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Principal Investigator: Saurabh Suhas Thosar
Organization: OREGON HEALTH & SCIENCE UNIVERSITY
Fiscal Year: 2024
Award: $612,666
Funding agency: National Heart Lung and Blood Institute
Project Summary
Hypertension (HTN) is a leading cause of morbidity and mortality in the United States and affects approximately
45% of US adults. Blood pressure (BP) is almost invariably higher during the day; however, the relative drop in
overnight BP is a better predictor of overall CV risk than daytime BP. Generally, patients with HTN are classified
into: (1) dipping, where the average nighttime BP drops by ≥10% from the daytime average; and (2) non-dipping,
where the average nighttime BP does not dip by 10%. More than 30% of patients with HTN have a non-dipping
BP profile, which is associated with a significantly increased risk for adverse outcomes, including end-organ
damage, and mortality, compared to patients with dipping HTN. It is unclear what causes non-dipping HTN, but
the circadian system and sleep likely play a role because both systems affect the day-night variation in BP. Our
goal is to determine, in patients with untreated HTN, the separate contributions of the internal circadian system
and sleep to the non-dipping BP profile and the day/night variability in associated CV variables, including
estimates of sympathetic and parasympathetic activity, renin-angiotensin-aldosterone system activity, and
vascular endothelial function.
Our specific aims are to determine: 1) if circadian rhythms in BP are altered in non-dipping HTN and 2) the role
of sleep in non-dipping HTN. We hypothesize that: 1) BP circadian rhythms are altered in non-dipping compared
to dipping HTN, resulting in a reduced nocturnal BP decline; 2) sleep duration is shorter in non-dipping than
dipping HTN, and 3) the absence of sleep attenuates overnight BP drop in dipping HTN more than non-dipping
HTN. An exploratory aim is to determine if two weeks of sleep regularization increases overnight BP dipping.
Thirty-two participants (16 dippers, 16 non-dippers, 16 females, and 16 males) will partake in all studies. We will
first quantify sleep duration using unattended polysomnography in participants’ homes. Second, we will uncover
circadian rhythms in BP by employing a 40-h constant routine protocol, where all participants will be monitored
in the laboratory during uninterrupted rested wakefulness in a semi-recumbent posture, dim light, and without
time cues. Third, we will conduct a randomized crossover trial in dim light in the laboratory, during which overnight
sleep is permitted or not. BP and mechanistic CV markers are continuously measured in the circadian study and
the crossover trial. In the crossover trial, we will also measure sympathetic activity using microneurography and
24-h BP on the days of the trials. Finally, we will pilot test a two-week sleep regularization schedule, including
maintaining a self-selected bedtime, to its impact on overnight BP dipping.
These highly controlled experiments will enable us to document the separate roles of the circadian system and
sleep in non-dipping HTN. Understanding underlying CV mechanisms will provide potential pharmacological
targets for evidence-based chronotherapy in HTN. Understanding the role of sleep will provide future
opportunities to formally test sleep extension or regularization as behavioral therapies for non-dipping HTN.
Terms: <21+ years old><Address><Adult><Adult Human><Affect><Aldosterone><Anti-Hypertensive Agents><Anti-Hypertensive Drugs><Anti-Hypertensives><Attenuated><Autonomic nervous system><BP control><BP management><BP reduction><BP2><Beds><Behavior><Behavior Conditioning Therapy><Behavior Modification><Behavior Therapy><Behavior Treatment><Behavioral><Behavioral Conditioning Therapy><Behavioral Modification><Behavioral Therapy><Behavioral Treatment><Biological><Blood Pressure><Cardiac><Cardiovascular><Cardiovascular Body System><Cardiovascular Organ System><Cardiovascular system><Categories><Cessation of life><Chronotherapy><Circadian Rhythms><Classification><Clinical><Clinical Trials><Conditioning Therapy><Cross-Over Designs><Cross-Over Trials><Crossover Design><Crossover Trials><Cues><Data><Death><Drops><Drugs><Epidemic><Equilibrium><Event><Female><Future><Goals><Guidelines><Health Expenditures><Heart Vascular><Home><Hour><Hypertension><Hypotensive Agent><Hypotensive Drugs><IBP2><IGF-BP53><IGFBP2><IGFBP2 gene><Individual><Insulin-Like Growth Factor Binding Protein 2><Laboratories><Laboratory Study><Light><Measures><Medication><Minor><Monitor><Morbidity><Morbidity - disease rate><Nyctohemeral Rhythm><Organ><Outcome><Participant><Patients><Pattern><Persons><Pharmaceutical Preparations><Photoradiation><Polysomnography><Posture><Protocol><Protocols documentation><Public Health><Randomized><Recommendation><Renin-Angiotensin-Aldosterone System><Research><Rest><Risk><Risk Factors><Role><Schedule><Sleep><Sleep Disorders><Sleep Monitoring><Somnography><Standardization><Syndrome><System><Systematics><Testing><Time><Twenty-Four Hour Rhythm><United States><Variant><Variation><Vascular Endothelium><Vascular Hypertensive Disease><Vascular Hypertensive Disorder><Wakefulness><Work><adulthood><adverse consequence><adverse outcome><anti-hypertension><attenuate><attenuates><balance><balance function><behavior intervention><behavioral intervention><biologic><blood pressure control><blood pressure elevation><blood pressure management><blood pressure reduction><blood pressure variability><cardiovascular disease risk><cardiovascular disorder risk><cardiovascular risk><cardiovascular risk factor><circadian><circadian process><circulatory system><daily biorhythm><design><designing><drug/agent><elevated blood pressure><evidence base><experiment><experimental research><experimental study><experiments><falls><health care expenditure><healthcare expenditure><high blood pressure><homes><hyperpiesia><hyperpiesis><hypertensive><hypertensive disease><hypertensive disorder><improved><increase in blood pressure><increased blood pressure><lower BP><lower blood pressure><lowers blood pressure><male><medical expenditure><mortality><new drug target><new druggable target><new pharmacotherapy target><new therapeutic target><new therapy target><normotensive><novel drug target><novel druggable target><novel pharmacotherapy target><novel therapeutic target><novel therapy target><pharmacologic><pilot test><polysomnographic><poor sleep><randomisation><randomization><randomly assigned><reduce BP><reduce blood pressure><reduction in BP><reduction in blood pressure><side effect><sleep diseases><sleep dysfunction><sleep illness><sleep measurement><sleep onset><sleep pattern><sleep polysomnography><sleep problem><social role>