Dataset Information

Differential Effect of Plasma Estradiol on Subclinical Atherosclerosis Progression in Early vs Late Postmenopause.

ABSTRACT: Context:The Early vs Late Intervention Trial with Estradiol showed that hormone therapy (HT) reduced progression of atherosclerosis when initiated in early but not in late postmenopause. Objective:This posttrial analysis examined the association between plasma estradiol (E2) levels and atherosclerosis determined by rate of change in carotid artery intima-media thickness (CIMT) and tested whether this association is equally evident in early (<6 years) vs late (?10 years) postmenopause. Design:Randomized controlled trial stratified by time since menopause (ClinicalTrials.gov no. NCT00114517). Mixed-effects linear models tested the association of E2 levels with CIMT rate of change. Setting:Los Angeles, California. Participants:Healthy women in postmenopause. Intervention:Oral E2 with/without cyclic vaginal progesterone. Main Outcome Measures:Plasma E2 levels and CIMT assessed every 6 months over an average of 4.8 years. Results:Among 596 women in postmenopause, higher E2 level was inversely associated with CIMT progression in those in early postmenopause (P = 0.041) and positively associated with CIMT progression in those in late postmenopause (P = 0.006) (P for interaction <0.001). CIMT progression rates for the lowest vs highest quartile of E2 levels among women in early postmenopause were 8.5 and 7.2 ?m/y, respectively , whereas among women in late postmenopause they were 9.8 and 11.7 ?m/y, respectively. Conclusion:E2 levels were differentially associated with atherosclerosis progression according to timing of HT initiation. With higher E2 levels, CIMT progression rate was decreased among women in early postmenopause but increased among women in late postmenopause. These results support the timing hypothesis of HT initiation on cardiovascular benefit, with reduced atherosclerosis progression for initiation during early postmenopause.

SUBMITTER: Sriprasert I

PROVIDER: S-EPMC6300071 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Differential Effect of Plasma Estradiol on Subclinical Atherosclerosis Progression in Early vs Late Postmenopause.

Sriprasert Intira I Hodis Howard N HN Karim Roksana R Stanczyk Frank Z FZ Shoupe Donna D Henderson Victor W VW Mack Wendy J WJ

The Journal of clinical endocrinology and metabolism 20190201 2

<h4>Context</h4>The Early vs Late Intervention Trial with Estradiol showed that hormone therapy (HT) reduced progression of atherosclerosis when initiated in early but not in late postmenopause.<h4>Objective</h4>This posttrial analysis examined the association between plasma estradiol (E2) levels and atherosclerosis determined by rate of change in carotid artery intima-media thickness (CIMT) and tested whether this association is equally evident in early (<6 years) vs late (≥10 years) postmenopa ...[more]

PMID: 30272234

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Project description:ObjectiveWhile the risk of acute coronary events has been associated with biological variability of circulating cholesterol, the association with variability of other atherogenic lipids remains less understood. We evaluated the longitudinal variability of 284 lipids and investigated their association with asymptomatic coronary atherosclerosis. Approach and Results: Circulating lipids were extracted from fasting blood samples of 83 community-sampled symptom-free participants (age 41-75 years), collected longitudinally over 6 months. Three types of coronary plaque volume (calcified, lipid-rich, and fibrotic) were quantified using computed tomography coronary angiogram. We first deconvoluted between-subject (CVg) and within-subject (CVw) lipid variabilities. We then tested whether the mean lipid abundance was different across groups categorized by Framingham risk score and plaques phenotypes (lipid-rich, fibrotic, and calcified). Finally, we investigated whether visit-to-visit variability of each lipid was associated with plaque burden. Most lipids (72.5%) exhibited higher CVg than CVw. Among the lipids (n=145) with 1.2-fold higher CVg than CVw, 26 species including glycerides and ceramides were significantly associated with Framingham risk score and the 3 plaque phenotypes (false discovery rate <0.05). In an exploratory analysis of person-specific visit-to-visit variability without multiple testing correction, high variability of 3 lysophospholipids (lysophosphatidylethanolamines 16:0, 18:0, and lysophosphatidylcholine O-18:1) was associated with lipid-rich and fibrotic (noncalcified) plaque volume while high variability of diacylglycerol 18:1_20:0, triacylglycerols 52:2, 52:3, and 52:4, ceramide d18:0/20:0, dihexosylceramide d18:1/16:0, and sphingomyelin 36:3 was associated with calcified plaque volume.ConclusionsHigh person-specific longitudinal variation of specific nonsterol lipids is associated with the burden of subclinical coronary atherosclerosis. Larger studies are needed to confirm these exploratory findings.

Project description:Persistent seed banks are predicted to have an important impact on population genetic processes by increasing effective population size and storing past genetic diversity. Accordingly, persistent seed banks may buffer genetic effects of disturbance, fragmentation and/or selection. However, empirical studies surveying the relationship between aboveground and seed bank genetics under changing environments are scarce. Here, we compared genetic variation of aboveground and seed bank cohorts in 15 populations of the partially cleistogamous Viola elatior in two contrasting early and late successional habitats characterized by strong differences in light-availability and declining population size. Using AFLP markers, we found significantly higher aboveground than seed bank genetic diversity in early successional meadow but not in late successional woodland habitats. Moreover, individually, three of eight woodland populations even showed higher seed bank than aboveground diversity. Genetic differentiation among populations was very strong (фST = 0.8), but overall no significant differentiation could be detected between above ground and seed bank cohorts. Small scale spatial genetic structure was generally pronounced but was much stronger in meadow (Sp-statistic: aboveground: 0.60, seed bank: 0.32) than in woodland habitats (aboveground: 0.11; seed bank: 0.03). Our findings indicate that relative seed bank diversity (i.e. compared to aboveground diversity) increases with ongoing succession and despite decreasing population size. As corroborated by markedly lower small-scale genetic structure in late successional habitats, we suggest that the observed changes in relative seed bank diversity are driven by an increase of outcrossing rates. Persistent seed banks in Viola elatior hence will counteract effects of drift and selection, and assure a higher chance for the species' long term persistence, particularly maintaining genetic variation in declining populations of late successional habitats and thus enhancing success rates of population recovery after disturbance events.

Dataset Information

Differential Effect of Plasma Estradiol on Subclinical Atherosclerosis Progression in Early vs Late Postmenopause.

Publications

Differential Effect of Plasma Estradiol on Subclinical Atherosclerosis Progression in Early vs Late Postmenopause.

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