A Longitudinal Study to Identify Mechanisms of Menopause on Cardiovascular Disease Risk

Study Overview
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Brief Summary
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With the cessation of estrogen production at menopause, the risk of cardiovascular disease like arthrosclerosis, myocardial infarction and stroke increases dramatically. Physical activity is the single most powerful drug for maintaining and improving cardiovascular health, but recent data suggest that the positive effect of physical activity is lost at menopause. In this project the investigators will follow a cohort of 200 women from before the women enter menopause and until at least 10 years past menopause. By advanced invasive methodologies the investigators will monitor the changes that occur in the blood vessels of the circulation, the heart and the brain and combine this with microRNA sequencing of blood and tissue samples.

Official Title
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A Longitudinal Study to Identify Mechanisms of Menopause on Cardiovascular Disease Risk

Conditions
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Menopause, Cardiovascular Diseases, Vascular Dilation, Physical Activity

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Normal ECG Regular menstruation Exclusion Criteria: Participation in other clinical projects Smokes or has smoked within the last 10 years On hormone therapy Has chronic diseases that are not expected, cf. the groups sought. Including heart problems, atrial fibrillation, cancer, immune diseases and previous strokes with functionally significant sequelae Being treated with oral steroids Has alcohol / drug abuse or is being treated with disulfiram (Antabus) Is unable to understand the contents of the document with informed consent or the experimental procedures Pregnancy or breastfeeding Systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg ovariectomy BMI>28

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 61 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Invasive vascular function | Changes in vascular function across the menopausal transition (pre, 1yr. 3yr. , 5 yr., 10 yr. and 20 yr. post menopause Vascular function is assessed by intra-arterial infusions of acetylcholine and epoprostenol) in the brachial artery using ultrasound doppler | pre, 1yr. 3yr. , 5 yr., 10 yr. and 20 yr. post menopause | 
| Non-invasive vascular function | Changes in vascular function across the menopausal transition (pre, 1yr. 3yr. , 5 yr., 10 yr. and 20 yr. post menopause Vascular function is assessed by flow-mediated dilation (FMD) in the brachial artery using ultrasound doppler | pre, 1yr. 3yr. , 5 yr., 10 yr. and 20 yr. post menopause | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in skeletal muscle expression of protein | Changes in skeletal muscle expression of protein across the menopausal transition, and with different physical activity levels. (pre, 1yr. 3yr. , 5 yr., 10 yr. and 20 yr. post menopause Western blots will be used to determine endothelial nitric oxide synthase (eNOS), cyclo-oxygenase 1 and 2, prostacyclin synthase, endothelin receptor A and B, VEGF (vascular endothelial growth factor), Thrombospondin-1, Flk-1 (VEGF receptor). All protein content measures will be presented as arbitrary units. | pre, 1yr. 3yr. , 5 yr., 10 yr. and 20 yr. post menopause | 
| Changes in skeletal muscle and blood sample expression of RNA | Changes in skeletal muscle and blood sample expression of RNA across the menopausal transition, and with different physical activity levels. (pre, 1yr. 3yr. , 5 yr., 10 yr. and 20 yr. post menopause. RNA sequencing will be used to determine changes in RNA profile, with specific focus on microRNA. | pre, 1yr. 3yr. , 5 yr., 10 yr. and 20 yr. post menopause | 
| Blood pressure | Changes in blood pressure across the menopausal transition | pre, 1yr. 3yr. , 5 yr., 10 yr. and 20 yr. post menopause |