# Risk Factors for CVD in Women

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $781,114

## Abstract

ABSTRACT
Recent advances in metabolomics have led to the identification of numerous blood metabolites related
to the risk of cardiovascular events. Although these metabolites show great promise as potential novel
biomarkers for coronary heart disease (CHD), their relation with coronary risk remains poorly defined
due to several knowledge gaps − no prior prospective study has jointly assessed metabolites by taking
into account pathways related to biological function; no study has considered changes in metabolite
levels over time in relation to subsequent CHD; and research on the dynamic interrelationships of
metabolites with traditional CHD risk factors and dietary intakes is limited. The overarching goal of
this competing renewal is to fill important gaps in knowledge regarding the metabolomics of
CHD, using an exceptionally cost-efficient design that leverages existing resources from three large
and well-established U.S. cohorts: the Nurses’ Health Study (NHS), the NHS2, and the VITamin D and
OmegA-3 TriaL (VITAL, men and women, ~20% African Americans). Using novel analytical approaches,
we propose to develop and validate Metabolomics Risk Scores (MRSs) that incorporate comprehensive
metabolite profiling (at overall and pathway levels) for their associations with incident CHD in NHS (700
cases and paired controls) and VITAL (650 cases and paired controls, replication cohort) (Aim 1).
Taking advantage of repeated blood collections at two time points approximately 10 years apart in NHS,
we will examine whether temporal changes in MRS are related to incident CHD (Aim 2). We will also
assess whether biochemical CHD risk factors, and temporal changes in these risk factors, mediate the
coronary risk associated with MRS (Aim 3). Finally, using objective dietary data assessed by ‘gold
standard’ methods, we will develop Dietary Metabolite Indexes (DMIs) that predict MRS and
prospectively analyze relations between temporal changes in DMIs and incident CHD risk (Aim 4). This
competing renewal builds upon our long-standing research on risk factors for CHD in the Nurses’
Health Study (research that has resulted in more than 350 publications over the past 34 years) and
extends our work to the study of novel metabolomic risk factors. The findings of our proposed project
may elucidate new etiologic pathways for atherothrombotic vascular disease, as well as provide novel
prevention options and therapeutic strategies for cardiovascular disease. Thus, the proposed study has
the potential to have major clinical and public health impact.

## Key facts

- **NIH application ID:** 9869020
- **Project number:** 5R01HL034594-33
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** JoAnn Elisabeth Manson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $781,114
- **Award type:** 5
- **Project period:** 1984-12-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9869020

## Citation

> US National Institutes of Health, RePORTER application 9869020, Risk Factors for CVD in Women (5R01HL034594-33). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9869020. Licensed CC0.

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