The Longitudinal Evaluation of Ovarian Aging and Cardiovascular Risk

NCT03825120 | Enrolling By Invitation

• 2 other identifiers: R01AG0533321R01AG053332-01A1
• Study Type: observational
• Target: 865
• Locations: 1 country
• Sites: 1

Brief Summary

Despite significant improvements in prevention and treatment of cardiovascular disease (CVD), the growing aging population suggests CVD will continue to pose a significant public health burden. Women are a special group where microvascular disease is more common and traditional risk factors may not fully identify risk. Women's reproductive history (e.g. menarcheal age, menstrual cycles, infertility, pregnancy, menopause) may pose unique risk and suggests an opportunity for new approaches. The investigators propose a women-centered approach for early identification of women at risk that investigates the unique loss of reproductive function at an age long before other vital systems fail. Despite its importance, little is known about the determinants or correlates of ovarian aging, or the health implications, especially in diverse communities. Only recently have reliable biomarkers of the remaining oocyte pool been available for use in normally cycling women. This availability gives us a unique opportunity to characterize the association between "ovarian age" (cross-sectional) and the rate of "ovarian aging" or oocyte decline over time (longitudinal) and the health implications of accelerated oocyte loss. The investigators hypothesize ovarian age/aging provides a window onto the general health of women. The investigators suggest it is not the progressive deficiency of estrogen with menopause that increases risk, but common underlying cellular aging mechanisms first evident in young populations as lower ovarian reserve (follicle number) due to the unique sensitivity of the ovary. Studies of cellular aging focused on mitochondrial dysfunction, oxidative stress, inflammation, and telomere length have identified correlations with CVD risk. Improved understanding of the mechanisms of cellular aging suggests telomere shortening and dysfunction may drive mitochondrial dysfunction and potentially the parallel between cellular aging and CVD. The oocyte is particularly sensitive to mitochondrial dysfunction, having 10 times the number of mitochondria as any somatic cell. Additionally, mitochondrial dysfunction and telomere shortening have been associated with ovarian aging. This begs the question of whether, given the susceptibility of the ovary to mitochondrial dysfunction, accelerated ovarian aging may be a harbinger of subsequent CVD risk. To address this critical question, the investigators propose to leverage the largest and most ethnically diverse population of normal reproductive-aged women, with detailed measures of ovarian age, and to deploy peripheral endothelial function testing, a non-invasive sensitive marker of early CVD risk. Ovarian aging is thought to be largely genetically determined, but the impact of race/ethnicity has not been fully explored. Evaluating the impact of ethnicity on ovarian aging, and combining this information with the impact of modifiable behavioral risk factors, may help clarify CVD risk in young, ethnically-diverse, reproductive-age women. The investigators believe improving our understanding of factors that affect the rate of oocyte/follicle loss and the relationship with CVD risk factors will promote a novel method to identify women at earlier and/or increased cardiac risk.

Conditions

Infertility; Cardiovascular Risk Factor

Keywords

reproductive health; fertility; infertility; aging; health; cardiovascular disease; cardiovascular disease risk

Outcome Measures

Primary Outcomes (1)

• Change in the EndoScore or reactive hyperemia ratio, an index of peripheral endothelial function, as assessed by the FDA-approved EndoPAT 2000

  Endothelium-mediated changes in vascular tone will be represented by the EndoScore or ratio of Reactive Hyperemia pre-occlusion to post-occlusion of the brachial artery (via blood pressure cuff). A score \> 1.67 is considered "normal" and a score \<= 1.67 is "abnormal". The EndoPAT 2000 machine will be used for this measure, which is the only non-invasive method of measuring endothelial function or the state of arterial health. Well-functioning arteries protect blood vessels from hardening (or atherosclerosis) and plaque build up. The EndoScore score will be the primary measure for cardiovascular (CV) disease risk, as actual CV event rates will be too low for many years

  2 times, once at each of 2 study visits ~1 year apart

Study Arms (1)

Women from original OVA cohort

Eligibility Criteria

• Age: 35 Years - 55 Years
• Sex: female
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

* member of Northern California Kaiser Permanente Health Plan at time of enrollment into original OVA cohort * self-identifying as Caucasian, Chinese, Filipino, African-American, or Hispanice (Mexican or Central American)

You may qualify if:

• Enrollment into the original OVA cohort (NCT00501800)

You may not qualify if:

• Not a member of the original OVA cohort

Sponsors & Collaborators

• University of California, San Francisco: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94115, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

blood and urine

MeSH Terms

Conditions

Infertility; Cardiovascular Diseases

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases

Study Officials

• Marcelle I Cedars, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2019
• First Posted: January 31, 2019
• Study Start: August 15, 2018
• Primary Completion: May 2, 2025
• Study Completion: December 2, 2025
• Last Updated: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)