Publications by authors named "Cora E Lewis"

530 Publications

Patterns of weight change in a weight gain prevention study for young adults.

Obesity (Silver Spring) 2021 Sep 21. Epub 2021 Sep 21.

Warren Alpert Medical School, Brown University, Providence, Rhode Island, USA.

Objective: Recovery from weight regain is uncommon during weight loss treatment. This study examined whether participants in a weight gain prevention intervention similarly struggle to recover following weight gains and which factors predict transitions.

Methods: This is a secondary analysis of data from the Study of Novel Approaches to Weight Gain Prevention (SNAP), a randomized controlled trial comparing two weight gain prevention interventions with a control group. Young adults (n = 599; age 18-35 years) were followed over 3 years. Markov models identified transition rates in going above and returning below baseline weight across follow-up. Logistic regressions identified predictors of transitions.

Results: At each time point, approximately double the number of participants who transitioned from below to above baseline transitioned from above to below. The magnitude of weight changes from baseline and the number of weight loss strategies used predicted transitions from below to above and above to below baseline weight (with opposite relationships). Infrequent self-weighing and lower dietary restraint predicted transitions below to above baseline weight. Treatment arm, demographics, calorie consumption, and physical activity generally did not predict transitions.

Conclusions: Young adults engaging in weight gain prevention struggle to lose gained weight. Alternative strategies are needed to address weight gains in weight gain prevention interventions.
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http://dx.doi.org/10.1002/oby.23268DOI Listing
September 2021

Steps per Day and All-Cause Mortality in Middle-aged Adults in the Coronary Artery Risk Development in Young Adults Study.

JAMA Netw Open 2021 Sep 1;4(9):e2124516. Epub 2021 Sep 1.

Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.

Importance: Steps per day is a meaningful metric for physical activity promotion in clinical and population settings. To guide promotion strategies of step goals, it is important to understand the association of steps with clinical end points, including mortality.

Objective: To estimate the association of steps per day with premature (age 41-65 years) all-cause mortality among Black and White men and women.

Design, Setting, And Participants: This prospective cohort study was part of the Coronary Artery Risk Development in Young Adults (CARDIA) study. Participants were aged 38 to 50 years and wore an accelerometer from 2005 to 2006. Participants were followed for a mean (SD) of 10.8 (0.9) years. Data were analyzed in 2020 and 2021.

Exposure: Daily steps volume, classified as low (<7000 steps/d), moderate (7000-9999 steps/d), and high (≥10 000 steps/d) and stepping intensity, classified as peak 30-minute stepping rate and time spent at 100 steps/min or more.

Main Outcomes And Measures: All-cause mortality.

Results: A total of 2110 participants from the CARDIA study were included, with a mean (SD) age of 45.2 (3.6) years, 1205 (57.1%) women, 888 (42.1%) Black participants, and a median (interquartile range [IQR]) of 9146 (7307-11 162) steps/d. During 22 845 person years of follow-up, 72 participants (3.4%) died. Using multivariable adjusted Cox proportional hazards models, compared with participants in the low step group, there was significantly lower risk of mortality in the moderate (hazard ratio [HR], 0.28 [95% CI, 0.15-0.54]; risk difference [RD], 53 [95% CI, 27-78] events per 1000 people) and high (HR, 0.45 [95% CI, 0.25-0.81]; RD, 41 [95% CI, 15-68] events per 1000 people) step groups. Compared with the low step group, moderate/high step rate was associated with reduced risk of mortality in Black participants (HR, 0.30 [95% CI, 0.14-0.63]) and in White participants (HR, 0.37 [95% CI, 0.17-0.81]). Similarly, compared with the low step group, moderate/high step rate was associated with reduce risk of mortality in women (HR, 0.28 [95% CI, 0.12-0.63]) and men (HR, 0.42 [95% CI, 0.20-0.88]). There was no significant association between peak 30-minute intensity (lowest vs highest tertile: HR, 0.98 [95% CI, 0.54-1.77]) or time at 100 steps/min or more (lowest vs highest tertile: HR, 1.38 [95% CI, 0.73-2.61]) with risk of mortality.

Conclusions And Relevance: This cohort study found that among Black and White men and women in middle adulthood, participants who took approximately 7000 steps/d or more experienced lower mortality rates compared with participants taking fewer than 7000 steps/d. There was no association of step intensity with mortality.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.24516DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417757PMC
September 2021

Relationship of Patellofemoral Osteoarthritis to Changes in Performance-Based Physical Function Over 7 Years: The Multicenter Osteoarthritis Study.

J Rheumatol 2021 Sep 1. Epub 2021 Sep 1.

Faculty of Health Sciences and Bone and Joint Institute, Western University, London, Canada; Division of Rheumatology, Boston University School of Medicine, Boston, USA; Department of Biostatistics, Boston University School of Public Health, Boston, USA; Department of Physical Therapy, University of Delaware, Newark, USA; Department of Rheumatology, Massachusetts General Hospital, Boston, USA; Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, USA; Department of Epidemiology, The University of Iowa, Iowa City, USA; Department of Epidemiology, University of Alabama at Birmingham, Birmingham, USA; Department of Physical Therapy, Movement, and Rehabilitation Sciences, Northeastern University, Boston, USA. Funding: The Multicenter Osteoarthritis Study was funded by the NIH/NIA UO1 AG18820, UO1 AG18832, UO1 AG18947, and UO1 AG19069. Dr. Hart is funded by a Canadian Institutes of Health Research Fellowship. Dr. Stefanik is supported by NIH/NIAMS K23 AR070913. Dr. Neogi was supported by NIH/NIAMS K24AR070892. This work was also supported by NIH/NIAMS P30AR072571. Funding sources had no role in the study design, collection, analysis, and interpretation of the data or the decision to submit the manuscript for publication. Address correspondence to Joshua J. Stefanik Department of Physical Therapy, Movement, and Rehabilitation Sciences, Boston, MA, United States. E-mail:

Objective: Determine the relationship of patellofemoral osteoarthritis (OA) to changes in performancebased function over 7 years.

