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Rationale & Objective: The diagnosis and prognostication of chronic kidney disease (CKD) largely rely on glomerular measures that may not reflect tubular damage. We investigated the associations of urine kidney tubule biomarkers with estimated glomerular filtration rate (eGFR) change among middle-aged adults, when chronic diseases typically emerge. Study Design: An observational cohort study. Setting & Participants: A total of 1,145 participants of the Coronary Artery Risk Development in Young Adults (CARDIA) study without CKD, hypertension, or cardiovascular disease at the year 20 visit. Exposures: Seven different biomarkers of tubular health: urine epidermal growth factor (EGF), alpha-1-microglobulin (α1m), interleukin-18, kidney injury molecule-1, monocyte chemoattractant protein-1, uromodulin, and chitinase-3-like protein 1. Outcomes: Ten-year eGFR change and incident reduced eGFR (new onset of eGFR

Abstract Background Intensive glycemic control reduced coronary artery disease (CAD) events among the Action to Control Cardiovascular Disease Risk in Diabetes (ACCORD) participants with the haptoglobin (Hp) 2-2 phenotype only. It remains unknown whether Hp phenotype modifies the effect of an intensive lifestyle intervention (ILI) on CAD in type 2 diabetes. Methods Haptoglobin phenotype was measured in 4542 samples from the Action for Health in Diabetes (Look AHEAD) study. Cox regression models assessed the effect of ILI (focused on weight loss from caloric restriction and physical activity) versus diabetes support and education (DSE) on CAD events in each phenotype group, and within pre-specified subgroups including race/ethnicity, sex, history of cardiovascular disease, diabetes medication use, and diabetes duration. Results 1590 (35%) participants had the Hp2-2 phenotype. The ILI did not lower glycated hemoglobin (%HbA1c) to

Abstract Background Polycystic ovary syndrome (PCOS) is underdiagnosed, but factors associated with women’s report of diagnosis are not well-understood, particularly social determinants of health. Therefore, in a population-based cohort, we compared the characteristics of women with self-reported PCOS vs. women who have unrecognized PCOS vs. women without PCOS. Methods We performed a secondary data analysis of the Coronary Artery Risk Development in Young Adults (CARDIA) Study, a population-based, prospective cohort of Black and White women. Participants were women (n = 2028) who responded to the question, “Did a doctor or nurse ever tell you that you had polycystic ovarian syndrome or polycystic ovarian disease?” at the year 15 examination. Women who answered “yes” were defined as having self-reported PCOS. Women who answered “no or not sure” were defined as having unrecognized PCOS if they also had irregular menses and hyperandrogenemia between 20 and 30 years of age. Exposures of interest included social determinants of health, symptoms including irregular menses and hirsutism, and comorbid conditions. Results Forty-three (2.1%) of women had self-reported PCOS, 135 (6.7%) had unrecognized PCOS, and 1850 (91%) women were without PCOS. In logistic regression models adjusting for age, race, and center, women with self-reported PCOS were more likely to have obesity (OR 1.83, 95% CI 1.22, 2.75) and diabetes (OR 2.37, 95% CI 1.05, 5.33) compared to women without PCOS. Women with unrecognized PCOS were more likely to have hypertension (OR 1.68, 95% CI 1.03, 2.74) and food insecurity (OR 1.94, 95% CI 1.25, 3.01) compared to women without PCOS. Conclusions Unrecognized PCOS is common. Self-report of PCOS is not associated with access to healthcare. Women who report PCOS are more often obese and comorbidities may contribute to recognition of PCOS.

Objective: Having chronic conditions may result in reduced physical and cognitive function but less is known about multimorbidity with daily movement. We examined the association of multimorbidity and device-measured total daily movement in a nationally representative sample of US adults aged ≥ 30 years from the 2011–2014 National Health and Nutrition Examination Surveys. Methods: Any multimorbidity (≥2 conditions) and complex multimorbidity (≥3 conditions across ≥ 3 body systems) were quantified using 16 chronic conditions via self-report and/or clinical thresholds. Total movement over 24-hours (Monitor-Independent Movement Summary units [MIMS-units]) was measured using a wrist-worn device (ActiGraph GT3X). Multivariable linear regression examined the association of 1) each chronic condition, 2) number of conditions, 3) any multimorbidity, and 4) complex multimorbidity with total movement. Covariates included age, gender, race/ethnicity, educational attainment, and smoking status. Results: Among US adults (N = 7304, mean age: 53.2 ± 0.34 years, 53.2% female, 69.4% Non-Hispanic White), 62.2% had any multimorbidity with 34.2% having complex multimorbidity. After adjustment, a higher number of chronic conditions was associated with incrementally lower total movement (β MIMS-units [95% CI] compared to those with no chronic conditions; one: −419 [−772, −66], two: −605 [−933, −278], three: −1201 [−1506, −895], four: −1908 [−2351, −1465], 5+: −2972 [−3384, −2560]). Complex multimorbidity presence was associated with −1709 (95% CI: −2062, −1357) and −1269 (−1620, −918) lower total movement compared to those without multimorbidity and multimorbidity but not complex, respectively. Conclusions: Multimorbidity was associated with lower 24-h movement among US adults and may be helpful for identifying adults at risk for low movement.

Abstract Background Multivariate longitudinal data are under-utilized for survival analysis compared to cross-sectional data (CS - data collected once across cohort). Particularly in cardiovascular risk prediction, despite available methods of longitudinal data analysis, the value of longitudinal information has not been established in terms of improved predictive accuracy and clinical applicability. Methods We investigated the value of longitudinal data over and above the use of cross-sectional data via 6 distinct modeling strategies from statistics, machine learning, and deep learning that incorporate repeated measures for survival analysis of the time-to-cardiovascular event in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort. We then examined and compared the use of model-specific interpretability methods (Random Survival Forest Variable Importance) and model-agnostic methods (SHapley Additive exPlanation (SHAP) and Temporal Importance Model Explanation (TIME)) in cardiovascular risk prediction using the top-performing models. Results In a cohort of 3539 participants, longitudinal information from 35 variables that were repeatedly collected in 6 exam visits over 15 years improved subsequent long-term (17 years after) risk prediction by up to 8.3% in C-index compared to using baseline data (0.78 vs. 0.72), and up to approximately 4% compared to using the last observed CS data (0.75). Time-varying AUC was also higher in models using longitudinal data (0.86–0.87 at 5 years, 0.79–0.81 at 10 years) than using baseline or last observed CS data (0.80–0.86 at 5 years, 0.73–0.77 at 10 years). Comparative model interpretability analysis revealed the impact of longitudinal variables on model prediction on both the individual and global scales among different modeling strategies, as well as identifying the best time windows and best timing within that window for event prediction. The best strategy to incorporate longitudinal data for accuracy was time series massive feature extraction, and the easiest interpretable strategy was trajectory clustering. Conclusion Our analysis demonstrates the added value of longitudinal data in predictive accuracy and epidemiological utility in cardiovascular risk survival analysis in young adults via a unified, scalable framework that compares model performance and explainability. The framework can be extended to a larger number of variables and other longitudinal modeling methods. Trial registration ClinicalTrials.gov Identifier: NCT00005130, Registration Date: 26/05/2000.

