ONLINE SUPPLEMENT Olesen et al.
SUPPLEMENTARY ONLINE MATERIAL
Cardiovascular disease Mortality After Bilateral Oophorectomy:
A Prospective Cohort Study
Cathrine S. OLESEN, MSca,b, Trine KOCH, MSca,b, Cecilie S. ULDBJERG, MSca,b, Laura S. GREGERSEN, MSca,b, Jane CHRISTENSEN, PhDc, Christian DEHLENDORFF, PhDc, Lærke PRISKORN, PhDa,b, Louise F. WILSON, PhDd, Youn-Hee LIM, PhDe,f, Jeanette T. JØRGENSEN, PhDe, Zorana J. ANDERSEN, PhDe, Anders JUUL, MD,
PhDa,b,g, Julie ABILDGAARD, MD, PhD a,b,h, Martha HICKEY┼, MD, PhDi, , Elvira V. BRÄUNER┼, PhDa,b,*
aDepartment of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Denmark
bThe International Research and Research Training Centre in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Denmark
cStatistics and Dataanalysis, Danish Cancer Society, Copenhagen, Denmark
dThe University of Queensland, NHMRC Centre for Research Excellence on Women and Non-communicable Diseases (CREWaND), School of Public Health, Herston Road, Herston, Queensland, Australia
eSection of Environmental Health, Department of Public Health, University of Copenhagen, Copenhagen, Denmark
fSeoul National University Medical Research Center, Seoul, Republic of Korea
gCentre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Denmark
hDepartment of Obstetrics and Gynaecology, University of Melbourne, Melbourne, Victoria, Australia
┼These authors contributed equally
*Corresponding author:
Elvira Bräuner
Department of Growth and Reproduction, Rigshospitalet, section 5064
Blegdamsvej 9, DK-2100 Tel: +45 3545 5085
Email: [email protected]
Declaration of Interest: The authors report no conflict of interests Running head: Oophorectomy and cardiovascular mortality
Funding: The research being reported in this publication was funded by The Health Foundation of Denmark (Helsefonden, Grant no. 19-B-0077). The funding covered salary for Trine Koch and Elvira Bräuner. Louise Wilson was supported by an Australian National Health and Medical Research Council (NHMRC) Centres for Research Excellence grant (APP1153420). Martha Hickey is supported by a NHMRC Investigator Grant (ID number 1193838).
The funding bodies played no role in the design, collection, analysis or interpretation of data; in the writing of the manuscript; or in the decision to submit the manuscript for publication.
Word count: Abstract: 238 words, main text: 2615 words
Data Availability Statement: Data used in the present study is governed and maintained centrally by the Danish Data Health Authority and data access is regulated by EU General Data Protection Regulations (GPDR). Data are not publicly available and anonymized data can only be accessed after approval by the Danish Data Health Authority and the Danish Data Protection Agency. Further details and other data that support the findings of this study are available from the corresponding author upon request.
