Chronic psychosocial and financial burden accelerates 5-year telomere shortening: findings from the Coronary Artery Risk Development in Young Adults Study.

Leukocyte telomere length, a marker of immune system function, is sensitive to exposures such as psychosocial stressors and health-maintaining behaviors. Past research has determined that stress experienced in adulthood is associated with shorter telomere length, but is limited to mostly cross-sectional reports. We test whether repeated reports of chronic psychosocial and financial burden is associated with telomere length change over a 5-year period (years 15 and 20) from 969 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) Study, a longitudinal, population-based cohort, ages 18-30 at time of recruitment in 1985. We further examine whether multisystem resiliency, comprised of social connections, health-maintaining behaviors, and psychological resources, mitigates the effects of repeated burden on telomere attrition over 5 years. Our results indicate that adults with high chronic burden do not show decreased telomere length over the 5-year period. However, these effects do vary by level of resiliency, as regression results revealed a significant interaction between chronic burden and multisystem resiliency. For individuals with high repeated chronic burden and low multisystem resiliency (1 SD below the mean), there was a significant 5-year shortening in telomere length, whereas no significant relationships between chronic burden and attrition were evident for those at moderate and higher levels of resiliency. These effects apply similarly across the three components of resiliency. Results imply that interventions should focus on establishing strong social connections, psychological resources, and health-maintaining behaviors when attempting to ameliorate stress-related decline in telomere length among at-risk individuals.

Bidirectional associations of accelerometer-derived physical activity and stationary behavior with self-reported mental and physical health during midlife.

BACKGROUND: Moderate-to-vigorous intensity physical activity (MVPA) is associated with favorable self-rated mental and physical health. Conversely, poor self-rated health in these domains could precede unfavorable shifts in activity. We evaluated bidirectional associations of accelerometer-estimated time spent in stationary behavior (SB), light intensity physical activity (LPA), and MVPA with self-rated health over 10 years in in the CARDIA longitudinal cohort study. METHODS: Participants (n = 894, age: 45.1 ± 3.5; 63% female; 38% black) with valid accelerometry wear and self-rated health at baseline (2005-6) and 10-year follow-up (2015-6) were included. Accelerometry data were harmonized between exams and measured mean total activity and duration (min/day) in SB, LPA, and MVPA; duration (min/day) in long-bout and short-bout SB (≥30 min vs. < 30 min) and MVPA (≥10 min vs. < 10 min) were also quantified. The Short-Form 12 Questionnaire measured both a mental component score (MCS) and physical component score (PCS) of self-rated health (points). Multivariable linear regression associated baseline accelerometry variables with 10-year changes in MCS and PCS. Similar models associated baseline MCS and PCS with 10-year changes in accelerometry measures. RESULTS: Over 10-years, average (SD) MCS increased 1.05 (9.07) points, PCS decreased by 1.54 (7.30) points, and activity shifted toward greater SB and less mean total activity, LPA, and MVPA (all p < 0.001). Only baseline short-bout MVPA was associated with greater 10-year increases in MCS (+ 0.92 points, p = 0.021), while baseline mean total activity, MVPA, and long-bout MVPA were associated with greater 10-year changes in PCS (+ 0.53 to + 1.47 points, all p < 0.005). In the reverse direction, higher baseline MCS and PCS were associated with favorable 10-year changes in mean total activity (+ 9.75 cpm, p = 0.040, and + 15.66 cpm, p < 0.001, respectively) and other accelerometry measures; for example, higher baseline MCS was associated with - 13.57 min/day of long-bout SB (p < 0.001) and higher baseline PCS was associated with + 2.83 min/day of MVPA (p < 0.001) in fully adjusted models. CONCLUSIONS: The presence of bidirectional associations between SB and activity with self-rated health suggests that individuals with low overall activity levels and poor self-rated health are at high risk for further declines and supports intervention programming that aims to dually increase activity levels and improve self-rated health.

Cardiovascular risk and functional burden at midlife: Prospective associations of isotemporal reallocations of accelerometer-measured physical activity and sedentary time in the CARDIA study.

