Outi Uimari1,2,3,4,5, Juha Auvinen6,7, Jari Jokelainen6,7, Katri Puukka3,8, Aimo Ruokonen3,8, Marjo-Riitta Järvelin6,7, Terhi Piltonen9,2,3, Sirkka Keinänen-Kiukaanniemi6,7, Krina Zondervan4,5, Ilkka Järvelä9,2,3, Markku Ryynänen9,2,3, Hannu Martikainen9,2,3. 1. Department of Obstetrics and Gynaecology, Oulu University Hospital, PO Box 5000, 90014 Oulu, Finland outi.uimari@oulu.fi. 2. PEDEGO Research Unit, University of Oulu and Oulu University Hospital, PO Box 5000, 90014 Oulu, Finland. 3. Medical Research Center Oulu, University of Oulu and Oulu University Hospital, PO Box 5000, 90014 Oulu, Finland. 4. Endometriosis CaRe Centre, Nuffield Department of Obstetrics and Gyneacology, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK. 5. Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK. 6. Center for Life Course Health Research, University of Oulu, PO Box 8000, 90014 Oulu, Finland. 7. Unit of Primary Care, Oulu University Hospital, PO Box 5000, 90014 Oulu, Finland. 8. NordLab Oulu, Department of Clinical Chemistry, University Hospital of Oulu, University of Oulu, PO Box 5000, 90014 Oulu, Finland. 9. Department of Obstetrics and Gynaecology, Oulu University Hospital, PO Box 5000, 90014 Oulu, Finland.
Abstract
STUDY QUESTION: Are uterine fibroids associated with increased cardiovascular risk? SUMMARY ANSWER: This study reports an association between increased serum lipids and metabolic syndrome with an increased risk of uterine fibroids. WHAT IS KNOWN ALREADY: Recent studies suggest similarities in biological disease mechanisms and risk factors for fibroids and atherosclerosis: obesity, hypertension and abnormal serum lipids. These findings are awaiting confirmation that a population-based follow-up study could offer with extensive health examination data collection linked with a national hospital discharge register. STUDY DESIGN, SIZE, DURATION: The Northern Finland Birth Cohort (NFBC1966) is a population-based long-term follow-up study including all children with estimated date of delivery in 1966 in the Northern Finland area. The data were collected from national registries, postal questionnaires and clinical health examinations. The study population for this study comprised all females included in the NFBC1966 that underwent an extensive clinical health examination at age 46 years (n = 3635). PARTICIPANTS/MATERIALS, SETTING, METHODS: All females included in the NFBC1966 who were alive and traceable (n = 5118) were invited for the 46-year follow-up study; 3268 (63.9%) responded, returned the postal questionnaire and attended the clinical examination. Uterine fibroid cases were identified through the national hospital discharge register that has data on disease diagnoses based on WHO ICD-codes. Uterine fibroid codes, ICD-9: 218 and ICD-10: D25 were used for case identification. Self-reported fibroid cases were identified through the postal questionnaire. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 729 fibroid cases were identified, including 293 based on hospital discharge registries. With adjustment for BMI, parity, education and current use of exogenous hormones the risk of prevalent fibroids rose significantly for every 1 mmol/l increase in LDL (OR = 1.13, 95% CI: 1.02-1.26 for all cases) and triglycerides (OR = 1.27, 95% CI: 1.09-1.49 for all cases). Metabolic syndrome associated with hospital discharge-based fibroid diagnosis (OR = 1.48, 95% CI: 1.09-2.01). Additionally every 1 unit increase in waist-hip ratio associated with fibroids (OR = 1.32, 95% CI: 1.10-1.57). LIMITATIONS, REASONS FOR CAUTION: The case ascertainment may present some limitations. There was likely an under-identification of cases and misclassification of some cases as controls; this would have diluted the effects of reported associations. The data analysed were cross-sectional and therefore cause and effect for the associations observed cannot be distinguished. WIDER IMPLICATIONS OF THE FINDINGS: Increased serum lipids and metabolic syndrome are associated with increased risk of uterine fibroids. Along with central obesity these findings add to an increased risk for cardiovascular disease among women with fibroids. These observations may suggest that there are shared predisposing factors underlying both uterine fibroids and adverse metabolic and cardiac disease risk, or that metabolic factors have a role in biological mechanisms underlying fibroid development. STUDY FUNDING/COMPETING INTERESTS: This study was supported by the Academy of Finland, University Hospital Oulu, University of Oulu, Finland, Northern Finland Health Care Foundation, Duodecim Foundation, ERDF European Regional Development Fund-Well-being and health: Research in the Northern Finland Birth Cohort 1966. The authors declare no conflict of interest.
STUDY QUESTION: Are uterine fibroids associated with increased cardiovascular risk? SUMMARY ANSWER: This study reports an association between increased serum lipids and metabolic syndrome with an increased risk of uterine fibroids. WHAT IS KNOWN ALREADY: Recent studies suggest similarities in biological disease mechanisms and risk factors for fibroids and atherosclerosis: obesity, hypertension and abnormal serum lipids. These findings are awaiting confirmation that a population-based follow-up study could offer with extensive health examination data collection linked with a national hospital discharge register. STUDY DESIGN, SIZE, DURATION: The Northern Finland Birth Cohort (NFBC1966) is a population-based long-term follow-up study including all children with estimated date of delivery in 1966 in the Northern Finland area. The data were collected from national registries, postal questionnaires and clinical health examinations. The study population for this study comprised all females included in the NFBC1966 that underwent an extensive clinical health examination at age 46 years (n = 3635). PARTICIPANTS/MATERIALS, SETTING, METHODS: All females included in the NFBC1966 who were alive and traceable (n = 5118) were invited for the 46-year follow-up study; 3268 (63.9%) responded, returned the postal questionnaire and attended the clinical examination. Uterine fibroid cases were identified through the national hospital discharge register that has data on disease diagnoses based on WHO ICD-codes. Uterine fibroid codes, ICD-9: 218 and ICD-10: D25 were used for case identification. Self-reported fibroid cases were identified through the postal questionnaire. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 729 fibroid cases were identified, including 293 based on hospital discharge registries. With adjustment for BMI, parity, education and current use of exogenous hormones the risk of prevalent fibroids rose significantly for every 1 mmol/l increase in LDL (OR = 1.13, 95% CI: 1.02-1.26 for all cases) and triglycerides (OR = 1.27, 95% CI: 1.09-1.49 for all cases). Metabolic syndrome associated with hospital discharge-based fibroid diagnosis (OR = 1.48, 95% CI: 1.09-2.01). Additionally every 1 unit increase in waist-hip ratio associated with fibroids (OR = 1.32, 95% CI: 1.10-1.57). LIMITATIONS, REASONS FOR CAUTION: The case ascertainment may present some limitations. There was likely an under-identification of cases and misclassification of some cases as controls; this would have diluted the effects of reported associations. The data analysed were cross-sectional and therefore cause and effect for the associations observed cannot be distinguished. WIDER IMPLICATIONS OF THE FINDINGS: Increased serum lipids and metabolic syndrome are associated with increased risk of uterine fibroids. Along with central obesity these findings add to an increased risk for cardiovascular disease among women with fibroids. These observations may suggest that there are shared predisposing factors underlying both uterine fibroids and adverse metabolic and cardiac disease risk, or that metabolic factors have a role in biological mechanisms underlying fibroid development. STUDY FUNDING/COMPETING INTERESTS: This study was supported by the Academy of Finland, University Hospital Oulu, University of Oulu, Finland, Northern Finland Health Care Foundation, Duodecim Foundation, ERDF European Regional Development Fund-Well-being and health: Research in the Northern Finland Birth Cohort 1966. The authors declare no conflict of interest.
Authors: Yentl C Haan; Frederieke S Diemer; Lisa Van Der Woude; Gert A Van Montfrans; Glenn P Oehlers; Lizzy M Brewster Journal: J Clin Hypertens (Greenwich) Date: 2018-03-22 Impact factor: 3.738
Authors: Angela H E M Maas; Giuseppe Rosano; Renata Cifkova; Alaide Chieffo; Dorenda van Dijken; Haitham Hamoda; Vijay Kunadian; Ellen Laan; Irene Lambrinoudaki; Kate Maclaran; Nick Panay; John C Stevenson; Mick van Trotsenburg; Peter Collins Journal: Eur Heart J Date: 2021-03-07 Impact factor: 29.983
Authors: Shannon K Laughlin-Tommaso; Erika L Fuchs; Melissa F Wellons; Cora E Lewis; Ronit Calderon-Margalit; Elizabeth A Stewart; Pamela J Schreiner Journal: J Womens Health (Larchmt) Date: 2018-11-09 Impact factor: 3.017
Authors: C S Gallagher; N Mäkinen; H R Harris; N Rahmioglu; D I Chasman; S A Missmer; K T Zondervan; C C Morton; O Uimari; J P Cook; N Shigesi; T Ferreira; D R Velez-Edwards; T L Edwards; S Mortlock; Z Ruhioglu; F Day; C M Becker; V Karhunen; H Martikainen; M-R Järvelin; R M Cantor; P M Ridker; K L Terry; J E Buring; S D Gordon; S E Medland; G W Montgomery; D R Nyholt; D A Hinds; J Y Tung; J R B Perry; P A Lind; J N Painter; N G Martin; A P Morris Journal: Nat Commun Date: 2019-10-24 Impact factor: 17.694