hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of time-varying total PA and incident VTE risk, with women censored at death, loss to follow-up, and three years after their final PA measure. Results: At baseline, women were 64 years of age on average. Over an average of 9.9 years of follow-up, 1,403 women experienced incident VTE. In primary confounder-adjusted models, compared with women who reported no PA, higher tertiles of total PA were associated with a lower risk of incident VTE (high vs. no PA HR=0.60; 95% CI: 0.51, 0.71; p-trend Conclusions: Compared to no PA, higher tertiles of total PA were associated with a lower risk of incident VTE, even after adjusting for potential mediators reflecting physical function, health, BMI, and cardiovascular risk. Our results add to the apparent health benefits of even moderate amounts of recreational PA.

Background Current physical activity guidelines focus on volume and intensity for CVD prevention rather than common behaviors responsible for movement, including those for daily living activities. We examined the associations of a machine‐learned, accelerometer‐measured behavior termed daily life movement (DLM) with incident CVD. Methods and Results Older women (n=5416; mean age, 79±7 years; 33% Black, 17% Hispanic) in the Women’s Health Initiative OPACH (Objective Physical Activity and Cardiovascular Health) study without prior CVD wore ActiGraph GT3X+ accelerometers for up to 7 days from May 2012 to April 2014 and were followed for physician‐adjudicated incident CVD through February 28th, 2020 (n=616 events). DLM was defined as standing and moving in a confined space such as performing housework or gardening. Cox models estimated hazard ratios (HR) and 95% CI, adjusting for age, race and ethnicity, education, alcohol use, smoking, multimorbidity, self‐rated health, and physical function. Restricted cubic splines examined the linearity of the DLM‐CVD dose‐response association. We examined effect modification by age, body mass index, Reynolds Risk Score, and race and ethnicity. Adjusted HR (95% CIs) across DLM quartiles were: 1.00 (reference), 0.68 (0.55–0.84), 0.70 (0.56–0.87), and 0.57 (0.45–0.74); p‐trend0.09). There was no evidence of effect modification by age, body mass index, Reynolds Risk Score, or race and ethnicity. Conclusions Higher DLM was independently associated with a lower risk of CVD in older women. Describing the beneficial associations of physical activity in terms of common behaviors could help older adults accumulate physical activity.

OBJECTIVE The primary aim was to assess associations between total steps per day and incident diabetes, whereas the secondary aim was to assess whether the intensity and/or cadence of steps is associated with incident diabetes. RESEARCH DESIGN AND METHODS Women without physician-diagnosed diabetes (n = 4,838; mean [SD] age 78.9 [6.7] years) were followed up to 6.9 years; 395 developed diabetes. Hip-worn ActiGraph GT3X+ accelerometers worn for 1 week enabled measures of total, light-intensity, and moderate- to vigorous-intensity (MV-intensity) steps per day. Using Cox proportional hazards analysis we modeled adjusted change in the hazard rate for incident diabetes associated with total, light-intensity, and MV-intensity steps per day. We further estimated the proportion of the steps-diabetes association mediated by BMI. RESULTS On average, participants took 3,729 (SD 2,114) steps/day, of which 1,875 (791) were light-intensity steps and 1,854 ± 1,762 were MV-intensity. More steps per day were associated with a lower hazard rate for incident diabetes. Confounder-adjusted models for a 2,000 steps/day increment yielded hazard ratio (HR) 0.88 (95% CI 0.78–1.00; P = 0.046). After further adjustment for BMI, HR was 0.90 (95% CI 0.80–1.02; P = 0.11). BMI did not significantly mediate the steps-diabetes association (proportion mediated = 17.7% [95% CI −55.0 to 142.0]; P = 0.09]). The relationship between MV-intensity steps per day (HR 0.86 [95% CI 0.74–1.00]; P = 0.04) and incident diabetes was stronger than for light-intensity steps per day (HR 0.97 [95% CI 0.73–1.29]; P = 0.84). CONCLUSIONS These findings suggest that for older adults, more steps per day are associated with lower incident diabetes and MV-intensity steps are most strongly associated with a lower hazard of diabetes. This evidence supports that regular stepping is an important risk factor for type 2 diabetes prevention in older adults.

