# Compositional and Functional Alterations of HDL Over Ovarian Aging

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $382,261

## Abstract

Title: Compositional and Functional Alterations of HDL Over Ovarian Aging
PROJECT SUMMARY
This application is in response to the current NIA FOA: PA-17-088 Secondary Analyses of Existing
Cohorts, Data Sets and Stored Biospecimens to use data and biospecimens from the Study of Women’s
Health Across the Nation (SWAN) to address a critical question about clinical aging, i.e. how ovarian aging
impacts the role of high-density lipoproteins (HDL) on risk for cardiovascular disease (CVD). Multiple historic
epidemiologic studies reported an inverse association between high-density lipoprotein cholesterol (HDL-C)
and CVD, which suggests a direct cardio-protective function of HDL-C. However, recent results from
Mendelian randomization studies and the failure of several HDL-C raising agents to reduce CVD risk, cast
doubt on a cardio-protective function of HDL-C . As women traverse menopause there appears to be a switch
in the direction of the association between HDL-C and CVD risk, with higher HDL-C level being associated with
lower CVD risk before menopause and with higher CVD risk after menopause. HDL is a family of
heterogeneous subclasses that vary in physico-chemical composition and function. HDL-C only measures the
cholesterol load of HDL particles and therefore may not reflect changes in HDL composition and function that
could accompany ovarian aging. Metrics of HDL composition and function provide a better ability to reflect the
athero-protective features of HDL than HDL-C. Biological changes in these novel metrics of HDL have not
been characterized over ovarian aging leading to uncertainty about the impact that the menopausal transition
(MT) may have on HDL athero-protective capacity. The MT is a phase of life when women experience an
acceleration of subclinical CVD. It is critical to fully understand the nature of the biological changes in HDL that
accompany ovarian aging in midlife women. In response to the current NIA FOA: PA-17-088, the current
application aims to 1) characterize changes in HDL composition and function over the MT, and assess how
changes in HDL composition impact changes in HDL function in women at midlife; 2) evaluate the impacts of
hormonal, metabolic and inflammatory marker changes on HDL composition and function changes over the
MT; and to explore associations of changes in HDL composition and function with subclinical CVD progression
in midlife women and to assess potential pathways. Frozen specimens from women participated in SWAN, a
longitudinal study of ovarian aging, will be used to repeatedly measure 1) nuclear magnetic resonance HDL
subclasses; 2) HDL content of phospholipids and triglycerides; and 3) the ability of HDL particles to promote
cholesterol transport from peripheral cells (HDL-cholesterol efflux capacity), a key cardio-protective function of
HDL, over the MT. The combination of the incomparable longitudinal menopause cohort (SWAN) and the
comprehensive proposed panel of well-developed HDL composition and ...

## Key facts

- **NIH application ID:** 9894706
- **Project number:** 5R01AG058690-03
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Samar R El Khoudary
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $382,261
- **Award type:** 5
- **Project period:** 2018-07-15 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9894706

## Citation

> US National Institutes of Health, RePORTER application 9894706, Compositional and Functional Alterations of HDL Over Ovarian Aging (5R01AG058690-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9894706. Licensed CC0.

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