# Mediterranean diet, Metabolites, and cardiovascular Disease

> **NIH NIH R01** · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · 2020 · $552,958

## Abstract

Heart failure (HF), atrial fibrillation (AF), and peripheral artery disease (PAD) have emerged as 
important cardiovascular diseases (CVDs) contributing to the increasing burden of chronic diseases and 
escalating health care costs in the United States and globally. Recent advances in metabolomics 
have allowed investigators to assay hundreds of metabolites from a small volume of blood, 
providing a comprehensive  picture of an individual’s metabolic status that may underlie the 
effects of diet on disease risk. However, few studies have assessed the association between 
metabolite profiles and risk of HF, AF, and PAD. In this competing rewewal application, we propose 
a nested case-control design to conduct targeted and untargeted metabolomics analyses of incident 
cases of HF (n=332), AF (n=594), and PAD (n=196) and matched controls in a cohort of 7,447 
participants during the active intervention and extended follow-up periods (2003-2018) in the 
PREDIMED trial. Our specific aims are: 1). To examine the associations between approximately 400 
known metabolites at baseline and risk of HF, AF, and PAD, using a nested case-control design. 2). 
To conduct pathway analysis and agnostic network modeling that integrate non-targeted metabolites 
with known metabolites to identify novel metabolomic signatures of risk of HF, AF, and PAD. 3). To 
assess whether the randomized dietary interventions modify the effect of baseline metabolite 
profiles on HF, AF, and PAD risk.  In addition, we will explore both unique and common metabolites 
and metabolic pathways associated with incident HF, AF, and PAD and will replicate novel 
metabolites identified in the PREDIMED cohort in the  Atherosclerosis Risk in Communities (ARIC) 
study, an independent multi-ethnic cohort in the US. This competing renewal application represents 
an extension of our long-standing research on the Mediterranean  diet and CVD to new clinical 
endpoints in the context of the landmark PREDIMED trial. This research has important implications 
for the US population because the current Dietary Guidelines for Americans recommend the 
Mediterranean diet as one of healthy dietary patterns for CVD prevention. The current cycle of the 
grant  has been highly productive with 11 papers published or submitted, contributing to new 
knowledge about mechanisms underlying diet and CVD and new statistical methods for analyzing 
nutritional metabolomics data. This competing renewal, built on the numerous strengths of the 
PREDIMED trial and a multi-disciplinary and cohesive team, has the potential to advance our 
understanding of CVD pathophysiology and produce knowledge that can directly inform specific 
dietary interventions to prevent overall CVD and its subtypes.

## Key facts

- **NIH application ID:** 9963038
- **Project number:** 5R01HL118264-08
- **Recipient organization:** HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH
- **Principal Investigator:** Frank B Hu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $552,958
- **Award type:** 5
- **Project period:** 2013-07-15 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9963038

## Citation

> US National Institutes of Health, RePORTER application 9963038, Mediterranean diet, Metabolites, and cardiovascular Disease (5R01HL118264-08). Retrieved via AI Analytics 2026-06-08 from https://api.ai-analytics.org/grant/nih/9963038. Licensed CC0.

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