Referent (n=22,358)
Unilateral oophorectomy
(n=1,035)
Bilateral oophorectomy
(n=2,040) Age at baseline (years), median (5th-95th
percentile)a
50 (44; 71) 49 (44; 65) 50 (45; 68) Body Mass Index, (kg/m2), n (%) a
BMI <18.5 586 (2.6) 24 (2.3) 30 (1.5)
BMI 18.5-24.9 15,466 (69.2) 704 (68.0) 1,383 (67.8)
BMI 25-29.9 5,081 (22.7) 247 (23.9) 469 (23.0)
BMI ≥30 1,225 (5.5) 60 (5.8) 158 (7.7)
Physical activity, n (%) a
Low 1,552 (6.9) 59 (5.7) 124 (6.1)
Moderate 14,825 (66.3) 691 (66.8) 1,428 (70.0)
High 5,981 (26.8) 285 (27.5) 488 (23.9)
Smoking status, n (%) a
Never 7,589 (33.9) 341 (32.9) 746 (36.6)
Previous 6,845 (30.6) 308 (29.8) 637 (31.2)
Current 7,924 (35.5) 386 (37.3) 657 (32.2)
Alcohol consumption, (units/week), n (%)a,b
None 3,530 (15.8) 153 (14.8) 344 (16.9)
Low drinker (< 7) 8,253 (36.9) 381 (36.8) 757 (37.1)
Moderate drinker (7-14) 5,501 (24.6) 249 (24.0) 491 (24.1)
Heavy drinker (> 14) 5,074 (22.7) 252 (24.4) 448 (21.9)
Oral contraceptives (ever use), n (%)a 12,819 (57.3) 661 (63.9) 1,145 (56.1) Hormone therapy (ever use), n (%)a 5,730 (25.6) 395 (38.2) 927 (45.4) High blood pressure, n (%)a 2,918 (13.1) 124 (12.0) 275 (13.5)
High cholesterol, n (%)a 228 (1.0) 9 (0.9) 22 (1.1)
Hysterectomy, n (%)c 2,145 (9.6) 475 (45.9) 1,660 (81.4)
CV mortality, n (%)d 707 (3.2) 15 (1.5) 50 (2.5)
aBaseline questionaire data
bIncluding beer (regular and strong), wine (red and white) and liquor
cAscertained using ICD disease/procedure codes in the Danish Patient Registry/Cancer Registry
dAscertained using ICD codes for specific cause of death in the Danish Cause of Death Registry
All included (n= 25,338) All excluded (n=3,393) Age at baseline (years), median (5th-95th percentile)a 50 (44; 70) 53 (45; 76)
Body Mass Index, (kg/m2), n (%)
BMI <18.5 639 (2.5) 121 (3.6)
BMI 18.5-24.9 17,487 (69.0) 2,147 (63.3)
BMI 25-29.9 5,776 (22.8) 830 (24.5)
BMI ≥30 1,436 (5.7) 184 (5.4)
Missing 111 (3.2)
Physical activity, n (%)a
Low 1,730 (6.8) 323 (9.5)
Moderate 16,876 (66.6) 1,942 (57.3)
High 6,732 (26.6) 767 (22.6)
Missing - 361 (10.6)
Smoking status, n (%) a
Never 8,646 (34.1) 791 (23.3)
Previous 7,765 (30.7) 731 (21.6)
Current 8,927 (35.2) 906 (26.7)
Missing - 965 (28.4)
Alcohol consumption, (units/week), n (%)a,b
None 4,012 (15.9) 588 (17.3)
Low drinker (< 7) 9,359 (36.9) 903 (26.6)
Moderate drinker (7-14) 6,215 (24.5) 503 (14.8)
Heavy drinker (> 14) 5,752 (22.7) 537 (15.9)
Missing - 862 (25.4)
Oral contraceptives (ever use), n (%) a 14,555 (57.4) 1,640 (48.3)
Missing - 180 (5.3)
Hormone therapy (ever use), n (%)a 6,999 (27.6) -
Missing - 3,393 (100.0)
High blood pressure, n (%) a 3,306 (13.1) 606 (17.9)
Missing - 45 (1.3)
High cholesterol, n (%) a 258 (1.0) 32 (0.9)
Missing - 961 (28.3)
CV mortality, n (%)c 772 (3.1) 185 (5.5)
Missing - 0 (0.0)
aFrom baseline questionnaire.
bIncluding beer (regular and strong), wine (red and white) and liquor
cAscertained using ICD codes for specific cause of death in the Danish Cause of Death Registry
ONLINE SUPPLEMENT Olesen et al.
