# Association of Physical Activity and Sedentary Behavior with Incident Cardiovascular Disease Event Risk and All-Cause Mortality: Role of Heart Rate Variability and Influence of Diabetes Status

> **NIH NIH R21** · UNIVERSITY OF MINNESOTA · 2020 · $115,563

## Abstract

PROJECT SUMMARY: Sedentary behavior (SB) is an emerging public health concern. Recent studies indicate
SB to have a positive, dose-dependent relationship with cardiovascular disease (CVD), independent of physical
activity (PA). While PA has a clear inverse, dose-dependent relationship with CVD, most U.S. adults do not meet
PA recommendations, with one-third completely sedentary. The newest PA recommendations therefore note the
need to reduce SB in addition to increasing PA. Yet, SB recommendations remain non-specific. To develop
specific SB recommendations (e.g., max hrs/d of SB), in-depth studies of physiological mechanisms linking PA
and SB to CVD are crucial. While we know PA is critical to lowering CVD risk in persons with type 2 diabetes
(T2D), how SB contributes to this population’s CVD risk is a noted research gap. The influence of PA and SB on
glycemic control is well-researched. One relatively unstudied mechanism possibly connecting PA and SB to CVD
is how the influence of these behaviors on glycemic control may impact cardiac autonomic function (CAF) and
later CVD risk. Heart rate variability (HRV) is a ‘gold standard’ measure of CAF that can be measured by
clinicians quickly and non-invasively, with impaired HRV predictive of adverse CVD outcomes and all-cause
mortality. In those with T2D, hyperglycemia is particularly damaging to the parasympathetic nervous system due
to the stimulation of higher inflammatory molecule circulation. Higher inflammatory molecule circulation is related
to impaired HRV and hypothesized to promote higher CVD risk in those with T2D. Importantly, individuals with
higher PA levels have better HRV indices (i.e., improved CAF) relative to less active individuals. Thus, HRV may
be a salient physiological mechanism linking PA and SB to CVD. As PA and SB have important independent
influences on glycemic control, we need to investigate how PA and SB may impact CVD risk in those with and
without T2D while examining whether HRV may be an important causal mediator. No known study has assessed
this important pathway. By pooling individual-level data from six prospective cohort studies (N=44,034), we will
address three novel specific Aims. For Aim 1, we will examine the independent associations between PA and
SB with CVD risk. In Aim 2, we will investigate how T2D status modifies the independent associations between
PA and SB with CVD risk. These Aims will uniquely contribute to the small literature base regarding the influence
of SB on CVD risk, particularly in those with T2D. Finally, for Aim 3, we will study whether HRV partially mediates
the associations between PA and SB with CVD risk in those with and without T2D. Aim 3 addresses calls from
major scientific organizations to study novel mechanisms linking PA and SB to CVD. We will also assess the
preceding Aims with all-cause mortality as the outcome (Exploratory Aim). Discerning HRV’s mediation of these
associations is important as: (1) HRV, as a non-invasive CAF i...

## Key facts

- **NIH application ID:** 10046429
- **Project number:** 1R21HL150428-01A1
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** MARK A PEREIRA
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $115,563
- **Award type:** 1
- **Project period:** 2020-09-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10046429

## Citation

> US National Institutes of Health, RePORTER application 10046429, Association of Physical Activity and Sedentary Behavior with Incident Cardiovascular Disease Event Risk and All-Cause Mortality: Role of Heart Rate Variability and Influence of Diabetes Status (1R21HL150428-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10046429. Licensed CC0.

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