Clinical trial NCT03938155: Women's Advanced Risk-assessment in Manitoba
Official title: Women's Advanced Risk-assessment in Manitoba (WARM) Hearts - Examining Cardiovascular Disease Risk in Middle Aged and Older Women
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Cardiovascular Disease (CVD)
Cardiovascular Risk Factor
Vascular Stiffness
Keywords: female
humans
aged
cardiovascular system
cardiovascular diseases
cardiovascular diseases/epidemiology
early diagnosis
frailty
frailty elderly
prospective studies
Manitoba/epidemiology
gastrointestinal microbiome
cohort studies
cause of death
risk assessment
biomarkers
risk factors
pulse wave analysis
accelerometry
exercise
physical fitness
gender
sex
women
early detection
screening program
Lead sponsor: St. Boniface Hospital
Sponsor class: OTHER
First posted: 2019-05-06
Enrollment: 1000
Sex: FEMALE
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: One-thousand female participants 55 years of age or older will be recruited through a convenience sample method. Namely, we will utilize radio interviews on popular local stations to discuss the study as well as presentations at community events related to cardiovascular health. Articles will be published in a local newspaper and poster advertisements will also be placed in key locations related to the Winnipeg Regional Health Authority. Potential study participants interested in participating will contact the research coordinator in person, by email, or via telephone.

Brief summary: The main objective of this study is to test the ability of novel cardiovascular disease (CVD) prognostic tools to identify women at risk for future CVD. We plan to establish a cardiovascular health screening program at the St. Boniface Hospital and to test the efficacy of these tests for predicting adverse cardiovascular outcomes amongst a cohort of 1000 Manitoban women aged 55 years and older in the 5-year period after screening.

A second purpose of this project is to identify novel CVD biomarkers that may indicate a person is at risk for cardiovascular disease. Therefore, we plan to ask participants for permission to collect and store a sample of both their blood and stool for future research.

Detailed description: Women tend to develop heart disease approximately 10-15 years later than men, with a prevalence rate similar between sexes after women turn 55 years of age. Unfortunately, women have been under represented in cardiovascular disease (CVD) research, leading to the development of screening tools that are not able to adequately identify women at risk. Current methods of CVD risk in women in the clinical setting (Framingham Risk Score) underestimate this risk as compared to men. Thus, it appears that current screening tools are not sensitive to women's cardiovascular health, which may result in a missed diagnosis of CVD risk.

Efforts to prevent CVD focus on traditional risk factors (e.g. age, sex, smoking, cholesterol and blood pressure), which do estimate 10-year risk for heart attacks. However, this approach does not determine how well the cardiovascular system is functioning for individuals. A better approach may be the addition of non-invasive procedures to detect early stages of CVD for individual patients, which are not yet available in the primary care setting.

This project builds off of Dr. Duhamel's previous work looking at novel prognostic CVD testing in women, which successfully recruited 1030 women into "The Assessment of Large and Small Artery Elasticity for the Early Detection of Cardiovascular Disease trial (see ClinicalTrials.gov Identifier: NCT02863211)" trial in a 20 month period ending May 2017. Data from that research was presented at the 2018 Canadian Women's Heart Health Summit and identified that the addition of frailty assessments to health screening has the potential to identify women with elevated CVD risk. We are taking that knowledge forward and have developed this new trial to include additional frailty measurement approaches to determine if their addition further enhances CVD risk screening.

If this new research demonstrates that the proposed CVD risk screening approach is superior to the Framingham Risk Score (FRS) at identifying individuals who have early markers of cardiovascular disease, individuals with elevated CVD risk may be empowered to participate in interventions known to restore cardiovascular health.

Trial Objectives and Purpose

The main objective of this study is to test the ability of novel CVD prognostic tools to identify women at risk for future CVD. We plan to establish a cardiovascular health screening program at the St. Boniface Hospital and to test the efficacy of these tests for predicting adverse cardiovascular outcomes amongst a cohort of 1000 Manitoban women aged 55 years and older in the 5-year period after screening.

A second purpose of this project is to identify novel CVD biomarkers that may indicate a person is at risk for cardiovascular disease. Therefore, we plan to ask participants for permission to collect and store a sample of both their blood and stool for future research.

We are recruiting exclusively women for our study for several reasons. Women are often under-represented in cardiovascular clinical trials, which is an issue because their clinical presentation and prognosis of cardiovascular disease is different, as compared to men. For example, the assortment of traditional risk factors under estimate the risk of experiencing an adverse cardiovascular event in women, as compared to men. This is an issue because the standard method to predict future adverse cardiac events utilizes the traditional risk factors. Moreover, women who suffer a heart attack are more likely to die, have a second heart attack, develop heart failure, or consequentially suffer sudden cardiac death, as compared to men. Thus, it is important to develop new strategies to increase the predictive value of cardiovascular screening methods.

Recruitment of Subjects

We will recruit by convenience sample, 1000 Manitoban women 55 years of age and older with no previous history of CVD using print, online and media advertisements around the University of Manitoba and the Winnipeg Regional Health Authority during hosted events. Potential study participants interested in participating will contact the research coordinator in person, by email, or via telephone. The research coordinator will briefly describe the study and assess potential participants for eligibility in the study. Specifically, participants will be asked via telephone if they have been previously hospitalized for ischemic heart disease, acute myocardial infarction, stroke/transient ischemic attack, percutaneous coronary intervention, coronary artery bypass surgery, congestive heart failure, or peripheral artery disease previously).