Background This study evaluated the association between changes in physical performance and blood pressure (BP) (e.g., systolic [SBP], diastolic [DBP], pulse pressure) in older women. Methods 5627 women (mean age 69.8 ± 3.7 y) with grip strength, chair stand, gait speed performance and clinic-measured BP at baseline and at least one follow-up (years 1, 3 or 6) were included. Generalized estimating equation analysis of multivariable models with standardized point estimates described the longitudinal association between physical performance and BP changes in the overall cohort, and in models stratified by baseline cardiovascular disease (CVD), time-varying antihypertensive medication use (none, ≥1) and enrollment age (65–69 y; 70–79 y). Results Overall, each z-score unit increment in grip strength was associated with 0.59 mmHg (95% CI 0.10, 1.08) higher SBP, and 0.39 mmHg (95% CI 0.11, 0.67) higher DBP. In stratified models, a standardized increment in grip strength was associated with higher SBP in women without CVD (0.81; 95% CI 0.23–1.39), among antihypertensive medication users (0.93; 95% CI 0.44, 1.41) and non-users (0.37; 95% CI 0.03, 0.71), and in those aged 65–69 y (0.64; 95% CI 0.04, 1.24). Similarly, a standardized increment in any of the three performance measures was associated with modestly higher DBP in antihypertensive medication users, and those aged 70–79 y. Associations between any performance measure and pulse pressure change were not significant. Conclusion These results suggest a positive, and statistically significant relationship between physical performance and BP that appears to be influenced by CVD history, antihypertensive medication use, and age.

Achieving recommended levels of physical activity is important for optimal cardiovascular health and can help reduce cardiovascular disease risk. Emerging evidence suggests that physical activity fluctuates throughout the life course. Some life events and transitions are associated with reductions in physical activity and, potentially, increases in sedentary behavior. The aim of this scientific statement is to first provide an overview of the evidence suggesting changes in physical activity and sedentary behavior across life events and transitions. A second aim is to provide guidance for health care professionals or public health workers to identify changes and promote physical activity during life events and transitions. We offer a novel synthesis of existing data, including evidence suggesting that some subgroups are more likely to change physical activity behaviors in response to life events and transitions. We also review the evidence that sedentary behavior changes across life events and transitions. Tools for health care professionals to assess physical activity using simple questions or wearable devices are described. We provide strategies for health care professionals to express compassion as they ask about life transitions and initiate conversations about physical activity. Last, resources for life phase–specific, tailored physical activity support are included. Future research needs include a better characterization of physical activity and sedentary behavior across life events and transitions in higher-risk subgroups. Development and testing of interventions designed specifically to combat declines in physical activity or increases in sedentary behavior during life events and transitions is needed to establish or maintain healthy levels of these cardiovascular health–promoting behaviors.

Highlights • In older women, lower Short Physical Performance Battery (SPPB) scores were associated with higher incident heart failure (HF) risk. • SPPB-HF associations were consistent in women with obesity, diabetes, hypertension, and low physical activity. • Including the SPPB routinely in clinical evaluations could enhance HF prevention., 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 (n = 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; P-trend0.10. 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.

Heart failure (HF) is a complex clinical syndrome hallmarked by an inability to match cardiac output with metabolic demand, resulting in exercise intolerance. HF is increasingly prevalent in an aging population and accounts for substantial burden of health care costs and morbidity. Because many of the central and peripheral mechanisms of HF respond favorably to exercise training, its role in HF treatment is becoming established. The role of habitual physical activity in the primary prevention of HF is less clear; however, available evidence is supportive. This article reviews recently published studies on exercise training and usual physical activity in HF treatment and prevention, discusses potential mechanisms, and suggests areas where further research is needed.

