Aside from age, elevated blood pressure is the most predominant cardiovascular disease risk factor worldwide. In the United States it is estimated that ~60% of the adult population have elevated blood pressure in either the prehypertensive (120-139/80-89 mmHg) or hypertensive (>140/90 mmHg) range. Both prehypertension (particularly systolic BP >130 mmHg) and hypertension are associated with increased risk for myocardial infarction, heart failure, stroke and vascular disease. Endothelial dysfunction is a major factor underlying the increased risk of vascular events with elevated blood pressure. In addition, insufficient nightly sleep (<7 hr/night) and poor sleep quality have been linked not only to the etiology of elevated blood pressure but are also a prevalent, often ignored, comorbidity. Indeed, short sleep duration and/or poor sleep quality is now considered to be a plausible risk factor for elevated blood pressure and a harbinger of increased cardiovascular risk. A high prevalence of insufficient nightly sleep has been reported in hypertensive adults. Importantly, habitual sleep duration of less than 7 hr/night is independently associated with an increased risk of stroke and coronary artery disease. The influence of insufficient sleep on vascular endothelial function in adults with elevated blood pressure is unknown. Moreover, given the emerging relation between sleep duration and quality and blood pressure, sleep represents an important, and currently neglected, therapeutic target for improving vascular health and, in turn, reducing cardiovascular risk in adults with elevated blood pressure. The present proposal will test the following hypotheses: 1) that chronic insufficient sleep is associated with diminished endothelium- dependent nitric oxide-mediated vasodilation and endothelial tissue-type plasminogen activator release in adults with elevated blood pressure. Furthermore, the postulated diminishment in endothelial vasodilator and fibrinolytic function with insufficient sleep will be due, at least in part, to increased oxidative stress; and 2) increasing sleep duration and improving sleep quality (utilizing individualized targeted sleep interventions) will increase both endothelium-dependent nitric oxide-mediated vasodilation and endothelial tissue-type plasminogen activator release in adults with elevated blood pressure. Increases in endothelial vasodilator and fibrinolytic function will be due, at least in part, to reduced oxidative stress. To test these hypotheses, 124 middle-aged adults with elevated blood pressure (>130/80 mmHg) will be studied. Endothelial vasodilator and fibrinolytic function will be assessed, in vivo, using an isolated forearm model. The proposed study will provide new and clinically important information regarding the influence of insufficient sleep on vascular endothelial function in adults with elevated blood pressure. Moreover, determining the possible cardioprotective effects of improving sleep and circadian physiology on vascular endothelial vasodilator and fibrinolytic function in adults with elevated blood pressure is clinically innovative, novel and critical to the development of optimal strategies (both primary and adjunctive) to mitigate blood pressure-related cardiovascular risk.

Public Health Relevance

The experimental aim of this proposal is two-fold: 1) to determine the influence of chronic insufficient sleep (< 6.5 hours/night) on vascular endothelial vasodilator and fibrinolytic function in adults with elevated blood pressure (BP>130/80 mmHg); and 2) to determine whether increasing habitual sleep duration and sleep quality will improve vascular endothelial function in adults with elevated blood pressure.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL135598-01
Application #
9229742
Study Section
Clinical and Integrative Cardiovascular Sciences Study Section (CICS)
Program Officer
Mcdonald, Cheryl
Project Start
2016-12-20
Project End
2020-11-30
Budget Start
2016-12-20
Budget End
2017-11-30
Support Year
1
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of Colorado at Boulder
Department
Physiology
Type
Schools of Arts and Sciences
DUNS #
007431505
City
Boulder
State
CO
Country
United States
Zip Code
80303
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Bammert, Tyler D; Hijmans, Jamie G; Reiakvam, Whitney R et al. (2017) High glucose derived endothelial microparticles increase active caspase-3 and reduce microRNA-Let-7a expression in endothelial cells. Biochem Biophys Res Commun 493:1026-1029