Clinical Impact of Hormone Replacement Therapy on Atrial Fibrillation in Postmenopausal Women: A Nationwide Cohort Study.
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SUBMITTER: Lee J
PROVIDER: S-EPMC8658255 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Hormone replacement therapy (HRT) is associated with risk of vascular disease. The association between atrial fibrillation (AF), vascular events, and different HRTs, including estradiol and conjugated equine estrogens (CEE), has been controversial in previous studies. Thus, we conducted a retrospective cohort study to investigate these associations. Female patients (>45 years old) first diagnosed with menopause were enrolled from National Health Insurance Research Dataset (1998-2008). Cox regression analysis estimated risk of new-onset AF, stroke, and major adverse cardiac events (MACE) after exposure to estradiol or CEE. Of 5489 females (mean age = 55 years) enrolled, 1815 treated with estradiol and 3674 treated with CEE. Incidence per 10(3) person-years of AF, stroke, and MACE in CEE vs estradiol patients was 2.23 vs. 0.92, 14.0 vs. 9.09, and 15.55 vs. 10.47. As compared with patients treated with estradiol, those treated with CEE had a significantly higher incidence of AF, stroke, and MACE. The adjusted hazard ratios for each category were 1.96, 1.30, and 1.26, respectively. The significant results remained similar, even after use of propensity-score-matched strategy. In conclusion, CEE was associated with a higher risk of AF, stroke, and MACE than estradiol in menopausal females. Further exploration of underlying mechanisms is necessary.
| S-EPMC4823790 | biostudies-literature
Project description:ObjectiveLimited data exist on the association between menopause and atrial fibrillation (AF). We sought to examine the relationship between menopausal age, postmenopausal hormone therapy (PHT) use and incident AF.MethodsThe Women's Health Study (WHS) enrolled 39 876 female health professionals between 1992 and 1995. We prospectively examined 30 034 women in WHS using Cox proportional-hazard models. Participants were free of cardiovascular disease and AF at baseline and had not undergone hysterectomy without bilateral oophorectomy prior to menopause. Incident AF was confirmed by medical record review.ResultsAt baseline, median age was 53 years (IQR 49-60), median menopausal age was 50 years (IQR 46-52) and 14 415 (48.0%) had prior PHT use. Over a median follow-up of 20.5 years, 1350 AF events occurred. In multivariable analysis, relative hazards for AF were lower among women with younger age at menopause but did not differ significantly from women with the oldest menopausal age (<45: HR 0.82, 95% CI 0.67 to 1.02; 45-49: HR 0.90, 95% CI 0.74 to 1.08; 50-54: HR 0.89, 95% CI 0.75 to 1.06; >54 years: referent). Use of oestrogen-alone PHT, but not oestrogen and progesterone, was independently associated with AF risk (HR 1.22; 95% CI 1.02 to 1.45 vs HR 1.04; 95% CI 0.86 to 1.26). This relationship was not attenuated by intermediary cardiovascular events.ConclusionsIn this large prospective study, menopausal age was not significantly related to incident AF, while use of oestrogen monotherapy was associated with increased AF risk. Our findings suggest a pathophysiological link between unopposed oestrogen exposure and AF in women.Clinical trial registrationNCT000000479; Post-results.
| S-EPMC5831356 | biostudies-literature
Project description:BackgroundThe prognostic implications of new-onset atrial fibrillation (AF) in conjunction with transcatheter aortic valve replacement (TAVR) is sparsely examined. Therefore, we aimed to examine the impact of first-time detected AF after TAVR on all-cause mortality and heart failure (HF).MethodsWith Danish nationwide data from 2008 to 2021, we identified all patients who underwent TAVR and were alive 30 days after discharge (index date). Patients were categorized into i) no AF; ii) history of AF; and iii) first-time detected AF within 30 days after discharge. From the index date, two-year rates of all-cause mortality and HF admissions were compared using multivariable adjusted Cox analysis.ResultsWe identified 6,807 patients surviving 30 days beyond TAVR: 4,229 (62.1%) without AF (55% male, median age 81), 2,283 (33.6%) with history of AF (58% male, median age 82), and 291 (4.3%) with first-time detected AF (56% male, median age 81). Compared with patients without AF, adjusted analysis yielded increased associated hazard ratio (HR) of all-cause mortality in patients with history of AF (1.53 [95% confidence interval [CI], 1.32-1.77]) and in patients with first-time detected AF (2.06 (95%CI, 1.55-2.73]). Further, we observed increased associated HRs of HF admissions in patients with history of AF (1.70 [95%CI, 1.45-1.99]) and in patients with first-time detected AF (1.77 [95%CI, 1.25-2.50]).ConclusionIn TAVR patients surviving 30 days beyond discharge, first-time detected AF appeared to be at least as strongly associated with two-year rates of all-cause mortality and HF admissions, as compared with patients with history of AF.
