Reexamining Her Cardiovascular Risk - Ottawa WomeN's Longitudinal Cohort Study

Cardiovascular Diseases Clinical Trial

— HER-CROWN  

Official title:

Reexamining Her Cardiovascular Risk - Ottawa WomeN's Longitudinal Cohort Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05632601
• Other study ID #: 20220586-01H
• Status: Recruiting
• Phase: N/A
• Start date: April 26, 2023
• Est. completion date: May 24, 2024

Study information

• Verified date: May 2023
• Source: Ottawa Heart Institute Research Corporation
• Contact: Kerri-Anne Mullen, PhD
• Phone: 6136967000
• Email: kmullen[@]ottawaheart.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 210
• Est. completion date: May 24, 2024
• Est. primary completion date: May 24, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 25 Years to 55 Years

Eligibility

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)

Related Conditions & MeSH terms

• Cardiovascular Diseases

Intervention

Diagnostic Test:
• PET scan
PET scan

Locations

Country	Name	City	State
Canada	University of Ottawa Heart Institute	Ottawa	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Ottawa Heart Institute Research Corporation

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Demographics questionnaire	Demographics and socioeconomic information	18 months
Primary	Medical History Questionnaire	Past, present medical history, medication, and women's health related information	18 months
Primary	General Anxiety Disorder-7 (GAD-7)	This is calculated by assigning scores of 0, 1, 2, and 3 to the response categories, respectively, of "not at all," "several days," "more than half the days," and "nearly every day." GAD-7 total score for the seven items ranges from 0 to 21.; 0-4: minimal anxiety 5-9: mild anxiety 10-14: moderate anxiety 15-21: severe anxiety	18 months
Primary	Patient Health Questionnaire (PHQ)-9	Several days = 1 More than half the days = 2 Nearly every day = 3; 1-4 Minimal depression 5-9 Mild depression 10-14 Moderate depression 15-19 Moderately severe depression 20-27 Severe depression	18 months
Primary	Perceived Stress Scale (PSS)	PSS scores are obtained by reversing responses (e.g., 0 = 4, 1 = 3, 2 = 2, 3 = 1 & 4 = 0) to the four positively stated items (items 4, 5, 7, & 8) and then summing across all scale items. A short 4 item scale can be made from questions 2, 4, 5 and 10 of the PSS 10 item scale.	18 months
Primary	The Index of Spouse Abuse (ISA)	Both the ISA-P and ISA-NP scores range from 0 to 100 where a low score indicates the relative absence of abuse and the higher scores represent the presence of a greater degree or amount of abuse.	18 months
Primary	Childhood Trauma Questionnaire (CTQ)	Responses are measured on a 5-point Likert scale (1 = never true, 2 = rarely true, 3 = sometimes true, 4 = often true, 5 = very often true). Each subscale is represented by five questions with a score range from 5 to 25; scores fall into four categories: none to low trauma exposure, low to moderate trauma exposure, moderate to severe trauma exposure and severe to extreme trauma exposure for each scale.	18 months
Primary	PTSD Checklist-5 (PCL-5)	Respondents are asked to rate how bothered they have been by each of 20 items in the past month on a 5- point Likert scale ranging from 0-4. Items are summed to provide a total severity score (range = 0-80). 0 = Not at all 1 = A little bit 2 = Moderately 3 = Quite a bit 4 = Extremely	18 months
Primary	SF-12	SF-12v2 items are scored so that a higher score indicates a better health state. For example, functioning items are scored so that a high score indicates better functioning, and the pain item is scored so that a high score indicates freedom from pain. After data entry, items are scored in three steps: item recoding for the four items that require recoding; computing scale scores by summing across items in the same scale (raw scale scores); and,; transforming raw scale scores to a 0-100 scale (transformed scale scores).	18 months
Primary	Substance use questionnaire	Nicotine, alcohol, cannabis use measure questionnaire. No score.	18 months
Primary	International Physical Activity Questionnaire (IPAQ)	Scoring a HIGH level of physical activity on the IPAQ means your physical activity levels equate to approximately one hour of activity per day or more at least a moderate intensity activity level. Scoring a MODERATE level of physical activity on the IPAQ means you are doing some activity more than likely equivalent to half an hour of at least moderate intensity physical activity on most days. Scoring a LOW level of physical activity on the IPAQ means that you are not meeting any of the criteria for either MODERATE of HIGH levels of physical activity.	18 months
Primary	The Newest Vital Sign (NVS)	Score by giving 1 point for each correct answer (maximum 6 points). Score of 0-1 suggests high likelihood (50% or more) of limited literacy. Score of 2-3 indicates the possibility of limited literacy. Score of 4-6 almost always indicates adequate literacy.	18 months
Primary	Arterial tonometry	Arterial stiffness and arterial age	18 months
Primary	Coronary CTA	Coronary artery calcium, plaque presence and plaque characteristics	18 months
Primary	Cardiac PET	Coronary perfusion and microvascular function	18 months
Primary	Transthoracic echocardiography	Cardiac structure and function	18 months
Primary	Blood work	CBC, electrolytes, creatinine, fasting lipids, fasting glucose, HbA1c, hs-troponin, NT-proBNP, Lipoprotein (a), LH, FSH, estradiol, progesterone, additional sample for biobanking ßhCG test for subsamples participating in PET and Coronary CTA	18 months
Primary	Satisfaction Questionnaire	participant satisfaction and acceptability questionnaire. No score.	18 months