Methods: 2666 participants (62.2±8.0 years, BMI 30.6±5.9kg/m; 60% female) from the Multicenter Osteoarthritis Study with knee radiographs at baseline and who completed repeated chair stands and 20- meter walk test at baseline, 2.5, 5, and 7 years were included. Generalized linear models assessed the relation of radiographic patellofemoral OA and radiographic patellofemoral OA with frequent knee pain to longitudinal changes in performance-based function. Analyses were adjusted for age, sex, BMI, tibiofemoral OA, and injury/surgery.

Results: Linear models demonstrated a significant group by time interaction for the repeated chair stands (p=0.04) and the 20-meter walk test (p<0.0001). Those with radiographic patellofemoral OA took 1.01seconds longer on the repeated chair stands (p=0.02) and 1.69seconds longer on the 20-meter walk test (p<0.0001) at 7 years compared with baseline. When examining the relation of radiographic patellofemoral OA with frequent knee pain to performance-based function there was a significant group by time interaction for repeated chair stands (p=0.05) and the 20-meter walk test (p<0.0001). Those with radiographic patellofemoral OA with frequent knee pain increased their time on the repeated chair stands by 1.12seconds (p=0.04) and 1.91seconds (p<0.0001) on the 20-meter walk test over 7 years.

Conclusion: Individuals with radiographic patellofemoral OA and those with radiographic patellofemoral OA with frequent knee pain have worsening of performance-based function over time. This knowledge may present opportunities to plan for early treatment strategies for patellofemoral OA to limit functional decline over time.
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http://dx.doi.org/10.3899/jrheum.210270DOI Listing
September 2021

Epigenetic Age Acceleration Reflects Long-Term Cardiovascular Health.

Circ Res 2021 Aug 25. Epub 2021 Aug 25.

Preventive Medicine, Northwestern University Feinberg School of Medicine, UNITED STATES.

Epigenetic aging is a novel measure of biological age, reflecting exposures and disease risks independent of chronological age. It may serve as a useful biomarker of cardiovascular health (CVH) and/or cardiovascular disease (CVD) risk for early detection or prevention. To examine associations between GrimAge acceleration (GrimAA), a measure of epigenetic aging calculated from the residuals of GrimAge regressed on chronological age, and two repeated CVH measures: a full score for the AHA "Life's Simple 7" (diet, smoking, physical activity, BMI, blood pressure, total cholesterol, and glucose) and a clinical CVH score (BMI, blood pressure, cholesterol, and glucose). We used Illumina array DNA methylation data from two prospective cohort studies: The Coronary Artery Risk Development in Young Adults (CARDIA) study and Framingham Heart Study (FHS), to calculate GrimAA and model associations with CVH. CARDIA randomly selected 1,118 participants for assays at Y15 (2000-2001; mean age 40) and/or Y20 (2005-2006); in FHS, 2,106 Offspring participants had DNA methylation measured at exam 8 (2005-2008; mean age 66). We examined multiple cross-sectional and longitudinal models of GrimAA and each CVH score measured at CARDIA Y0-Y20 and FHS exams 7-8. In CARDIA clinical CVH score from Y0-Y20 was associated with Y15 and Y20 GrimAA (β range -0.41 to -0.21 years per 1-point increase in CVH; p range <0.01 to 0.01), as was full score (β range -0.65 to -0.67 years; p<0.01 for all). These findings were validated in FHS (clinical score β range -0.51 to -0.54 years; full score β range -0.76 to -0.83 years; p<0.01 for all). Our data demonstrate that faster GrimAA is associated with the loss of CVH from young age. Epigenetic age may be a useful biomarker of CVD risk and provides biological insight into the role of epigenetic mechanisms linking age-related CVH loss and CVD.
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http://dx.doi.org/10.1161/CIRCRESAHA.121.318965DOI Listing
August 2021

Number and timing of ambulatory blood pressure monitoring measurements.

Hypertens Res 2021 Aug 11. Epub 2021 Aug 11.

Department of Medicine, Columbia University Irving Medical Center, New York City, NY, USA.

Ambulatory blood pressure (BP) monitoring (ABPM) may cause sleep disturbances. Some home BP monitoring (HBPM) devices obtain a limited number of BP readings during sleep and may be preferred to ABPM. It is unclear how closely a few BP readings approximate a full night of ABPM. We used data from the Jackson Heart (N = 621) and Coronary Artery Risk Development in Young Adults (N = 458) studies to evaluate 74 sampling approaches to estimate BP during sleep. We sampled two to four BP measurements at specific times from a full night of ABPM and computed chance-corrected agreement (i.e., kappa) of nocturnal hypertension (i.e., mean asleep systolic BP ≥ 120 mmHg or diastolic BP ≥ 70 mmHg) defined using the full night of ABPM and subsets of BP readings. Measuring BP at 2, 3, and 4 h after falling asleep, an approach applied by some HBPM devices obtained a kappa of 0.81 (95% confidence interval [CI]: 0.78, 0.85). The highest kappa was obtained by measuring BP at 1, 2, 4, and 5 h after falling asleep: 0.84 (95% CI: 0.81, 0.87). In conclusion, measuring BP three or four times during sleep may have high agreement with nocturnal hypertension status based on a full night of ABPM.
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http://dx.doi.org/10.1038/s41440-021-00717-yDOI Listing
August 2021

Effect of intensive blood pressure lowering on left atrial remodeling in the SPRINT.

Hypertens Res 2021 Aug 6. Epub 2021 Aug 6.

Epidemiological Cardiology Research Center, Department of Epidemiology and Prevention, Division of Public Health Sciences and Department of Medicine, Section on Cardiology, Wake Forest School of Medicine, Winston-Salem, NC, USA.

