Hormones and cardiovascular disease, what the Danish Nurse Cohort learned us
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1 Hormones and cardiovascular disease, what the Danish Nurse Cohort learned us Ellen Løkkegaard, Clinical Associate Professor, Ph.d. Dept. Obstetrics and Gynecology. Hillerød Hospital, University of Copenhagen
2 Design: Longitudinal observational study 1993 The Danish Nurse Cohort Study Questionnaire 23,178 female Danish Nurses >44 years Respons n=19,898 (86%) Postmenopausal women n=13,084
3 Design: Longitudinal observational study 1993 Questionnaire 23,178 female Danish Nurses >44 years Respons n=19,898 (86%) Never Users 58% Postmenopausal women n=13,084 HRT Exposure 10% Unopposed Estrogen Past Users 14% Current Users 28% 18% Combined Estrogen+progestin
4 Design: Longitudinal observational study 1993 Questionnaire 23,178 female Danish Nurses >44 years Respons n=19,898 (86%) Postmenopausal women n=13,084 Covariates Smoking Alcohol/week Body mass Index (BMI) Physical activity Hypertension Heart medication Diabetes Metabolic disease Familiar predisposition Self-rated health
5 Design: Longitudinal observational study 1993 Questionnaire National Registers of Hospital Discharges and Death End of 1998 Registers 23,178 female Danish Nurses >44 years Respons n=19,898 (86%) Ischemic Heart Disease - of those MI Stroke n=351 n=108 n=144 Death n=971 Postmenopausal women n=13,084
6 Cox proportional harzard p h(t,x) = h0(t) exp[ Σ βi xi ] i=1 Event Censur End of follow-up Age
![] i=1 Event Censur End of](/docs-images/46/343923/images/page_6.jpg "follow-up 45 50 55 60 65")
7 Hazard ratios (95% confidence intervals) for risk of death, according to use of hormone replacement therapy at baseline BMJ VOLUME FEBRUARY 2003 bmj.com
8 Hazard ratios (95% confidence intervals) for risk of ischemic heart disease and myocardial infarction according to use of hormone replacement therapy at baseline. BMJ VOLUME FEBRUARY 2003 bmj.com
9 Differential effects Hormone exposition Cardiovascular disease Cardiovascular risk-factor, present Confounder Hormone exposition Cardiovascular disease Cardiovascular Confounder risk-factor, not present
10 Ischemic heart disease Kaplan - Meier estimater No diabetes 0.50 Never HT Ever HT 0.25 Diabetes Never HT Ever HT age Løkkegaard, E et al. BMJ 2003;326:426
11 Risk of ischemic heart disease with Hormone Therapy stratified on presence of diabetes Løkkegaard, E et al. BMJ 2003;326:426 Copyright 2003 BMJ Publishing Group Ltd.
12 The Danish Nurse Cohorte vs. literature Cardiovascular disease Stroke Review (Nelson, 2002) The Danish Nurse Cohort The Women s health initiative, JAMA 2002
13 Danish Nurse Cohorte vs. literature Total follow-up due to national registerbased end-point definitions No healthy user bias in the Danish Nurse Cohort study No protective effect from hormone therapy on cardiovascular disease
14 DAnish HOrmone Register Study (DAHORS)
15 DAnish Hormone Register Study (DAHORS)
16 DAnish Hormone Register Study (DAHORS)
17 DAnish Hormone Register Study (DAHORS)
18 National register based observational study 1995 National prescription registry 698,098 healthy women Above 51 years 2,987,068 person years Eur Heart Journal (2008) 29, HT Exposure 18% 8% 74% Never Previous Current
19 National register based observational study Endpoints 1995 National prescription registry 698,098 healthy women Above 51 years 2,987,068 person years Eur Heart Journal (2008) 29, Ult National Patient - and Cause of Death Registry 4947 incident cases of Myocardial infarctions (MI) (ICD I21-I22)
20 National register based observational study Covariates Age 51-54, 55-59, 60-64, Calendar year 1995, 1996, ) Other medications for Hypertension Diabetes Hypercholesterolemia Antiarrhythmics Geographical region Region Education No occupational practice Occupational practice Academic education Unknown Eur Heart Journal (2008) 29,
21 Risk of Myocardial Infarction for women aged Never 0,0 1,0 2,0 1,00 Estrogen 0,94 WHI E 0,95 Continous comb. 1,35 WHI E+P 1,24 Eur Heart Journal (2008) 29,
22 DAHORS versus Never 0,0 1,0 2,0 WHI 1,00 Estrogen 0,94 WHI E 0,95 Continous comb. 1,35 WHI E+P 1,24
23 Modification from concomitant intake of medication for diabetes No, previous 0,0 1,0 2,0 3,0 0,85 Diabetes, previous 1,07 No,current 1,10 P-value for interaction 0.51 Eur Heart Journal (2008) 29, Diabetes,current 1,01
24 Danish Nurse Cohorte vs. DaHoRS The interaction between use of hormone therapy and medication for diabetes and risk of cardiovascular disease found in the Danish Nurse Cohort Study was not retrieved. Mayby there is an unhealthy user bias in the Danish Nurse Cohort study implying nurses having severe diabetes use HT more often. No protective effect from hormone therapy on cardiovascular disease, rather increased risk with combined therapy.
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