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

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.

Study Overview

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

• Study Type: Observational
• Enrollment (Anticipated): 200

Contacts and Locations

• Study Contact: Name: Lasse Gliemann, PhD; Phone Number: +4535321632; Email: gliemann@nexs.ku.dk

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • Recruiting
    • Deparment of Nutrition, Exercise and Sports
    • Contact: Lasse Gliemann, PhD
    • Principal Investigator: Lasse Gliemann, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 36 years to 57 years (Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Healthy women between 40-61 years of age, who are menstruating regularly, but that are close to the menopause ( will be estimated through hormonal levels).

It is anticipated that the population will have different physical activity levels, and the population will thus be stratified from this, to investigate the role of different habitual physical activity level.

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Copenhagen
• Investigators: Principal Investigator: Lasse Gliemann, PhD, Department of Nutrition, Exercise and Sports, University of Copenhagen, 2200 Copenhagen, Denmark

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2022
• Primary Completion (Anticipated): December 1, 2040
• Study Completion (Anticipated): August 1, 2045

Study Registration Dates

• First Submitted: November 15, 2022
• First Submitted That Met QC Criteria: December 3, 2022
• First Posted (Actual): December 13, 2022

Study Record Updates

• Last Update Posted (Actual): May 10, 2023
• Last Update Submitted That Met QC Criteria: May 9, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases
• Other Study ID Numbers: KISO STUDY

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO