Clinical trial NCT05632601: Reexamining Her Cardiovascular Risk - Ottawa WomeN's Longitudinal Cohort Study
Official title: Reexamining Her Cardiovascular Risk - Ottawa WomeN's Longitudinal Cohort Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Cardiovascular Diseases
Keywords: cardiovascular disease
sex-specific risk factor
hypertensive disorder of pregnancy
Early menopause
Polycystic ovarian syndrome
Rheumatologic inflammatory disorders
breast cancer
gestational diabetes
Primary ovarian insufficiency
Lead sponsor: Ottawa Heart Institute Research Corporation
Sponsor class: OTHER
First posted: 2022-11-30
Enrollment: 210
Sex: FEMALE
Minimum age (years): 25
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A single-site, two-group, matched-cohort Vanguard study will be completed to test feasibility outcomes to inform a large, multi-site, two-group, longitudinal matched-cohort study.
Primary purpose: OTHER

Brief summary: The full HER CROWN will be a prospective cohort study to propose a novel, women-specific cardiovascular risk score/ algorithm in the prediction of hard cardiovascular outcomes (myocardial infarction, unstable angina, coronary revascularization, stroke, total and cardiovascular mortality). This future study will be the first longitudinal cohort study, to our knowledge, that is focused entirely on researching the pathophysiology and natural history of cardiovascular disease in women with known female-specific risk factors. Further, the investigators are aiming to recruit a sample that is representative of the ethnic distribution in Canada. The proposed pilot study is a feasibility study as an essential preparatory step for HER CROWN.

Detailed description: Cardiovascular diseases (CVD), including ischemic heart disease (IHD), peripheral vascular disease (PVD), and stroke, remain the leading preventable cause of death among Canadian women, resulting in over 34,000 deaths per year (age-standardized death rate: 25.1%). Nearly 40% of CVD-related deaths in women are due to IHD. Increased awareness efforts and effective treatments have led to an overall decline in CVD mortality among men and women in high income countries over the past few decades; however, alarmingly, an increase in CVD mortality has been observed in women in the most recent 5 to 10 years in Canada and the United States, and an upward trend in rates of AMI among younger women.

CVD in women remains understudied, under-diagnosed, and undertreated. Clinical guidelines are largely based on studies of men. Several existing large longitudinal cohort studies (e.g., the Nurses' Health Study, The Framingham Heart Study, the PURE study) have included women; however, they have not focused recruitment specifically on high-risk cohorts of women or on risk factors that are unique to women, more common in women, or that disproportionately affect women; they have not used novel measures of subclinical disease in women (e.g., coronary computed tomography angiography and cardiac Rb-positive emission tomography); and most have not recruited representative samples of women in terms of ethnicity or socioeconomic status. CVD risk calculators (e.g., Framingham, the American College of Cardiology ASCVD) focus on traditional risk factors (e.g., tobacco smoking, hypertension, diabetes), do not include sex-specific CVD risk factors or factors that disproportionately affect women, and thus tend to underestimate risk in women. Female-specific factors that have been associated with CVD risk include: premature or late menarche, abnormal menses, premature or early menopause, gestational hypertensive disorders, gestational diabetes, preterm delivery, pregnancy loss, hormonal contraceptive use, and polycystic ovarian syndrome. Risk factors that are under-recognized or disproportionately affect women include: rheumatologic inflammatory disorders (RIDs), depression, anxiety, chronic stress, abuse and intimate partner violence, and health literacy. In addition, a more feminine gender role has been shown to be associated with higher risk of reinfarction after premature acute coronary syndrome, but no additional research on gender roles and future cardiovascular risk is available. Importantly, novel cardiovascular risk markers such as measures of arterial stiffness and aging, among others, have not been prospectively evaluated in a female population. As such, additional longitudinal research is needed to understand the natural history of CVD and the impact of these 'non-conventional' risk factors in women.

A recent article published in the Lancet by a multi-national group of women's heart health experts reviewed existing evidence, identified knowledge gaps, and provided specific recommendations related to CVD research, prevention, treatment, and access to care for women. The HER CROWN longitudinal cohort study will respond to three important gaps identified in this review, specifically: 1) describe the pathophysiology and natural history of cardiovascular disease in women; 2) determine the impact of sex-specific, psychosocial, and socioeconomic risk factors on CVD in women; and, 3) improve CVD risk prediction/ risk stratification models for women. The Vanguard phase of the study will evaluate the feasibility of the full study being planned.

The full HER CROWN will be a prospective matched-cohort study to propose a novel, women-specific cardiovascular risk score/ algorithm in the prediction of hard cardiovascular outcomes (myocardial infarction, unstable angina, coronary revascularization, stroke, total and cardiovascular mortality). This future study will be the first longitudinal cohort study, to our knowledge, that is focused entirely on researching the pathophysiology and natural history of cardiovascular disease in women with known female-specific risk factors. Further, the investigators are aiming to recruit a sample that is representative of the ethnic distribution in Canada. The proposed pilot study is a feasibility study as an essential preparatory step for HER CROWN. The study will be cross-disciplinary, including investigators who specialize in the treatment of cardiovascular disease in women, epidemiology and administrative data, cardiovascular imaging, biomarker research, physical activity, nutrition, nicotine addiction, and mental health who will each inform outcomes and sub-studies.

Eligibility criteria: Inclusion Criteria:

* Female Sex
* Between 25-55 years of age
* Ontario resident with a valid OHIP card

A prior or current diagnosis of:

* Pre-eclampsia, eclampsia, gestational hypertension
* Gestational diabetes
* Primary ovarian insufficiency (menopause \< age 40)
* Early menopause (menopause between ages 40-45)
* Polycystic ovarian syndrome (PCOS)
* Rheumatologic inflammatory disorders (Lupus, Rheumatoid Arthritis, Psoriatic Arthritis)
* Breast cancer

OR

No prior history of sex-specific or female-predominant risk factors outlined in the SSR group

Exclusion Criteria:

* Male sex
* Currently pregnant
* Prior diagnosis of any of the following:
* CVD including coronary heart disease, heart failure, congenital heart disease, stroke/transient ischemic attack, valvular heart disease, peripheral vascular disease, aortapathy, atrial fibrillation or flutter, other CVD
* Neurodegenerative disease known to affect the heart (e.g., muscular dystrophy)
* Untreated serious mental illness (e.g., untreated psychosis)

Primary outcomes:
measure: Demographics questionnaire
timeFrame: 18 months
measure: Medical History Questionnaire
timeFrame: 18 months
measure: General Anxiety Disorder-7 (GAD-7)
timeFrame: 18 months
measure: Patient Health Questionnaire (PHQ)-9
timeFrame: 18 months
measure: Perceived Stress Scale (PSS)
timeFrame: 18 months
measure: The Index of Spouse Abuse (ISA)
timeFrame: 18 months
measure: Childhood Trauma Questionnaire (CTQ)
timeFrame: 18 months
measure: PTSD Checklist-5 (PCL-5)
timeFrame: 18 months
measure: SF-12
timeFrame: 18 months
measure: Substance use questionnaire
timeFrame: 18 months
measure: International Physical Activity Questionnaire (IPAQ)
timeFrame: 18 months
measure: The Newest Vital Sign (NVS)
timeFrame: 18 months
measure: Arterial tonometry
timeFrame: 18 months
measure: Coronary CTA
timeFrame: 18 months
measure: Cardiac PET
timeFrame: 18 months
measure: Transthoracic echocardiography
timeFrame: 18 months
measure: Blood work
timeFrame: 18 months
measure: Satisfaction Questionnaire
timeFrame: 18 months
Secondary outcomes:
Other outcomes:
Locations:
city: Ottawa
country: Canada
facility: University of Ottawa Heart Institute
state: Ontario
Study officials:
affiliation: UOHI
name: Kerri-Anne Mullen, PhD
role: PRINCIPAL_INVESTIGATOR
References: