Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12618000005257
Ethics application status
Approved
Date submitted
27/11/2017
Date registered
10/01/2018
Date last updated
10/01/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Arterial Stiffness in women, during the menopausal transition and beyond, as a predictor of cardiovascular disease: a twelve-year followup to assess the contribution of hormonal factors in a representative sample of urban Australian women
Scientific title
A twelve-year followup study to assess arterial stiffness as a predictor of cardiovascular disease in a representative sample of urban Australian women
Secondary ID [1] 293458 0
None
Universal Trial Number (UTN)
Trial acronym
LAW study (Longitudinal Assessment of Ageing in Women) - the arterial compliance project is a sub-study of the LAW study
Linked study record
O ’ Neill SM, Liu J, O ’ Rourke MF, Khoo SK. The menopausal transition does not appear
to accelerate age-related increases in arterial stiffness. CLIMACTERIC 2012;15:1–8

The cited paper reported on the cr0ss-sectional analysis of the arterial stiffness project of the LAW study. The conclusion was that the data should be confirmed with the results of longitudinal data.

Health condition
Health condition(s) or problem(s) studied:
Heart disease in women 305638 0
Menopause 305739 0
Condition category
Condition code
Cardiovascular 304863 304863 0 0
Diseases of the vasculature and circulation including the lymphatic system
Reproductive Health and Childbirth 305087 305087 0 0
Menstruation and menopause

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
The proposed study will replicate a previous cross-sectional study of the relationship between
menopause status and arterial stiffness in a subset of a multidisciplinary assessment of the effects of ageing in women. The results of the cross-sectional study (see earlier citation) demonstrated that ageing was the factor most strongly associated with increasing aortic stiffness. Menopause, per se, did not appear to alter gradual age-dependent changes in arterial stiffness. However, this study was limited by its five-year time span, and the numbers of women who were approaching the menopausal transition at the time of the study
This replication will involve re-testing the same sample of women twelve years after their initial assessment when all pre-menopausal women in the original sample will almost certainly have entered or passed through the menopausal transition.

The retest procedure should take approximately one hour to complete and was conducted in the Betty Byrne Henderson Women's Health Research Centre, Royal Brisbane Women's Hospital Herston, QLD.
Brachial systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured
in the sitting position after approximately 5 minutes of rest using a mercury sphygmomanometer. BP measurement was recorded as an average of three readings at two-minute intervals.
Arterial stiffness (pulse wave velocity and pulse wave analysis) was measured non-invasively (using SphygmoCor® technology). All assessments were undertaken by the same specially trained registered nurses using the same equipment. SBP and DBP were entered into the SphygmoCor software to allow for calibration of the radial pressure waveform. Height, weight, body mass index (BMI), details of medical history, family history of diabetes and cardiovascular disease (CVD), smoking history, menopause status, use of cardiovascular medication and hormone therapy were also entered into the SphygmoCor database.
All participants were studied in the supine position. Radial artery waveforms were
recorded in all subjects with a high-fidelity tonometer (Millar Instruments, Houston, Texas) from the right wrist. Pulse wave analysis (SphygmoCor version CvMSV9. AtCor Medical Pty
Ltd., Sydney, Australia) was used to generate a corresponding central waveform with a
generalized transfer function, which has been validated against invasive recordings of the
aortic pressure wave. Four or five studies of pulse wave analysis (PWA) were collected from each subject, and the mean values used in the subsequent analysis. Only studies with a quality index of over 90% were accepted. With the SphygmoCor software, Augmentation Pressure (AP) is calculated as the difference between the second and first systolic peaks, and Augmentation Index calculated as AP expressed as a percentage of the pulse pressure (PP).
The aortic pulse wave velocity (PWV) was measured with the same machine, at the femoral (site A) and carotid (site B) arteries with simultaneous electrocardiograph (ECG) using the Lead II ECG configuration. PWV distance was measured (in millimeters) superficially by subtracting the distance between the carotid site and the suprasternal notch from the distance between the suprasternal notch (via the umbilicus) and the femoral site.
Intervention code [1] 299698 0
Not applicable
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 304059 0
The aim of this composite primary outcome study was to determine the relationship between menopause status and parameters of arterial stiffness including: pulse wave velocity (PWV), augmentation index (AI), and augmentation index @75 (AIx@75), in a cohort of urban Australian women followed up for 12 years.

