# The Roles of the Metabolome and Dietary Protein Intake in Left Ventricular Diastolic Function

> **NIH NIH F30** · TULANE UNIVERSITY OF LOUISIANA · 2020 · $46,705

## Abstract

The pathophysiologic model of heart failure with preserved ejection fraction (HFpEF) has evolved over the past
several years with evidence suggesting a role of metabolic impairment in disease pathogenesis. Due to the
increasing frequency of and therapeutic challenges associated with HFpEF, there is a need to improve our
understanding of subclinical HFpEF correlates to prevent disease manifestation. Diastolic dysfunction is one
key defining feature on the causal disease pathway of HFpEF, yet the metabolic profile and nutritional risk
factors associated with this subclinical phenotype remain ill-defined, especially in diverse populations. To
address this knowledge gap, we propose the first epidemiological study aimed at identifying novel
metabolites and dietary patterns associated with diastolic dysfunction. We will leverage untargeted
metabolomics data, along with longitudinal measures of both diastolic function and dietary protein intake in up
to 912 Bogalusa Heart Study (BHS) participants. The BHS is a NIH-funded longitudinal study that examines
cardiovascular health across the lifespan, providing an ideal setting for the proposed work. Left ventricular
diastolic function will be assessed through seven key 2-dimensional and Doppler echocardiography
parameters: mitral annular velocity, peak early filling velocity, peak velocity caused by atrial contraction,
isovolumic relaxation time, deceleration time, left atrial maximal volume index, and peak tricuspid regurgitation
velocity. Likewise, given the blood pressure lowering properties of dietary protein, a key mechanism that may
help preserve diastolic function, we will characterize dietary patterns by focusing on different sources of protein
consumption. In Aim 1, we will take advantage of untargeted serum metabolome profiles of BHS participants,
derived using ultrahigh performance liquid chromatography-tandem mass spectroscopy, to examine novel
associations of metabolites and metabolite pathways with diastolic function in adults. Multivariable-adjusted
methods and network-based statistical approaches will be used to test associations of metabolites and
metabolite pathways with diastolic function in combined and race-stratified analyses. To validate results, novel
BHS findings will be tested for significance among 1,000 adults of the Multi-Ethnic Study of Atherosclerosis.
Dietary patterns in childhood and adolescence will then be characterized by: 1) calculating mean intakes of six
major protein sources, meat, poultry, dairy, fish, grains, and vegetables, across the two time-points; and 2)
estimating the change in intake of major protein sources between the two time-points. We will test whether
these specific protein consumption patterns associate with diastolic function, controlling for covariables
collected at the time of dietary assessment (Aim 2). In Aim 3, we will conduct integrative studies to identify
dietary protein-derived metabolites and detect biological pathways underlying diastolic dy...

## Key facts

- **NIH application ID:** 10124993
- **Project number:** 5F30HL147486-02
- **Recipient organization:** TULANE UNIVERSITY OF LOUISIANA
- **Principal Investigator:** Alexander C. Razavi
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $46,705
- **Award type:** 5
- **Project period:** 2019-07-15 → 2021-05-20

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10124993

## Citation

> US National Institutes of Health, RePORTER application 10124993, The Roles of the Metabolome and Dietary Protein Intake in Left Ventricular Diastolic Function (5F30HL147486-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10124993. Licensed CC0.

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