Dataset Information

Characterization of vascular disease risk in postmenopausal women and its association with cognitive performance.

ABSTRACT:

Objectives

While global measures of cardiovascular (CV) risk are used to guide prevention and treatment decisions, these estimates fail to account for the considerable interindividual variability in pre-clinical risk status. This study investigated heterogeneity in CV risk factor profiles and its association with demographic, genetic, and cognitive variables.

Methods

A latent profile analysis was applied to data from 727 recently postmenopausal women enrolled in the Kronos Early Estrogen Prevention Study (KEEPS). Women were cognitively healthy, within three years of their last menstrual period, and free of current or past CV disease. Education level, apolipoprotein E ?4 allele (APOE4), ethnicity, and age were modeled as predictors of latent class membership. The association between class membership, characterizing CV risk profiles, and performance on five cognitive factors was examined. A supervised random forest algorithm with a 10-fold cross-validation estimator was used to test accuracy of CV risk classification.

Results

The best-fitting model generated two distinct phenotypic classes of CV risk 62% of women were "low-risk" and 38% "high-risk". Women classified as low-risk outperformed high-risk women on language and mental flexibility tasks (p?=?0.008) and a global measure of cognition (p?=?0.029). Women with a college degree or above were more likely to be in the low-risk class (OR?=?1.595, p?=?0.044). Older age and a Hispanic ethnicity increased the probability of being at high-risk (OR?=?1.140, p?=?0.002; OR?=?2.622, p?=?0.012; respectively). The prevalence rate of APOE-?4 was higher in the high-risk class compared with rates in the low-risk class.

Conclusion

Among recently menopausal women, significant heterogeneity in CV risk is associated with education level, age, ethnicity, and genetic indicators. The model-based latent classes were also associated with cognitive function. These differences may point to phenotypes for CV disease risk. Evaluating the evolution of phenotypes could in turn clarify preclinical disease, and screening and preventive strategies. ClinicalTrials.gov NCT00154180.

SUBMITTER: Dowling NM

PROVIDER: S-EPMC3714288 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Characterization of vascular disease risk in postmenopausal women and its association with cognitive performance.

Dowling N Maritza NM Gleason Carey E CE Manson Joann E JE Hodis Howard N HN Miller Virginia M VM Brinton Eliot A EA Neal-Perry Genevieve G Santoro M Nanette MN Cedars Marcelle M Lobo Rogerio R Merriam George R GR Wharton Whitney W Naftolin Frederick F Taylor Hugh H Harman S Mitchell SM Asthana Sanjay S

PloS one 20130717 7

<h4>Objectives</h4>While global measures of cardiovascular (CV) risk are used to guide prevention and treatment decisions, these estimates fail to account for the considerable interindividual variability in pre-clinical risk status. This study investigated heterogeneity in CV risk factor profiles and its association with demographic, genetic, and cognitive variables.<h4>Methods</h4>A latent profile analysis was applied to data from 727 recently postmenopausal women enrolled in the Kronos Early E ...[more]

PMID: 23874743

Similar Datasets

Project description:ImportanceAtherosclerotic cardiovascular disease (ASCVD) may have unique risk factors in women. Most women have a history of pregnancy; common adverse pregnancy outcomes (APOs) appear to be associated with ASCVD, but prior studies have limitations.ObjectiveTo assess whether APOs are associated with increased ASCVD risk independently of traditional risk factors.Design, setting, and participantsThe APO history among participants in the Women's Health Initiative, a large multiethnic cohort of postmenopausal women, was assessed. The associations of 5 self-reported APOs (gestational diabetes, hypertensive disorders of pregnancy, low birth weight [ie, birth weight less than 2.49 kg], high birth weight [ie, birth weight greater than 4.08 kg], and preterm delivery by 3 weeks or more) with ASCVD were analyzed, adjusting for traditional ASCVD risk factors. Data were collected and analyzed in 2017.ExposuresAPOs (gestational diabetes, hypertensive disorders of pregnancy, low birth weight, high birth weight, and preterm delivery).Main outcomes and measuresAdjudicated ASCVD.ResultsA total of 48 113 Women's Health Initiative participants responded to the survey; the median (interquartile range) age at time of enrollment was 60.0 (55.0-64.0) years. A total of 13 482 participants (28.8%) reported 1 or more APOs. Atherosclerotic cardiovascular disease was more frequent in women who reported an APO compared with those without APOs (1028 of 13 482 [7.6%] vs 1758 of 30 522 [5.8%]). Each APO, analyzed separately, was significantly associated with ASCVD, and gestational diabetes, hypertensive disorders of pregnancy, low birth weight, and preterm delivery remained significant after adjustment for traditional ASCVD risk factors. When all APOs were analyzed together, hypertensive disorders of pregnancy (odds ratio, 1.27; 95% CI, 1.15-1.40) and low birth weight (odds ratio, 1.12; 95% CI, 1.00-1.26) remained independently associated with ASCVD. All findings were materially unchanged by additional adjustment for parity, body mass index, and socioeconomic factors.Conclusions and relevanceIn this large multiethnic cohort of women, hypertensive disorders of pregnancy and low birth weight were independently associated with ASCVD after adjustment for risk factors and other APOs.