Upstream therapy of atrial remodeling may decrease atrial fibrillation and associated thromboembolism. We examined the impact of intensive BP lowering on ECG-defined left atrial abnormalities in the SPRINT. SPRINT was a randomized clinical trial comparing outcomes when a systolic BP of <120 mmHg (standard treatment) was the target. We included SPRINT participants without baseline atrial fibrillation who had a technically interpretable baseline ECG and at least one follow-up ECG. The primary outcome was incident left atrial abnormality, defined as P-wave terminal force in V (PTFV) > 4000 μV × ms. Secondary outcomes were regression of the left atrial abnormality and the change in PTFV from baseline across follow-up ECGs. Cox regression was used to examine the associations between treatment assignment and incident left atrial abnormality and its regression. We used linear mixed models to examine the changes in PTFV. Of 9361 SPRINT participants, 7738 qualified for this analysis, of whom 5544 did not have baseline left atrial abnormalities. Intensive BP management was not associated with incident left atrial abnormality (HR, 0.96; 95% CI, 0.87-1.07) or regression of the baseline left atrial abnormality (HR, 1.09; 95% CI, 0.98-1.21). The change in PTFV from baseline through follow-up did not differ significantly between treatment groups (difference in μV × ms per year, 6; 95% CI, -67 to 79). Thus, among patients in a randomized clinical trial, we found no difference in the progression or regression of ECG-defined left atrial abnormalities with intensive BP management compared to standard BP management.
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http://dx.doi.org/10.1038/s41440-021-00713-2DOI Listing
August 2021

Obesity as an isolated contraindication to kidney transplantation in the end-stage renal disease population: A cohort study.

Obesity (Silver Spring) 2021 Sep 2;29(9):1538-1546. Epub 2021 Aug 2.

Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama, USA.

Objective: The aim of this study was to characterize end-stage renal disease (ESRD) patients with obesity as their only contraindication to listing and to quantify wait-list and transplant access.

Methods: Using the US Renal Data System, a retrospective cohort study of incident dialysis cases (2012 to 2014) was performed. The primary outcomes were time to wait-listing and time to transplantation.

Results: Of 157,572 dialysis patients not already listed, 39,844 had BMI as their only demonstrable transplant contraindication. They tended to be younger, female, and Black. Compared with patients with BMI < 35, those with BMI 35 to 39.9, 40 to 44.9, and ≥45 were, respectively, 15% (adjusted hazard ratio [aHR] 0.85; 95% CI: 0.83-0.88; p < 0.001), 45% (aHR 0.55; 95% CI: 0.52-0.57; p < 0.001), and 71% (aHR 0.29; 95% CI: 0.27-0.31; p < 0.001) less likely to be wait-listed. Wait-listed patients with BMI 35 to 39.9 were 24% less likely to achieve transplant (aHR 0.76; 95% CI: 0.72-0.80; p < 0.0001), BMI 40 to 44.9 were 21% less likely (aHR 0.79; 95% CI: 0.72-0.86; p < 0.0001), and BMI ≥ 45 were 15% less likely (aHR 0.85; 95% CI: 0.75-0.95; p = 0.004) compared with patients with BMI < 35.

Conclusions: Obesity was the sole contraindication to wait-listing for 40,000 dialysis patients. They were less likely to be wait-listed. For those who were, they had a lower likelihood of transplant. Aggressive weight-loss interventions may help this population achieve wait-listing and transplant.
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http://dx.doi.org/10.1002/oby.23195DOI Listing
September 2021

Who loses weight in a weight gain prevention program? A comparison of weight losers and weight maintainers at 3 years.

Health Psychol 2021 Jul 29. Epub 2021 Jul 29.

Weight Control and Diabetes Research Center.

Objective: Despite weight loss challenges in young adulthood, 17% of participants in the Study of Novel Approaches to Weight Gain Prevention (SNAP) weight gain prevention study lost ≥ 5% of their body weight at 3 years. These "weight losers" ( = 88) were compared to "weight maintainers" ( = 143), who successfully prevented weight gains by staying within ± 2.5% of their baseline weight at 3 years.

Method: Weight losers and maintainers ( = 231; 18-35 years old) were drawn from the SNAP randomized controlled trial ( = 599), which compared two weight gain prevention interventions with a control group. Participants completed anthropometric and psychosocial assessments at baseline, 4 months (end of face-to-face intervention), and 1, 2, and 3 years.

Results: Three-year weight losers had significantly greater weight losses than maintainers by 4 months, and weight trajectories continued to diverge. Three-year weight change group was not associated with treatment assignment. At pretreatment, weight losers were heavier, closer to their self-reported highest ever weight, and further away from their self-identified ideal weight. Across treatment, weight losers had greater dietary restraint and autonomous motivation, had lower disinhibition and self-identified ideal weight, and self-weighed more frequently than weight maintainers.

Conclusions: Weight gain prevention messaging may be sufficient to initiate weight loss in a subset of young adults who are heavier and closer to their highest weight at baseline. Psychological and behavioral characteristics more consistent with weight loss may explain differences in weight outcomes between losers and maintainers at 3 years. Future studies may consider the effects of weight gain prevention versus weight loss messaging in tailoring weight control interventions for young adults. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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http://dx.doi.org/10.1037/hea0001082DOI Listing
July 2021

Making large changes or small changes to prevent weight gain in young adulthood: which is preferred and by whom?

Transl Behav Med 2021 Jul 22. Epub 2021 Jul 22.

Alpert Medical School of Brown University, Miriam Hospital, Providence, RI 02903, USA.

Knowledge of participant treatment preferences can inform decision-making regarding treatment dissemination and future participant adoption. To compare participant perceptions of two evidence-based approaches for weight gain prevention in young adults to identify the intervention with the greatest likelihood of adoption. As part of a randomized trial (Study of Novel Approaches to Weight Gain Prevention [SNAP]; n = 599) testing weight gain prevention interventions in young adults (18-35 years), individuals assigned to self-regulation interventions using either large changes or small changes reported on perceived personal effectiveness and difficulty of treatment over 3 years. Treatment satisfaction at 2-year follow-up was also reported. Pre-randomization, participants believed the large change intervention would be more personally effective than the small change intervention, although they also considered it more complex. Older age, lower body mass index (p = 0.056), and desire to maintain versus lose weight predicted greater perceived effectiveness of the small change relative to large change intervention. Over follow-up, the large change intervention was no longer perceived as more effective, but perceived effectiveness aligned with assigned treatment. The small change intervention was rated as less complex than the large change intervention at 4 months, but not at other follow-ups. At study conclusion, participants were largely satisfied with both treatments; however, in the small change intervention, individuals who were not successful at preventing weight gain were less satisfied than individuals who were successful. The large and small change interventions are both appropriate for dissemination with no clear advantages based on the participant perceptions.
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http://dx.doi.org/10.1093/tbm/ibab099DOI Listing
July 2021

Lifestyle behaviors among adults recommended for ambulatory blood pressure monitoring according to the 2017 ACC/AHA blood pressure guideline.

Am J Hypertens 2021 Jul 16. Epub 2021 Jul 16.

Department of Medicine, Division of Cardiology, Columbia University Irving Medical Center, New York, New York.

Background: The 2017 American College of Cardiology/American Heart Association blood pressure (BP) guideline recommends ambulatory BP monitoring (ABPM) to exclude white coat hypertension (WCH) among adults with office systolic BP (SBP)/diastolic BP (DBP) of 130-159/80-99 mmHg, and masked hypertension (MHT) among adults with office SBP/DBP of 120-129/75-79 mmHg after a 3-month trial of lifestyle modification. We estimated the proportion of individuals with ideal lifestyle factors among those who meet these office BP criteria for being recommended ABPM.

Methods: We analyzed data from participants not taking antihypertensive medication in the Coronary Artery Risk Development in Young Adults (CARDIA) and Jackson Heart Study (JHS) who met the office BP criteria for screening for WCH (CARDIA n=490, JHS n=873) and MHT (CARDIA n=486, JHS n=614). We estimated the prevalence of lifestyle factors including ideal body mass index (BMI), physical activity, diet and alcohol use among participants who met office BP criteria for WCH screening and for MHT screening.

Results: Among participants who met office BP criteria for WCH screening, 15.5% in CARDIA and 3.6% in JHS had 3 or more ideal lifestyle factors. Among participants who met office BP criteria for MHT screening, 22.6% in CARDIA and 4.7% in JHS had 3 or more ideal lifestyle factors. Ideal BMI, diet, and physical activity was present in less than half of participants in each sample who met office BP criteria for WCH or MHT screening.

Conclusions: Few participants who met office BP criteria for the screening of WCH or MHT had ideal lifestyle factors.
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http://dx.doi.org/10.1093/ajh/hpab110DOI Listing
July 2021

The Coronary Artery Risk Development In Young Adults (CARDIA) Study: JACC Focus Seminar 8/8.

J Am Coll Cardiol 2021 Jul;78(3):260-277

National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA.

The CARDIA (Coronary Artery Risk Development in Young Adults) study began in 1985 to 1986 with enrollment of 5,115 Black or White men and women ages 18 to 30 years from 4 US communities. Over 35 years, CARDIA has contributed fundamentally to our understanding of the contemporary epidemiology and life course of cardiovascular health and disease, as well as pulmonary, renal, neurological, and other manifestations of aging. CARDIA has established associations between the neighborhood environment and the evolution of lifestyle behaviors with biological risk factors, subclinical disease, and early clinical events. CARDIA has also identified the nature and major determinants of Black-White differences in the development of cardiovascular risk. CARDIA will continue to be a unique resource for understanding determinants, mechanisms, and outcomes of cardiovascular health and disease across the life course, leveraging ongoing pan-omics work from genomics to metabolomics that will define mechanistic pathways involved in cardiometabolic aging.
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http://dx.doi.org/10.1016/j.jacc.2021.05.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285563PMC
July 2021

Changes in mood and health-related quality of life in Look AHEAD 6 years after termination of the lifestyle intervention.

Obesity (Silver Spring) 2021 Aug 14;29(8):1294-1308. Epub 2021 Jul 14.

Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.

Objective: The Action for Health in Diabetes (Look AHEAD) study previously reported that intensive lifestyle intervention (ILI) reduced incident depressive symptoms and improved health-related quality of life (HRQOL) over nearly 10 years of intervention compared with a control group (the diabetes support and education group [DSE]) in participants with type 2 diabetes and overweight or obesity. The present study compared incident depressive symptoms and changes in HRQOL in these groups for an additional 6 years following termination of the ILI in September 2012.

Methods: A total of 1,945 ILI participants and 1,900 DSE participants completed at least one of four planned postintervention assessments at which weight, mood (via the Patient Health Questionnaire-9), antidepressant medication use, and HRQOL (via the Medical Outcomes Scale, Short Form-36) were measured.

Results: ILI participants and DSE participants lost 3.1 (0.3) and 3.8 (0.3) kg [represented as mean (SE); p = 0.10], respectively, during the 6-year postintervention follow-up. No significant differences were observed between groups during this time in incident mild or greater symptoms of depression, antidepressant medication use, or in changes on the physical component summary or mental component summary scores of the Short Form-36. In both groups, mental component summary scores were higher than physical component summary scores.

Conclusions: Prior participation in the ILI, compared with the DSE group, did not appear to improve subsequent mood or HRQOL during 6 years of postintervention follow-up.
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http://dx.doi.org/10.1002/oby.23191DOI Listing
August 2021

Associations between menopause, cardiac remodeling, and diastolic function: the CARDIA study.

Menopause 2021 Jun 14. Epub 2021 Jun 14.

Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, GA Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, MN Department of Epidemiology, University of Alabama at Birmingham School of Public Health, Birmingham, AL National Heart, Lung, and Blood Institute, Bethesda, MD Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL Kaiser Permanente, Oakland, CA.

Objectives: Heart failure with preserved ejection fraction (HFpEF) affects more women than men. Menopause may influence HFpEF development in women. We assessed cross-sectional and longitudinal associations between menopause and echocardiographic measures of left ventricular (LV) function and cardiac remodeling.

Methods: We studied 1,723 women with available echo data from at least two of: year 5 (Y5) (1990-1991), Y25 (2010-2011), or Y30 (2015-2016) in the Coronary Artery Risk Development in Young Adults study. Cardiac structure and function were measured using 2D and Doppler echocardiography. Cross-sectional associations between menopausal status and repeated echo measures at Y25 and Y30 were analyzed using linear mixed models. Two-segmented models were used to compare longitudinal changes in echocardiographic measures in the premenopausal period to changes in the postmenopausal period.

Results: Mean ± SD age (years) at enrollment was 27 ± 3 in those with menopause by Y25, 25 ± 3 in those with menopause between Y25 and Y30, and 21 ± 3 in those premenopausal at Y30. There were no significant differences in race, body mass index, systolic blood pressure, or diabetes between the groups. Postmenopausal women had higher early diastolic mitral inflow (E) to annular (e') velocity ratio than premenopausal after adjusting for demographics and risk factors (P < 0.05). Menopause was associated with relative increases in the rates of change in LV mass and left atrial volume, even after adjustment. Change in E/e' ratio was similar before and after menopause.

Conclusions: Menopause is associated cross-sectionally with worse diastolic function and longitudinally with adverse LV and left atrial remodeling. This may contribute to the increased HFpEF risk in postmenopausal women.

Video Summary:http://links.lww.com/MENO/A787.
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http://dx.doi.org/10.1097/GME.0000000000001815DOI Listing
June 2021

Characterizing the Spectrum of Bladder Health and Lower Urinary Tract Symptoms (LUTS) Among Women: Results From the CARDIA Study.

Urology 2021 Jun 2. Epub 2021 Jun 2.

School of Public Health, Birmingham, AL.

Objectives: To operationalize a new definition for bladder health, we examined the distribution of lower urinary tract symptoms (LUTS) and impact, along with associated factors, among women in the Coronary Artery Risk Development in Young Adults (CARDIA) study.

Methods: We performed cluster analyses using validated LUTS symptom burden and impact scales collected between 2005-2006 and 2010-2011. We performed multinomial logistic regression analyses to evaluate cardiovascular factors (metabolic syndrome, cardiovascular health behaviors, and inflammation) between clusters after adjusting for covariates (demographic, obstetric/gynecologic, co-morbidities).

Results: Among CARDIA women (median age 51, range 42-59) with complete LUTS data (n = 1302), we identified and compared 4 cluster groups: women who reported no or very mild symptoms and no impact on well-being (bladder health, 44%, n = 569), versus women with LUTS and negative impact on well-being ranging from mild (31%, n = 407), moderate (20%, n = 259), to severe (5%, n = 67). With each 1-point lower BMI (kg/m), odds of membership in mild (OR 0.97, CI 0.95-0.99), moderate (OR 0.95, CI 0.93-0.98), and severe (OR 0.90, CI 0.88-0.94) LUTS cluster groups versus the bladder health group were lower. Compared to women with metabolic syndrome, women without metabolic syndrome had lower odds of membership in mild (OR 0.67, CI 0.45-0.99), moderate (OR 0.51, CI 0.33-0.79), and severe (OR 0.48, CI 0.24-0.94) LUTS cluster groups versus the bladder health group.

Conclusion: Two out of 5 midlife women met our definition of bladder health. Bladder health and cardiovascular health among women may share common factors, including lower BMI and the absence of metabolic syndrome.
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http://dx.doi.org/10.1016/j.urology.2021.05.032DOI Listing
June 2021

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

Prev Med 2021 09 19;150:106626. Epub 2021 May 19.

Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, MN, United States of America.

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.
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http://dx.doi.org/10.1016/j.ypmed.2021.106626DOI Listing
September 2021

Final Report of a Trial of Intensive versus Standard Blood-Pressure Control.

N Engl J Med 2021 05;384(20):1921-1930

The affiliations of the members of the writing committee are as follows: the Department of Epidemiology, School of Public Health (C.E.L.), and the Divisions of Preventive Medicine (C.E.L.) and Cardiovascular Disease (S.O.), Department of Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham; the Clinical Applications and Prevention Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (L.J.F., J.A.C., J.K.S.); the Division of Nephrology and Hypertension, University of Utah, and Medical Service, Veterans Affairs Salt Lake City Health Care System, Salt Lake City (S.B., A.K.C.); the Department of Preventive Medicine, University of Tennessee Health Science Center (W.C.C., K.C.J.), and Medical Service, Veterans Affairs Medical Center (W.C.C.), Memphis; the Department of Biostatistics and Data Science (G.W.E., D.M.R., W.T.A.), the Division of Cardiovascular Medicine (D.W.K.) and Section of Nephrology (M.V.R.), Department of Internal Medicine, and the Sticht Center for Healthy Aging and Alzheimer's Prevention and Division of Geriatric Medicine (K.M.S., J.D.W.), Wake Forest School of Medicine, Winston Salem, NC; the Division of Nephrology and Hypertension, Louis Stokes Cleveland Veterans Affairs Medical Center (M.R.), and the Division of Nephrology and Hypertension, University Hospitals Cleveland Medical Center, Case Western Reserve University (M.R., J.T.W.), Cleveland; and the Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans (P.K.W.).

Background: In a previously reported randomized trial of standard and intensive systolic blood-pressure control, data on some outcome events had yet to be adjudicated and post-trial follow-up data had not yet been collected.

Methods: We randomly assigned 9361 participants who were at increased risk for cardiovascular disease but did not have diabetes or previous stroke to adhere to an intensive treatment target (systolic blood pressure, <120 mm Hg) or a standard treatment target (systolic blood pressure, <140 mm Hg). The primary outcome was a composite of myocardial infarction, other acute coronary syndromes, stroke, acute decompensated heart failure, or death from cardiovascular causes. Additional primary outcome events occurring through the end of the intervention period (August 20, 2015) were adjudicated after data lock for the primary analysis. We also analyzed post-trial observational follow-up data through July 29, 2016.

Results: At a median of 3.33 years of follow-up, the rate of the primary outcome and all-cause mortality during the trial were significantly lower in the intensive-treatment group than in the standard-treatment group (rate of the primary outcome, 1.77% per year vs. 2.40% per year; hazard ratio, 0.73; 95% confidence interval [CI], 0.63 to 0.86; all-cause mortality, 1.06% per year vs. 1.41% per year; hazard ratio, 0.75; 95% CI, 0.61 to 0.92). Serious adverse events of hypotension, electrolyte abnormalities, acute kidney injury or failure, and syncope were significantly more frequent in the intensive-treatment group. When trial and post-trial follow-up data were combined (3.88 years in total), similar patterns were found for treatment benefit and adverse events; however, rates of heart failure no longer differed between the groups.