Research findings remain inconsistent whether caffeine consumption is associated with invasive breast cancer. We aimed to examine the association between caffeine intake from coffee and tea and incident invasive breast cancer among postmenopausal women. We included 79 871 participants in the Women's Health Initiative Observational Study in the current analysis. Incident invasive breast cancers were identified through September 30, 2015. Caffeine intake (mg/day) from caffeinated and decaffeinated coffee and tea was estimated based on self-reported frequency (cups/day) and average caffeine amount in each beverage. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Subgroup analyses were conducted to explore whether associations of caffeine intake from coffee and tea with invasive breast cancer were different by age, race and ethnicity, smoking status, body mass index, history of hormone therapy use, alcohol intake, and subtypes of breast cancer. During a median follow-up of 16.0 years, 4719 incident invasive breast cancers were identified. No significant association was found between caffeine intake from coffee and tea and invasive breast cancer incidence after adjusting for demographic, lifestyle, and reproductive factors: HRs (95% CIs) for increasing quartiles of caffeine intake compared to the lowest were 1.03 (0.94, 1.12), 1.04 (0.95, 1.13), and 1.03 (0.94, 1.13), respectively (P-for-trend = 0.54). No significant associations of coffee and tea intake (cups/day) with overall breast cancer risk were found. Our findings are consistent with others showing no clear association of caffeine consumption with invasive breast cancer among postmenopausal women. This article is protected by copyright. All rights reserved.

BACKGROUND Walking independently is basic to human functioning. The Lifestyle Interventions and Independence for Elders (LIFE) studies were developed to assess whether initiating physical activity could prevent major mobility disability (MMD) in sedentary older adults. METHODS We review the development and selected findings of the LIFE studies from 2000 through 2019, including the planning phase, the LIFE‐Pilot Study, and the LIFE Study. RESULTS The planning phase and the LIFE‐Pilot provided key information for the successful implementation of the LIFE Study. The LIFE Study, involving 1635 participants randomized at eight sites throughout the United States, showed that compared with health education, the physical activity program reduced the risk of the primary outcome of MMD (inability to walk 400 m: hazard ratio = 0.82; 95% confidence interval = 0.69‐0.98; P = .03), and that the intervention was cost‐effective. There were no significant effects on cognitive outcomes, cardiovascular events, or serious fall injuries. In addition, the LIFE studies provided relevant findings on a broad range of other outcomes, including health, frailty, behavioral outcomes, biomarkers, and imaging. To date, the LIFE studies have generated a legacy of 109 peer‐reviewed publications, 19 ancillary studies, and 38 independently funded grants and clinical trials, and advanced the development of 59 early career scientists. Data and biological samples of the LIFE Study are now publicly available from a repository sponsored by the National Institute on Aging (https://urldefense.proofpoint.com/v2/url?u=https-3A__agingresearchbiobank.nia.nih.gov&d=DwMFAg&c=pZJPUDQ3SB9JplYbifm4nt2lEVG5pWx2KikqINpWlZM&r=ZX4a6hcfLVk9tpCPmkSujQ&m=iTPARxl_LBOimJoAcWK4efKQBWBHszm-g4mUN_o5-bc&s=SrlCccrcYCFSyWnnprcB3rJXT3W3FkGkW0XmdJITNhE&e=). CONCLUSIONS The LIFE studies generated a wealth of important scientific findings and accelerated research in geriatrics and gerontology, benefiting the research community, trainees, clinicians, policy makers, and the general public. J Am Geriatr Soc 68:872–881, 2020, See related editorial by https://doi.org/10.1111/jgs.16374. in this issue.