Project description:Importance:Physical activity is inversely associated with hip fracture risk in older women. However, the association of physical activity with fracture at other sites and the role of sedentary behavior remain unclear. Objective:To assess the associations of physical activity and sedentary behavior with fracture incidence among postmenopausal women. Design, Setting, and Participants:The Women's Health Initiative prospective cohort study enrolled 77 206 postmenopausal women aged 50 to 79 years between October 1993 and December 1998 at 40 US clinical centers. Participants were observed for outcomes through September 2015, with data analysis conducted from June 2017 to August 2019. Exposures:Self-reported physical activity and sedentary time. Main Outcomes and Measures:Hazard ratios (HRs) and 95% CIs for total and site-specific fracture incidence. Results:During a mean (SD) follow-up period of 14.0 (5.2) years among 77 206 women (mean [SD] age, 63.4 [7.3] years; 66 072 [85.6%] white), 25 516 (33.1%) reported a first incident fracture. Total physical activity was inversely associated with the multivariable-adjusted risk of hip fracture (>17.7 metabolic equivalent [MET] h/wk vs none: HR, 0.82; 95% CI, 0.72-0.95; P for trend < .001). Inverse associations with hip fracture were also observed for walking (>7.5 MET h/wk vs none: HR, 0.88; 95% CI, 0.78-0.98; P for trend = .01), mild activity (HR, 0.82; 95% CI, 0.73-0.93; P for trend = .003), moderate to vigorous activity (HR, 0.88; 95% CI, 0.81-0.96; P for trend = .002), and yard work (HR, 0.90; 95% CI, 0.82-0.99; P for trend = .04). Total activity was positively associated with knee fracture (>17.7 MET h/wk vs none: HR, 1.26; 95% CI, 1.05-1.50; P for trend = .08). Mild activity was associated with lower risks of clinical vertebral fracture (HR, 0.87; 95% CI, 0.78-0.96; P for trend = .006) and total fractures (HR, 0.91; 95% CI, 0.87-0.94; P for trend < .001). Moderate to vigorous activity was positively associated with wrist or forearm fracture (HR, 1.09; 95% CI, 1.03-1.15; P for trend = .004). After controlling for covariates and total physical activity, sedentary time was positively associated with total fracture risk (>9.5 h/d vs <6.5 h/d: HR, 1.04; 95% CI, 1.01-1.07; P for trend = .01). When analyzed jointly, higher total activity mitigated some of the total fracture risk associated with sedentary behavior. Analysis of time-varying exposures resulted in somewhat stronger associations for total physical activity, whereas those for sedentary time were materially unchanged. Conclusions and Relevance:In older ambulatory women, higher total physical activity was associated with lower total and hip fracture risk but higher knee fracture risk. Mild activity and walking were associated with lower hip fracture risk, a finding with important public health implications because these activities are common in older adults. The positive association between sedentary time and total fracture risk requires further investigation.