Conclusions: Among patients who were at increased cardiovascular risk, targeting a systolic blood pressure of less than 120 mm Hg resulted in lower rates of major adverse cardiovascular events and lower all-cause mortality than targeting a systolic blood pressure of less than 140 mm Hg, both during receipt of the randomly assigned therapy and after the trial. Rates of some adverse events were higher in the intensive-treatment group. (Funded by the National Institutes of Health; SPRINT ClinicalTrials.gov number, NCT01206062.).
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http://dx.doi.org/10.1056/NEJMoa1901281DOI Listing
May 2021

Bidirectional associations of accelerometer measured sedentary behavior and physical activity with knee pain, stiffness, and physical function: The CARDIA study.

Prev Med Rep 2021 Jun 9;22:101348. Epub 2021 Mar 9.

Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA.

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.
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http://dx.doi.org/10.1016/j.pmedr.2021.101348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005813PMC
June 2021

Blood Pressure Levels in Young Adulthood and Midlife Stroke Incidence in a Diverse Cohort.

Hypertension 2021 May 29;77(5):1683-1693. Epub 2021 Mar 29.

Division of Research, Kaiser Permanente Northern California, Oakland (Y.G., J.S.R., M.N.N.-H., S.S.).

[Figure: see text].
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.16535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035276PMC
May 2021

Can MRI-defined osteoarthritis features explain anterior knee pain in individuals with, or at risk for, knee osteoarthritis? The MOST Study.

Arthritis Care Res (Hoboken) 2021 Mar 25. Epub 2021 Mar 25.

University of Delaware, (Department of Physical Therapy), Newark, USA.

Objective: The lack of strong association between knee osteoarthritis (OA) structural features and pain continues to perplex researchers and clinicians. Evaluating the patellofemoral joint in addition to the tibiofemoral joint alone has contributed to explaining this structure-pain discordance, hence justifying a more comprehensive evaluation of whole-knee OA and pain. We therefore evaluated the association between patellofemoral and tibiofemoral OA features with localized anterior knee pain (AKP) using two study designs.

Methods: Using cross-sectional data from the Multicenter Osteoarthritis Study, our first approach was a within-person, knee-matched design in which we identified participants with unilateral AKP. We then assessed MRI-derived OA features (cartilage damage, bone marrow lesions [BMLs], osteophytes, and inflammation) in both knees, and evaluated the association of patellofemoral and tibiofemoral OA features to unilateral AKP. In our second approach, MRIs from one knee per person were scored, and we evaluated the association of OA-features to AKP in participants with AKP and participants with no frequent knee pain.

Results: Using the first approach (n=71, 66% women, mean age 69 [SD 8] years), lateral patellofemoral osteophytes (odds ratio 5.0 [95% CI 1.7, 14.6]), whole-knee joint effusion-synovitis (4.7 [1.3, 16.2]), and infrapatellar synovitis (2.8 [1.0, 7.8]) were associated with AKP. Using the second approach (n=882, 59% women, mean age 69 [SD 7] years), lateral and medial patellofemoral cartilage damage (prevalence ratio 2.3 [1.3, 4.0] and 1.9 [1.1, 3.3]), and lateral patellofemoral BMLs (2.6 [1.5, 4.7]) were associated with AKP.

Conclusion: Patellofemoral but not tibiofemoral joint OA features, and inflammation were associated with AKP.
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http://dx.doi.org/10.1002/acr.24604DOI Listing
March 2021

Collaborative Cohort of Cohorts for COVID-19 Research (C4R) Study: Study Design.

medRxiv 2021 Mar 20. Epub 2021 Mar 20.

The Collaborative Cohort of Cohorts for COVID-19 Research (C4R) is a national prospective study of adults at risk for coronavirus disease 2019 (COVID-19) comprising 14 established United States (US) prospective cohort studies. For decades, C4R cohorts have collected extensive data on clinical and subclinical diseases and their risk factors, including behavior, cognition, biomarkers, and social determinants of health. C4R will link this pre-COVID phenotyping to information on SARS-CoV-2 infection and acute and post-acute COVID-related illness. C4R is largely population-based, has an age range of 18-108 years, and broadly reflects the racial, ethnic, socioeconomic, and geographic diversity of the US. C4R is ascertaining severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 illness using standardized questionnaires, ascertainment of COVID-related hospitalizations and deaths, and a SARS-CoV-2 serosurvey via dried blood spots. Master protocols leverage existing robust retention rates for telephone and in-person examinations, and high-quality events surveillance. Extensive pre-pandemic data minimize referral, survival, and recall bias. Data are being harmonized with research-quality phenotyping unmatched by clinical and survey-based studies; these will be pooled and shared widely to expedite collaboration and scientific findings. This unique resource will allow evaluation of risk and resilience factors for COVID-19 severity and outcomes, including post-acute sequelae, and assessment of the social and behavioral impact of the pandemic on long-term trajectories of health and aging.
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http://dx.doi.org/10.1101/2021.03.19.21253986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987050PMC
March 2021

Reply by Authors.

J Urol 2021 05 17;205(5):1414. Epub 2021 Mar 17.

Division of Biostatistics, University of Minnesota, Minneapolis, Minnesota.

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http://dx.doi.org/10.1097/JU.0000000000001581.02DOI Listing
May 2021

Executive function in individuals with clinically significant weight loss via behavioral intervention.

Obes Sci Pract 2021 Feb 16;7(1):25-34. Epub 2020 Oct 16.

University of Alabama at Birmingham Birmingham Alabama USA.

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 ( = 44). "Maintainers" ( = 16) maintained this minimum level of weight loss for ≥1 year. "Regainers" ( = 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 ( = 0.003, η = 0.19). There were no differences between maintainers and regainers in inhibitory control, verbal fluency, planning/organization, cognitive flexibility, or working memory (s > 0.05, ηs = 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.
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http://dx.doi.org/10.1002/osp4.458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909588PMC
February 2021

Long-Term Levels of LDL-C and Cognitive Function: The CARDIA Study.

J Int Neuropsychol Soc 2021 Feb 10:1-10. Epub 2021 Feb 10.

University of Alabama at Birmingham, Birmingham, AL, USA.

Objectives: It is uncertain if long-term levels of low-density lipoprotein-cholesterol (LDL-C) affect cognition in middle age. We examined the association of LDL-C levels over 25 years with cognitive function in a prospective cohort of black and white US adults.