| S-EPMC10359858 | biostudies-literature
Project description:Importance:Antithrombotic therapies are effective in both primary and secondary stroke prophylaxis in high-risk patients with atrial fibrillation (AF), but they are often underused in community practice. Objective:To examine prestroke and poststroke antithrombotic treatment patterns and long-term outcomes in patients with AF presenting with ischemic stroke. Design, Setting, and Participants:A retrospective cohort study of Danish patients with AF, with a prestroke CHA2DS2-VASc score of 1 or higher for men and 2 or higher for women, and presenting with ischemic stroke was conducted from January 1, 2004, to January 31, 2017. Data on hospital admission, prescription fillings, and vital status were assessed using several Danish nationwide registries. Exposures:Patients who survived 100 days after discharge were divided into 3 groups according to poststroke antithrombotic therapy: oral anticoagulation (OAC) therapy, antiplatelet therapy alone, or no antithrombotic therapy. Main Outcomes and Measures:Long-term outcomes (thromboembolic events and bleeding complications) were examined using multivariable Cox regression analyses across the 3 groups. Results:Among 30?626 patients with AF admitted with ischemic stroke, 11?139 patients (36.3%) received OAC therapy (44.3% female; median age, 79 years [interquartile range, 73-85 years]), 11?874 (38.8%) received antiplatelet therapy alone (55.0% female; median age, 82 years [interquartile range, 75-88 years]), and 7613 (24.9%) received no antithrombotic therapy before stroke (53.8% female; median age, 80 years [interquartile range, 71-86 years]). Following stroke, 31.3% of those receiving antiplatelet therapy alone and 43.7% of those receiving no antithrombotic therapy before stroke shifted to OAC therapy. Yet, 37.5% of patients with stroke did not receive OAC therapy following stroke. However, OAC treatment rates increased over time. During a maximum of 10 years of follow-up, 17.5%, 21.2%, and 21.5% experienced a new thromboembolic event and 72.7%, 86.4%, and 86.2% died among those treated with OAC therapy, antiplatelet therapy, or no antithrombotic therapy, respectively. Poststroke OAC therapy was associated with lower risk of recurrent thromboembolic events (adjusted hazard ratio, 0.81; 95% CI, 0.73-0.89) and no significant difference in bleeding complications (adjusted hazard ratio, 0.97; 95% CI, 0.86-1.10), compared with no poststroke antithrombotic therapy. In contrast, there were no significant differences for those treated with poststroke antiplatelet therapy and no antithrombotic therapy. Conclusions and Relevance:Patients with AF receiving poststroke OAC therapy had lower risk of recurrent thromboembolic events. Our findings suggest a substantial opportunity for improving primary and secondary stroke prophylaxis in high-risk patients with AF.
| S-EPMC6324317 | biostudies-other
Project description:The incidence and risk of tinnitus associated with hormone replacement therapy (HRT) in menopausal women have not yet been fully examined. We examined the medical records of menopausal women aged between 45 and 79 years from Taiwan's National Health Insurance Research Database of records between 1 January 2000 and 31 December 2010 to establish matched cohorts (13,920 HRT users and 41,760 nonusers). The incidence of tinnitus in HRT users and nonusers were matched 1:3 based on propensity-score matching over this ten year period. The Cox regression hazard model was used to identify risk factors of tinnitus, and results indicate that a significantly lower percentage of HRT users (P = 0.017) developed tinnitus in comparison with nonusers (0.43%, 60/13, 920 vs. 0.59%, 246/41, 760). Using Cox regressions analysis after adjustments for age and other variables (adjusted hazard ratio: 0.505 (95% confidence interval, 0.342-0.756)), we were also able to show that HRT users appeared to have a reduced risk of developing tinnitus in comparison with nonusers. Based on our observation of the lower incidence of tinnitus among HRT users in this cohort, we speculate that HRT may have provided potential benefits on the management and prevention of tinnitus among menopausal women.
| S-EPMC5929427 | biostudies-literature
Project description:The American Women’s Health Initiative study published in July 2002 caused considerable concern among hormone replacement therapy (HRT) users and prescribers in many countries. This study is an exploratory research comparing the genome wide expression profile in whole blood samples according to HRT use. Within the Norwegian Women and Cancer study, 100 postmenopausal women (50 HRT users and 50 non-HRT users) born between 1943 and 1949 with normal to high body mass index and no other medication use were selected. After total RNA extraction, amplification and labelling, the samples were hybridized together with a common reference (Universal human reference RNA, Stratagen) to Agilent Human 1A oligoarrays (G4110b, Agilent Technologies, Palo Alto, CA) containing 20,173 unique genes. Differentially expressed genes were used to build a classifier using the nearest shrunken centroids method (PAM). Then, we tested the significant changes in single genes by different methods like t-test, Significance Analysis of Microarrays (SAM) and Bayesian ANOVA analysis (BAM). Results did not reveal any distinct gene list which predicted accurately HRT exposure (error rate = 0.45). Classifier performance slightly improved (error rate = 0.29) including only women who were using continuous combined HRT treatment. According to the small amplitude of expression alterations observed after HRT use in whole blood, large sample sizes are needed to identify significant single genes differentially expressed. However, significant enrichments in biologic process of genes with small changes after HRT use were observed (e.g. receptor and transporter activities, immune response, frizzled signalling pathway, actin filament organization, glycogen metabolism). Keywords: gene expression profile and exposure
2005-10-25 | GSE3492 | GEO
Project description:The effect of hormone replacement therapy (HRT) on the malignant transformation of postmenopausal endometriosis remains unclear. This study aimed to investigate the impact of HRT on ovarian cancer occurrence in postmenopausal women with de novo endometriosis or a history of endometriosis. A total of 10,304 women that received HRT (the HRT group) and 10,304 that did not (the control group) were selected by 1:1 matching those that met the study criteria. Incidences of ovarian cancer (0.3% in the HRT group and 0.5% in the control group) and cumulative incidence rates of ovarian cancer were similar in the two groups. The overall mean duration of HRT was 1.4 ± 2.2 years, but the duration of HRT in women with ovarian cancer was 2.2 ± 2.9 years. After adjusting for co-variables, receipt of HRT, duration of HRT, combined use of estrogen and progesterone, and tibolone were not found to be risk factors for ovarian cancer. However, the use of estrogen alone was found to be a significant risk factor for ovarian cancer (HR 2.898; 95% CI 1.251-6.715; p = 0.013). With the exception of HRT using estrogen alone, HRT did not increase the risk of ovarian cancer in postmenopausal women with a history of endometriosis or de novo endometriosis.
| S-EPMC10046182 | biostudies-literature
Project description:Title: Transcriptome analysis of human endometrial tissues from healthy post-menoupausal women reflecting the endometrial response to 3-weeks treatment with tibolone, E2 and E2+MPA. In an observational, open, non-randomized, controlled study uterine tissues were collected in order to generate endometrial gene expression profiles. healthy postmenopausal women were enrolled into the following treatment groups: Control-group; Tibolone-group, 2,5 mg of tibolone (administered orally) every day, starting 21 days prior to surgery; Estradiol-group, 2 mg of estradiol (administered orally) every day, starting 21 days prior to surgery; Estradiol+progestagen-group, 2 mg of estradiol (administered orally) and 5 mg of MPA (Medroxy Progesteroneacetate, administered orally) every day, starting 21 days prior to surgery. Pure (100%) endometrium was isolated from the snap-frozen uterine tissues and used for RNA isolation. RNA was labeled and hybridized to whole genome Affymetrix U133plus2 GeneChips containing 54,614 probe sets, representing approximately 47,000 transcripts. Relative to the control group, 940 genes are regulated in the endometrium of E2 treated patients, whereas only 198 genes are significantly regulated in endometria from tibolone or E2+MPA treated patients. Furthermore, only 9% of E2 regulated genes are also regulated by tibolone (85 out of 940), only 5% are also regulated by E2+MPA treatment and the overlap between tibolone and E2+MPA treatment is about 10%. This indicated that tibolone-treatment results in a weak endometrial profile similarity to E2 treatment and no profile similarity to E2+MPA treatment. A more detailed analysis showed that down stream processes, such as regulation of the cell cycle, angiogenesis and cell proliferation are almost not affected by tibolone treatment but, in contrast, are significantly affected by E2. For example, upon staining with Ki67, a marker for mitotic activity, significantly increased stromal as well as glandular cell proliferation was observed in the endometria from the E2-only treated group, while tibolone treatment resulted only in a slight increase in stromal cell proliferation (and no increase in glandular cell proliferation). These results indicate that in contrast to long-term tibolone use, short-term (21-days) use results in some estrogenic stimulation of the endometrium, which is clearly far less and rather different from what is observed during E2 treatment. References: Klaassens et al., 2006 Hanifi-Moghaddam et al., 2007 Verheul et al., 2007
