# Leveraging a Unique existing Cohort to elucidate the Link between sleep and cardio-metabolic disease

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2020 · $634,189

## Abstract

PROJECT SUMMARY
Despite current evidence-based treatments for cardiovascular and metabolic diseases (CMD), these diseases
remain highly prevalent and a leading cause of death. Therefore, identifying new disease mechanisms is
paramount to further reduce and/or prevent CMD. Among potential CMD risk factors, the importance of
inadequate sleep is gaining recognition. In this project, we will capitalize on a large, ongoing family-based
study in Brazil that has recruited and enrolled approximately 2,700 participants. The primary objective of this
project is to examine detailed measures of sleep and their associations with biomarkers of CMD, to assess sex
differences in sleep and cardiometabolic disease, and to identify transcriptional and metabolic pathways as
potential mechanisms to explain the effects of sleep on CMD development. Accumulating data suggest that
specific EEG-based characteristics of sleep, such as slow-wave sleep (SWS) or slow-wave activity (SWA; EEG
spectral power in the 0.5-4 Hz range), are highly heritable traits that may be drivers of subclinical cardiac and
metabolic disease acting through the pleiotropic modulation of several risk factors. Furthermore, some
previous studies have found sex differences in the association between sleep and CMD, raising questions
about whether men or women are more vulnerable to the effects of inadequate sleep. Current research has not
fully explored the relationship between SWS/SWA and CMD, nor does it address the unknown underlying
mechanisms. Therefore, the current proposal aims to fill this gap in knowledge by adding PSG in 2,000
participants aged 18 to 90 years. We hypothesize: 1) that less SWS/SWA is associated with increased CMD
risk, including higher fasting glucose and estimated insulin resistance (HOMA), higher hemoglobin A1c and
dyslipidemia (high LDL or low HDL); 2) that the nature of the association between sleep and CMD will differ
between men and women; 3) that transcriptional and metabolomic signatures will differ between those at the
low and high ends of the distribution of SWA, and that these differences can inform on the upstream drivers
and downstream consequences of differing levels of SWA. We propose a cost-effective study that will leverage
an existing cohort and add sleep PSG/EEG, repeated CMD biomarkers, and (in a subset) metabolomics and
RNA sequencing to improve our understanding of the CMD implications of specific sleep EEG traits. These
objectives are concordant with the stated NHLBI scientific priorities, including an investigation into sleep-
related factors that account for differences in health among populations and identification of sleep as a factor
that accounts for individual differences in pathobiology.

## Key facts

- **NIH application ID:** 9870962
- **Project number:** 5R01HL141881-02
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Kristen Knutson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $634,189
- **Award type:** 5
- **Project period:** 2019-02-15 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9870962

## Citation

> US National Institutes of Health, RePORTER application 9870962, Leveraging a Unique existing Cohort to elucidate the Link between sleep and cardio-metabolic disease (5R01HL141881-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9870962. Licensed CC0.

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