Project description:ImportanceThe role of endogenous progesterone in the development of breast cancer remains largely unexplored to date, primarily owing to assay sensitivity limitations and low progesterone concentrations in postmenopausal women. Recently identified progesterone metabolites may provide insights as experimental data suggest that 5α-dihydroprogesterone (5αP) concentrations reflect cancer-promoting properties and 3α-dihydroprogesterone (3αHP) concentrations reflect cancer-inhibiting properties.ObjectiveTo evaluate the association between circulating progesterone and progesterone metabolite levels and breast cancer risk.Design, setting, and participantsUsing a sensitive liquid chromatography-tandem mass spectrometry assay, prediagnostic serum levels of progesterone and progesterone metabolites were quantified in a case-cohort study nested within the Breast and Bone Follow-up to the Fracture Intervention Trial (n = 15 595). Participation was limited to women not receiving exogenous hormone therapy at the time of blood sampling (1992-1993). Incident breast cancer cases (n = 405) were diagnosed during 12 follow-up years and a subcohort of 495 postmenopausal women were randomly selected within 10-year age and clinical center strata. Progesterone assays were completed in July 2017; subsequent data analyses were conducted between July 15, 2017, and December 20, 2018.ExposuresCirculating concentrations of pregnenolone, progesterone, and their major metabolites.Main outcomes and measuresDevelopment of breast cancer, with hazard ratios (HRs) and 95% CIs was estimated using Cox proportional hazards regression adjusted for key confounders, including estradiol. Evaluation of hormone ratios and effect modification were planned a priori.ResultsThe present study included 405 incident breast cancer cases and a subcohort of 495 postmenopausal women; the mean (SD) age at the time of the blood draw was 67.2 (6.2) years. Progesterone concentrations were a mean (SD) of 4.6 (1.7) ng/dL. Women with higher circulating progesterone levels were at an increased risk for breast cancer per SD increase in progesterone levels (HR, 1.16; 95% CI, 1.00-1.35; P = .048). The association with progesterone was linear in a 5-knot spline and stronger for invasive breast cancers (n = 267) (HR, 1.24; 95% CI, 1.07-1.43; P = .004). Among women in the lowest quintile (Q1) of circulating estradiol (<6.30 pg/mL) elevated progesterone concentrations were associated with reduced breast cancer risk per SD increase in progesterone levels (HR, 0.38; 95% CI, 0.15-0.95; P = .04) and increased risk among women in higher quintiles of estradiol (Q2-Q5; ≥6.30 pg/mL) (HR, 1.18; 95% CI, 1.04-1.35; P = .01; P = .04 for interaction).Conclusions and relevanceIn this case-cohort study of postmenopausal women, elevated circulating progesterone levels were associated with a 16% increase in the risk of breast cancer. Additional research should be undertaken to assess how postmenopausal breast cancer risk is associated with both endogenous progesterone and progesterone metabolites and their interactions with estradiol.

Project description:IntroductionWomen are at a higher risk of developing Alzheimer's disease (AD), and the decline in estrogens post-menopause is thought of as a factor increasing this risk. Estradiol (E2) is important in supporting cholinergic neuronal integrity, and cholinergic functioning may be negatively impacted following the loss of E2 post-menopause. The use of exogenous E2 has been observed to enhance cholinergically mediated cognitive performance in healthy post-menopausal women, which indicates a potentially protective mechanism. However, E2 is often co-administered with progestin or progesterone to prevent endometrial proliferation. Progesterone/progestins have previously been shown to have a detrimental effect on E2-mediated biological and cognitive effects mediated by cholinergic systems in preclinical models, therefore the present study aimed to assess whether progesterone would modify the effect of E2 to influence cognition during cholinergic blockade.MethodsTwenty participants completed 3-months of oral E2 treatment with micronized progesterone (mPRO) or with placebo (PLC) in a repeated-measures within-subjects crossover design, in which they also completed five anticholinergic challenge days per hormone treatment condition. During the challenge participants were administered low or high doses of the nicotinic cholinergic antagonist mecamylamine, the muscarinic cholinergic antagonist scopolamine, or placebo. Following drug administration participants performed cognitive tests sensitive to cholinergic tone, assessing attention, episodic memory, and working memory.ResultsSignificant decrements were found on some tasks when participants were taking E2+mPRO compared to E2 alone. Specifically, under more challenging task conditions and larger anticholinergic doses, participants showed poorer performance on the Critical Flicker Fusion task and the Stroop test and responded more conservatively on the N-back working memory task. Other tasks showed no differences between treatments under cholinergic blockade.DiscussionThe findings show that mPRO when taken in concert with E2, was detrimental to effortful cognitive performance, in the presence of cholinergic blockade. These results are important for assessing the impact of combined postmenopausal hormone treatment on cognitive performance that is dependent on cholinergic functioning after menopause.

Dataset Information

Characterization of vascular disease risk in postmenopausal women and its association with cognitive performance.

Objectives

Methods

Results

Conclusion

Publications

Characterization of vascular disease risk in postmenopausal women and its association with cognitive performance.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets