{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T10:20:44Z","timestamp":1777026044957,"version":"3.51.4"},"reference-count":56,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,27]],"date-time":"2022-12-27T00:00:00Z","timestamp":1672099200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Swedish Research Council","award":["Dnr:2018-02551"],"award-info":[{"award-number":["Dnr:2018-02551"]}]},{"name":"King Gustaf V\u2019s 80-Year Fund","award":["Dnr:2018-02551"],"award-info":[{"award-number":["Dnr:2018-02551"]}]},{"name":"Swedish Rheumatism Association","award":["Dnr:2018-02551"],"award-info":[{"award-number":["Dnr:2018-02551"]}]},{"name":"Ume\u00e5 University","award":["Dnr:2018-02551"],"award-info":[{"award-number":["Dnr:2018-02551"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Hormonal and reproductive factors affect the risk for cardiovascular events (CVE) in the general population. Although the risk of CVE is increased in rheumatoid arthritis (RA), the knowledge about the impact of hormonal factors for CVE in RA is sparse. Female postmenopausal patients \u226480 years with early RA were consecutively included in this observational study (n = 803) between 1 January 1996 until 31 December 2017. Questionnaires regarding hormonal factors were distributed from the index date. Data regarding CVE were obtained from the Swedish National Health Register and Cause of Death Register. Associations between CVE and hormonal factors were analyzed using Cox proportional hazard regression. Of the postmenopausal women, 64 women had a CVE after RA onset. The time period from menopause to RA onset was significantly longer for CVE cases with higher proportion of postmenopausal women. In Cox proportional hazard regression models, years from last childbirth and multiparity were associated with higher CVE risk. Adjustments for traditional risk factors did not affect the results except for hypertension. RA onset after menopause and a longer duration from menopause until onset increased the CVE risk. Multiparity was associated with higher CVE risk whilst oral contraceptives decreased the risk. These results can contribute to identification of high-risk patients for CVE beyond traditional risk factors.<\/jats:p>","DOI":"10.3390\/jcm12010208","type":"journal-article","created":{"date-parts":[[2022,12,28]],"date-time":"2022-12-28T05:31:54Z","timestamp":1672205514000},"page":"208","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Hormonal and Reproductive Factors in Relation to Cardiovascular Events in Women with Early Rheumatoid Arthritis"],"prefix":"10.3390","volume":"12","author":[{"given":"Antonia","family":"Boman","sequence":"first","affiliation":[{"name":"Department of Public Health and Clinical Medicine\/Rheumatology, Ume\u00e5 University, 90187 Ume\u00e5, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9600-5364","authenticated-orcid":false,"given":"Heidi","family":"Kokkonen","sequence":"additional","affiliation":[{"name":"Department of Public Health and Clinical Medicine\/Rheumatology, Ume\u00e5 University, 90187 Ume\u00e5, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ewa","family":"Berglin","sequence":"additional","affiliation":[{"name":"Department of Public Health and Clinical Medicine\/Rheumatology, Ume\u00e5 University, 90187 Ume\u00e5, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerd-Marie","family":"Alenius","sequence":"additional","affiliation":[{"name":"Department of Public Health and Clinical Medicine\/Rheumatology, Ume\u00e5 University, 90187 Ume\u00e5, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8259-3863","authenticated-orcid":false,"given":"Solbritt","family":"Rantap\u00e4\u00e4-Dahlqvist","sequence":"additional","affiliation":[{"name":"Department of Public Health and Clinical Medicine\/Rheumatology, Ume\u00e5 University, 90187 Ume\u00e5, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,27]]},"reference":[{"key":"ref_1","first-page":"445","article-title":"Cardiovascular morbidity and mortality in patients with seropositive rheumatoid arthritis in Northern Sweden","volume":"24","author":"Ohman","year":"1997","journal-title":"J. Rheumatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1136\/annrheumdis-2011-200726","article-title":"Risk of incident cardiovascular events in patients with rheumatoid arthritis: A meta-analysis of observational studies","volume":"71","author":"Thomas","year":"2012","journal-title":"Ann. Rheum. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1002\/art.20853","article-title":"Increased unrecognized coronary heart disease and sudden deaths in rheumatoid arthritis: A population-based cohort study","volume":"52","author":"Crowson","year":"2005","journal-title":"Arthritis Rheumatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2346","DOI":"10.1161\/CIRCULATIONAHA.106.678334","article-title":"Cardiovascular manifestations of rheumatologic diseases","volume":"116","author":"Roman","year":"2007","journal-title":"Circulation"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1002\/art.20855","article-title":"The risk of congestive heart failure in rheumatoid arthritis: A population-based study over 46 years","volume":"52","author":"Nicola","year":"2005","journal-title":"Arthritis Rheumatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"k1036","DOI":"10.1136\/bmj.k1036","article-title":"Increased cardiovascular risk in rheumatoid arthritis: Mechanisms and implications","volume":"361","author":"England","year":"2018","journal-title":"BMJ"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1002\/art.41381","article-title":"Anti-Citrullinated Protein Antibody Specificities, Rheumatoid Factor Isotypes, and Incident Cardiovascular Events in Patients With Rheumatoid Arthritis","volume":"72","author":"Westerlind","year":"2020","journal-title":"Arthritis Rheumatol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Radu, A.F., and Bungau, S.G. (2021). Management of Rheumatoid Arthritis: An Overview. Cells, 10.","DOI":"10.3390\/cells10112857"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2149","DOI":"10.1161\/CIRCULATIONAHA.115.017854","article-title":"Reproductive Risk Factors and Coronary Heart Disease in the Women\u2019s Health Initiative Observational Study","volume":"133","author":"Parikh","year":"2016","journal-title":"Circulation"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Merritt, M.A., Riboli, E., Murphy, N., Kadi, M., Tjonneland, A., Olsen, A., Overvad, K., Dossus, L., Dartois, L., and Clavel-Chapelon, F. (2015). Reproductive factors and risk of mortality in the European Prospective Investigation into Cancer and Nutrition; a cohort study. BMC Med., 13.","DOI":"10.1186\/s12916-015-0484-3"},{"key":"ref_11","first-page":"1254","article-title":"The role of female hormonal factors in the development of rheumatoid arthritis","volume":"56","author":"Pluchino","year":"2017","journal-title":"Rheumatology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1845","DOI":"10.1136\/annrheumdis-2017-211620","article-title":"Oral contraceptives, breastfeeding and the risk of developing rheumatoid arthritis: Results from the Swedish EIRA study","volume":"76","author":"Orellana","year":"2017","journal-title":"Ann. Rheumatol. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1007\/s10654-015-0004-y","article-title":"Postmenopausal hormone therapy and the risk of rheumatoid arthritis: Results from the Swedish EIRA population-based case-control study","volume":"30","author":"Orellana","year":"2015","journal-title":"Eur. J. Epidemiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"720","DOI":"10.3389\/fimmu.2017.00720","article-title":"Insight into the Endocrine System and the Immune System: A Review of the Inflammatory Role of Prolactin in Rheumatoid Arthritis and Psoriatic Arthritis","volume":"8","author":"Tang","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"69","DOI":"10.3109\/03009748309102886","article-title":"Effect of pregnancy and hormonal changes on the activity of rheumatoid arthritis","volume":"12","author":"Ostensen","year":"1983","journal-title":"Scand. J. Rheumatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1002\/1529-0131(199906)42:6<1219::AID-ANR19>3.0.CO;2-G","article-title":"Does rheumatoid arthritis remit during pregnancy and relapse postpartum? Results from a nationwide study in the United Kingdom performed prospectively from late pregnancy","volume":"42","author":"Barrett","year":"1999","journal-title":"Arthritis Rheumatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1002\/acr.22494","article-title":"Effect of age at menopause on disease presentation in early rheumatoid arthritis: Results from the Canadian Early Arthritis Cohort","volume":"67","author":"Wong","year":"2015","journal-title":"Arthritis Care Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1196\/annals.1351.019","article-title":"Epidemiological aspects of rheumatoid arthritis: The sex ratio","volume":"1069","author":"Kvien","year":"2006","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1161\/CIRCULATIONAHA.114.010070","article-title":"Age at menarche and risks of coronary heart and other vascular diseases in a large UK cohort","volume":"131","author":"Canoy","year":"2015","journal-title":"Circulation"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1136\/heartjnl-2017-312289","article-title":"Women\u2019s reproductive factors and incident cardiovascular disease in the UK Biobank","volume":"104","author":"Peters","year":"2018","journal-title":"Heart"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1161\/01.CIR.0000053441.43495.1A","article-title":"Is the association between parity and coronary heart disease due to biological effects of pregnancy or adverse lifestyle risk factors associated with child-rearing? Findings from the British Women\u2019s Heart and Health Study and the British Regional Heart Study","volume":"107","author":"Lawlor","year":"2003","journal-title":"Circulation"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e007058","DOI":"10.1161\/JAHA.117.007058","article-title":"Adolescent Childbirth Is Associated With Greater Framingham Risk Scores for Cardiovascular Disease Among Participants of the IMIAS (International Mobility in Aging Study)","volume":"6","author":"Rosendaal","year":"2017","journal-title":"J. Am. Heart Assoc."},{"key":"ref_23","first-page":"CD011054","article-title":"Combined oral contraceptives: The risk of myocardial infarction and ischemic stroke","volume":"8","author":"Roach","year":"2015","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e011056","DOI":"10.1161\/JAHA.118.011056","article-title":"Breastfeeding and Cardiovascular Disease Hospitalization and Mortality in Parous Women: Evidence From a Large Australian Cohort Study","volume":"8","author":"Nguyen","year":"2019","journal-title":"J. Am. Heart Assoc."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.ijcard.2020.12.022","article-title":"Association of the length of oestrogen exposure with risk of incident stroke in postmenopausal women: Insights from a 20-year prospective study","volume":"328","author":"Mishra","year":"2021","journal-title":"Int. J. Cardiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e006713","DOI":"10.1161\/JAHA.117.006713","article-title":"Duration of Reproductive Life Span, Age at Menarche, and Age at Menopause Are Associated With Risk of Cardiovascular Disease in Women","volume":"6","author":"Ley","year":"2017","journal-title":"J. Am. Heart Assoc."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1001\/jamacardio.2020.4105","article-title":"Association Between Reproductive Life Span and Incident Nonfatal Cardiovascular Disease: A Pooled Analysis of Individual Patient Data from 12 Studies","volume":"5","author":"Mishra","year":"2020","journal-title":"JAMA Cardiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.maturitas.2015.07.011","article-title":"Association between duration of reproductive lifespan and Framingham risk score in postmenopausal women","volume":"82","author":"Kim","year":"2015","journal-title":"Maturitas"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1002\/art.1780310302","article-title":"The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis","volume":"31","author":"Arnett","year":"1988","journal-title":"Arthritis Rheumatol."},{"key":"ref_30","unstructured":"(2022, October 30). Svensk Reumatologis Kvalitetsregister. Available online: https:\/\/srq.nu."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1002\/art.1780380107","article-title":"Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis","volume":"38","author":"Prevoo","year":"1995","journal-title":"Arthritis Rheumatol"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1845","DOI":"10.1002\/1529-0131(199810)41:10<1845::AID-ART17>3.0.CO;2-K","article-title":"Validation of rheumatoid arthritis improvement criteria that include simplified joint counts","volume":"41","author":"Haagsma","year":"1998","journal-title":"Arthritis Rheumatol"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"R56","DOI":"10.1186\/ar2214","article-title":"The PTPN22 1858C\/T polymorphism is associated with anti-cyclic citrullinated peptide antibody-positive early rheumatoid arthritis in northern Sweden","volume":"9","author":"Kokkonen","year":"2007","journal-title":"Arthritis Res. Ther."},{"key":"ref_34","first-page":"1974","article-title":"How to apply Larsen score in evaluating radiographs of rheumatoid arthritis in long-term studies","volume":"22","author":"Larsen","year":"1995","journal-title":"J. Rheumatol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1136\/bmj.300.6719.230","article-title":"Analysis of serial measurements in medical research","volume":"300","author":"Matthews","year":"1990","journal-title":"BMJ"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1002\/sim.4067","article-title":"Multiple imputation using chained equations: Issues and guidance for practice","volume":"30","author":"White","year":"2011","journal-title":"Stat. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.3899\/jrheum.131234","article-title":"The influence of early menopause on cardiovascular risk in women with rheumatoid arthritis","volume":"41","author":"Pfeifer","year":"2014","journal-title":"J. Rheumatol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"157","DOI":"10.7326\/0003-4819-89-2-157","article-title":"Menopause and coronary heart disease. The Framingham Study","volume":"89","author":"Gordon","year":"1978","journal-title":"Ann. Intern. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.1056\/NEJM199906103402306","article-title":"The protective effects of estrogen on the cardiovascular system","volume":"340","author":"Mendelsohn","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1056\/NEJMra000471","article-title":"Production and actions of estrogens","volume":"346","author":"Gruber","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1097\/gme.0b013e3182517bd0","article-title":"Early menopause predicts future coronary heart disease and stroke: The Multi-Ethnic Study of Atherosclerosis","volume":"19","author":"Wellons","year":"2012","journal-title":"Menopause"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1056\/NEJM199305273282104","article-title":"Number of pregnancies and the subsequent risk of cardiovascular disease","volume":"328","author":"Ness","year":"1993","journal-title":"N. Engl. J. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1177\/2047487316658571","article-title":"Parity, breastfeeding and risk of coronary heart disease: A pan-European case-cohort study","volume":"23","author":"Peters","year":"2016","journal-title":"Eur. J. Prev. Cardiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"454","DOI":"10.3109\/03009741003742763","article-title":"Influence of female hormonal factors, in relation to autoantibodies and genetic markers, on the development of rheumatoid arthritis in northern Sweden: A case-control study","volume":"39","author":"Berglin","year":"2010","journal-title":"Scand. J. Rheumatol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/S0049-0172(03)00084-2","article-title":"Estrogen and other female reproductive risk factors are not strongly associated with the development of rheumatoid arthritis in elderly women","volume":"33","author":"Merlino","year":"2003","journal-title":"Semin. Arthritis Rheumatol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1097\/MOL.0000000000000022","article-title":"Estrogens and cardiovascular disease risk revisited: The Women\u2019s Health Initiative","volume":"24","author":"Howard","year":"2013","journal-title":"Curr. Opin. Lipidol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"R131","DOI":"10.1186\/ar3442","article-title":"Cardiovascular events in early RA are a result of inflammatory burden and traditional risk factors: A five year prospective study","volume":"13","author":"Innala","year":"2011","journal-title":"Arthritis Res. Ther."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1002\/art.39098","article-title":"Disease activity in rheumatoid arthritis and the risk of cardiovascular events","volume":"67","author":"Solomon","year":"2015","journal-title":"Arthritis Rheumatol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1093\/oxfordjournals.aje.a116907","article-title":"Comparison of recalled and validated oral contraceptive histories","volume":"138","author":"Nischan","year":"1993","journal-title":"Am. J. Epidemiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1093\/ije\/27.6.1033","article-title":"Oral contraceptive use: Interview data versus pharmacy records","volume":"27","author":"Norell","year":"1998","journal-title":"Int. J. Epidemiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1212\/01.wnl.0000250238.69938.f5","article-title":"Risk of ischemic stroke and lifetime estrogen exposure","volume":"68","author":"Egido","year":"2007","journal-title":"Neurology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1136\/annrheumdis-2013-203567","article-title":"Parity and the risk of developing rheumatoid arthritis: Results from the Swedish Epidemiological Investigation of Rheumatoid Arthritis study","volume":"73","author":"Orellana","year":"2014","journal-title":"Ann. Rheumatol. Dis."},{"key":"ref_53","first-page":"207","article-title":"The effect of oral contraceptives and estrogen replacement therapy on the risk of rheumatoid arthritis: A population based study","volume":"31","author":"Doran","year":"2004","journal-title":"J. Rheumatol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1136\/ard.50.2.72","article-title":"Oral contraception and its possible protection against rheumatoid arthritis","volume":"50","author":"Hazes","year":"1991","journal-title":"Ann. Rheum. Dis."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/S0049-0172(97)80025-X","article-title":"Oral contraceptives and rheumatoid arthritis: Results from a primary care-based incident case-control study","volume":"26","author":"Brennan","year":"1997","journal-title":"Semin. Arthritis Rheum."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1097\/00001648-199003000-00012","article-title":"The relationship of oral contraceptive use to rheumatoid arthritis","volume":"1","author":"Moskowitz","year":"1990","journal-title":"Epidemiology"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/1\/208\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:52:58Z","timestamp":1760147578000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/1\/208"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,27]]},"references-count":56,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["jcm12010208"],"URL":"https:\/\/doi.org\/10.3390\/jcm12010208","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,27]]}}}