Cardiovascular risk and functional burden, or the accumulation of cardiovascular risk factors coupled with functional decline, may be an important risk state analogy to multimorbidity. We investigated prospective associations of sedentary time (ST), light intensity physical activity (LPA), and moderate to vigorous intensity physical activity (MVPA) with cardiovascular risk and functional burden at midlife. Participants were 1648 adults (mean ± SD age = 45 ± 4 years, 61% female, 39% Black) from Coronary Artery Risk Development in Young Adults (CARDIA) who wore accelerometers in 2005-2006 and 2015-2016. Cardiovascular risk and functional burden was defined as ≥2 cardiovascular risk factors (untreated/uncontrolled hypertension and hypercholesterolemia, type 2 diabetes, reduced kidney function) and/or functional decline conditions (reduced physical functioning and depressive symptoms). Prospective logistic regression models tested single activity, partition, and isotemporal substitution associations of accelerometer-measured ST, LPA, and MVPA with cardiovascular risk and functional burden 10 years later. In isotemporal models of baseline activity, reallocating 24 min of ST to MVPA was associated with 15% lower odds of cardiovascular risk and functional burden (OR: 0.85; CI: 0.75, 0.96). Reallocating 24 min of LPA to MVPA was associated with a 14% lower odds of cardiovascular risk and functional burden (OR: 0.86; CI: 0.75, 0.99). In longitudinal isotemporal models, similar beneficial associations were observed when 10-year increases in MVPA replaced time in ST or LPA. Findings suggest that maintaining an MVPA dose reflecting daily physical activity recommendations in early midlife is associated with lower odds of cardiovascular risk and functional burden later in midlife.

Associations of diet, physical activity and polycystic ovary syndrome in the Coronary Artery Risk Development in Young Adults Women's Study.

BACKGROUND: Current evidence supports the adoption of healthy diet and physical activity (PA) behaviors in patients with polycystic ovary syndrome (PCOS), given the positive effects of those behaviors on physical well-being. An improved understanding of the associations between diet and PA with PCOS is needed to ascertain whether tailored dietary and PA recommendations are needed for this population. Thus, we investigated the associations of diet and PA with PCOS and its isolated features. METHODS: Cross-sectional study. Of the 748 women who were included in this study from the Coronary Artery Risk Development in Young Adults (CARDIA) Women's Study, 40 were classified as having PCOS, 104 had isolated hyperandrogenism (HA) and 75 had isolated oligomenorrhea (OA). Dietary intake was measured using the CARDIA diet history questionnaire and diet quality was scored using the Alternative Healthy Eating Index 2010; a higher score indicated a better quality diet. Self-reported PA was measured using a validated interviewer-administered questionnaire. Polytomous logistic regression analyses examined the associations between diet and PA with PCOS, HA, and OA status (outcomes), adjusting for age, race, total energy intake, education, and/or body mass index. The threshold for statistical significance was set at p < 0.05. RESULTS: Mean age of the participants was 25.4 years (SD 3.6) and 46.8% of participants were Black women. There was little to no association of total energy intake, nutrients, diet quality, and PA with PCOS, HA or OA status. CONCLUSION: Energy intake, nutrient composition, diet quality, and PA were not associated with PCOS, supporting recent PCOS guidelines of using national recommendations for the general population to encourage health-promoting behaviors among women with PCOS. However, longitudinal studies evaluating changes in diet and physical activity in relation to the development and/or the progression of PCOS are needed to establish a causal association.

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

INTRODUCTION: Cardiovascular risk factors in midlife have been linked to late life risk for Alzheimer's disease and related dementias (ADRD). The relation of vascular risk factors on cognitive decline within midlife has been less studied. METHODS: Using data from the Study of Women's Health Across the Nation, we examined associations of midlife hypertension, elevated lipid levels, diabetes, fasting glucose, central adiposity, and Framingham heart age with rates of cognitive decline in women who completed multiple cognitive assessments of processing speed, and working and verbal memory during midlife. RESULTS: Diabetes, elevated fasting glucose, central obesity, and heart age greater than chronological age were associated with rate of decline in processing speed during midlife. Vascular risk factors were not related to rate of decline in working or verbal memory. DISCUSSION: Midlife may be a critical period for intervening on cardiovascular risk factors to prevent or delay later life cognitive impairment and ADRD.

Bidirectional 10-year associations of accelerometer-measured sedentary behavior and activity categories with weight among middle-aged adults.

BACKGROUND: Although higher sedentary behavior (SB) with low light intensity (LPA) and moderate-to-vigorous intensity physical activity (MVPA) are thought to increase risk for obesity, other data suggest excess weight may precede these behaviors in the causal pathway. We aimed to investigate 10-year bidirectional associations between SB and activity with weight. METHODS: Analysis included 886 CARDIA participants (aged 38-50 years, 62% female, 38% black) with weight and accelerometry ( ≥ 4 days with ≥ 10 h/day) collected in 2005-6 (ActiGraph 7164) and 2015-6 (ActiGraph wGT3X-BT). Accelerometer data were calibrated, harmonized, and expressed as counts per minute (cpm) and time-dependent intensity categories (min/day of SB, LPA, and MVPA; SB and MVPA were also separated into long-bout and short-bout categories). Linear regression models were constructed to estimate adjusted associations of baseline activity with 10-year change in weight and vice versa. When activity categories were the independent variables, standardized regression coefficients (ßstd.) estimated associations of replacing SB with a one SD increase in other categories, adjusted for accelerometer wear time. RESULTS: Over 10-years, weight increased by a mean 2.55 ± 8.05 kg and mean total activity decreased by 50 ± 153 cpm. In adjusted models, one SD higher baseline mean total activity (ßstd. = -1.4 kg, p < 0.001), LPA (ßstd. = -0.80 kg, p = 0.013), total MVPA (ßstd. = -1.07 kg, p = 0.001), and long-bout MVPA (ßstd. = -1.20 kg, p < 0.001) were associated with attenuated 10-year weight gain. Conversely, a one SD higher baseline weight was associated with unfavorable 10-year changes in daily activity profile including increases in SB (ßstd. = 12.0 min, p < 0.001) and decreases in mean total activity (ßstd. = 14.9 cpm, p = 0.004), LPA (ßstd. = 8.9, p = 0.002), and MVPA (ßstd. = 3.5 min, p = 0.001). Associations varied by race and gender. CONCLUSIONS: Higher SB with lower activity and body weight were bidirectionally related. Interventions that work simultaneously to replace SB with LPA and long-bout MVPA while also using other methods to address excess weight may be optimal.

Body mass index versus bioelectrical impedance analysis for classifying physical function impairment in a racially diverse cohort of midlife women: the Study of Women's Health Across the Nation (SWAN).

BACKGROUND: Body composition strongly influences physical function in older adults. Bioelectrical impedance analysis (BIA) differentiates fat mass from skeletal muscle mass, and may be more useful than body mass index (BMI) for classifying women on their likelihood of physical function impairment. AIMS: This study tested whether BIA-derived estimates of percentage body fat (%BF) and height-normalized skeletal muscle mass (skeletal muscle mass index; SMI) enhance classification of physical function impairment relative to BMI. METHOD: Black, White, Chinese, and Japanese midlife women (N = 1482) in the Study of Women's Health Across the Nation (SWAN) completed performance-based measures of physical function. BMI (kg/m2) was calculated. %BF and SMI were derived through BIA. Receiver-operating characteristic (ROC) curve analysis, conducted in the overall sample and stratified by racial group, evaluated optimal cutpoints of BMI, %BF, and SMI for classifying women on moderate-severe physical function impairment. RESULTS: In the overall sample, a BMI cutpoint of ≥ 30.1 kg/m2 correctly classified 71.1% of women on physical function impairment, and optimal cutpoints for %BF (≥ 43.4%) and SMI (≥ 8.1 kg/m2) correctly classified 69% and 62% of women, respectively. SMI did not meaningfully enhanced classification relative to BMI (change in area under the ROC curve = 0.002; net reclassification improvement = 0.021; integrated discrimination improvement = - 0.003). Optimal cutpoints for BMI, %BF, and SMI varied substantially across race. Among Black women, a %BF cutpoint of 43.9% performed somewhat better than BMI (change in area under the ROC curve = 0.017; sensitivity = 0.69, specificity = 0.64). CONCLUSION: Some race-specific BMI and %BF cutpoints have moderate utility for identifying impaired physical function among midlife women.

Perceived and objective characteristics of the neighborhood environment are associated with accelerometer-measured sedentary time and physical activity, the CARDIA Study.

We investigated cross-sectional and longitudinal associations of neighborhood environment characteristics with accelerometer-measured sedentary time (SED), light-intensity physical activity (LPA), and moderate-to-vigorous intensity physical activity (MVPA). Participants were 2120 men and women in the year 20 (2005-2006) and year 30 CARDIA exams (2015-2016). Year 20 neighborhood characteristics included neighborhood cohesion, resources for physical activity, poverty, and racial residential segregation. Physical activity was measured by accelerometer at years 20 and 30. Multivariable linear regression models examined associations of standardized neighborhood measures at year 20 with SED, LPA, and MVPA assessed that year, and with 10-year changes in SED, LPA, and MVPA. Cross-sectionally, a one standard deviation (SD) increase in cohesion was associated with 4.06 less SED min/day (95% CI: -7.98, -0.15), and 4.46 more LPA min/day (95% CI: 0.88, 8.03). Each one SD increase in resources was associated with 1.19 more MVPA min/day (95% CI: 0.06, 2.31). A one SD increase in poverty was associated with 11.18 less SED min/day (95% CI: -21.16, -1.18) and 10.60 more LPA min/day (95% CI: 1.79, 19.41) among black men. No neighborhood characteristic was associated with 10-year changes in physical activity in the full sample; however, a one SD increase in cohesion was associated with a 10-year decrease of 25.44 SED min/day (95% CI: -46.73, -4.14) and an increase of 19.0 LPA min/day (95% CI, 1.89, 36.10) in black men. Characteristics of the neighborhood environment are associated with accelerometer-measured physical activity. Differences were observed by race and sex, with more robust findings observed in black men.

Ten-Year Changes in Accelerometer-Based Physical Activity and Sedentary Time During Midlife: The CARDIA Study.

We describe 10-year changes in accelerometer-determined physical activity (PA) and sedentary time in a midlife cohort of the Coronary Artery Risk Development in Young Adults Study, within and by race and sex groups. Participants (n = 962) wore the accelerometer with valid wear (≥4 of 7 days, ≥10 hours per day) at baseline (2005-2006; ages 38-50 years) and 10-year follow-up (2015-2016; ages 48-60 years). Data were calibrated to account for accelerometer model differences. Participants (mean age = 45.0 (standard deviation, 3.5) years at baseline) had reduced accelerometer counts overall (mean = -65.5 (standard error (SE), 10.2) counts per minute/day), and within race and sex groups (all P < 0.001). Sedentary time increased overall (mean = 37.9 (SE, 3.7) minutes/day) and within race and sex groups, whereas light-intensity PA (mean = -30.6 (SE, 2.7) minutes/day) and moderate- to vigorous-intensity PA (mean = -7.5 (SE, 0.8) minutes/day) declined overall and within race and sex groups (all P < 0.001). Significant differences in 10-year change estimates were noted by race and sex groups for accelerometer counts, sedentary time, and moderate- to vigorous-intensity PA bouts; black men had the greatest reductions in PA compared with other groups. PA declines during midlife were characterized by reductions in light-intensity PA with increases in sedentary time, which may have important health consequences. Targeted efforts are needed to preserve PA, regardless of intensity level, across midlife.

Clinical importance of non-participation in a maximal graded exercise test on risk of non-fatal and fatal cardiovascular events and all-cause mortality: CARDIA study.

While poor performance during a maximal graded exercise test (GXT) predicts cardiovascular events and premature mortality, the potential clinical importance of non-participation in a GXT, either for medical or non-medical reasons, is currently unknown. Data are from 4086 and 3547 Coronary Artery Risk Development in Young Adults (CARDIA) participants who attended the Year 7 (ages 25-37years) and/or 20 exams (ages 38-50years), respectively, which included a GXT. Cox proportional hazard models were used to examine the effect of GXT disposition (at Year 7 and 20, separately) on risk of non-fatal and fatal cardiovascular events and all-cause mortality obtained through 28years of follow-up. A GXT was not conducted or completed according to protocol in 12.9% and 19.1% of participants attending the Year 7 and 20 exams, respectively. After adjustment, participants who missed the Year 20 GXT for medical reasons had a higher risk of cardiovascular events [HR: 4.06 (95% CI: 1.43, 11.5)] and all-cause mortality [HR: 3.07 (95% CI: 1.11, 12.3)] compared to GXT completers; participants who missed at Year 20 for non-medical reasons also had higher risk of all-cause mortality [HR: 2.53 (95% CI: 1.61, 3.99)]. Findings suggest that non-participation in a GXT, regardless of medical or non-medical reason, to be an important predictor of excess risk of adverse health outcomes and premature mortality. Additional patient follow-up, including identification of potential targets for intervention (e.g., weight management and smoking cessation programs), should be conducted at the point of a missed GXT.