ObjectiveTo identify the risk factors of women who fell with injury relative to women who did not fall or fell without injury and to describe the circumstances and consequences of injurious and non-injurious falls.MethodsWe analysed 5074 older women from the Objective Physical Activity and Cardiovascular Health Study who prospectively tracked their falls using a 13-month calendar. Women with a reported fall were phone interviewed about fall-related details, including injuries. Risk factors were identified from surveys and clinical home visits. Logistic regression models were used to calculate adjusted ORs and 95% CIs for injurious falls relative to not falling or falling without injury. Circumstances of injurious and non-injurious falls were compared.ResultsAt least one fall was experienced by 1481 (29%) participants. Of these, 1043 were phone interviewed, of whom 430 (41%) reported at least one injurious fall. Relative to not falling, the risk factor most strongly associated with experiencing an injurious fall was having fallen ≥2 times (OR 4.0, CI 2.7 to 5.8) in the past year. Being black was protective for fall-related injury (OR 0.6, CI 0.4 to 0.9). No strong associations in risk factors were observed for injurious relative to non-injurious falls. Injurious falls were more likely to occur away from and outside of the home (pConclusionFalling repeatedly is a powerful risk factor for injurious falls. Those who have fallen more than once should be prioritised for interventions to mitigate the risk of an injurious fall.

Background The extent to which the composition and diversity of the oral microbiome varies with age is not clearly understood. Methods The 16S rRNA gene of subgingival plaque in 1219 women, aged 53–81 years, was sequenced and its taxonomy annotated against the Human Oral Microbiome Database (v.14.5). Composition of the subgingival microbiome was described in terms of centered log(2)-ratio (CLR) transformed OTU values, relative abundance, and prevalence. Correlations between microbiota abundance and age were evelauted using Pearson Product Moment correlations. P-values were corrected for multiple testing using the Bonferroni method. Results Of the 267 species identified overall, Veillonella dispar was the most abundant bacteria when described by CLR OTU (mean 8.3) or relative abundance (mean 8.9%); whereas Streptococcus oralis, Veillonella dispar and Veillonella parvula were most prevalent (100%, all) when described as being present at any amount. Linear correlations between age and several CLR OTUs (Pearson r = − 0.18 to 0.18), of which 82 (31%) achieved statistical significance (P P P Conclusions We identified associations between several bacterial species and age across the age range of postmenopausal women studied. Understanding the functions of these bacteria could identify intervention targets to enhance oral health in later life.

Understanding of the oral microbiome in relation to periodontal disease in older adults is limited. The composition and diversity of the subgingival microflora and their oligotypes in health and levels of periodontal disease were investigated in this study on older postmenopausal women. The 16S rRNA gene was sequenced using the Illumina MiSeq platform in 1,206 women aged 53 to 81 y. Presence and severity of periodontal disease were defined by Centers for Disease Control and Prevention/American Academy of Periodontology criteria. Composition of the microbiome was determined by 16S rRNA amplicon sequencing and the abundance of taxa described by the centered log2-ratio (CLR) transformed operational taxonomic unit (OTU) values. Differences according to periodontal disease status were determined by analysis of variance with Bonferroni correction. Bacteria oligotypes associated with periodontal disease and health were determined by minimum entropy decomposition and their functions estimated in silico using PICRUSt. Prevalence of none/mild, moderate, and severe periodontal disease was 25.1%, 58.3%, and 16.6%, respectively. Alpha diversity of the microbiome differed significantly across the 3 periodontal disease categories. β-Diversity differed between no/mild and severe periodontal disease, although considerable overlap was noted. Of the 267 bacterial species identified at ≥0.02% abundance, 56 (20.9%) differed significantly in abundance according to periodontal disease status. Significant linear correlations for pocket depth and clinical attachment level with bacterial amounts were observed for several taxa. Of the taxa differing in abundance according to periodontal disease status, 53% had multiple oligotypes appearing to differ between none/mild and severe periodontal disease. Among older women, taxonomic differences in subgingival microbiome composition and diversity were observed in relation to clinical periodontal disease measures. Potential differences in bacterial subspecies (oligotypes) and their function were also identified in periodontal disease compared with health.