Effects of moderate/vigorous activity on 3-year body composition changes in postmenopausal women: a target trial emulation.

Background and Objective Postmenopausal women tend to experience significant changes in body composition, particularly abdominal adipose tissue (AAT) deposition patterns, which are hypothesized to be critical factors influencing future cardiometabolic disease risk. Physical activity has a demonstrable effect on body composition and overall health. However, there is little evidence for how different intensities and durations of physical activity over a sustained period of time influence AAT patterns and other measures of body composition in postmenopausal women. We emulated a target trial of physical activity interventions, including the 2018 Physical Activity Guidelines for Americans recommendations, on 3-year changes in AAT and body composition. Methods We analyzed observational data from 4,451 postmenopausal women aged 50-79 years in the Women's Health Initiative (WHI) to emulate a three-year target trial of adhering to increasing minutes of moderate (at least 15, 30, 75, 150, 300 minutes/week) and vigorous (at least 15, 30, 75, 150 minutes/week) physical activity aligned with the physical activity guidelines. All participants had repeated whole body Dual X-Ray Absorptiometry (DXA) scans with derived abdominal visceral (VAT) and subcutaneous adipose tissue (SAT). The measured differences in average levels of VAT, SAT, and other body composition measures determined at end of follow-up were estimated with the parametric-g formula. Results Over 3 years, interventions of increasing minutes of moderate activity would result in dose-dependent reductions in abdominal VAT, SAT, and overall body fat, and increases in lean soft tissue, with the greatest estimated benefit at the 2018 physical activity guideline recommendation of 150 mins/wk or more. Compared to no intervention, if all participants had adhered to at least 150 mins/wk of moderate physical activity, they would have 16.8 cm2 lower VAT (95% CI -23.1, -10.4), 26.8 cm2 lower SAT (95% CI -36.3, -17.3), 1.3% lower total body fat% (95% CI -1.8, -0.7), 1.2 % higher total lean soft tissue% (95% CI 0.7, 1.8), and 2.6 kg lower total bodyweight (95% CI -3.6, -1.5). We saw similar patterns in our vigorous-intensity activity interventions - if all participants adhered to at least 150 mins/wk, they would have experienced 6.7 cm2 lower VAT (95% CI -17.7, 4.3), 13.3 cm2 lower SAT (95% CI -28.8, 2.1), 1.0 % lower total body fat percent (95% CI -2.0, 0.0 ), % higher total lean soft tissue percent (95% CI) and a 0.9 kg lower total bodyweight (95% CI -2.7, 0.8). Conclusion This hypothetical emulated intervention indicated that postmenopausal women who adhere to physical activity guideline recommendations would experience beneficial changes in abdominal VAT, SAT, and overall body composition over 3 years. The study results underscore the imperative to explore further how physical activity may serve as a potential determinant of body composition.

Stroke Incidence in Patients With Hypertension According to Cardiorespiratory Fitness.

BACKGROUND: Hypertension and physical inactivity are risk factors for stroke. The effect of cardiorespiratory fitness (CRF) on stroke risk in patients with hypertension has not been assessed. We evaluated stroke incidence in patients with hypertension according to CRF and changes in CRF. METHODS: We included 483 379 patients with hypertension (mean age±SD; 59.4±9.0 years) and no evidence of unstable cardiovascular disease as indicated by a standardized exercise treadmill test. Patients were assigned to 5 age- and sex-specific CRF categories based on peak metabolic equivalents achieved at the initial exercise treadmill test and in 4 categories based on metabolic equivalent changes over time (n=110 576). Multivariable Cox models, adjusted for age, and comorbidities were used to estimate hazard ratios and 95% CIs for stroke risk. RESULTS: During a median follow-up of 10.6 (interquartile range, 6.6-14.6) years, 15 925 patients developed stroke with an average yearly rate of 3.1 events/1000 person-years. Stroke risk declined progressively with higher CRF and was 55% lower for the High-fit individuals (hazard ratio, 0.45 [95% CI, 0.42-0.48]) compared with the Least-fit. Similar associations were observed across the race, sex, and age spectra. Poor CRF was the strongest predictor of stroke risk of all comorbidities studied (hazard ratio, 2.24 [95% CI, 2.10-2.40]). Changes in CRF reflected inverse and proportional changes in stroke risk. CONCLUSIONS: Poor CRF carried a greater risk than any of the cardiac risk factors in patients with hypertension, regardless of age, race, or sex. The lower stroke risk associated with improved CRF suggests that increasing physical activity, even later in life, may reduce stroke risk.

Associations of Relative Intensity of Physical Activity With Incident Cardiovascular Events and All-Cause Mortality.

BACKGROUND: The relative intensity of physical activity (PA) can be estimated as the percent of one's maximal effort required. METHODS: We compared associations of relative and absolute intensity PA with incident major cardiovascular disease (CVD) and all-cause mortality in 5 633 women from the Objective Physical Activity and Cardiovascular Health Study (mean age 78.5 ±â€…6.7). Absolute intensity was measured by accelerometry. Relative intensity was estimated by dividing accelerometer-estimated metabolic equivalents (METs) by maximal MET capacity. Both were aggregated into mean daily hours of light intensity PA (LPA) and moderate-to-vigorous PA (MVPA). Cox proportional hazard models estimated hazard ratios (HRs) for 1-hour higher amounts of PA on outcomes. RESULTS: During follow-up (median = 7.4 years), there were 748 incident CVD events and 1 312 deaths. Greater LPA and MVPA, on either scale, were associated with reduced risk of both outcomes. HRs for a 1-hour increment of absolute LPA were 0.88 (95% CI: 0.83-0.93) and 0.88 (95% CI: 0.84-0.92) for incident CVD and mortality, respectively. HRs for a 1-hour increment of absolute MPVA were 0.73 (95% CI: 0.61-0.87) and 0.55 (95% CI: 0.48-0.64) for the same outcomes. HRs for a 1-hour increment of relative LPA were 0.70 (95% CI: 0.59-0.84) and 0.78 (95% CI: 0.68-0.89) for incident CVD and mortality, respectively. HRs for a 1-hour increment of relative MPVA were 0.89 (95% CI: 0.83-0.96) and 0.82 (95% CI: 0.77-0.87) for the same outcomes. On the relative scale, LPA was more strongly, and inversely associated with both outcomes than relative MVPA. Absolute MVPA was more strongly inversely associated with the outcomes than relative MVPA. CONCLUSIONS: Findings support the continued shift in the PA intensity paradigm toward recommendation of more movement, regardless of intensity. Relative LPA--a modifiable, more easily achieved behavioral target, particularly among ambulatory older adults--was associated with reduced risk of incident major CVD and death.

Accelerometry-assessed physical activity and sedentary behavior patterns using single- and multi-component latent class analysis among postmenopausal women.

BACKGROUND: Patterns of physical activity and sedentary behavior among postmenopausal women are not well characterized. OBJECTIVES: To describe the patterns of accelerometer-assessed physical activity and sedentary behavior among postmenopausal women. DESIGN: Cross-sectional study. METHODS: Women 63-97 years (n = 6126) wore an ActiGraph GT3X + accelerometer on their hip for 1 week. Latent class analysis was used to classify women by patterns of percent of wake time in physical activity and sedentary behavior over the week. RESULTS: On average, participants spent two-thirds of their day in sedentary behavior (62.3%), 21.1% in light low, 11.0% in light high, and 5.6% in moderate-to-vigorous physical activity. Five classes emerged for each single-component model for sedentary behavior and light low, light high, and moderate-to-vigorous physical activity. Six classes emerged for the multi-component model that simultaneously considered the four behaviors together. CONCLUSION: Unique profiles were identified in both single- and multi-component models that can provide new insights into habitual patterns of physical activity and sedentary behavior among postmenopausal women. IMPLICATIONS: The multi-component approach can contribute to refining public health guidelines that integrate recommendations for both enhancing age-appropriate physical activity levels and reducing time spent in sedentary behavior.

Correlates of physical activity and sedentary behavior among cancer survivors and cancer-free women: The Women's Health Accelerometry Collaboration.

BACKGROUND: Describing correlates of physical activity (PA) and sedentary behavior (SB) among postmenopausal cancer survivors can help identify risk profiles and can be used to support development of targeted interventions to improve PA and reduce SB in this population. OBJECTIVE: To describe PA/SB and identify correlates of PA/SB among cancer and cancer-free post-menopausal women. METHODS: Women from the Women's Health Study (N = 16,629) and Women's Health Initiative/Objective Physical Activity and Cardiovascular Health Study (N = 6,079) were asked to wear an accelerometer on the hip for 7 days. Multiple mixed-effects linear regression models were used to identify sociodemographic-, health-, and chronic condition-related correlates (independent variables) associated with PA and SB (dependent variables) among women with (n = 2,554) and without (n = 20,154) a history of cancer. All correlates were mutually adjusted for each other. RESULTS: In unadjusted analyses, women with a history of cancer took fewer mean daily steps (4,572 (standard deviation 2557) vs 5,029 (2679) steps/day) and had lower mean moderate-to-vigorous PA (74.9 (45.0) vs. 81.6 (46.7) minutes/day) than cancer-free women. In adjusted analyses, for cancer and cancer-free women, age, diabetes, overweight, and obesity were inversely associated with all metrics of PA (average vector magnitude, time in moderate-to-vigorous PA, step volume, time at ≥40 steps/minutes, and peak 30-minute step cadence). In unadjusted analyses, mean SB was similar for those with and without cancer (529.7 (98.1) vs. 521.7 (101.2) minutes/day). In adjusted analyses, for cancer and cancer-free women, age, diabetes, cardiovascular disease, current smoking, overweight, and obesity were positive correlates of SB, while Black or Hispanic race/ethnicity, weekly/daily alcohol intake, and excellent/very good/good self-rated health were inverse correlates of SB. CONCLUSION: Several sociodemographic, health, and chronic conditions were correlates of PA/SB for postmenopausal women with and without cancer. Future studies should examine longitudinal relationships to gain insight into potential determinants of PA/SB.

Systolic Blood Pressure and Survival to Very Old Age: Results From the Women's Health Initiative.

BACKGROUND: The relationship between systolic blood pressure (SBP) and longevity is not fully understood. We aimed to determine which SBP levels in women ≥65 years of age with or without blood pressure medication were associated with the highest probability of surviving to 90 years of age. METHODS: The study population consisted of 16 570 participants enrolled in the Women's Health Initiative who were eligible to survive to 90 years of age by February 28, 2020, without a history of cardiovascular disease, diabetes, or cancer. Blood pressure was measured at baseline (1993 through 1998) and then annually through 2005. The outcome was defined as survival to 90 years of age with follow-up. Absolute probabilities of surviving to 90 years of age were estimated for all combinations of SBP and age using generalized additive logistic regression modeling. The SBP that maximized survival was estimated for each age, and a 95% CI was generated. RESULTS: During a median follow-up of 19.8 years, 9723 of 16 570 women (59%) survived to 90 years of age. Women with an SBP between 110 and 130 mm Hg at attained ages of 65, 70, 75, and 80 years had a 38% (95% CI, 34%-48%), 54% (52%-56%), 66% (64%-67%), or 75% (73%-78%) absolute probability to survive to 90 years of age, respectively. The probability of surviving to 90 years of age was lower for greater SBP levels. Women at the attained age of 80 years with 0%, 20%, 40%, 60%, 80%, or 100% time in therapeutic range (defined as an SBP between 110 and 130 mm Hg) had a 66% (64%-69%), 68% (67%-70%), 71% (69%-72%), 73% (71%-74%), 75% (72%-77%), or 77% (74%-79%) absolute survival probability to 90 years of age. CONCLUSIONS: For women >65 years of age with low cardiovascular disease and other chronic disease risk, an SBP level <130 mm Hg was found to be associated with longevity. These findings reinforce current guidelines targeting an SBP target <130 mm Hg in older women.

Association between dietary patterns and periodontal disease: The OsteoPerio cohort study.

AIM: To examine the association of dietary patterns with periodontal disease (PD) and its progression over 5 years. MATERIALS AND METHODS: Analyses involved 1197 post-menopausal women from the OsteoPerio cohort. Dietary patterns assessed include Healthy Eating Index-2015 (HEI), Alternative HEI (AHEI), Dietary Approaches to Stop Hypertension (DASH) and alternate Mediterranean Diet (aMed) at baseline (the average of two food frequency questionnaires administered between 1993 and 2001). At baseline and the 5-year follow-up, periodontal assessments evaluated alveolar crestal height (ACH), probing pocket depth (PPD), clinical attachment loss (CAL), percentage of gingival sites bleeding on probing (%BOP) and missing teeth due to PD. Linear and logistic regression were used to examine the associations. RESULTS: Cross-sectionally, HEI and aMed were associated with smaller CAL and %BOP; along with DASH, they were associated with a decreased odds of teeth missing due to PD. AHEI and aMed were associated with a decreased odds of severe PD. Prospectively, AHEI was associated with greater ACH progression. This association was attenuated to the null after loss of ACH was imputed for teeth lost due to PD over follow-up, or after excluding participants with diabetes, osteoporosis, hypertension or heart disease at baseline. CONCLUSIONS: Better adherence to healthy dietary patterns was associated with better PD measures cross-sectionally but greater progression of ACH over 5 years. The latter might be explained by incident tooth loss due to PD and pre-existing comorbidities.

Development, validation, and transportability of several machine-learned, non-exercise-based VO2max prediction models for older adults.

