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      Hormone Replacement Therapy and Risk of New-Onset Atrial Fibrillation after Myocardial Infarction - A Nationwide Cohort Study

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          Abstract

          Objectives

          Our aim was to assess the association between use of hormone replacement therapy (HRT) and risk of new-onset atrial fibrillation (AF) after myocardial infarction.

          Design, Setting and Participants

          We used Danish nationwide registers of hospitalizations and prescriptions to identify all women admitted with myocardial infarction in the period 1997 to 2009 and with no known diagnosis of AF. Their use of overall HRT and HRT categories was assessed. Multivariable Cox proportional hazards analysis was used to calculate the risk of new-onset AF first year after discharge, comparing use of HRT to no use.

          Main Outcome Measures

          New-onset atrial fibrillation.

          Results

          In the period 1997 to 2009, 32 925 women were discharged alive after MI. In the first year after MI, new-onset AF was diagnosed in 1381 women (4.2%). Unadjusted incidence rates of AF decreased with use of HRT (incidence rate 37.4 for use of overall HRT and 53.7 for no use). Overall HRT was associated with a decreased risk of AF (HR 0.82, 95% confidence interval [CI] 0.68–1.00). The lowest risk of AF was found in women ≥80 years old for use of overall HRT and vaginal estrogen (HR 0.63, CI 0.42–0.94, and HR 0.58, CI 0.34–0.99, respectively). Decreased risk of AF with use of overall HRT and HRT categories was also found in other age groups.

          Conclusions

          Use of HRT is associated with a decreased risk of new-onset AF in women with myocardial infarction first year after discharge. The underlying mechanisms remain to be determined. Unmeasured confounding might be one of them.

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          Most cited references37

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          Independent risk factors for atrial fibrillation in a population-based cohort. The Framingham Heart Study.

          To determine the independent risk factors for atrial fibrillation. Cohort study. The Framingham Heart Study. A total of 2090 men and 2641 women members of the original cohort, free of a history of atrial fibrillation, between the ages of 55 and 94 years. Sex-specific multiple logistic regression models to identify independent risk factors for atrial fibrillation, including age, smoking, diabetes, electrocardiographic left ventricular hypertrophy, hypertension, myocardial infarction, congestive heart failure, and valve disease. During up to 38 years of follow-up, 264 men and 298 women developed atrial fibrillation. After adjusting for age and other risk factors for atrial fibrillation, men had a 1.5 times greater risk of developing atrial fibrillation than women. In the full multivariable model, the odds ratio (OR) of atrial fibrillation for each decade of advancing age was 2.1 for men and 2.2 for women (P < .0001). In addition, after multivariable adjustment, diabetes (OR, 1.4 for men and 1.6 for women), hypertension (OR, 1.5 for men and 1.4 for women), congestive heart failure (OR, 4.5 for men and 5.9 for women), and valve disease (OR, 1.8 for men and 3.4 for women) were significantly associated with risk for atrial fibrillation in both sexes. Myocardial infarction (OR, 1.4) was significantly associated with the development of atrial fibrillation in men. Women were significantly more likely than men to have valvular heart disease as a risk factor for atrial fibrillation. The multivariable models were largely unchanged after eliminating subjects with valvular heart disease. In addition to intrinsic cardiac causes such as valve disease and congestive heart failure, risk factors for cardiovascular disease also predispose to atrial fibrillation. Modification of risk factors for cardiovascular disease may have the added benefit of diminishing the incidence of atrial fibrillation.
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            Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group.

            Observational studies have found lower rates of coronary heart disease (CHD) in postmenopausal women who take estrogen than in women who do not, but this potential benefit has not been confirmed in clinical trials. To determine if estrogen plus progestin therapy alters the risk for CHD events in postmenopausal women with established coronary disease. Randomized, blinded, placebo-controlled secondary prevention trial. Outpatient and community settings at 20 US clinical centers. A total of 2763 women with coronary disease, younger than 80 years, and postmenopausal with an intact uterus. Mean age was 66.7 years. Either 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate in 1 tablet daily (n = 1380) or a placebo of identical appearance (n = 1383). Follow-up averaged 4.1 years; 82% of those assigned to hormone treatment were taking it at the end of 1 year, and 75% at the end of 3 years. The primary outcome was the occurrence of nonfatal myocardial infarction (MI) or CHD death. Secondary cardiovascular outcomes included coronary revascularization, unstable angina, congestive heart failure, resuscitated cardiac arrest, stroke or transient ischemic attack, and peripheral arterial disease. All-cause mortality was also considered. Overall, there were no significant differences between groups in the primary outcome or in any of the secondary cardiovascular outcomes: 172 women in the hormone group and 176 women in the placebo group had MI or CHD death (relative hazard [RH], 0.99; 95% confidence interval [CI], 0.80-1.22). The lack of an overall effect occurred despite a net 11% lower low-density lipoprotein cholesterol level and 10% higher high-density lipoprotein cholesterol level in the hormone group compared with the placebo group (each P<.001). Within the overall null effect, there was a statistically significant time trend, with more CHD events in the hormone group than in the placebo group in year 1 and fewer in years 4 and 5. More women in the hormone group than in the placebo group experienced venous thromboembolic events (34 vs 12; RH, 2.89; 95% CI, 1.50-5.58) and gallbladder disease (84 vs 62; RH, 1.38; 95% CI, 1.00-1.92). There were no significant differences in several other end points for which power was limited, including fracture, cancer, and total mortality (131 vs 123 deaths; RH, 1.08; 95% CI, 0.84-1.38). During an average follow-up of 4.1 years, treatment with oral conjugated equine estrogen plus medroxyprogesterone acetate did not reduce the overall rate of CHD events in postmenopausal women with established coronary disease. The treatment did increase the rate of thromboembolic events and gallbladder disease. Based on the finding of no overall cardiovascular benefit and a pattern of early increase in risk of CHD events, we do not recommend starting this treatment for the purpose of secondary prevention of CHD. However, given the favorable pattern of CHD events after several years of therapy, it could be appropriate for women already receiving this treatment to continue.
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              The Danish prescription registries.

              The extensive computerisation of Danish pharmacies has permitted the establishment of two large prescription registries: The Odense University Pharmacoepidemiological Database (OPED) and the Pharmacoepidemiological Prescription Database of North Jutland (PDNJ). The Danish prescription registries content, coverage, completeness and the quality of the data are discussed in this article. Furthermore, conditions for access to the data are presented. The two prescription registries cover a background population of approximately one million or 18% of the Danish population. The populations covered by the registries are stable and representative of the Danish population in general. The registries cover all reimbursed medicine at the level of the individual user. Registration of a unique and permanent personal identifier enables the compilation of longitudinal drug histories and allows the linking of prescription data to other population-based Danish registries. The degree of completeness of the Danish prescription registries is excellent for reimbursed prescription drugs. A small number of comparison studies also indicate high validity of the register information. The Danish prescription registries represent a useful new data source for pharmacoepidemiological studies.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2012
                17 December 2012
                : 7
                : 12
                : e51580
                Affiliations
                [1 ]Department of Cardiology, Copenhagen University Hospital Gentofte, Hellerup, Denmark
                [2 ]Faculty of Health Sciences, Panum Institute, University of Copenhagen, Copenhagen, Denmark
                [3 ]Department of Internal Medicine, Copenhagen University Hospital Holbæk, Holbæk, Denmark
                Indiana University School of Medicine, United States of America
                Author notes

                Competing Interests: Dr. Gislason has received a research grant from the Novo Nordisk Foundation and is owner of Novo Nordisk shares. Dr. Ahlehoff has received honoraria from Abbott and Pfizer. All other authors: No conflicting interests.

                Conceived and designed the experiments: DMB CTP GHG. Performed the experiments: DMB JL. Analyzed the data: DMB PRH JL OA CA TBJ JR CTP GHG. Wrote the paper: DMB. Acquisition of data: DMB CTP. Funding and supervision: DMB PRH CTP GHG. Critical revision of the manuscript: DMB PRH JL OA CA TBJ JR CTP GHG. Final approval of the submitted manuscript: DMB PRH JL OA CA TBJ JR CTP GHG.

                Article
                PONE-D-12-19292
                10.1371/journal.pone.0051580
                3524193
                23284717
                d4c65ed3-388e-4b12-9571-069082c6379a
                Copyright @ 2012

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 19 June 2012
                : 2 November 2012
                Page count
                Pages: 7
                Funding
                DMB was supported by the Danish Heart Foundation [grant 08-4-R65-A1904-B844-22440F], and the Lundbeck Foundation [grant R31-A2566]. Dr. Gislason has received a research grant from the Novo Nordisk Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine
                Anatomy and Physiology
                Endocrine System
                Endocrine Physiology
                Hormones
                Cardiovascular
                Arrhythmias
                Cardiovascular Diseases in Women
                Coronary Artery Disease
                Myocardial Infarction
                Epidemiology
                Cardiovascular Disease Epidemiology
                Pharmacoepidemiology
                Obstetrics and Gynecology
                Menopause
                Women's Health
                Cardiovascular Diseases in Women

                Uncategorized
                Uncategorized

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