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

Recruiting

• Conditions: Menopause; Vascular Dilation; Physical Activity; Cardiovascular Diseases

• Registration Number: NCT05647876
• Lead Sponsor: University of Copenhagen

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-11-15
• Study First Submitted QC: 2022-12-03
• Study First Posted: 2022-12-13
• Study Start: 2022-12-16
• Status Verified: 2023-05
• Last Update Submitted: 2023-05-09
• Last Update Posted: 2023-05-10
• Primary Completion: 2040-12
• Study Completion: 2045-08

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 200

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Invasive vascular function	pre, 1yr. 3yr. , 5 yr., 10 yr. and 20 yr. post menopause	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
Non-invasive vascular function	pre, 1yr. 3yr. , 5 yr., 10 yr. and 20 yr. post menopause	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

Secondary Outcome Measures

Name	Time	Method
Changes in skeletal muscle expression of protein	pre, 1yr. 3yr. , 5 yr., 10 yr. and 20 yr. post menopause	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.
Changes in skeletal muscle and blood sample expression of RNA	pre, 1yr. 3yr. , 5 yr., 10 yr. and 20 yr. post menopause	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.
Blood pressure	pre, 1yr. 3yr. , 5 yr., 10 yr. and 20 yr. post menopause	Changes in blood pressure across the menopausal transition

Trial Locations

Locations (1)

Deparment of Nutrition, Exercise and Sports; 🇩🇰 Copenhagen, Denmark