Physical activity trajectories during midlife and subsequent risk of physical functioning decline in late mid-life: The Study of Women's Health Across the Nation (SWAN).

The purpose of this study was to examine the importance of midlife physical activity on physical functioning in later life. Data are from 1771 Study of Women's Health Across the Nation (SWAN) participants, aged 42-52 (46.4±2.7) years at baseline (1996-97). Latent class growth analysis was used to identify physical activity trajectory groups using reported sports and exercise index data collected at seven time-points from baseline to Visit 13 (2011-13); objective measures of physical functioning performance were collected at Visit 13. The sports and exercise index (henceforth: physical activity) is a measure of moderate to vigorous intensity physical activity during discretionary periods of the day. Multivariable linear regression analyses were used to model each continuous physical performance measure as a function of the physical activity trajectory class. Across midlife, five physical activity trajectory classes emerged, including: lowest (26.2% of participants), increasing (13.4%), decreasing (22.4%), middle (23.9%), and highest (14.1%) physical activity. After full adjustment, women included in the middle and highest physical activity groups demonstrated ≥5% better physical functioning performance than those who maintained low physical activity levels (all comparisons; p<0.05). Statistically significant differences were also noted when physical activity trajectory groups were compared to the increasing physical activity group. Results from the current study support health promotion efforts targeting increased (or maintenance of) habitual physical activity in women during midlife to reduce future risk of functional limitations and disability. These findings have important public health and clinical relevance as future generations continue to transition into older adulthood.

Long- and Short-term Exposure to Air Pollution and Inflammatory/Hemostatic Markers in Midlife Women.

BACKGROUND: Studies have reported associations between long-term air pollution exposures and cardiovascular mortality. The biological mechanisms connecting them remain uncertain. METHODS: We examined associations of fine particles (PM2.5) and ozone with serum markers of cardiovascular disease risk in a cohort of midlife women. We obtained information from women enrolled at six sites in the multi-ethnic, longitudinal Study of Women's Health Across the Nation, including repeated measurements of high-sensitivity C-reactive protein, fibrinogen, tissue-type plasminogen activator antigen, plasminogen activator inhibitor type 1, and factor VIIc (factor VII coagulant activity). We obtained residence-proximate PM2.5 and ozone monitoring data for a maximum five annual visits, calculating prior year, 6-month, 1-month, and 1-day exposures and their relations to serum markers using longitudinal mixed models. RESULTS: For the 2,086 women studied from 1999 to 2004, PM2.5 exposures were associated with all blood markers except factor VIIc after adjusting for age, race/ethnicity, education, site, body mass index, smoking, and recent alcohol use. Adjusted associations were strongest for prior year exposures for high-sensitivity C-reactive protein (21% increase per 10 µg/m³ PM2.5, 95% confidence interval [CI]: 6.6, 37), tissue-type plasminogen activator antigen (8.6%, 95% CI: 1.8, 16), and plasminogen activator inhibitor (35%, 95% CI: 19, 53). An association was also observed between year prior ozone exposure and factor VIIc (5.7% increase per 10 ppb ozone, 95% CI: 2.9, 8.5). CONCLUSIONS: Our findings suggest that prior year exposures to PM2.5 and ozone are associated with adverse effects on inflammatory and hemostatic pathways for cardiovascular outcomes in midlife women.

Is self-reported physical functioning associated with incident cardiometabolic abnormalities or the metabolic syndrome?

BACKGROUND: Physical functioning may be an important pre-clinical marker of chronic disease, used as a tool to identify patients at risk for future cardiometabolic abnormalities. This study evaluated if self-reported physical functioning was associated with the development of cardiometabolic abnormalities or their clustering (metabolic syndrome) over time. METHODS: Participants (n = 2,254) from the Study of Women's Health Across the Nation who reported physical functioning on the Short Form health survey and had a metabolic syndrome assessment (elevated fasting glucose, blood pressure, triglycerides and waist circumference; reduced HDL cholesterol) in 2000 were included. Discrete survival analysis was used to assess the 10-year risk of developing metabolic syndrome or a syndrome component through 2010. RESULTS: At baseline, the prevalence of metabolic syndrome was 22.0%. Women with substantial limitations (OR = 1.60; 95% CI: 1.12, 2.29) in physical functioning were significantly more likely to develop the metabolic syndrome compared with women reporting no limitations. Self-reported physical functioning was significantly associated with incident hypertension and increased waist circumference. CONCLUSIONS: Simple screening tools for cardiometabolic risk in clinical settings are needed. Self-reported physical functioning assessments are simple tools that may allow healthcare providers to more accurately predict the course of chronic conditions.

Is heart rate variability associated with frequency and intensity of vasomotor symptoms among healthy perimenopausal and postmenopausal women?

OBJECTIVE: Research has suggested that the autonomic nervous system (ANS) is involved in the experience of vasomotor symptoms (VMS) during menopause. We examined the relationship of VMS intensity and heart rate variability (HRV), a measure of ANS function. METHODS: Women (n = 282) were recruited from three American states for a clinical trial of yoga, exercise, and omega-3 fatty acid supplements for VMS. To be eligible, women had to report at least 14 VMS per week, with some being moderate to severe. Sitting electrocardiograms were recorded for 15 min using Holter monitors at both baseline and 12-week follow-up. Time and frequency domain HRV measures were calculated. Women completed daily diary measures of VMS frequency and intensity for 2 weeks at baseline and for 1 week at the follow-up assessment 12 weeks later. Multivariable linear regression was used to assess the relationship between VMS and baseline HRV measures and to compare change in HRV with change in VMS over the 12 weeks. RESULTS: Baseline HRV was not associated with either VMS frequency or intensity at baseline. Change in HRV was not associated with change in VMS frequency or intensity across the follow-up. INTERPRETATION: Heart rate variability (HRV) was not associated with basal VMS frequency or intensity in perimenopausal and postmenopausal women experiencing high levels of VMS. Autonomic function may be associated with the onset or presence of VMS, but not with the number or intensity of these symptoms.

Moderate and Vigorous Intensity Exercise During Pregnancy and Gestational Weight Gain in Women with Gestational Diabetes.

Objectives To estimate the associations of moderate and vigorous intensity exercise during pregnancy with the rate of gestational weight gain (GWG) from gestational diabetes (GDM) diagnosis to delivery, overall and stratified by prepregnancy overweight/obesity. Methods Prospective cohort study with physical activity reported shortly after the GDM diagnosis and prepregnancy weight and post-diagnosis GWG obtained from electronic health records (n = 1055). Multinomial logistic regression models in the full cohort and stratified by prepregnancy overweight/obesity estimated associations of moderate and vigorous intensity exercise with GWG below and above the Institute of Medicine's (IOM) prepregnancy BMI-specific recommended ranges for weekly rate of GWG in the second and third trimesters. Results In the full cohort, any participation in vigorous intensity exercise was associated with decreased odds of GWG above recommended ranges as compared to no participation [odds ratio (95 % confidence interval): 0.63 (0.40, 0.99)], with a significant trend for decreasing odds of excess GWG with increasing level of vigorous intensity exercise. Upon stratification by prepregnancy overweight/obesity, significant associations were only observed for BMI ≥ 25.0 kg/m(2): any vigorous intensity exercise, as compared to none, was associated with 54 % decreased odds of excess GWG [0.46 (0.27, 0.79)] and significant trends were detected for decreasing odds of GWG both below and above the IOM's recommended ranges with increasing level of vigorous exercise (both P ≤ 0.03). No associations were observed for moderate intensity exercise. Conclusions for Practice In women with GDM, particularly overweight and obese women, vigorous intensity exercise during pregnancy may reduce the odds of excess GWG.

Lactation and Progression to Type 2 Diabetes Mellitus After Gestational Diabetes Mellitus: A Prospective Cohort Study.

BACKGROUND: Lactation improves glucose metabolism, but its role in preventing type 2 diabetes mellitus (DM) after gestational diabetes mellitus (GDM) remains uncertain. OBJECTIVE: To evaluate lactation and the 2-year incidence of DM after GDM pregnancy. DESIGN: Prospective, observational cohort of women with recent GDM. (ClinicalTrials.gov: NCT01967030). SETTING: Integrated health care system. PARTICIPANTS: 1035 women diagnosed with GDM who delivered singletons at 35 weeks' gestation or later and enrolled in the Study of Women, Infant Feeding and Type 2 Diabetes After GDM Pregnancy from 2008 to 2011. MEASUREMENTS: Three in-person research examinations from 6 to 9 weeks after delivery (baseline) and annual follow-up for 2 years that included 2-hour, 75-g oral glucose tolerance testing; anthropometry; and interviews. Multivariable Weibull regression models evaluated independent associations of lactation measures with incident DM adjusted for potential confounders. RESULTS: Of 1010 women without diabetes at baseline, 959 (95%) were evaluated up to 2 years later; 113 (11.8%) developed incident DM. There were graded inverse associations for lactation intensity at baseline with incident DM and adjusted hazard ratios of 0.64, 0.54, and 0.46 for mostly formula or mixed/inconsistent, mostly lactation, and exclusive lactation versus exclusive formula feeding, respectively (P trend = 0.016). Time-dependent lactation duration showed graded inverse associations with incident DM and adjusted hazard ratios of 0.55, 0.50, and 0.43 for greater than 2 to 5 months, greater than 5 to 10 months, and greater than 10 months, respectively, versus 0 to 2 months (P trend = 0.007). Weight change slightly attenuated hazard ratios. LIMITATION: Randomized design is not feasible or desirable for clinical studies of lactation. CONCLUSION: Higher lactation intensity and longer duration were independently associated with lower 2-year incidences of DM after GDM pregnancy. Lactation may prevent DM after GDM delivery. PRIMARY FUNDING SOURCE: National Institute of Child Health and Human Development.

Is Surgical Menopause Associated With Future Levels of Cardiovascular Risk Factor Independent of Antecedent Levels? The CARDIA Study.

In the present study, we compared changes in risk factors for cardiovascular disease (CVD) before and after natural menopause (NM), hysterectomy with at least 1 ovary conserved (HOC), or hysterectomy with bilateral oophorectomy (HBSO). Data were obtained from women 18-30 years of age who were enrolled in the Coronary Artery Risk Development in Young Adults Study (1985-2011). Piecewise linear mixed models were used to examine changes in CVD risk factors from baseline to the index visit (the first visit after the date of NM or hysterectomy) and after index visit until the end of follow-up. During 25 years of follow-up, 1,045 women reached menopause (for NM, n = 588; for HOC, n = 304; and for HBSO, n = 153). At baseline, women with either type of hysterectomy had less favorable values for CVD risk factors. When comparing the annual rates of change of all CVD risk factors from baseline until the index visit to those from the index visit to the end of follow-up, we saw a small increase in rate of change for high-density lipoprotein cholesterol (ß = 0.28 mg/dL; P = 0.002) and a decrease for triglycerides (ß =-0.006 mg/dL; P = 0.027) for all groups. Hysterectomy was not associated with risk factors for CVD after accounting for baseline values. However, antecedent young-adult levels of CVD risk factors were strong predictors of levels of postmenopausal risk factors.

Placebo improvement in pharmacologic treatment of menopausal hot flashes: time course, duration, and predictors.

OBJECTIVES: To characterize the time course, duration of improvement, and clinical predictors of placebo response in treatment of menopausal hot flashes. METHODS: Data were pooled from two trials conducted in the Menopausal Strategies: Finding Lasting Answers to Symptoms and Health network, providing a combined placebo group (n = 247) and a combined active treatment group (n = 297). Participants recorded hot flash frequency in diaries twice daily during treatment (Weeks 0-8) and subsequent follow-up (Weeks 9-11). The primary outcome variable was clinically significant improvement, defined as a 50% or greater decrease in hot flash frequency from baseline and calculated for each week in the study. Subgroups were defined a priori using standard clinical definitions for significant improvement and partial improvement. Clinical and demographic characteristics of the participants were evaluated as predictors of improvement. RESULTS: Clinically significant improvement with placebo accrued each treatment week, with 33% significantly improved at Week 8. Of placebo responders who were improved at both Weeks 4 and 8, 77% remained clinically improved at Week 11 after treatment ended. Independent predictors of significant placebo improvement in the final multivariable model were African American race (odds ratio [OR] = 5.61, 95% confidence interval [CI] = 2.41-13.07, p < .001), current smokers (OR = 2.30, 95% CI = 1.05-5.06, p = .038), and hot flash severity in screening (OR = 1.45, 95% CI = 1.00-2.10, p = .047). CONCLUSIONS: Clinically significant improvement with placebo accrued throughout treatment with a time course similar to improvement with active drug. A meaningful number of participants in the placebo group sustained a clinically significant response after stopping placebo pills. The results suggest that nonspecific effects are important components of treatment and warrant further studies to optimize their contributions in clinical care.

Prospective association of polycystic ovary syndrome with coronary artery calcification and carotid-intima-media thickness: the Coronary Artery Risk Development in Young Adults Women's study.

OBJECTIVE: To study the independent associations of polycystic ovary syndrome (PCOS), and its 2 components, hyperandrogenism and anovulation, with coronary artery calcification (CAC) and carotid artery intima-media thickness (IMT). APPROACH AND RESULTS: At the year 20 of the Coronary Artery Risk Development in Young Adults (CARDIA) study, a population-based multicenter cohort of young adults, women (mean age, 45 years) with information on menses and hirsutism in their twenties were assessed for CAC (n=982) and IMT (n=988). We defined PCOS as women who had both irregular menses and hyperandrogenism (n=55); isolated oligomenorrhea (n=103) as women who only had irregular menses; and isolated hyperandrogenism (n=156) as women who had either hirsutism or increased testosterone levels. Logistic regressions and general linear models were used to estimate the associations between components of PCOS and subclinical CVD. The prevalence of CAC was 10.3% overall. Women with PCOS had a multivariable adjusted odds ratio of 2.70 (95% confidence interval, 1.31-5.60) for CAC. Women with either isolated oligomenorrhea or isolated hyperandrogenism had no increased risk of CAC when compared with unexposed women. Women with PCOS had significantly increased bulb and internal carotid-IMT measurements; however, no significant differences were noted in bulb or internal carotid artery IMT among women with either isolated oligomenorrhea or isolated hyperandrogenism when compared with unexposed women. There were no differences in common carotid-IMT among the 4 study groups. CONCLUSIONS: In this study, women with PCOS, manifested as both anovulation and hyperandrogenism, but not women with one of these manifestations alone, were at increased risk for the development of subclinical CVD.

Exercise as a vital sign: a quasi-experimental analysis of a health system intervention to collect patient-reported exercise levels.

BACKGROUND: Lack of regular physical activity is highly prevalent in U.S. adults and significantly increases mortality risk. OBJECTIVE: To examine the clinical impact of a newly implemented program ("Exercise as a Vital Sign" [EVS]) designed to systematically ascertain patient-reported exercise levels at the beginning of each outpatient visit. DESIGN AND PARTICIPANTS: The EVS program was implemented in four of 11 medical centers between April 2010 and October 2011 within a single health delivery system (Kaiser Permanente Northern California). We used a quasi-experimental analysis approach to compare visit-level and patient-level outcomes among practices with and without the EVS program. Our longitudinal observational cohort included over 1.5 million visits by 696,267 adults to 1,196 primary care providers. MAIN MEASURES: Exercise documentation in physician progress notes; lifestyle-related referrals (e.g. exercise programs, nutrition and weight loss consultation); patient report of physician exercise counseling; weight change among overweight/obese patients; and HbA1c changes among patients with diabetes. KEY RESULTS: EVS implementation was associated with greater exercise-related progress note documentation (26.2 % vs 23.7 % of visits, aOR 1.12 [95 % CI: 1.11-1.13], p < 0.001) and referrals (2.1 % vs 1.7 %; aOR 1.14 [1.11-1.18], p < 0.001) compared to visits without EVS. Surveyed patients (n = 6,880) were more likely to report physician exercise counseling (88 % vs. 76 %, p < 0.001). Overweight patients (BMI 25-29 kg/m(2), n = 230,326) had greater relative weight loss (0.20 [0.12 - 0.28] lbs, p < 0.001) and patients with diabetes and baseline HbA1c > 7.0 % (n = 30,487) had greater relative HbA1c decline (0.1 % [0.07 %-0.13 %], p < 0.001) in EVS practices compared to non-EVS practices. CONCLUSIONS: Systematically collecting exercise information during outpatient visits is associated with small but significant changes in exercise-related clinical processes and outcomes, and represents a valuable first step towards addressing the problem of inadequate physical activity.