BACKGROUND: There exist few maximal oxygen uptake (VO2max) non-exercise-based prediction equations, fewer using machine learning (ML), and none specifically for older adults. Since direct measurement of VO2max is infeasible in large epidemiologic cohort studies, we sought to develop, validate, compare, and assess the transportability of several ML VO2max prediction algorithms. METHODS: The Baltimore Longitudinal Study of Aging (BLSA) participants with valid VO2max tests were included (n = 1080). Least absolute shrinkage and selection operator, linear- and tree-boosted extreme gradient boosting, random forest, and support vector machine (SVM) algorithms were trained to predict VO2max values. We developed these algorithms for: (a) the overall BLSA, (b) by sex, (c) using all BLSA variables, and (d) variables common in aging cohorts. Finally, we quantified the associations between measured and predicted VO2max and mortality. RESULTS: The age was 69.0 ± 10.4 years (mean ± SD) and the measured VO2max was 21.6 ± 5.9 mL/kg/min. Least absolute shrinkage and selection operator, linear- and tree-boosted extreme gradient boosting, random forest, and support vector machine yielded root mean squared errors of 3.4 mL/kg/min, 3.6 mL/kg/min, 3.4 mL/kg/min, 3.6 mL/kg/min, and 3.5 mL/kg/min, respectively. Incremental quartiles of measured VO2max showed an inverse gradient in mortality risk. Predicted VO2max variables yielded similar effect estimates but were not robust to adjustment. CONCLUSION: Measured VO2max is a strong predictor of mortality. Using ML can improve the accuracy of prediction as compared to simpler approaches but estimates of association with mortality remain sensitive to adjustment. Future studies should seek to reproduce these results so that VO2max, an important vital sign, can be more broadly studied as a modifiable target for promoting functional resiliency and healthy aging.

Low physical function following cancer diagnosis is associated with higher mortality risk in postmenopausal women.

BACKGROUND: Postmenopausal women with cancer experience an accelerated physical dysfunction beyond what is expected through aging alone due to cancer and its treatments. The aim of this study was to determine whether declines in physical function after cancer diagnosis are associated with all-cause mortality and cancer-specific mortality. METHODS: This prospective cohort study included 8068 postmenopausal women enrolled in the Women's Health Initiative with a cancer diagnosis and who had physical function assessed within 1 year of that diagnosis. Self-reported physical function was measured using the 10-item physical function subscale of the 36-Item Short Form Health Survey. Cause of death was determined by medical record review, with central adjudication and linkage to the National Death Index. Death was adjudicated through February 2022. RESULTS: Over a median follow-up of 7.7 years from cancer diagnosis, 3316 (41.1%) women died. Our results showed that for every 10% difference in the physical function score after cancer diagnosis versus pre-diagnosis, all-cause mortality and cancer-specific mortality were reduced by 12% (hazard ratio [HR] = 0.88, 95% confidence interval [95% CI] = 0.87 to 0.89 and HR = 0.88, 95% CI = 0.86 to 0.91, respectively). Further categorical analyses showed a significant dose-response relationship between postdiagnosis physical function categories and mortality outcomes (P < .001 for trend), where the median survival time for women in the lowest physical function quartile was 9.1 years (Interquartile range [IQR] = 8.6-10.6 years) compared with 18.4 years (IQR = 15.8-22.0 years) for women in the highest physical function quartile. CONCLUSION: Postmenopausal women with low physical function after cancer diagnosis may be at higher risk of mortality from all causes and cancer-related mortality.

Defining Porphyromonas gingivalis strains associated with periodontal disease.

Porphyromonas gingivalis, a Gram-negative anaerobic bacterium commonly found in human subgingival plaque, is a major etiologic agent for periodontitis and has been associated with multiple systemic pathologies. Many P. gingivalis strains have been identified and different strains possess different virulence factors. Current oral microbiome approaches (16S or shotgun) have been unable to differentiate P. gingivalis strains. This study presents a new approach that aims to improve the accuracy of strain identification, using a detection method based on sequencing of the intergenic spacer region (ISR) which is variable between P. gingivalis strains. Our approach uses two-step PCR to amplify only the P. gingivalis ISR region. Samples are then sequenced with an Illumina sequencer and mapped to specific strains. Our approach was validated by examining subgingival plaque from 153 participants with and without periodontal disease. We identified the avirulent strain ATCC33277/381 as the most abundant strain across all sample types. The W83/W50 strain was significantly enriched in periodontitis, with 13% of participants harboring that strain. Overall, this approach can have significant implications not only for the diagnosis and treatment of periodontal disease but also for other diseases where P. gingivalis or its toxins have been implicated, such as Alzheimer's disease.

Prevalence of frequent premature ventricular contractions and nonsustained ventricular tachycardia in older women screened for atrial fibrillation in the Women's Health Initiative.

BACKGROUND: Frequent premature ventricular contractions (PVCs) and nonsustained ventricular tachycardia (NSVT) have been associated with cardiovascular disease and mortality. Their prevalence, especially in ambulatory populations, is understudied and limited by few female participants and the use of short-duration (24- to 48-hour) monitoring. OBJECTIVE: The objective of this study was to report the prevalence of frequent PVCs and NSVT in a community-based population of women likely to undergo electrocardiogram (ECG) screening by sequential patch monitoring. METHODS: Participants from the Women's Health Initiative Strong and Healthy (WHISH) trial with no history of atrial fibrillation (AF) but 5-year predicted risk of incident AF ≥5% by CHARGE-AF score were randomly selected to undergo screening with 7-day ECG patch monitors at baseline, 6 months, and 12 months. Recordings were reviewed for PVCs and NSVT (>5 beats); data were analyzed with multivariate regression models. RESULTS: There were 1067 participants who underwent ECG screening at baseline, 866 at 6 months, and 777 at 12 months. Frequent PVCs were found on at least 1 patch from 4.3% of participants, and 1 or more episodes of NSVT were found in 12 (1.1%) women. PVC frequency directly correlated with CHARGE-AF score and NSVT on any patch. Detection of frequent PVCs increased with sequential monitoring. CONCLUSION: In postmenopausal women at high risk for AF, frequent PVCs were relatively common (4.3%) and correlated with higher CHARGE-AF score. As strategies for AF screening continue to evolve, particularly in those individuals at high risk of AF, the prevalence of incidental ventricular arrhythmias is an important benchmark to guide clinical decision-making.

Accelerometer-Measured Physical Activity, Sedentary Time, and Heart Failure Risk in Women Aged 63 to 99 Years.

Importance: Heart failure (HF) prevention is paramount to public health in the 21st century. Objective: To examine incident HF and its subtypes with preserved ejection fraction (HFpEF) and reduced EF (HFrEF) according to accelerometer-measured physical activity (PA) and sedentary time. Design, Setting, and Participants: This was a prospective cohort study, the Objective Physical Activity and Cardiovascular Health (OPACH) in Older Women study, conducted from March 2012 to April 2014. Included in the analysis were women aged 63 to 99 years without known HF, who completed hip-worn triaxial accelerometry for 7 consecutive days. Follow-up for incident HF occurred through February 2022. Data were analyzed from March to December 2023. Exposure: Daily PA (total, light, moderate to vigorous PA [MVPA], steps) and sedentary (total, mean bout duration) behavior. Main Outcomes and Measures: Adjudicated incident HF, HFpEF, and HFrEF. Results: A total of 5951 women (mean [SD] age, 78.6 [6.8] years) without known HF were included in this analysis. Women self-identified with the following race and ethnicity categories: 2004 non-Hispanic Black (33.7%), 1022 Hispanic (17.2%), and 2925 non-Hispanic White (49.2%). There were 407 HF cases (257 HFpEF; 110 HFrEF) identified through a mean (SD) of 7.5 (2.6) years (range, 0.01-9.9 years) of follow-up. Fully adjusted hazard ratios (HRs) for overall HF, HFpEF, and HFrEF associated with a 1-SD increment were 0.85 (95% CI, 0.75-0.95), 0.78 (95% CI, 0.67-0.91), and 1.02 (95% CI, 0.81-1.28) for minutes per day total PA; 0.74 (95% CI, 0.63-0.88), 0.71 (95% CI, 0.57-0.88), and 0.83 (95% CI, 0.62-1.12) for steps per day; and 1.17 (95% CI, 1.04-1.33), 1.29 (95% CI, 1.10-1.51), and 0.94 (95% CI, 0.75-1.18) for minutes per day total sedentary. Cubic spline curves for overall HF and HFpEF were significant inverse for total PA and steps per day and positive for total sedentary. Light PA and MVPA were inversely associated with overall HF (HR per 1 SD: 0.88; 95% CI, 0.78-0.98 and 0.84; 95% CI, 0.73-0.97) and HFpEF (0.80; 95% CI, 0.70-0.93 and 0.85; 95% CI, 0.72-1.01) but not HFrEF. Associations did not meaningfully differ when stratified by age, race and ethnicity, body mass index, physical function, or comorbidity score. Results for sedentary bout duration were inconsistent. Conclusions and Relevance: Higher accelerometer-measured PA (MVPA, light PA, steps per day) was associated with lower risk (and greater total sedentary time with higher risk) of overall HF and HFpEF in a racially and ethnically diverse cohort of older women. Increasing PA and reducing sedentary time for primary HFpEF prevention may have relevant implications for cardiovascular resilience and healthy aging in later life.

Prospective Associations of Accelerometer-Measured Machine-Learned Sedentary Behavior With Death Among Older Women: The OPACH Study.

BACKGROUND: Sedentary behavior is a recognized mortality risk factor. The novel and validated convolutional neural network hip accelerometer posture algorithm highly accurately classifies sitting and postural changes compared with accelerometer count cut points. We examined the prospective associations of convolutional neural network hip accelerometer posture-classified total sitting time and mean sitting bout duration with all-cause and cardiovascular disease (CVD) death. METHODS AND RESULTS: Women (n=5856; mean±SD age, 79±7 years; 33% Black women, 17% Hispanic or Latina women, 50% White women) in the Women's Health Initiative Objective Physical Activity and Cardiovascular Health (OPACH) Study wore the ActiGraph GT3X+ for ~7 days from May 2012 to April 2014 and were followed through February 19, 2022 for all-cause and CVD death. The convolutional neural network hip accelerometer posture algorithm classified total sitting time and mean sitting bout duration from GT3X+ output. Over follow-up (median, 8.4 years; range, 0.1-9.9), there were 1733 deaths (632 from CVD). Adjusted Cox regression hazard ratios (HRs) comparing women in the highest total sitting time quartile (>696 min/d) to those in the lowest (<556.0 min/d) were 1.57 (95% CI; 1.35-1.83; P-trend<0.001) for all-cause death and 1.78 (95% CI; 1.36-2.31; P-trend<0.001) for CVD death. HRs comparing women in the longest mean sitting bout duration quartile (>15 minutes) to the shortest (<9.3 minutes) were 1.43 (95% CI; 1.23-1.66; P-trend<0.001) for all-cause death and 1.52 (95% CI; 1.18-1.96; P-trend<0.001) for CVD death. Apparent nonlinear associations for total sitting time suggested higher all-cause death (P nonlinear=0.009) and CVD death (P nonlinear=0.008) risk after ~660 to 700 min/d. CONCLUSIONS: Higher total sitting time and longer mean sitting bout duration are associated with higher all-cause and CVD mortality risk among older women. These data support interventions aimed at reducing both total sitting time and interrupting prolonged sitting.

Adverse pregnancy outcomes and risk of type 2 diabetes in postmenopausal women.

BACKGROUND: Although gestational diabetes mellitus and delivering high-birthweight infants are known to predict a higher risk of future type 2 diabetes mellitus, the association of hypertensive disorders of pregnancy and other adverse pregnancy outcomes with type 2 diabetes mellitus is not well established. OBJECTIVE: This study aimed to examine the associations between different types of adverse pregnancy outcomes and incident type 2 diabetes mellitus among postmenopausal women. STUDY DESIGN: The Women's Health Initiative, a nationwide cohort of postmenopausal women, collected self-reported history of adverse pregnancy outcomes, including gestational diabetes mellitus, hypertensive disorders of pregnancy, preterm birth, and delivering low- birthweight (<2500 g) or high-birthweight (>4500 g) infants. Participants were followed up annually for self-reported incident type 2 diabetes mellitus treated with medication from baseline (1993-1998) to March 2021. This study used logistic regression to examine the associations of any and individual adverse pregnancy outcomes with diabetes mellitus. Stratified analyses were performed to assess effect modification by body mass index, race and ethnicity, education, parity, breastfeeding, and age at first birth. RESULTS: This analysis included 49,717 women without a history of diabetes mellitus at enrollment who had a least 1 pregnancy and responded to the questionnaire about adverse pregnancy outcomes. After adjusting for body mass index, demographic, lifestyle, and reproductive factors, gestational diabetes mellitus (odds ratio, 2.26; 95% confidence interval, 1.94-2.63), high birthweight (odds ratio, 1.30; 95% confidence interval, 1.18-1.44), and hypertensive disorders of pregnancy (odds ratio, 1.18; 95% confidence interval, 1.08-1.30) were independently associated with higher odds of type 2 diabetes mellitus, whereas preterm birth and low birthweight were not associated with diabetes mellitus risk. A history of ≥2 adverse pregnancy outcomes was associated with higher odds of type 2 diabetes mellitus (odds ratio, 1.55; 95% confidence interval, 1.28-1.88). This study further observed higher odds of type 2 diabetes mellitus (odds ratio, 3.69; 95% confidence interval, 2.38-5.70) among women with a history of both gestational diabetes mellitus and hypertensive disorders of pregnancy than those without any adverse pregnancy outcomes. CONCLUSION: Postmenopausal women with a history of gestational diabetes mellitus, those delivering high-birthweight infants, or those with hypertensive disorders of pregnancy are at risk of future type 2 diabetes mellitus. In addition, women with ≥2 conditions had an augmented risk and might be prioritized for screening and prevention efforts for type 2 diabetes mellitus.

Caregiving and all-cause mortality in postmenopausal women: Findings from the Women's Health Initiative.

BACKGROUND: Caregiving is commonly undertaken by older women. Research is mixed, however, about the impact of prolonged caregiving on their health, well-being, and mortality risk. Using a prospective study design, we examined the association of caregiving with mortality in a cohort of older women. METHODS: Participants were 158,987 postmenopausal women aged 50-79 years at enrollment into the Women's Health Initiative (WHI) who provided information on current caregiving status and caregiving frequency at baseline (1993-1998) and follow-up (2004-2005). Mortality was ascertained from baseline through March of 2019. Cox regression with caregiving status defined as a time-varying exposure was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for mortality, adjusting for sociodemographic factors, smoking, and history of diabetes, hypertension, cardiovascular disease (CVD), and cancer. Stratified analyses explored whether age, race-ethnicity, depressive symptoms, frequency of caregiving, optimism, and living status modified the association between caregiver status and mortality. RESULTS: At baseline, 40.7% of women (mean age 63.3 years) self-identified as caregivers. During a mean 17.5-year follow-up, all-cause mortality (50,526 deaths) was 9% lower (multivariable-adjusted HR = 0.91, 95% CI: 0.89-0.93) in caregivers compared to non-caregivers. The inverse association between caregiving and all-cause mortality did not differ according to caregiving frequency or when stratified by age, race-ethnicity, depressive symptoms, optimism, or living status (interaction p > 0.05, all). Caregiving was inversely associated with CVD and cancer mortality. CONCLUSION: Among postmenopausal women residing across the United States, caregiving was associated with lower mortality. Studies detailing the type and amount of caregiving are needed to further determine its impact on older women.

Alcohol Consumption and the Diversity of the Oral Microbiome in Postmenopausal Women.

BACKGROUND: Alcohol reduces neutrophil function and decreases salivary flow, which could affect the composition of the oral microbiome. OBJECTIVE: We hypothesized that the α- and ß-diversity of the oral microbiome and the relative abundance of bacterial taxa would differ by frequency and type of alcohol consumption. METHODS: We used a food frequency questionnaire to assess the frequency of consumption of beer, wine, and liquor (drinks/week) in a sample of 1179 postmenopausal women in the Osteoporosis and Periodontal Disease Study. Women were categorized as nondrinkers, drinking <1 drink/wk, ≥1 to <7 drinks/wk, or ≥7 drinks/wk for total alcohol consumption and for beer, wine, and liquor consumption. The composition and diversity of the oral microbiome was assessed from subgingival plaque samples using 16S ribosomal RNA amplicon sequencing. Permutational multivariate analysis of variance (PERMANOVA) was used to examine ß-diversity (between-sample diversity) in the microbiome between alcohol consumption categories. Analysis of covariance was used to examine the mean α-diversity (within-sample diversity), assessed by the Shannon index (species evenness), Chao1 index (species richness), and observed operational taxonomic unit (OTU) count and the mean relative abundance of 245 bacterial taxa across alcohol consumption categories. RESULTS: Over half of the participants (67%) consumed alcohol, with 14% reporting ≥1 drink/d. The ß-diversity across categories of total alcohol consumption, but not categories of alcohol type, was statistically significantly different (P for PERMANOVA = 0.016). Mean α-diversity measures were statistically significantly higher (P < 0.05) in the highest category of total alcohol and wine consumption compared to nondrinkers; no significant associations were found for beer or liquor consumption. The relative abundance of 1 OTU, Selenomonassp._oral_taxon_133, was significantly lower in the highest level of total alcohol consumption compared to nondrinkers after adjustment for multiple comparisons. CONCLUSIONS: Alcohol consumption was associated with the diversity and composition of the subgingival microbiome.

Cardiorespiratory fitness and risk of heart failure with preserved ejection fraction.