Danish National Patient Registry
The NPR is a Danish health register established in 1977 to register all information on in-patients in Danish hospitals (1). Since 2007 the register has contained information on all patients, both psychiatric and somatic in- and out-patients, at Danish hospitals. Data in the NPR covers clinical information on patient’s diagnoses and surgical procedures. More-over, information on patient’s CPR number, hospital ward, date and time of activity and accidents leading to hospital contact are covered in the register. Until 1995, surgical procedures and diagnoses were coded according to the International Classification of Diseases, Eighth Revision (ICD-8).
From 1995 procedures and diagnoses were coded according to the International Classification of Diseases, Tenth Revision (ICD-10) (1). The NPR was used to extract data on procedure codes and dates of hysterectomy and/or oophorectomy (unilateral and bilateral) in the nurses. The following procedure codes were utilized to identify nurses with hysterectomy and/or oophorectomy and date of procedure:
Hysterectomy in DNPR:
ICD-8 codes: 61000 (supra-vaginal hysterectomy), 61020 (abdominal hysterectomy), 61040 (vaginal hysterectomy with ovarian conservation), 61050 (laparoscopic assisted hysterectomy), 61100 (hysterectomy with removal of lymph nodes), 72650 (vaginal hysterectomy)
ICD-10 codes: KLCC10 (supra-vaginal hysterectomy), KLCC11 (laparoscopic supra-vaginal hysterectomy), KLCD00 (total hysterectomy), KLCD01 (total laparoscopic hysterectomy), KLCD10 (vaginal hysterectomy), KLCD11 (laparoscopic assisted vaginal hysterectomy)
Unilateral oophorectomy in DNPR:
ICD-8 codes: 60100 (unilateral oophorectomy), 60101 (unilateral endoscopic oophorectomy), 60300 (unilateral salpingo-oophorectomy).
ICD-10 codes: KLAE10 (unilateral oophorectomy), KLAE11 (unilateral laparoscopic oophorectomy), KLAF00 (unilateral salpingo-oophorectomy), KLAF01 (unilateral laparoscopic salpingo-oophorectomy)
Bilateral oophorectomy in DNPR:
ICD-8 codes: 60120 (bilateral oophorectomy), 60121 (bilateral endoscopic oophorectomy), 60320 (bilateral salpingo-oophorectomy).
ICD-10 codes: KLAE20 (bilateral oophorectomy), KLAE21 (bilateral laparoscopic oophorectomy), KLAF10 (bilateral salpingo-oophorectomy), KLAF11 (bilateral laparoscopic salpingo- oophorectomy).
Causes of death Registry (CDR)
The CDR is administered by the Danish Health Data Authority and has covered information on all causes of deaths occurring in Denmark since 1970 (2). The purpose of the register is to provide information for research and public health monitoring. Data in the register is based on electronic death certificates completed by physicians. It has been mandatory by law for physicians to complete a death certificate for deaths occurring in Denmark since 1871. The CDR comprises the CPR number of the deceased person, data on the death, place of death, the main underlying and up to three contributory causes of death, among others. Deaths are coded utilizing ICD-8 codes (<1995) and ICD-10 codes (≥1995) (5). Information on CV mortality was extracted from this registry. The utilized ICD-8 and -10 death codes for CV mortality were:
ICD-8 codes (<1995): 410.0 – 414.0 (ischemic heart disease), 427.9 & 441.2 (other CVD), 433.9 &
436.9 (cerebrovascular disease), 450.0 (stroke).
ICD-10 codes (≥1995): I10.0-15.9 (hypertensive heart disease), I20.0-25.9 (ischemic heart disease), I63.0-66.9 (stroke), I46.0-47.9 (cardia arrest & tachycardia), I70.0-71.9 & I74.0 (other CVD).
ONLINE SUPPLEMENT Olesen et al.
References
1. Lynge E, Sandegaard JL, Rebolj M. The Danish National Patient Register. Scand J Public Health. 2011 Jul 1;39(7_suppl):30–3.
2. Helweg-Larsen K. The Danish Register of Causes of Death. Scand J Public Health. 2011 Jul 1;39(7_suppl):26–9.
