Transcript Complimentary Slide Presentation.

AHA Scientific Sessions 2007
Orlando, Nov 6th, 2007
Anticonceptive Drug Use and Increased
Carotid and Femoral Plaque Prevalence:
Population Data from ASKLEPIOS
Ernst Rietzschel1,2
1 Department of Cardiovascular Diseases, Ghent University,
Marc De Buyzere1
2 Department of Public Health, Ghent University,
Dirk De Bacquer2
3 Department of Molecular Biotechnology, Ghent University
3
Sofie Bekaert
4 Hydraulics Laboratory, IBITECH, Ghent University
5 Association of Primary Care Physicians ASKLEPIOS, Erpe-Mere
Patrick Segers4
P. Cassiman5
P. Verdonck4
Guy De Backer2
Thierry Gillebert1
on behalf of the Asklepios investigators.
Presenter Disclosure Information :
No relationships to disclose. No unlabeled/unapproved uses of drugs or products.
Oral Contraceptive Use Linked to Higher Arterial Plaque Levels
BACKGROUND:
•
Combination therapy with the female hormones estrogen and
progestin are among the most frequently used drugs in the world
with approx. 100 million women taking oral contraceptives (OC).
UN Population Division (2006). World Contraceptive Use 2005
•
Recent large trials (WHI, HERS, Wisdom) have cast doubt on the
cardiovascular safety of hormonal replacement therapy (HRT).
Anderson et al, JAMA 2004 ; Manson et al, NEJM 2003; Hsia et al Arch Intern Med 2006; Hulley et al,
JAMA 1998
•
In contrast to the active controversy surrounding HRT, very little
attention has been focused on OC, a drug therapy using 10 to 100
fold higher levels of estrogen than HRT.
•
Current evidence indicates an increased thrombotic risk (venous >
arterial) for current OC users. This increased risk is believed to fall
back to baseline upon cessation, without subclinical damage
Baillargeon et al, JCEM 2005; Rosendaal et al ATVB 2002
accumulation.
E. Rietzschel, on behalf of the ASKLEPIOS investigators
AHA Scientific sessions 2007
Oral Contraceptive Use Linked to Higher Arterial Plaque Levels
EXPERIMENTAL QUESTION
• We describe the relation between carotid and femoral atherosclerosis
and long-term OC exposure.
• Null hypothesis = no harm
STUDY SETTING : Random community sample
• 2524 apparently healthy 35-55 year-old subjects from Erpe-Mere
• Risk factors extensively profiled
• Atherosclerosis imaging (GE/Vingmed VIVID 7 - 10-12 MHz probe).
• Bilateral carotid and femoral arteries
• Plaque = a focal protrusion >50% compared to adjacent sites with an
absolute thickness >1.5 mm or with a protrusion into the lumen of >0.5 mm.
• OC exposure was calculated from data provided by the subject,
and validated in conjunction with their primary care physician.
Rationale, Design, Methods and Baseline Characteristics of the Asklepios Study.
Rietzschel et al. European Journal of Cardiovascular Prevention & Rehabilitation (2007)
E. Rietzschel, on behalf of the ASKLEPIOS investigators
AHA Scientific sessions 2007
Oral Contraceptive Use Linked to Higher Arterial Plaque Levels
BASELINE CHARACTERISTICS
Age (median; years)
45.7
25.1  4.7
BMI (kg/m2)
Metabolic syndrome (IDF)
12 %
Total cholesterol / HDL-cholesterol (mg/dl)
214  36 / 71  17
Systolic BP / diastolic BP (mmHg)
123  14 / 78  10
High - sensitive CRP (mg/l)
1.42 [ 0.62 – 3.42 ]
Active smoking (%)
17.7%
Fasting glycemia >=100 mg/dl or diabetes
9.7%
OC Exposure
•
81% of our 1301 women have taken OC for ≥ 1 year.
(2002 US data: 82% of women 15-44y. CDC 2004)
•
Median OC exposure was 13 years.
E. Rietzschel, on behalf of the ASKLEPIOS investigators
AHA Scientific sessions 2007
Oral Contraceptive Use Linked to Higher Arterial Plaque Levels
•
•
Prevalence of Unilateral disease (right or left artery)
Odds ratio’s (OR) per 10 years of OC exposure were
• carotid plaque 1.17 (1.00-1.33); p<0.05
• femoral plaque 1.28 (1.10-1.47); p<0.01
Effect of OC exposure (per 10 years)
OR for having unilateral plaque
Carotid plaque
Femoral plaque
0.6
0.8
1.0
1.2
1.4
1.6
1.8
2.0
Adjusted for age, smoking, blood pressure, total & HDL-cholesterol, body mass index,
diabetes, physical activity, fruit, vegetable and alcohol intake, educational achievement
and drug therapy (lipid-lowering, antihypertensive, aspirin)
E. Rietzschel, on behalf of the ASKLEPIOS investigators
AHA Scientific sessions 2007
Oral Contraceptive Use Linked to Higher Arterial Plaque Levels
•
•
•
Prevalence of bilateral disease (right + left artery)
More specific and stringent phenotype
OR per 10 years OC exposure were:
• carotid plaque 1.42 (1.03-1.84); p<0.05
• femoral plaque 1.34 (1.05-1.63); p<0.05
Effect of OC exposure (per 10 years)
OR for having bilateral plaque
Carotid plaque
Femoral plaque
0.6
0.8
1.0
1.2
1.4
1.6
1.8
2.0
Adjusted for age, smoking, blood pressure, total & HDL-cholesterol, body mass index, diabetes, physical activity, fruit,
vegetable and alcohol intake, educational achievement and drug therapy (lipid-lowering, antihypertensive, aspirin)
E. Rietzschel, on behalf of the ASKLEPIOS investigators
AHA Scientific sessions 2007
Oral Contraceptive Use Linked to Higher Arterial Plaque Levels
CONCLUSIONS
• Use of OC is very common and associated with an
unexpected increase in prevalence of carotid and
femoral atherosclerosis in young, apparently healthy
women.
• Our results suggest a 20-30% increased prevalence of
plaque in the carotid and femoral arteries per 10 years of
OC exposure.
• In the light of widespread (>80% of our population sample; 100
million women globally) and usually prolonged OC use (>10
years) these results suggest that OC use could be an
important factor in the global atherosclerotic burden.
E. Rietzschel, on behalf of the ASKLEPIOS investigators
AHA Scientific sessions 2007
Oral Contraceptive Use Linked to Higher Arterial Plaque Levels
DISCUSSION
• Current thrombotic risk  Current thrombotic risk +
accumulation of subclinical atherosclerotic damage
Born 1947 - 1967
1945
1950
1955
1960
18 years: 1965 - 1985
1965
1970
Pil introduction (B) 1st gen
1975
1980
2nd gen
Study start 2002
1985
1990
1995
2000
3rd gen
• Mechanisms ?
1. Hormonal: HRT benefit/harm not fully clarified
2. Adverse impact of classic CRF : BP: + 4-9 mmHg, HDL, LDL
E. Rietzschel, on behalf of the ASKLEPIOS investigators
AHA Scientific sessions 2007
Oral Contraceptive Use Linked to Higher Arterial Plaque Levels
Short-term
Scientific
Confirmation
Long-term
More research
No discontinuation !
OC users
Check & Control
classic risk factors
E. Rietzschel, on behalf of the ASKLEPIOS investigators
Opportunity for
better prevention
AHA Scientific sessions 2007
Dept. Cardiovascular Diseases
Faculty of Medicine, Ghent University
Promotor Prof. Thierry Gillebert MD, PhD
Investigators: Ernst Rietzschel, MD &
Marc De Buyzere, BSc, Michel Langlois, MD,
PhD (clinical chemistry (AZ St-Jan, Bruges)
Dept. Epidemiology and Public Health
Faculty of Medicine, Ghent University
Promotor Prof. Guy De Backer, MD, PhD
Investigator : Prof. Dirk De Bacquer, PhD
Primary Care Physicians :
Asklepios VOF (89)
Communities Erpe-Mere –
Nieuwerkerken & MDC
Department of Molecular Biotechnology,
Faculty of Bioscience Engineering, Ghent
University
Promotor Prof. Patrick Van Oostveldt, PhD
Investigators : Ir. Sofie Bekaert, PhD, Tim De Meyer
Cardiovascular Mechanics and
Biofluid Dynamics Research Unit
Institute Biomedical Technology
(IBiTech), Ghent University
Promotor Prof. ir Pascal Verdonck, PhD
Investigators : Prof. Ir. Patrick Segers, PhD,
Ir. Tom Claessens, Ir. Sebastiaan Vermeersch