PWV is the 'gold standard' for assessing arterial stiffness and was measured non-invasively using SphygmoCor technology. AIx and AIx@75 may also be used to support PWV and are measured simultaneously. (See description under step #3)
Timepoint [1] 304059 0
Each subject was retested for arterial stiffness 12 years after the original test, using non-invasive methodology (SphygmoCor, Atcor Medical). The retesting occurred within an 18-month period, beginning in July 2013.
Secondary outcome [1] 340815 0
The number of reported cardiac events including cardiac deaths in the cohort between baseline and 12-year follow up. Details of cardiac events were collected at the time of retest and included: history of myocardial infarction, angina, transient ischaemia attack, coronary artery bypass procedure, stent procedure, stroke, venous thromboembolism, cardiac arrhythmia.
Timepoint [1] 340815 0
12 year follow-up

Eligibility
Key inclusion criteria
Women who had participated in the arterial compliance project of the original LAW study during 2001-2002 were invited to participate in the retest project.
The LAW study (an age stratified prospective multidisciplinary study conducted at the RBWH)- a total of 511 urban women were randomly selected from the Brisbane North electoral roll within four age cohorts: 40–49, 50–59,60–69 and 70–79 years.

Eligible women were restricted; to the geographic area of North Brisbane, defined as all suburbs north of the Brisbane river; women who were ambulatory or able to be transported; available and willing to undergo the comprehensive examinations; and willing to provide informed consent.

It was estimated that there would be 350 women available of the original cohort of 468 who
participated in the cross-sectional arterial compliance project (2001-2002) of the LAW study,
Minimum age
40 Years
Maximum age
80 Years
Sex
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Women who were not ambulatory, or due to illness and unable to attend the research unit, as well as those with conditions such as atrial fibrillation which would have affected the testing itself.

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
A 12- year longitudinal design will be used to capture the menopause effect with age as an
explanatory variable. The Statistical Package for the Social Sciences software (SPSS, Chicago,
IL, Version 21.0) and SAS program (version 9.3) will be used for multiple regression analysis to
investigate the association and correlation between menopausal transition and the rate of arterial stiffening (PWV, AIX, AIx@75).
There were 468 patients in the cross- sectional study. Of the original cohort, it is expected that
350 subjects will be followed-up at the 12-year retest. A sample size of 350 women will achieve a statistical power of 90% in detecting a statistically significant difference (a = 0.05).

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
10/07/2013
Date of last participant enrolment
Anticipated
Actual
30/04/2014
Date of last data collection
Anticipated
Actual
18/12/2014
Sample size
Target
350
Accrual to date
Final
324
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 9446 0
Royal Brisbane & Womens Hospital - Herston
Recruitment postcode(s) [1] 18164 0
4029 - Royal Brisbane Hospital

Funding & Sponsors
Funding source category [1] 298082 0
Other
Name [1] 298082 0
Arterial Compliance Trust Account
Country [1] 298082 0
Australia
Primary sponsor type
Individual
Name
Clinical Associate Professor Sheila O'Neill
Address
Betty Byrne Henderson Women's Health Research Centre, c/o PO Box 3275, Manuka, ACT 2603
Country
Australia
Secondary sponsor category [1] 297161 0
None
Name [1] 297161 0
Address [1] 297161 0
Country [1] 297161 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299104 0
Human Research Ethics Committee, Royal Brisbane and Women's Hospital Metro North Hospital and Health Service
Ethics committee address [1] 299104 0
Royal Brisbane Women's Hospital, Butterfield Street, Herston, QLD 4029.
Ethics committee country [1] 299104 0
Australia
Date submitted for ethics approval [1] 299104 0
22/04/2013
Approval date [1] 299104 0
06/06/2013
Ethics approval number [1] 299104 0
HREC/13/QRBW/136

Summary
Brief summary
The proposed study will help resolve a long-running controversy in women’s health. For the first time in Australia, it will provide longitudinal (12-year) data abut the relationship between the rate of increase in arterial stiffness in women (a known risk factor for cardiovascular disease) and the withdrawal of oestrogen through the menopausal transition
Trial website
Not applicable
Trial related presentations / publications
None
Public notes

Contacts
Principal investigator
Name 79302 0
A/Prof Sheila O'Neill
Address 79302 0
Betty Byrne Henderson Women's Health Research Centre, Royal Brisbane Women's Hospital, Herston Qld 4006

Postal address: PO Box 3275 Manuka, ACT 2603
Country 79302 0
Australia
Phone 79302 0
+61 2 6193 3792
Fax 79302 0
Email 79302 0
[email protected]
Contact person for public queries
Name 79303 0
A/Prof Sheila O'Neill
Address 79303 0
Betty Byrne Henderson Women's Health Research Centre, c/o PO Box 3275, Manuka, ACT 2603
Country 79303 0
Australia
Phone 79303 0
+61 2 6193 3792
Fax 79303 0
Email 79303 0
[email protected]
Contact person for scientific queries
Name 79304 0
A/Prof Sheila O'Neill
Address 79304 0
Betty Byrne Henderson Women's Health Research Centre, c/o PO Box 3275, Manuka, ACT 2603
Country 79304 0
Australia
Phone 79304 0
61 2 6193 3792
Fax 79304 0
Email 79304 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseMenopause and accelerated aortic stiffness.2024https://dx.doi.org/10.1016/j.maturitas.2023.107900
N.B. These documents automatically identified may not have been verified by the study sponsor.