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      Pregnancy Loss and the Risk of Myocardial Infarction, Stroke, and All‐Cause Mortality: A Nationwide Partner Comparison Cohort Study

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          Abstract

          Background

          Pregnancy loss has been associated with myocardial infarction, stroke, and all‐cause mortality in women through unknown mechanisms. The aim of this study was to examine these associations in women and their male partners.

          Methods and Results

          In this register‐based cohort study, all people born between 1957 and 1997, residing in Denmark between 1977 and 2017, and with a registered partner of the opposite sex were eligible for inclusion. Male partners through cohabitation, marriage, or paternity constituted the male cohort. Exposure to pregnancy loss was categorized as follows: 0, 1, 2, or ≥3 pregnancy losses. The outcomes of interest were myocardial infarction, stroke, and all‐cause mortality. The Cox proportional hazards model estimated hazard ratios (HRs), adjusted for age, calendar year, parity, and parental history of myocardial infarction or stroke.

          During follow‐up, 1 112 507 women experienced 4463 events of myocardial infarction compared with 13 838 events among 1 120 029 male partners. With the no pregnancy loss group as reference, the adjusted HRs of myocardial infarction in the female cohort after 1, 2, and ≥3 pregnancy losses were as follows: 1.1 (95% CI, 1.0–1.2), 1.3 (95% CI, 1.1–1.5), and 1.4 (95% CI, 1.1–1.8), respectively. In the male partner cohort, the corresponding estimates were 1.0 (95% CI, 1.0–1.1), 1.1 (95% CI, 1.0–1.2), and 1.0 (95% CI, 0.8–1.2), respectively. The outcome of stroke showed similar results. Pregnancy loss was not significantly associated with increased mortality in either sex.

          Conclusions

          Pregnancy loss or stillbirth was significantly associated with myocardial infarction and stroke in women but not their male partners. Pregnancy loss or stillbirth was not significantly associated with all‐cause mortality in women or male partners.

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          Most cited references34

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          Regression Models and Life-Tables

          D R Cox (1972)
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            The Danish Civil Registration System as a tool in epidemiology.

            The methodological advances in epidemiology have facilitated the use of the Danish Civil Registration System (CRS) in ways not previously described systematically. We reviewed the CRS and its use as a research tool in epidemiology. We obtained information from the Danish Law on Civil Registration and the Central Office of Civil Registration, and used existing literature to provide illustrative examples of its use. The CRS is an administrative register established on April 2, 1968. It contains individual-level information on all persons residing in Denmark (and Greenland as of May 1, 1972). By January 2014, the CRS had cumulatively registered 9.5 million individuals and more than 400 million person-years of follow-up. A unique ten-digit Civil Personal Register number assigned to all persons in the CRS allows for technically easy, cost-effective, and unambiguous individual-level record linkage of Danish registers. Daily updated information on migration and vital status allows for nationwide cohort studies with virtually complete long-term follow-up on emigration and death. The CRS facilitates sampling of general population comparison cohorts, controls in case-control studies, family cohorts, and target groups in population surveys. The data in the CRS are virtually complete, have high accuracy, and can be retrieved for research purposes while protecting the anonymity of Danish residents. In conclusion, the CRS is a key tool for epidemiological research in Denmark.
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              The Danish Civil Registration System.

              The Danish Civil Registration System (CRS) was established in 1968, and all persons alive and living in Denmark were registered for administrative use. CRS includes individual information on the unique personal identification number, name, gender, date of birth, place of birth, citizenship, identity of parents and continuously updated information on vital status, place of residence and spouses. Since 1968, CRS has recorded current and historical information on all persons living in Denmark. Among persons born in Denmark in 1960 or later it contains complete information on maternal identity. For women born in Denmark in April 1935 or later it contains complete information on all their children. CRS contains complete information on immigrations and emigrations from 1969 onwards, permanent residence in a Danish municipality from 1971 onwards, and full address in Denmark from 1977 onwards. CRS in connection with other registers and biobanks will continue to provide the basis for significant knowledge relevant to the aetiological understanding and possible prevention of human diseases.
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                Author and article information

                Contributors
                anders.mikkelsen@regionh.dk
                Journal
                J Am Heart Assoc
                J Am Heart Assoc
                10.1002/(ISSN)2047-9980
                JAH3
                ahaoa
                Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
                John Wiley and Sons Inc. (Hoboken )
                2047-9980
                25 July 2023
                01 August 2023
                : 12
                : 15 ( doiID: 10.1002/jah3.v12.15 )
                : e028620
                Affiliations
                [ 1 ] Department of Gynaecology Copenhagen University Hospital–Rigshospitalet Copenhagen Denmark
                [ 2 ] Department of Obstetrics and Gynaecology Copenhagen University Hospital Herlev Herlev Denmark
                [ 3 ] Department of Obstetrics and Gynaecology Copenhagen University Hospital Hvidovre Hvidovre Denmark
                [ 4 ] The Recurrent Pregnancy Loss Unit The Capital Region, Copenhagen University Hospitals Rigshospitalet and Hvidovre Hvidovre Denmark
                [ 5 ] Novo Nordisk Foundation Center for Protein Research University of Copenhagen Copenhagen Denmark
                [ 6 ] Methods and Analysis, Statistics Denmark Copenhagen Denmark
                [ 7 ] Department of Cardiology and Clinical Research, Nordsjaellands Hospital Hillerød Denmark
                [ 8 ] Department of Cardiology Aalborg University Hospital Aalborg Denmark
                [ 9 ] Department of Clinical Medicine University of Copenhagen Copenhagen Denmark
                Author notes
                [*] [* ]Correspondence to: Anders Pretzmann Mikkelsen, MD, PhD, Rigshospitalet, Blegdamsvej 9, Department 4232, 2100 Copenhagen, Denmark. Email: anders.mikkelsen@ 123456regionh.dk
                [*]

                These authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.

                Author information
                https://orcid.org/0000-0002-7583-9826
                https://orcid.org/0000-0002-8047-2459
                https://orcid.org/0000-0002-8250-6798
                https://orcid.org/0000-0003-0128-8432
                https://orcid.org/0000-0003-2892-6131
                https://orcid.org/0000-0003-2106-8103
                https://orcid.org/0000-0002-7071-5496
                Article
                JAH38341 JAHA/2022/028620-T
                10.1161/JAHA.122.028620
                10492966
                37489734
                cf70985d-5640-416d-bda6-6e84ccce4a91
                © 2023 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 27 October 2022
                : 07 February 2023
                Page count
                Figures: 3, Tables: 2, Pages: 10, Words: 5437
                Funding
                Funded by: Rigshospitalet, Copenhagen University Hospital , doi 10.13039/501100005111;
                Award ID: E‐22515‐01
                Funded by: Ole Kirks Foundation
                Categories
                Original Research
                Original Research
                Epidemiology
                Custom metadata
                2.0
                01 August 2023
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.3.2 mode:remove_FC converted:11.08.2023

                Cardiovascular Medicine
                epidemiology,miscarriage,myocardial infarction,pregnancy loss,stroke,risk factors,women

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