Methods: Lipids were measured at baseline (1985-1986; age: 18-30 years) and at serial examinations conducted over 25 years. Time-averaged cumulative LDL-C was calculated using the area under the curve for 3,328 participants with ≥3 LDL-C measurements and a cognitive function assessment. Cognitive function was assessed at the Year 25 examination with the Digit Symbol Substitution Test [DSST], Rey Auditory Visual Learning Test [RAVLT], and Stroop Test. A brain magnetic resonance imaging (MRI) sub-study (N = 707) was also completed at Year 25 to assess abnormal white matter tissue volume (AWMV) and gray matter cerebral blood flow volume (GM-CBFV) as secondary outcomes.

Results: There were 15.6%, 32.9%, 28.9%, and 22.6% participants with time-averaged cumulative LDL-C <100 mg/dL, 101-129 mg/dL, 130-159 mg/dL, and ≥160 mg/dL, respectively. Standardized differences in all cognitive function test scores ranged from 0.16 SD lower to 0.09 SD higher across time-averaged LDL-C categories in comparison to those with LDL-C < 100 mg/dL. After covariate adjustment, participants with higher versus lower time-averaged LDL-C had a lower RAVLT score (p-trend = 0.02) but no differences were present for DSST, Stroop Test, AWMV, or GM-CBFV.

Conclusion: Cumulative LDL-C was associated with small differences in memory, as assessed by RAVLT scores, but not other cognitive or brain MRI measures over 25 years of follow-up.
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http://dx.doi.org/10.1017/S1355617721000059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353005PMC
February 2021

Factors Associated with Weight Loss Maintenance and Weight Regain Among African American and White Adults Initially Successful at Weight Loss.

J Racial Ethn Health Disparities 2021 Feb 5. Epub 2021 Feb 5.

Division of Preventive Medicine, Department of Medicine, University of Alabama at Birmingham, 1717 11th Avenue South, Medical Towers 615, Birmingham, AL, 35205, USA.

Background: Providing ongoing treatment through extended care programs can improve weight loss maintenance (WLM), but the effectiveness of these programs for African Americans (AA) are mixed and may be due to unique cultural factors.

Purpose: To identify, prioritize, and organize factors associated with WLM as experienced by AA and White adults initially successful with weight loss.

Methods: Adults identified their greatest amount of lifetime weight loss, and those achieving ≥5% weight loss were classified as maintainers (continued >5% weight reduction for ≥1 year) or regainers (≤5% weight reduction) based on current weight. The nominal group technique was conducted to identify and rank WLM facilitators and barriers. Online card sorting tasks and hierarchical clustering were performed to illustrate conceptual relationships between facilitators (maintainers only) and barriers (regainers only).

Results: Participants (maintainers, n = 46; regainers, n = 58; 81.7% women, 48.1% AA) identified known factors associated with successful weight management (daily weighing, self-monitoring, regular physical activity, mindful eating). However, the perceived importance of these factors differed between groups (maintainer vs. regainers; AA vs. Whites). Unique factors affecting WLM were also identified (refresher groups recommended by White maintainers and regainers; self-accountability identified by AA maintainers). Salient facilitators and barriers were best represented in 2-3 clusters; each group had ≥1 unique cluster(s) revealing group-specific higher-order domains associated with successful WLM.

Conclusions: As lifestyle interventions for WLM (particularly for AA) are developed, attention to the preferences, and lived experiences of these groups is recommended. Strategies targeting physical activity maintenance and autonomy-supportive approaches may improve WLM among AA.
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http://dx.doi.org/10.1007/s40615-021-00985-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339173PMC
February 2021

The Association of Lactation Duration with Visceral and Pericardial Fat Volumes in Parous Women: The CARDIA Study.

J Clin Endocrinol Metab 2021 05;106(6):1821-1831

Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.

Background: Lactation is associated with lower risks for cardiovascular disease in women. Organ-related adiposity, which plays significant roles in the development of cardiometabolic diseases, could help explain this observation. We evaluated the association of lactation duration with visceral (VAT) and pericardial (PAT) fat volumes in women.

Methods: Data were obtained from 910 women enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study (1985-1986) without diabetes prior to pregnancy who had ≥1 birth during 25 years of follow-up and had VAT and PAT measured from computed tomographic scans in 2010-2011. Cumulative lactation duration across all births since baseline was calculated from self-reports collected at periodic exams.

Results: At baseline, the average age of women (48% black, 52% white) was 24 ± 3.7 years. After controlling for baseline age, race, smoking status, body mass index, fasting glucose, family history of diabetes, fat intake, total cholesterol, physical activity, and follow-up covariates (parity, gestational diabetes), the mean fat volumes across categories of lactation [none (n = 221), 1-5 months (n = 306), 6-11 months (n = 210), and ≥12 months (n = 173)] were 122.0, 113.7 105.0, and 110.1 cm3 for VAT and 52.2, 46.7, 44.5, and 43.4 cm3 for PAT, respectively. Changes in body weight from the first post-baseline birth to the end of follow-up mediated 21% and 18% of the associations of lactation with VAT and PAT, respectively.

Conclusions: In this prospective study, longer cumulative lactation duration was associated with lower VAT and PAT volumes, with weight gain partially mediating these associations.
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http://dx.doi.org/10.1210/clinem/dgaa980DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8118361PMC
May 2021

Gestational Diabetes History and Glucose Tolerance After Pregnancy Associated With Coronary Artery Calcium in Women During Midlife: The CARDIA Study.

Circulation 2021 Mar 1;143(10):974-987. Epub 2021 Feb 1.

Vanderbilt University, Memphis, TN (M.W., J.J.C.).

Background: Gestational diabetes (GD) leads to earlier onset and heightened risk of type 2 diabetes, a strong risk factor for cardiovascular disease (CVD). However, it is unclear whether attaining normoglycemia can ameliorate the excess CVD risk associated with GD history. This study sought to evaluate GD history and glucose tolerance after pregnancy associated with coronary artery calcification (CAC) in women, a manifestation of atherosclerotic CVD and a predictor of CVD clinical events.

Methods: Data were obtained from the CARDIA study (Coronary Artery Risk Development in Young Adults), a US multicenter, community-based prospective cohort of young Black (50%) and White adults aged 18 to 30 years at baseline (1985-1986). The sample included 1133 women without diabetes at baseline, who had ≥1 singleton births (n=2066) during follow-up, glucose tolerance testing at baseline and up to 5 times during 25 years (1986-2011), GD status, and CAC measurements obtained from 1 or more follow up examinations at years 15, 20, and 25 (2001-2011). CAC was measured by noncontrast cardiac computed tomography; dichotomized as Any CAC (score>0) or No CAC (score=0). Complementary log-log models for interval-censored data estimated adjusted hazard ratios of CAC and 95% confidence intervals for GD history and subsequent glucose tolerance groups (normoglycemia, prediabetes, or incident diabetes) on average 14.7 years after the last birth adjusted for prepregnancy and follow-up covariates.

Results: Of 1133 women, 139 (12.3%) reported GD and were 47.6 years of age (4.8 SD) at follow-up. CAC was present in 25% (34/139) of women with GD and 15% (149/994) of women with no GD. In comparison with no GD/normoglycemia, adjusted hazard ratios (95% CIs) were 1.54 (1.06-2.24) for no GD/prediabetes and 2.17 (1.30-3.62) for no GD/incident diabetes, and 2.34 (1.34-4.09), 2.13 (1.09-4.17), and 2.02 (0.98-4.19) for GD/normoglycemia, GD/prediabetes, and GD/incident diabetes, respectively (overall =0.003).

Conclusions: Women without previous GD showed a graded increase in the risk of CAC associated with worsening glucose tolerance. Women with a history of GD had a 2-fold higher risk of CAC across all subsequent levels of glucose tolerance. Midlife atherosclerotic CVD risk among women with previous GD is not diminished by attaining normoglycemia.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.047320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940578PMC
March 2021

Donor-specific phenotypic variation in hiPSC cardiomyocyte-derived exosomes impacts endothelial cell function.

Am J Physiol Heart Circ Physiol 2021 03 8;320(3):H954-H968. Epub 2021 Jan 8.

Section of Genomic Pediatrics, Department of Pediatrics, Medicine and Physiology, Children's Research Institute and Genomic Sciences and Precision Medicine Center, Medical College of Wisconsin, Milwaukee, Wisconsin.

Exosomes are an important mechanism of cell-cell interaction in the cardiovascular system, both in maintaining homeostasis and in stress response. Interindividual differences that alter content in exosomes may play a role in cardiovascular disease pathology. To study the effect of interindividual cardiomyocyte (CM) variation, we characterized exosomal content in phenotypically diverse human induced pluripotent stem cell-derived CMs (hiPSC-CMs). Cell lines were generated from six participants in the HyperGEN cohort: three with left ventricular hypertrophy (LVH) and three with normal left ventricular mass (LVM). Sequence analysis of the intracellular and exosomal RNA populations showed distinct expression pattern differences between hiPSC-CM lines derived from individuals with LVH and those with normal LVM. Functional analysis of hiPSC-endothelial cells (hiPSC-ECs) treated with exosomes from both hiPSC-CM groups showed significant variation in response, including differences in tube formation, migration, and proliferation. Overall, treatment of hiPSC-ECs with exosomes resulted in significant expression changes associated with angiogenesis and endothelial cell vasculogenesis. However, the hiPSC-ECs treated with exosomes from the LVH-affected donors exhibited significantly increased proliferation but decreased tube formation and migration, suggesting angiogenic dysregulation. The intracellular RNA and the miRNA content in exosomes are significantly different in hiPSC-CMs derived from LVH-affected individuals compared with those from unaffected individuals. Treatment of endothelial cells with these exosomes functionally affects cellular phenotypes in a donor-specific manner. These findings provide novel insight into underlying mechanisms of hypertrophic cell signaling between different cell types. With a growing interest in stem cells and exosomes for cardiovascular therapeutic use, this also provides information important for regenerative medicine.
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http://dx.doi.org/10.1152/ajpheart.00463.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8294700PMC
March 2021

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

BMC Public Health 2021 01 6;21(1):35. Epub 2021 Jan 6.

Division of Nutritional Sciences, Cornell University, Savage Hall, Ithaca, NY, 14853, USA.

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.
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http://dx.doi.org/10.1186/s12889-020-10028-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789704PMC
January 2021

Measuring Bladder Health: Development and Cognitive Evaluation of Items for a Novel Bladder Health Instrument.

J Urol 2021 05 22;205(5):1407-1414. Epub 2020 Dec 22.

Division of Biostatistics, University of Minnesota, Minneapolis, Minnesota.

Purpose: We describe the item development and cognitive evaluation process used in creating the Prevention of Lower Urinary Tract Symptoms Bladder Health Instrument (PLUS-BHI).

Materials And Methods: Questions assessing bladder health were developed using reviews of published items, expert opinion, and focus groups' transcript review. Candidate items were tested through cognitive interviews with community-dwelling women and an online panel survey. Items were assessed for comprehension, language, and response categories and modified iteratively to create the PLUS-BHI.

Results: Existing measures of bladder function (storage, emptying, sensation components) and bladder health impact required modification of time frame and response categories to capture a full range of bladder health. Of the women 167 (18-80 years old) completed individual interviews and 791 women (18-88 years) completed the online panel survey. The term "bladder health" was unfamiliar for most and was conceptualized primarily as absence of severe urinary symptoms, infection, or cancer. Coping mechanisms and self-management strategies were central to bladder health perceptions. The inclusion of prompts and response categories that captured infrequent symptoms increased endorsement of symptoms across bladder function components.

Conclusions: Bladder health measurement is challenged by a lack of awareness of normal function, use of self-management strategies to mitigate impact on activities, and a common tendency to overlook infrequent lower urinary tract symptoms. The PLUS-BHI is designed to characterize the full spectrum of bladder health in women and will be validated for research use.
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http://dx.doi.org/10.1097/JU.0000000000001581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068674PMC
May 2021

Cerebral small vessel disease genomics and its implications across the lifespan.

Nat Commun 2020 12 8;11(1):6285. Epub 2020 Dec 8.

University of Alabama at Birmingham School of Medicine, Birmingham, AL, 35233, USA.

White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.
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http://dx.doi.org/10.1038/s41467-020-19111-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722866PMC
December 2020
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