R01HL155395

The Role of Irregular Sleep Schedules as a Ubiquitous Marker of Chronic Circadian Disruption in Cardiometabolic Disease Development - Abstract

Although circadian rhythms are established as a fundamental mechanism in various biologic processes, including metabolic and cardiovascular functioning, less is known regarding how disruption of circadian rhythms may contribute to the development of cardiometabolic disease in broader human populations.

Prior epidemiologic studies have predominantly focused on specific populations who experience extreme circadian disruption, such as rotating night shift workers. In this application, we will consider irregular sleep schedules as a ubiquitous marker of chronic circadian disruption and evaluate its role in cardiometabolic disease development.

First, we will leverage the wealth of data from the UK Biobank (UKB), which has measured habitual sleep using accelerometer among 92,644 participants. We will characterize the dose-response relationships of irregular sleep schedules with the risk of hypertension, diabetes, and cardiovascular disease and identify potential thresholds to define what level of sleep variability may be cardiometabolically unhealthy. We will also evaluate whether the observed associations differed by sociodemographic factors (e.g., age, sex, race/ethnicity) or other sleep traits (e.g., average sleep duration and insomnia symptoms).

Further, given that sleep regularity represents a highly modifiable risk factor, we will evaluate whether regular sleep schedules may counteract genetic predisposition to cardiometabolic disease.

Second, in the Nurses' Health Study 3 (NHS3), we propose to measure habitual sleep using Fitbit and plasma metabolomics among 1,000 nurses, encompassing a wide range of variations in sleep schedules (including a random subset with night shift work). We hypothesize that irregular sleep schedules are associated with altered metabolites exhibiting circadian rhythms, such as omega-3 fatty acids, linoleate, arginine, and tyrosine. We further hypothesize that this metabolic profile mediates the associations between irregular sleep and cardiometabolic traits, including obesity, blood pressure, and heart rate variability.

In addition, we will collect new data on several emerging risk factors for irregular sleep that have not been examined in previous work, including mobile device use, late eating, breakfast skipping, pet ownership, and childbearing/rearing in women.

To increase rigor, reproducibility, and generalizability, we will confirm our primary findings from UKB and NHS3 in the diverse Multi-Ethnic Study of Atherosclerosis (N=2,156), which has existing data on objectively measured habitual sleep, genomics, metabolomics, and conventional epidemiologic risk factors.

Overall, this project will provide larger-scale, more diverse, and more in-depth evidence for the cardiometabolic impact of irregular sleep schedules in US and European populations, elucidate underlying biologic mechanisms, and ultimately foster the development of potential public health recommendations and interventions to reduce irregular sleep and improve cardiometabolic health.

Brigham & Womens Hospital

THE NATIONAL CENTER ON SLEEP DISORDERS RESEARCH (NCSDR) SUPPORTS RESEARCH AND RESEARCH TRAINING RELATED TO SLEEP DISORDERED BREATHING, AND THE FUNDAMENTAL FUNCTIONS OF SLEEP AND CIRCADIAN RHYTHMS. THE CENTER ALSO STEWARDS SEVERAL FORUMS THAT FACILITATE THE COORDINATION OF SLEEP RESEARCH ACROSS NIH, OTHER FEDERAL AGENCIES AND OUTSIDE ORGANIZATIONS, INCLUDING THE SLEEP DISORDERS RESEARCH ADVISORY BOARD AND AN NIH-WIDE SLEEP RESEARCH COORDINATING COMMITTEE. THE CENTER ALSO PARTICIPATES IN THE TRANSLATION OF NEW SLEEP RESEARCH FINDINGS FOR DISSEMINATION TO HEALTH CARE PROFESSIONALS AND THE PUBLIC. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO STIMULATE TECHNOLOGICAL INNOVATION, USE SMALL BUSINESS TO MEET FEDERAL RESEARCH AND DEVELOPMENT NEEDS, FOSTER AND ENCOURAGE PARTICIPATION IN INNOVATION AND ENTREPRENEURSHIP BY SOCIALLY AND ECONOMICALLY DISADVANTAGED PERSONS, AND INCREASE PRIVATE-SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT FUNDING. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE TECHNOLOGICAL INNOVATION, FOSTER TECHNOLOGY TRANSFER THROUGH COOPERATIVE R&D BETWEEN SMALL BUSINESSES AND RESEARCH INSTITUTIONS, AND INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL R&D.

93.837 - Cardiovascular Diseases Research

National Heart Lung and Blood Institute (NHLBI) [HHS - NIH]

Boston, Massachusetts 021155804 United States

Single Zip Code

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)

Amendment Since initial award the total obligations have increased 392% from $714,766 to $3,519,838.