AIMS: Preventive strategies for heart failure with preserved ejection fraction (HFpEF) include pharmacotherapies and lifestyle modifications. However, the association between cardiorespiratory fitness (CRF) assessed objectively by a standardized exercise treadmill test (ETT) and the risk of HFpEF has not been evaluated. Thus, we evaluated the association between CRF and HFpEF incidence. METHODS AND RESULTS: We assessed CRF in US Veterans (624 551 men; mean age 61.2 ± 9.7 years and 43 179 women; mean age 55.0 ± 8.9 years) by a standardized ETT performed between 1999 and 2020 across US Veterans Affairs Medical Centers. All had no evidence of heart failure or myocardial infarction prior to completion of the ETT. We assigned participants to one of five age- and gender-specific CRF categories (quintiles) based on peak metabolic equivalents (METs) achieved during the ETT and four categories based on CRF changes in those with two ETT evaluations (n = 139 434) ≥1.0 year apart. During a median follow-up of 10.1 years (interquartile range 6.0-14.3 years), providing 6 879 229 person-years, there were 16 493 HFpEF events with an average annual rate of 2.4 events per 1000 person-years. The adjusted risk of HFpEF decreased across CRF categories as CRF increased, independent of comorbidities. For fit individuals (≥10.5 METs) the hazard ratio (HR) was 0.48 (95% confidence interval [CI] 0.46-0.51) compared with least fit (≤4.9 METs; referent). Being unfit carried the highest risk (HR 2.88, 95% CI 2.67-3.11) of any other comorbidity. The risk of unfit individuals who became fit was 37% lower (HR 0.63, 95% CI 0.57-0.71), compared to those who remained unfit. CONCLUSIONS: Higher CRF levels are independently associated with lower HFpEF in a dose-response manner. Changes in CRF reflected proportional changes in HFpEF risk, suggesting that the HFpEF risk was modulated by CRF.

Association between long-term exposure to ambient air pollution and lesion ischemia in patients with atherosclerosis.

BACKGROUND AND AIMS: Air pollution has been associated with coronary artery disease. The underlying mechanisms were understudied, especially in relation to coronary stenosis leading to myocardial ischemia. Advances in computed tomography (CT) allow for novel quantification of lesion ischemia. We aim to investigate associations between air pollution exposures and fractional flow reserve on CT (CT-FFR), a measure of coronary artery blood flow. METHODS: CT-FFR, which defines a ratio of maximal myocardial blood flow compared to its normal value (range: 0-100%), was characterized in 2017 patients with atherosclerosis between 2015 and 2017. Exposures to ozone (O3), nitrogen dioxide (NO2), and fine particulate matter (PM2.5) were estimated using high-resolution exposure models. Linear and logistic regression models were used to assess the association of each air pollutant with CT-FFR and with the prevalence of clinically relevant myocardial ischemia (CT-FFR <75%). RESULTS: Participants were on average 60.1 years old. Annual mean O3, NO2, PM2.5 were 61, 47 and 60 µg/m3, respectively. Mean CT-FFR value was 76.9%. In the main analysis, a higher level of O3 was associated with a lower CT-FFR value (-1.74%, 95% CI: -2.85, -0.63 per 8 µg/m3) and a higher prevalence of myocardial ischemia (odds ratio: 1.32, 95% CI: 1.05-1.65), adjusting for potential confounders such as risk factors and plaque phenotypes, independent of the effects of exposure to NO2 and PM2.5. No associations were observed for PM2.5 or NO2 with CT-FFR. CONCLUSIONS: Long-term exposure to O3 is associated with lower CT-FFR value in atherosclerotic patients, indicating higher risk of lesion ischemia.

Calibrating Physical Activity and Sedentary Behavior for Hip-Worn Accelerometry in Older Women With Two Epoch Lengths: The Women's Health Initiative Objective Physical Activity and Cardiovascular Health Calibration Study.

Purpose: The purpose of this study was to develop 60-second epoch accelerometer intensity cutpoints for vertical axis count and vector magnitude (VM) output from hip-worn tri-axial accelerometers among women 60-91 years. We also compared these cutpoints against cutpoints derived by multiplying 15-second epoch cutpoints 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, assembling a puzzle), low light (washing/drying dishes), high light (laundry, dust mopping), or MVPA (400-meter walk) intensity. Oxygen uptake was measured using an Oxycon™ portable calorimeter. Sedentary behavior and physical activity intensity cutpoints for vertical axis and VM counts were derived for 60-second epochs from receiver operating characteristic (ROC) and by multiplying the 15-second cutpoints by four); both were compared to oxygen uptake. Results: The median age was 74.5 years (interquartile range 70-83). The 60-second epoch cutpoints for vertical counts were 0 sedentary, 1-73 low light, 74-578 high light, and >=579 MVPA. The 60-second epoch cutpoints for VM were 0-88 sedentary, 89-663 low light, 664-1730 high light, and >=1731 MVPA. For both sets of cutpoints, the ROC approach yielded more accurate estimates than the multiplication approach. Conclusion: The derived 60-second epoch cutpoints for vertical counts and VM can be applied to epidemiologic studies to define sedentary behavior and physical activity intensities in older adult populations.