They will then be invited to attend two testing appointments: one at the Active Living Centre at the University of Manitoba and then one at the Asper Clinical Research Institute approximately one week later. Written informed consent will be obtained after describing the nature of the study before enrolment. Sufficient time will be allowed for potential participants to provide their consent. The procedures for conducting informed consent will be documented in the study records and a copy of the signed consent will be given to the participants enrolled in the study.

Trial Design

A prospective, observational clinical trial design will be utilized to determine if the use of novel CVD prognostic tools identifies individuals that are at high risk for experiencing an adverse cardiovascular event in the 5-year period after screening.

Women that respond to the advertisements will be recruited to participate in the study. Each participant will complete the WARM Hearts protocol. A blood sample (15 ml) will also be taken to measure cholesterol, blood sugar, and novel blood-based biomarkers, such as epigenetic and genetic markers of cardiovascular disease risk. Stool samples will be collected in order to characterize the gut microbiome.

We plan to utilize each individual's Personal Health Information Number (PHIN) to follow the study participants and to determine if they experienced an adverse cardiovascular outcome using the Manitoba Centre for Health Policy Population Health Research Data Repository. The repository contains anonymized information, which is linkable across files through a fictitious number assigned to the records. We have defined adverse cardiovascular outcomes as hospitalization or death due to ischemic heart disease, acute myocardial infarction, stroke, transient ischemic attack, peripheral artery disease, percutaneous coronary intervention, coronary artery bypass surgery, congestive heart failure, prescription of cardiac medication, or new onset hypertension. This information will be assessed using information from the Manitoba Centre for Health Policy Population Health Research Data Repository and will be used to compare adverse cardiovascular events with the novel CVD screening tools to determine if they predicted which individuals were at moderate to high risk of an adverse cardiovascular event over the 5-year period after screening. All participants will be asked if they are willing to participate in future research studies. If they are, they may be contacted in regard to potential participation in additional studies conducted by the Duhamel lab group.

Study Procedures

After enrolment, patients will be asked to attend two visits approximately one week apart. Each appointment visit will last approximately 90 minutes and will comprise of the following:

* Demographic information
* Medical history
* Cognitive impairment
* Body composition, as characterized by bioelectrical impedance analysis and measurement of waist circumference
* Body mass index
* Grip strength
* Gait speed
* Fried frailty phenotype (self-reported exhaustion, unintentional weight loss, and Physical activity levels)
* Physical functioning as assessed by the Senior's Fitness Test
* Heart rate variability at rest and in response to six minutes of walking, with aerobic intensity assessed by accelerometer.
* A series of self-report questionnaires to characterize:

  1. Established cardiovascular risk factors
  2. Reproductive health (menstrual history, contraception use, pregnancy history, menopause status, hormone therapy use)
  3. Daily physical activity levels
  4. Quality of life
  5. Self-esteem
  6. Gender roles, relations and identity
  7. Sleep quality
  8. Nutrition intake
  9. Self-compassion
  10. Health anxiety
  11. Depression symptoms
* Blood sampling to measure cholesterol, blood glucose, and other markers of cardiovascular disease, such as but not limited to immune cell characterization
* Non-invasive measures of arterial stiffness
* Resting blood pressure
* Blood pressure in response to 3 minutes of moderate exercise
* Objectively assessed physical activity levels as measured by an accelerometer worn for approximately one week
* Stool sample collection to characterize gut microbiome

Eligibility criteria: Inclusion Criteria:

* women aged 55 and older
* possess a Manitoba Personal Health Information Number

Exclusion Criteria:

Previous hospitalization or treatment for:

* Ischemic heart disease
* Acute myocardial infarction
* Stroke/Transient ischemic attack
* Percutaneous coronary intervention
* Coronary artery bypass surgery
* Congestive heart failure
* Peripheral artery disease
* Congenital heart defects
* Arrhythmia

Additional exclusion:

* Medical advice against physical activity
* Previous participant in the Assessment of Large and Small Artery Elasticity for the Early Detection of Cardiovascular Disease (NCT02863211)

Primary outcomes:
measure: Ischemic heart disease
timeFrame: 5 years post-screening
measure: Acute myocardial infarction
timeFrame: 5 years post-screening
measure: Stroke
timeFrame: 5 years post-screening
measure: Transient ischemic attack
timeFrame: 5 years post-screening
measure: Percutaneous coronary intervention
timeFrame: 5 years post-screening
measure: Coronary artery bypass surgery
timeFrame: 5 years post-screening
measure: Congestive heart failure
timeFrame: 5 years post-screening
measure: Future diagnosis of hypertension
timeFrame: 5 years post-screening
Secondary outcomes:
Other outcomes:
Locations:
city: Winnipeg
country: Canada
facility: St. Boniface Hospital Albrechtsen Research Centre
state: Manitoba
Study officials:
References:
citation: Rose AV, Boreskie KF, Hay JL, Thompson L, Arora RC, Duhamel TA. Protocol for the WARM Hearts study: examining cardiovascular disease risk in middle-aged and older women - a prospective, observational cohort study. BMJ Open. 2021 May 25;11(5):e044227. doi: 10.1136/bmjopen-2020-044227.