Abstract Background Animal and human studies suggest the gut microbiome is linked to diabetes but additional data are needed on the associations of the gut microbiome to specific diabetes characteristics. The aim of this study was to examine the associations of gut microbiome composition to insulin resistance [Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)], duration of diabetes, and 4 stages of diabetes [normoglycemia, pre-diabetes, and diabetes with (+) and without (−) medication for diabetes]. Methods Data are from a sub-sample (n = 605) of Black and White participants from the 30-year follow-up exam of the prospectively followed community-based Coronary Artery Risk Development in Young Adults cohort (2015–2016; aged 48–60 years). Stool samples were collected and sequenced using the 16S ribosomal RNA method. Microbial measures included: α diversity (within-person), β diversity (between-person), and taxonomies. All analyses were adjusted for demographic, clinical, lifestyle factors, and use of relevant medications (full adjustment). Multivariate linear regression models were used to assess the association of diabetes characteristics with α diversity and genera abundance, while the association with β diversity was analyzed using permutational multivariate analysis of variance. Statistical significance was set to p-value

Abstract Gait alterations in those with mild unilateral knee pain during walking may provide clues to modifiable alterations that affect progression of knee pain and osteoarthritis (OA). To examine this, we applied machine learning (ML) approaches to gait data from wearable sensors in a large observational knee OA cohort, the Multicenter Osteoarthritis (MOST) study. Participants completed a 20-m walk test wearing sensors on their trunk and ankles. Parameters describing spatiotemporal features of gait and symmetry, variability and complexity were extracted. We used an ensemble ML technique (“super learning”) to identify gait variables in our cross-sectional data associated with the presence/absence of unilateral knee pain. We then used logistic regression to determine the association of selected gait variables with odds of mild knee pain. Of 2066 participants (mean age 63.6 [SD: 10.4] years, 56% female), 21.3% had mild unilateral pain while walking. Gait parameters selected in the ML process as influential included step regularity, sample entropy, gait speed, and amplitude dominant frequency, among others. In adjusted cross-sectional analyses, lower levels of step regularity (i.e., greater gait variability) and lower sample entropy(i.e., lower gait complexity) were associated with increased likelihood of unilateral mild pain while walking [aOR 0.80 (0.64–1.00) and aOR 0.79 (0.66–0.95), respectively].

Abstract Objective Obesity in pregnancy and gestational diabetes (GDM) increase cardiometabolic disease risk but are difficult to disentangle. This study aimed to test the hypothesis that 4–10 years after a pregnancy complicated by overweight/obesity and GDM (OB‐GDM), women and children would have greater adiposity and poorer cardiometabolic health than those with overweight/obesity (OB) or normal weight (NW) and no GDM during the index pregnancy. Methods In this cross‐sectional study, mother‐child dyads were stratified into three groups based on maternal health status during pregnancy (OB‐GDM = 67; OB = 76; NW = 76). Weight, height, waist and hip circumferences, and blood pressure were measured, along with fasting glucose, insulin, HbA1c, lipids, adipokines, and cytokines. Results Women in the OB and OB‐GDM groups had greater current adiposity and poorer cardiometabolic health outcomes than those in the NW group (p

Abstract Background Although physical activity is generally protective of cardiovascular disease (CVD), less is known about how young adult physical activity relates to premature CVD events. The objective of this study was to determine the association between level and change in physical activity from young adulthood to middle age and incidence of premature CVD events before age 60. Methods We analyzed data collected across four urban sites from nine visits over 30 years of follow-up (1985–2016) from the Coronary Artery Risk Development in Young Adults (CARDIA) study, a prospective community-based cohort study of 5115 Black and White women and men aged 18–30 years at baseline (1985–1986). Linear mixed models were used to develop individualized moderate-to-vigorous intensity self-reported physical activity trajectories per participant. Fatal and nonfatal coronary heart disease (CHD), heart failure, and stroke outcomes were analyzed separately and as a combined CVD event outcome. Results Overall, physical activity declined in young adults as they progressed through middle age. Lower physical activity scores (per 100 exercise units) in 18 year-olds were associated with higher odds of premature CHD (AOR 1.14, 95% CI 1.02–1.28), heart failure (AOR 1.21, 95% CI 1.05–1.38), stroke (AOR 1.20, 95% CI 1.04–1.39), and any CVD (AOR 1.15, 95% CI 1.06–1.24) events. Each additional annual 1-unit reduction in the physical activity score was associated with a higher annual odds of incident heart failure (1.07, 95% CI 1.02–1.13), stroke (1.06, 95% CI 1.00–1.13), and CVD (1.04, 95% CI 1.01–1.07) events. Meeting the minimum (AOR 0.74, 95% CI 0.0.57–0.96) and twice the minimum (AOR 0.55, 95% CI 0.34–0.91) Department of Health and Human Services physical activity guidelines through follow up was protective of premature CVD events. Conclusions Given recent trends in declining physical activity with age and associated premature CVD events, the transition from young adult to midlife is an important time period to promote physical activity.

In 1985 to 1986, the CARDIA (Coronary Artery Risk Development in Young Adults) study enrolled 5115 Black or White participants, including 2788 women, aged 18 to 30 years. Over the following 35 years, the CARDIA study amassed extensive longitudinal data on women's reproductive milestones, spanning menarche to menopause. Although not initially conceived as a study of women's health, >75 CARDIA study publications address relationships between reproductive factors and events with cardiovascular and metabolic risk factors, subclinical and clinical cardiovascular disease, and social determinants of health. The CARDIA study was one of the earliest population‐based reports to note Black‐White differences in age at menarche and associations with cardiovascular risk factors. Adverse pregnancy outcomes, particularly gestational diabetes and preterm birth, have been assessed along with postpartum behaviors, such as lactation. Existing studies have examined risk factors for adverse pregnancy outcomes and lactation, as well as their relationship to future cardiovascular and metabolic risk factors, diagnoses, and subclinical atherosclerosis. Ancillary studies examining components of polycystic ovary syndrome and ovarian biomarkers, such as anti‐Müllerian hormone, have facilitated examination of reproductive health in a population‐based cohort of young adult women. As the cohort transitioned through menopause, examination of the importance of premenopausal cardiovascular risk factors along with menopause has improved our understanding of shared mechanisms. The cohort is now aged in the 50s to mid‐60s, and women will begin to experience a greater number of cardiovascular events as well as other conditions, such as cognitive impairment. Thus, in the next decade, the CARDIA study will provide a unique resource for understanding how the women's reproductive life course epidemiology informs cardiovascular risk, as well as reproductive and chronological aging.

Objective: Pain persistence following knee replacement (KR) occurs in ∼20–30% of patients. Although several studies have identified preoperative risk factors for persistent post-KR pain, few have focused on post-KR contributing factors. We sought to determine whether altered nociceptive signaling and other peripheral nociceptive drivers present post-operatively contribute to post-KR pain. Design: We included participants from the Multicenter Osteoarthritis Study who were evaluated ∼12 months after KR. We evaluated the relation of measures of pain sensitivity [pressure pain threshold (PPT), temporal summation (TS), and conditioned pain modulation (CPM)] and the number of painful body sites to post-KR WOMAC knee pain, and of the number of painful sites to altered nociceptive signaling using linear or logistic regression models, as appropriate. Results: 171 participants (mean age 69 years, 62% female) were included. TS was associated with worse WOMAC pain post-KR (β ​= ​0.77 95% CI:0.19–1.35) and reduced odds of achieving patient acceptable symptom state (aOR ​= ​0.54 95%CI:0.34–0.88). Inefficient CPM was also associated with worse WOMAC pain post-KR (β ​= ​1.43 95% CI:0.15–2.71). In contrast, PPT was not associated with these outcomes. The number of painful body sites present post-KR was associated with TS (β ​= ​0.05, 95% CI:0.01, 0.05). Conclusions: Post-KR presence of central sensitization and inefficient descending pain modulation was associated with post-KR pain. We also noted that presence of other painful body sites contributes to altered nociceptive signaling, and this may thus also contribute to the experience of knee pain post-KR. Our findings provide novel insights into central pain mechanisms and other peripheral pain sources contributing to post-KR persistent knee pain.

Objective: Osteoarthritis (OA) is highly heterogeneous and has both biomechanical and systemic components that may not have the same etiology. We therefore aimed to identify specific knee OA phenotypes that may be more strongly associated with hand OA to refine the criteria used to define multi-joint OA. Design: We assessed data from the Multicenter Osteoarthritis Study (MOST). We ascertained hand OA from bilateral hand photographs; scores for each joint row were summed to yield an aggregate hand OA score. Knee OA was ascertained from bilateral posteroanterior knee radiographs read for Kellgren-Lawrence grade and individual radiographic features. We tested associations between hand and knee OA with phenotypes including symptomatic OA, hyper- and atrophic knee OA, and one excluding post-traumatic OA. Associations between hand and knee OA were assessed with logistic regression, adjusted for age. Results: We studied 2493 participants with hand and knee OA measures. Median age was 63 years with 57% women. 55% had an aggregate hand OA score ≥2; frequency of knee OA phenotypes ranged from 8% to 34%. The age-adjusted odds ratio (OR) was 1.14 (95% confidence interval (CI) ​= ​1.04–1.26) for knee OA per standard deviation of the hand OA aggregate score. Hand OA associations with symptomatic knee OA and knee OA excluding post-traumatic knee OA were OR ​= ​1.16 (95% CI ​= ​1.03–1.31) and OR ​= ​1.21 (95% CI ​= ​1.08–1.35), respectively. No other knee OA phenotype reached statistical significance. Conclusions: Age-adjusted associations between hand and knee OA were modest and were largely similar across knee OA phenotypes.

BackgroundRisk of incident cardiovascular disease (CVD) in head and neck squamous cell carcinoma (HNSCC) patients is under-reported. We assessed the association of HNSCC-related factors and traditional risk factors with 1- and 5-year CVD risk in HNSCC patients without prevalent CVD at cancer diagnosis.MethodsA clinical cohort of 1,829 HNSCC patients diagnosed between 2012 and 2018, at a National Cancer Institute (NCI)-designated cancer center was included. Information on HNSCC-related factors [HNSCC anatomical subsite, stage at diagnosis, treatment, and tumor human papillomavirus (HPV) status] were extracted from the tumor registry. Data on traditional risk factors (hypertension, dyslipidemia, diabetes, tobacco smoking status, and obesity) were extracted from the electronic health records system (EHR) at baseline (HNSCC diagnosis). A composite of ischemic heart disease, heart failure, and ischemic stroke was the outcome of interest in time to event analysis. Hazard ratio (HR) (95% CI) were reported with death as a competing risk.ResultsIn patients diagnosed with HNSCC, 10.61% developed incident CVD events by 1-year post cancer diagnosis. One-year CVD risk was lower in patients using antihypertensive medications at baseline, compared to patients without baseline hypertension [HR (95% CI): 0.41 (0.24–0.61)]. One-year CVD risk was high in patients receiving HNSCC surgery. Patients receiving radiation therapy had a higher 5-year CVD risk than surgery patients [HR (95% CI): 2.17 (1.31–3.04)]. Patients using antihypertensive medications had a lower 5-year CVD risk than patients without baseline hypertension [HR (95% CI): 0.45 (0.22–0.75)]. Older age and diabetes were associated with increased 1- and 5-year CVD risk. HPV-negative patients were older (p 0.006) and had a higher 5-year cumulative incidence of CVD (p 0.013) than HPV-positive patients.ConclusionTraditional risk factors and cancer-related factors are associated with CVD risk in HNSCC patients. Future research should investigate the role of antihypertensive medications in reducing CVD risk in HNSCC patients.

BACKGROUND Little attention has been paid to how well the American Heart Association's cardiovascular health (CVH) score predicts early‐onset diabetes in young adults. We investigated the association of CVH score with early‐ and later‐onset diabetes and with subsequent complications of diabetes. METHODS AND RESULTS Our sample included 4547 Black and White adults in the CARDIA (Coronary Artery Risk Development in Young Adults) study without diabetes at baseline (1985–1986; aged 18–30 years) with complete data on the CVH score at baseline, including smoking, body mass index, physical activity, diet quality, total cholesterol, blood pressure, and fasting blood glucose. Incident diabetes was determined based on fasting glucose, 2‐hour postload glucose, hemoglobin A1c, or self‐reported medication use throughout 8 visits for 30 years. Multinomial logistic regression was used to assess the association between CVH score and diabetes onset at age

More than half of U.S. young adults have low ten-year but high lifetime risk of cardiovascular disease (CVD). Improving primary prevention in young adulthood may help reduce persistent CVD disparities and overall CVD morbidity and mortality. The National Heart, Lung, and Blood Institute (NHLBI) convened a workshop in 2021 to identify potential trial opportunities in CVD prevention in young adults. The workshop identified promising interventions that could be tested, including interventions that focus on a single cardiovascular risk factor (e.g., lipids or inflammation) to multiple risk factor interventions (e.g., multicomponent lifestyle interventions or fixed-low dose combination of medications). Given the sample size and duration for a trial with hard endpoints, more research is needed on the utility of intermediate endpoints identified noninvasively such as subclinical coronary atherosclerosis as a surrogate endpoint. For now, clinical outcomes trials with hard endpoints will more likely change clinical practice. Trial efficiency depends on accurate identification of high-risk young adults, which can potentially be done using traditional risk equations, coronary artery calcium screening, computerized tomography coronary angiography, and polygenic risk scores. Trials in young adults should include enhanced recruitment strategies with intense community engagement to enroll a trial population that is racially, ethnically, geographically, and socially diverse. Despite the challenges in conducting large prevention trials in young adults, recent advances including innovation in clinical trial conduct, new therapies and successful interventions in older populations, and an increasing recognition of a lifespan approach to risk assessment have made such trials more feasible than ever. Disclosures: The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services.

Objective Hypomagnesemia increases the risk of chondrocalcinosis and calcium pyrophosphate disease. We examined whether the use of drugs that can cause hypomagnesemia, diuretics and proton pump inhibitors (PPIs), increases the risk of chondrocalcinosis. Methods Participants in the Multicenter Osteoarthritis (MOST) Study obtained weight‐bearing knee radiographs, and their medication use was recorded at baseline and 30‐, 60‐, 84‐, and 144‐month examinations. We read radiographs serially for chondrocalcinosis and characterized incident chondrocalcinosis when it first appeared. We classified diuretic use as thiazide, loop, and other. To test drug effects on incident chondrocalcinosis at each interval (eg, 30‐60 months), we excluded persons with chondrocalcinosis at the interval’s beginning. For each drug, we evaluated exposure at the beginning and end of the interval. We conducted knee‐based analyses using Bayesian mixed‐effects discrete time survival models adjusted for age, sex, body mass index, radiographic osteoarthritis, race, and clinic site. Results Of 5272 knees, 196 developed chondrocalcinosis. Thiazide use (21.7% of examinations) and PPI use (13.7%) were common. Neither loop nor other diuretic use was associated with incident chondrocalcinosis. Thiazide use at the beginning and end of the interval of incidence conferred a high risk (hazard ratio [HR] = 2.18; 95% confidence interval [CI] 1.23‐3.89), but use at the beginning of the interval was not associated with risk (HR = 1.04). PPI use at the interval’s beginning increased risk of chondrocalcinosis (HR = 2.29; 95% CI 1.37‐3.79). Conclusion Thiazide diuretics, but not other diuretics, and PPI use probably increase the risk of chondrocalcinosis. These findings may have important clinical implications.

Abstract Background Executive function (EF) is associated with obesity development and self‐management. Individuals who demonstrate or self‐report poorer EF performance tend to have poorer short‐term outcomes in obesity treatment. There may be distinct behavioral self‐management strategies and EF domains related to initial weight loss as compared to weight loss maintenance. Objective To characterize EF in individuals who achieved clinically significant weight loss via behavioral intervention and examine potential differences in EF between those who maintained versus regained lost weight. Methods Participants who previously achieved ≥5% weight loss via lifestyle intervention were included (N = 44). “Maintainers” (n = 16) maintained this minimum level of weight loss for ≥1 year. “Regainers” (n = 28) regained some or all initially lost weight. Performance‐based EF, intelligence quotient, health literacy, depression, anxiety, binge eating, demographics, and medical/weight history were assessed using a cross‐sectional design. Descriptive statistics and age‐, gender‐, education‐adjusted reference ranges were used to characterize EF. Analyses of covariance were conducted to examine EF differences between maintainers and regainers. Results The sample consisted primarily of females with obesity over age 50. Approximately half self‐identified as African–American. Decision‐making performance was better in maintainers than regainers (p = 0.003, partη2 = 0.19). There were no differences between maintainers and regainers in inhibitory control, verbal fluency, planning/organization, cognitive flexibility, or working memory (ps > 0.05, partη2s = 0.003–0.07). At least 75% of the sample demonstrated average‐above average EF test performance, indicated by scaled scores ≥13 or t‐scores > 60. Conclusions Most individuals with obesity who achieved clinically significant weight loss via behavioral intervention had average to above average EF. Individuals who maintained (vs. regained) their lost weight performed better on tests of decision‐making.

Abstract 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

Introduction—Oxidative stress is linked to cardiovascular diseases (CVD) and is suggested to vary by sex. However, few population-level studies have explored these associations and the majority comprise populations with advanced CVD. We assessed urinary isoprostane concentrations, a standard measure of oxidative stress, in a relatively young and healthy cohort, hypothesizing that higher oxidative stress is associated with an adverse cardiometabolic profile and female sex. Methods—Oxidative stress was measured in 475 women and 266 men, aged 48–55 years, from the Coronary Artery Risk Development in Young Adults (CARDIA) study using urinary 8-isoprostane (IsoP) and 2,3-dinor-8-isoprostane (IsoP-M). Multivariable-adjusted regression was used to evaluate cross-sectional associations. As secondary analysis, previously measured plasma F2-isoprostanes (plasma IsoP) from another CARDIA subset was similarly analyzed. Results—Mean (SD) ages for men and women were 52.1(2.3) and 52.2(2.2) years, respectively (p = 0.46), and 39% of the participants self-identified as Black (vs. White). Before adjustments, female sex was associated with higher median urinary IsoP (880 vs. 704 ng/g creatinine in men; p < 0.01) and IsoP m (1675 vs. 1284 ng/g creatinine in men; p < 0.01). Higher body mass index (BMI), high-density cholesterol (HDL-C), and triglycerides, current smoking, and less physical activity were associated with higher oxidative stress. Diabetes was not associated with urinary IsoP but was associated with lower IsoP m and plasma IsoP. Higher serum creatinine showed diverging associations with higher plasma and lower urinary isoprostane concentrations. Conclusions—Different isoprostane entities exhibit varying association patterns with CVD risk factors, and therefore are complementary, rather than interchangeable, in assessment of oxidative stress. Still, consistently higher isoprostanes among women, smokers, less active persons, and those with higher BMI and plasma triglycerides could reflect higher oxidative stress among these groups. While urinary isoprostanes are indexed to urinary creatinine due to variations in concentration, caution should be exercised when comparing groups with differing serum creatinine.

White matter hyperintensities (WMH) are a common brain-imaging feature of cerebral small vessel disease. Here, the authors carry out a GWAS and followup analyses for WMH-volume, implicating several variants with potential for risk stratification and drug targeting.

Objective. We evaluated the association of apolipoprotein B (apoB) with low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and triglycerides (TG) in early adulthood with concordant/discordant associations and midlife NAFLD. Methods. Participants from the CARDIA study were included (n = 2,655; baseline mean age: 25.0, 59.1% female, and 48.6% black). NAFLD was defined as liver attenuation ≤40 Hounsfield units after excluding other causes of liver fat. Logistic regression models assessed the odds of Y25 NAFLD among tertiles of apoB, LDL-C, non-HDL-C, and TG and quartiles of the apoB/TG ratio. Discordance/concordance analyses examined the association of apoB with each lipid marker and Y25 NAFLD. Results. The Y25 NAFLD prevalence was 10%. The high-tertile TG group (OR 1.87, 95% CI, and 1.30–2.69) and the low- (OR 1.98, 95% CI, and 1.30–3.01) and middle-apoB/TG ratio groups (OR 1.78, 95% CI, and 1.17–2.72) had the greatest odds of midlife NAFLD. Using discordance/concordance analysis, the high-apoB/high-TG group had the highest odds of NAFLD (OR 1.69, 95% CI, and 1.09–2.61) followed by the low-apoB/high-TG group. The high apoB/low TG group had the lowest odds of NAFLD. Conclusions. Among the studied lipid markers in early adulthood, TG levels have the strongest and most consistent association with midlife NAFLD.

Abstract Aims The long‐term impact of coffee or tea consumption on subclinical left ventricular (LV) systolic or diastolic function has not been previously studied. We examined the association between coffee or tea consumption beginning in early adulthood and cardiac function in midlife. Methods and results We investigated 2735 Coronary Artery Risk Development in Young Adults (CARDIA) study participants with long‐term total caffeine intake, coffee, and tea consumption data from three visits over a 20 year interval and available echocardiography indices at the CARDIA Year‐25 exam (2010–2011). Linear regression models were used to assess the association between caffeine intake, tea, and coffee consumption (independent variables) and echocardiography outcomes [LV mass, left atrial volume, and global longitudinal strain (GLS), LV ejection fraction (LVEF), and transmitral Doppler early filling velocity to tissue Doppler early diastolic mitral annular velocity (E/e´)]. Models were adjusted for standard cardiovascular risk factors, socioeconomic status, physical activity, alcohol use, and dietary factors (calorie intake, whole and refined grain intake, and fruit and vegetable consumption). Mean (standard deviation) age was 25.2 (3.5) years at the CARDIA Year‐0 exam (1985–1986), 57.4% were women, and 41.9% were African‐American. In adjusted multivariable linear regression models assessing the relationship between coffee consumption and GLS, beta coefficients when comparing coffee drinkers of 4 cups/day with non‐coffee drinkers were β = −0.30%, P 0.05; respectively (more negative values implies better systolic function). In adjusted multivariable linear regression models assessing the relationship between coffee consumption and E/e´, beta coefficients when comparing coffee drinkers of 4 cups/day with non‐coffee drinkers were β = −0.29, P .05; and β = −0.37, P > 0.05, respectively (more negative values implies better diastolic function). High daily coffee consumption (>4 cups/day) was associated with worse LVEF (β = −1.69, P 0.05 for all). Conclusions Low‐to‐moderate daily coffee consumption from early adulthood to middle age was associated with better LV systolic and diastolic function in midlife. High daily coffee consumption (>4cups/day) was associated with worse LV function. There was no association between caffeine or tea intake and cardiac function.

Objective: To determine reliability among four experienced and calibrated readers in cross-sectional and longitudinal semi-quantitative MRI assessments of knee osteoarthritis (OA) in the Multicenter Osteoarthritis (MOST) study. Design: From all MOST participants with at least one knee with readable 60-month and 84-month paired knee MRIs (1.0 ​T extremity systems), we selected 10 subjects having a spectrum of baseline disease severity of cartilage, bone marrow lesions, and meniscal damage and a spectrum of longitudinal changes in severity at 24 months follow-up. MRIs were independently assessed using the WORMS grading system by four musculoskeletal radiologists with the chronological sequence known to the readers. Kappa statistics were used to determine agreement between each pair of readers and Kendall's coefficient of concordance to determine average agreement across readers. Results: For most features, cross-sectional reliability was substantial to almost perfect. Regarding longitudinal reliability (detection of longitudinal change), inter-reader reliability as weighted kappa values ranged from 0.62 to 0.78 for cartilage damage, 0.75–0.88 for bone marrow lesions, 0.75–0.92 for meniscal tears, 0.67–0.95 for meniscal extrusion, 0.51–0.77 for bone attrition, 0.43–0.76 for osteophytes, 0.31–0.70 for Hoffa-synovitis, and 0.47–0.85 for effusion-synovitis. Kendall's coefficient ranged from 0.65 to 0.98. Conclusion: High levels of cross-sectional reliability and moderate to high longitudinal reliability was achieved using four experienced readers in semiquantitative MRI-assessment of most knee OA features.

The objective was to examine bidirectional associations of accelerometer estimated sedentary time and physical activity with reported knee symptoms. Participants were 2,034 adults (mean age 45.3 ± 3.6 years, 58.7% female) from CARDIA. Generalized estimating equations for logistic regression and linear mixed regression models examined associations of accelerometer estimated sedentary time, light-intensity physical activity (LPA), and moderate-to-vigorous intensity physical activity (MVPA) at baseline (2005–06) with knee discomfort, pain, stiffness, and physical function (yes/no and continuous scores from short-form WOMAC function scale) at the 5- and 10-year follow-up exams. Linear regression models examined associations between knee symptoms at the 5-year follow-up with accelerometer estimates at the 10-year follow-up. Models were adjusted for confounders; individuals with comorbidities were excluded in sensitivity analyses. A 30 min/day increment in sedentary time at baseline was associated with lower odds of knee symptoms at the 5- and 10-year follow-up (OR: 0.95, 95% CI range: 0.92–0.98), while LPA and MVPA were associated with greater odds of knee symptoms (LPA OR range: 1.04–1.05, 95% CI range: 1.01–1.09; MVPA OR range: 1.17–1.19, 95% CI range: 1.06–1.32). Report of knee symptoms at the 5-year follow-up was associated with 13.52–17.51 (95% CI range: −29.90, −0.56) fewer minutes/day of sedentary time and 14.58–17.51 (95% CI range: 2.48, 29.38) more minutes/day of LPA at the 10-year follow-up, compared to those reporting no symptoms. Many associations were no longer statistically significant when excluding individuals with comorbidities. Findings support a bidirectional association of accelerometer estimated sedentary time and physical activity with knee symptoms across midlife.

GWAS have identified more than 500 genetic loci associated with blood lipid levels. Here, the authors report a genome-wide analysis of interactions between genetic markers and physical activity, and find that physical activity modifies the effects of four genetic loci on HDL or LDL cholesterol.

Abstract Background Young adults (YA) are at high-risk for unhealthy dietary behaviors and weight gain. The Study of Novel Approaches to Weight Gain Prevention (SNAP) Trial demonstrated that two self-regulation approaches were effective in reducing weight gain over 2 years compared with control. The goal of this analysis was to examine effects of intervention on dietary outcomes and the association of diet changes with weight change. Methods Participants were 599 YA, age 18–35 years, BMI 21.0–30.0 kg/m2 (27.4 ± 4.4 years; 25.4 ± 2.6 kg/m2; 22% men; 73% non-Hispanic White), who were recruited in Providence, RI and Chapel Hill, NC and randomized to self-regulation with Small Changes (SC), self-regulation with Large Changes (LC) or Control (C). SC and LC emphasized frequent self-weighing to cue behavior changes (small daily changes vs. periodic large changes) and targeted high-risk dietary behaviors. Diet and weight were assessed at baseline, 4 months and 2 years. Results LC and SC had greater decreases in energy intake than C at 4 months but not 2 years. LC had the greatest changes in percent calories from fat at 4 months, but differences were attenuated at 2 years. No differences in diet quality were observed. Across conditions, increased total energy consumption, fast food, meals away from home, and binge drinking, and decreased dietary quality and breakfast consumption were all associated with weight gain at 2 years. Conclusions This study suggests the need to strengthen interventions to produce longer term changes in dietary intake and helps to identify specific behaviors associated with weight gain over time in young adults. Trial registration Clinicaltrials.gov #NCT01183689, registered August 18, 2010.

Obesity is a global pandemic, but there is yet no effective measure to control it. Recent metabolomics studies have identified a signature of altered amino acid profiles to be associated with obesity, but it is unclear whether these findings have actionable clinical potential. The aims of this study were to reveal the metabolic alterations of obesity and to explore potential strategies to mitigate obesity. We performed targeted metabolomic profiling of the plasma/serum samples collected from six independent cohorts and conducted an individual data meta-analysis of metabolomics for body mass index (BMI) and obesity. Based on the findings, we hypothesized that restriction of branched-chain amino acids (BCAAs), phenylalanine, or tryptophan may prevent obesity and tested our hypothesis in a dietary restriction trial with eight groups of 4-week-old male C57BL/6J mice (n = 5/group) on eight different types of diets, respectively, for 16 weeks. A total of 3397 individuals were included in the meta-analysis. The mean BMI was 30.7 ± 6.1 kg/m2, and 49% of participants were obese. Fifty-eight metabolites were associated with BMI and obesity (all p ≤ 2.58 × 10−4), linked to alterations of the BCAA, phenylalanine, tryptophan, and phospholipid metabolic pathways. The restriction of BCAAs within a high-fat diet (HFD) maintained the mice’s weight, fat and lean volume, subcutaneous and visceral adipose tissue weight, and serum glucose and insulin at levels similar to those in the standard chow group, and prevented obesity, adipocyte hypertrophy, adipose inflammation, and insulin resistance induced by HFD. Our data suggest that four metabolic pathways, BCAA, phenylalanine, tryptophan, and phospholipid metabolic pathways, are altered in obesity and restriction of BCAAs within a HFD can prevent the development of obesity and insulin resistance in mice, providing a promising strategy to potentially mitigate diet-induced obesity.

Background Women who deliver preterm infants (

Background Reproductive events, that is, a preterm birth (PTB), small‐for‐gestational‐age infant (SGA), and vasomotor symptoms of menopause, are associated with subclinical atherosclerotic cardiovascular disease (ASCVD). We evaluated whether women with a past PTB and/or SGA (henceforth PTB/SGA) were more likely to have severe vasomotor symptoms of menopause and whether the estimated 10‐year ASCVD risk was higher in women with PTB/SGA and vasomotor exposures. Methods and Results We assigned 1866 women (mean age=55±1 years) in the CARDIA (Coronary Artery Risk Development in Young Adults) study to the following categories of reproductive exposures: none, PTB/SGA only, vasomotor symptoms only, or both PTB/SGA and vasomotor symptoms. We used Kruskal‐Wallis tests to evaluate the differences in pooled cohort equation ASCVD risk scores by category and linear regression to evaluate the associations of categories with ASCVD risk scores adjusted for study center, body mass index, education, current hormone replacement therapy use, parity, and hysterectomy. Women with PTB/SGA were more likely to have severe vasomotor symptoms, 36% versus 30%, P

Background Non‐alcoholic fatty liver disease (NAFLD) is associated with high cardiovascular morbidity/mortality, including heart failure. Abnormalities in left ventricular (LV) structure/function are associated with heart failure risk. Methods and Results Participants from the population‐based CARDIA (Coronary Artery Risk Development in Young Adults) study year 25 exam (2010–2011, aged 43–55 years, 61% women, 48% black) with computed tomography measured liver fat and comprehensive echocardiography were included. Echocardiography was repeated at year 30 follow‐up (aged 47–62 years, N=1827). NAFLD was defined as liver attenuation ≤40 HU after exclusions. LV geometry was classified into normal and abnormal by integrating relative wall thickness and LV mass index. Diastolic function was defined using Doppler and tissue Doppler imaging. Systolic function was assessed with myocardial strain measured by speckle tracking. NAFLD prevalence was 8.7% (n=159). NAFLD participants had higher LV mass, relative wall thickness, incident LV hypertrophy and abnormal LV geometry versus non‐NAFLD (P

Background Nocturnal hypertension, defined by a mean asleep systolic blood pressure (SBP)/diastolic blood pressure (BP) ≥120/70 mm Hg, and nondipping SBP, defined by an awake‐to‐asleep decline in SBP

An increase in the volume of the brain lateral ventricles is a sign of normal aging, but can also be associated with neurological and psychiatric disorders. Here, Vojinovic et al. identify seven genetic loci in a GWA study for ventricular volume in 23,500 individuals and find correlation with thalamus volume.

Abstract Background Behavioral interventions for obesity produce clinically meaningful weight loss, but weight regain following treatment is common. Extended care programs attenuate weight regain and improve weight loss maintenance. However, less is known about the most effective ways to deliver extended care, including contact schedules. Methods We compared the 12-month weight regain of an extended care program utilizing a non-conventional, clustered campaign treatment schedule and a self-directed program among individuals who previously achieved ≥5% weight reductions. Participants (N = 108; mean age = 51.6 years; mean weight = 92.6 kg; 52% African American; 95% female) who achieved ≥5% weight loss during an initial 16-week behavioral obesity treatment were randomized into a 2-arm, 12-month extended care trial. A clustered campaign condition included 12 group-based visits delivered in three, 4-week clusters. A self-directed condition included provision of the same printed intervention materials but no additional treatment visits. The study was conducted in a U.S. academic medical center from 2011 to 2015. Results Prior to randomization, participants lost an average of −7.55 ± 3.04 kg. Participants randomized to the 12-month clustered campaign program regained significantly less weight (0.35 ± 4.62 kg) than self-directed participants (2.40 ± 3.99 kg), which represented a significant between-group difference of 2.28 kg (p = 0.0154) after covariate adjustments. This corresponded to maintaining 87% and 64% of lost weight in the clustered campaign and self-directed conditions, respectively, which was a significant between-group difference of 29% maintenance of lost weight after covariate adjustments, p = 0.0396. Conclusions In this initial test of a clustered campaign treatment schedule, this novel approach effectively promoted 12-month maintenance of lost weight. Future trials should directly compare the clustered campaigns with conventional (e.g., monthly) extended care schedules. Trial registration Clinicaltrials.gov NCT02487121 . Registered 06/26/2015 (retrospectively registered)

Abstract Background Limited evidence exists to inform physical activity (PA) and sedentary behavior guidelines for older people, especially women. Rigorous evidence on the amounts, intensities, and movement patterns associated with better health in later life is needed. Methods/Design The Objective PA and Cardiovascular Health (OPACH) Study is an ancillary study to the Women’s Health Initiative (WHI) Program that examines associations of accelerometer-assessed PA and sedentary behavior with cardiovascular and fall events. Between 2012 and 2014, 7048 women aged 63–99 were provided with an ActiGraph GT3X+ (Pensacola, Florida) triaxial accelerometer, a sleep log, and an OPACH PA Questionnaire; 6489 have accelerometer data. Most women were in their 70s (40%) or 80s (46%), while approximately 10% were in their 60s and 4% were age 90 years or older. Non-Hispanic Black or Hispanic/Latina women comprise half of the cohort. Follow-up includes 1-year of falls surveillance with monthly calendars and telephone interviews of fallers, and annual follow-up for outcomes with adjudication of incident cardiovascular disease (CVD) events through 2020. Over 63,600 months of calendar pages were returned by 5,776 women, who reported 5,980 falls. Telephone interviews were completed for 1,492 women to ascertain the circumstances, injuries and medical care associated with falling. The dataset contains extensive information on phenotypes related to healthy aging, including inflammatory and CVD biomarkers, breast and colon cancer, hip and other fractures, diabetes, and physical disability. Discussion This paper describes the study design, methods, and baseline data for a diverse cohort of postmenopausal women who wore accelerometers under free-living conditions as part of the OPACH Study. By using accelerometers to collect more precise and complete data on PA and sedentary behavior in a large cohort of older women, this study will contribute crucial new evidence about how much, how vigorous, and what patterns of PA are necessary to maintain optimal cardiovascular health and to avoid falls in later life. Clinical trials registration ClinicalTrials.gov identifier NCT00000611 . Registered 27 October 1999.

Background Diminished peak lung function in young adulthood is a risk factor for future chronic obstructive pulmonary disease. The association between lung disease and cardiovascular disease later in life is well documented. Whether peak lung function measured in young adulthood is associated with risk of future cardiovascular events is unknown. Methods and Results CARDIA (The Coronary Artery Risk Development in Young Adults) study is a prospective, multicenter, community‐based, longitudinal cohort study including 4761 participants aged 18 to 30 years with lung function testing we investigated the association between lung health in young adulthood and risk of subsequent cardiovascular events. We performed Cox proportional hazards regression to test the association between baseline and years 10 and 20 pulmonary function with incident cardiovascular events. Linear and logistic regression was performed to explore the associations of lung function with development of risk factors for cardiovascular disease as well as carotid intima‐media thickness and coronary artery calcified plaque. At baseline, mean age (±SD) was 24.9±3.6 years. Baseline forced expiratory volume in 1 second (hazard ratio) per −10‐unit decrement in percent predicted forced expiratory volume in 1 second (hazard ratio, 1.18; 95% CI, 1.06–1.31 [P=0.002]) and FVC per −10‐unit decrement in percent predicted FVC (hazard ratio, 1.19; 95% CI, 1.06–1.33 [P=0.003]) were associated with future cardiovascular events independent of traditional cardiovascular risk factors. Baseline lung function was associated with heart failure and cerebrovascular events but not coronary artery disease events. Conclusions Lung function in young adulthood is independently associated with cardiovascular events into middle age. This association appears to be driven by heart failure and cerebrovascular events rather than coronary heart disease. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT00005130.

Background Intensive systolic blood pressure (SBP) lowering significantly reduced cardiovascular disease (CVD) events in SPRINT (Systolic Blood Pressure Intervention Trial) but not in ACCORD BP (Action to Control Cardiovascular Risk in Diabetes Blood Pressure). Methods and Results SPRINT tested the effects of intensive (

Background Visceral adipose tissue (VAT) and other measures of central obesity predict incident atherosclerotic cardiovascular disease (ASCVD) events in middle‐aged individuals, but these associations are less certain in older individuals age 70 years and older. Our objective was to estimate the associations of VAT and the android–gynoid fat mass ratio, another measure of central obesity, with incident ASCVD events among a large cohort of older men. Methods and Results Two thousand eight hundred ninety‐nine men (mean [SD] age 76.3 [5.5] years) enrolled in the Outcomes of Sleep Disorders in Older Men study had rigorous adjudication of incident ASCVD events (myocardial infarction, coronary heart disease death, or fatal or nonfatal stroke). We used proportional hazards models to estimate the hazard ratios for incident ASCVD per SD increase of VAT or android–gynoid fat mass ratio (measured at baseline with dual‐energy absorptiometry), adjusted for age, race, education, systolic blood pressure, smoking status, oxidized low‐density lipoprotein level, treatment for hypertension, statin use, aspirin use, presence of diabetes mellitus, and study enrollment site. Over a mean (SD) follow‐up period of 7.9 (3.4) years, 424 men (14.6%) had an incident ASCVD event. Neither VAT nor android–gynoid fat mass ratio were associated with incident ASCVD events, either unadjusted or after multivariable‐adjustment (hazard ratios [95% confidence interval ] per SD increase 1.02 [0.92–1.13] and 1.05 [0.95–1.17], respectively). Conclusions Central adipose tissue, as measured by VAT or android–gynoid fat mass ratio, was not associated with incident ASCVD events in this study of older men.

Background Blacks have higher blood pressure levels compared with whites beginning in childhood. Few data are available on racial differences in the incidence of hypertension from young adulthood through middle age. Methods and Results We calculated the cumulative incidence of hypertension from age 18 to 55 years among participants in the CARDIA (Coronary Artery Risk Development in Young Adults) study. Incident hypertension was defined by the first visit with mean systolic blood pressure ≥130 mm Hg, mean diastolic blood pressure ≥80 mm Hg, or self‐reported use of antihypertensive medication. Among 3890 participants without hypertension at baseline (aged 18–30 years), cumulative incidence of hypertension by age 55 years was 75.5%, 75.7%, 54.5%, and 40.0% in black men, black women, white men, and white women, respectively. Among participants with systolic blood pressure/diastolic blood pressure

BackgroundThe relationship between light intensity physical activity (PA), which is common in older adults, and cardiovascular disease (CVD) risk factors is unclear. This study examined associations of accelerometer‐measured PA intensity with CVD risk factors in older women of different race‐ethnicities. Methods and ResultsCross‐sectional analyses were conducted in 4832 women (mean age 78.9 years; 52.5% white, 30.5% black, 17.1% Hispanic) who were without known CVD and wore triaxial accelerometers a minimum of 4 of 7 days with ≥10 hours/d awake wear‐time. Vector magnitude counts per 15‐s epoch were used to define time spent in low light (19–225 counts/15 s), high light (226–518), and moderate‐to‐vigorous; ≥519) intensity PA. Fasting CVD biomarkers, resting blood pressure, waist girth, body mass index, and 10‐year predicted CVD risk (Reynolds Risk Score) were measured. After adjusting for age, wear time, race‐ethnicity, and potential confounders, each PA measure was favorably associated with mean high‐density lipoprotein, triglyceride, glucose, C‐reactive protein, body mass index, waist girth, and Reynolds Risk Score (P

BackgroundDespite evidence suggesting that early metabolic dysfunction impacts cardiovascular disease risk, current guidelines focus on risk assessments later in life, missing early transitions in metabolic risk that may represent opportunities for averting the development of cardiovascular disease. Methods and ResultsIn 4420 young adults in the Coronary Artery Risk Development in Young Adults (CARDIA) study, we defined a “metabolic” risk score based on components of the Third Report of the Adult Treatment Panel's definition of metabolic syndrome. Using latent class trajectory analysis adjusted for sex, race, and time‐dependent body mass index, we identified 6 distinct metabolic trajectories over time, specified by initial and final risk: low‐stable, low‐worsening, high‐stable, intermediate‐worsening, intermediate‐stable, and high‐worsening. Overall, individuals gained weight over time in CARDIA with statistically but not clinically different body mass index trend over time. Dysglycemia and dyslipidemia over time were highest in initially high or worsening trajectory groups. Divergence in metabolic trajectories occurred in early adulthood (before age 40), with 2 of 3 individuals experiencing an increase in metabolic risk over time. Membership in a higher‐risk trajectory (defined as initially high or worsening over time) was associated with greater prevalence and extent of coronary artery calcification, left ventricular mass, and decreased left ventricular strain at year 25. Importantly, despite similar rise in body mass index across trajectories over 25 years, coronary artery calcification and left ventricular structure and function more closely tracked risk factor trajectories. ConclusionsTransitions in metabolic risk occur early in life. Obesity‐related metabolic dysfunction is related to subclinical cardiovascular phenotypes independent of evolution in body mass index, including coronary artery calcification and myocardial hypertrophy and dysfunction.

BackgroundThe classic view of blood pressure (BP) reactivity to psychological stress in relation to cardiovascular risks assumes that excess reactivity is worse and lower reactivity is better. Evidence addressing how stress‐induced BP reactivity in young adults is associated with midlife cognitive function is sparse. Methods and ResultsWe assessed BP reactivity during a star tracing task and a video game in adults aged 20 to 32 years. Twenty‐three years later, cognitive function was assessed with use of the Digit Symbol Substitution Test (a psychomotor speed test), the Rey Auditory Verbal Learning Test (a verbal memory test), and the modified Stroop test (an executive function test). At the time of follow‐up, participants (n=3021) had a mean age of 50.2 years; 56% were women, and 44% were black. In linear regression models adjusted for demographic and clinical characteristics including baseline and follow‐up resting BP, lower systolic BP (SBP) reactivity during the star tracing and video game was associated with worse Digit Symbol Substitution Test scores (β [SE]: 0.11 [0.02] and 0.05 [0.02], respectively) and worse performance on the Stroop test (β [SE]: −0.06 [0.02] and −0.05 [0.02]; all P

Practice guidelines recommend addressing obesity for people with knee OA, however, the association of obesity with walking independent of pain is not known. We investigated this association within the Multicenter Osteoarthritis Study, a cohort of older adults who have or are at high risk of knee OA. Subjects wore a StepWatch to record steps taken over 7 days. We measured knee pain from a visual analogue scale and obesity by BMI. We examined the association of obesity with walking using linear regression adjusting for pain and covariates. Of 1788 subjects, the mean steps/day taken was 8872.9±3543.4. Subjects with a BMI ≥35 took 3355 fewer steps per day independent of knee pain compared with those with a BMI ≤25 (95% CI −3899, −2811). BMI accounted for 9.7% of the variability of walking while knee pain accounted for 2.9%. BMI was associated with walking independent of knee pain.

Sleep duration has been inversely associated with body mass index (BMI). We examined the relationship between self-reported sleep duration and BMI, waist circumference, and percent body fat in Black and White individuals from the CARDIA study. Box-Tidwell regression models were adjusted for age and race (Model 1), additional lifestyle and demographic variables (Model 2), and physical activity (Model 3). There were significant interactions between sleep and gender for the main outcome variables. In men, there was a trend for an inverse relationship between reported sleep duration and BMI in Model 2 (β=−0.20,P=.053) but not model 3 (β=−0.139,P=.191). In women, inverse relationships were observed between sleep duration and BMI (β=−0.294,P=.005) and waist circumference (β=−0.442,P=.059), in Model 2. These associations became nonsignificant in model 3 (BMI: β=−0.172,P=.084; waist circumference: β=−0.161,P=.474). Our results are consistent with previous findings that sleep is associated with BMI and other body composition variables. However, the relationship between self-reported sleep duration and body composition may be stronger in women than in men.