2008-08-21 | GSE12446 | GEO
Project description:ImportanceMenopause is associated with biological aging, and hormone therapy (HT) is associated with health outcomes in postmenopausal women.ObjectiveTo evaluate the association between HT use and discrepancies between chronological and biological age in postmenopausal women as well as the potential modifying role of socioeconomic status (SES).Design, setting, and participantsThis population-based, retrospective cohort study included postmenopausal women registered in the UK Biobank. A baseline survey on HT use and biological aging biomarkers was conducted from March 2006 to October 2010. Data analyses were conducted in December 2023.ExposuresInformation regarding HT use, the age at starting HT, and HT duration was collected via a touchscreen questionnaire. SES was evaluated by education, family income, occupation, and the Townsend Deprivation Index.Main outcomes and measuresBiological aging discrepancy was evaluated using validated phenotypic age, which was calculated using chronological age and 9 biomarkers measured at baseline. All-cause and cause-specific mortality were also assessed.ResultsAmong the 117 763 postmenopausal women (mean [SD] age, 60.2 [5.4] years), 47 461 (40.3%) ever used HT. The mean phenotypic age was 52.1 (7.9) years. Ever use of HT was associated with a smaller biological aging discrepancy than never use of HT (β, -0.17 years; 95% CI, -0.23 to -0.10 years). This smaller aging discrepancy was more evident in those who started HT at age 55 years or older (β, -0.32 years; 95% CI, -0.48 to -0.15 years) and in those who used HT for 4 to 8 years (β, -0.25 years; 95% CI, -0.35 to -0.15 years). The association between HT and a smaller aging discrepancy was more evident in women with low SES, with a significant interaction observed for education (higher education: β, -0.08 years [95% CI, -0.17 to 0.01]; other education: β, -0.23 [95% CI, -0.32 to -0.14] years; P for interaction = .02). Phenotypic aging discrepancy mediated 12.7% (95% CI, 6.3% to 23.9%) of the association between HT and all-cause mortality and cause-specific mortality.Conclusions and relevanceIn this study, postmenopausal women with historical HT use were biologically younger than those not receiving HT, with a more evident association observed in those with low SES. The biological aging discrepancy mediated the association between HT and decreased mortality. Promoting HT in postmenopausal women could be important for healthy aging.
| S-EPMC11362863 | biostudies-literature
Project description:AimsAtrial fibrillation (AF) is a risk for patients receiving thyroid hormone replacement therapy. No published work has focused on pharmacogenetics relevant to thyroid dysfunction and AF risk. We aimed to assess the effect of L-thyroxine on AF risk stratified by a variation in a candidate gene.Methods and resultsA retrospective follow-up study was done among European Caucasian patients from the Genetics of Diabetes Audit and Research in Tayside Scotland cohort (Scotland, United Kingdom). Linked data on biochemistry, prescribing, hospital admissions, demographics, and genetic biobank were used to ascertain patients on L-thyroxine and diagnosis of AF. A GWAS-identified insulin receptor-INSR locus (rs4804416) was the candidate gene. Cox survival models and sensitivity analyses by taking competing risk of death into account were used. Replication was performed in additional sample (The Genetics of Scottish Health Research register, GoSHARE), and meta-analyses across the results of the study and replication cohorts were done. We analyzed 962 exposed to L-thyroxine and 5,840 unexposed patients who were rs4804416 genotyped. The rarer G/G genotype was present in 18% of the study population. The total follow-up was up to 20 years, and there was a significant increased AF risk for patients homozygous carriers of the G allele exposed to L-thyroxine (RHR = 2.35, P = 1.6e-02). The adjusted increased risk was highest within the first 3 years of exposure (RHR = 9.10, P = 8.5e-04). Sensitivity analysis yielded similar results. Effects were replicated in GoSHARE (n = 3,190).ConclusionHomozygous G/G genotype at the INSR locus (rs4804416) is associated with an increased risk of AF in patients on L-thyroxine, independent of serum of free thyroxine and thyroid-stimulating hormone serum concentrations.
| S-EPMC8260687 | biostudies-literature