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Circadian rhythms and cardiovascular risk

昼夜节律和心血管风险

基本信息

批准号：
9109679
负责人：
STEVEN A SHEA
金额：
$ 68.29万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-07-15 至 2019-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9109679
关键词：
Adult Adverse event Affect Age Aldosterone Apnea Arousal Autonomic nervous system Behavior Behavior Control Behavioral Biological Biological Clocks Blood Blood Platelets Blood Pressure Blood coagulation Cardiac Cardiovascular Diseases Cardiovascular Physiology Cardiovascular system Catecholamines Cessation of life Chronotherapy Circadian Rhythms Coagulation Process Comorbidity Continuous Positive Airway Pressure Data Development Dilatation - action Environment Epinephrine Equilibrium Event Exercise General Population Health Heart Rate Hemostatic function Hormones Hour Human Hydrocortisone Hypertension Incidence Laboratories Lead Life Light Link Malondialdehyde Measures Mediating Modeling Myocardial Infarction Norepinephrine Obesity Obstructive Sleep Apnea Outcome Oxidative Stress P-Selectin Patients Pattern Periodicity Pharmaceutical Preparations Phase Physiology Plasma Plasminogen Activator Inhibitor 1 Plasminogen Inactivators Platelet Activation Platelet aggregation Play Population Posture Predisposition Protocols documentation Rest Risk Factors Risk Marker Role Schedule Sleep Sleep Apnea Syndromes Sleep Wake Cycle Stress Surface System Techniques Testing Thrombosis Thrombus Time Ventricular Arrhythmia Vulnerable Populations Wakefulness Withdrawal age group awake base cardiovascular disorder risk cardiovascular risk factor clinically relevant heart rate variability hemodynamics indexing interest novel research study response sex stressor sudden cardiac death treatment strategy

项目摘要

DESCRIPTION (provided by applicant): Adverse cardiovascular events, including sudden cardiac death, myocardial infarction and ventricular arrhythmias all have their highest incidence around 9 AM. In healthy humans, we discovered that our internal body clock causes many cardiovascular (CV) disease risk markers to peak at this time. These include sympatho-vagal responses to stress, markers of thrombosis or clot formation (PAI-1 and platelet aggregation), and the stress hormone cortisol. It is precisely at this vulnerable body clock time that people encounter additional stresses elicited by behaviors: arousal from sleep, altered posture, and increased activity also induce numerous CV responses. Some, such as increased sympatho-vagal balance and blood coagulability, might be beneficial in healthy people but represent risk factors in populations vulnerable to CV disease, such as those with hypertension or obstructive sleep apnea (OSA). Subjects with OSA are of particular interest from both CV risk and circadian rhythms perspectives because OSA increases vulnerability to CV disease, is associated with greater incidence of a perilous nocturnal non-dipping blood pressure (BP), and leads to completely different day/night patterns in incidence of myocardial infarction and sudden cardiac death - with peaks during the night rather than the morning. Our specific aims are to determine if endogenous circadian rhythms in CV function during rested wakefulness (Aim 1) and in the reactivity of CV function to standardized stressors (posture, exercise; Aim 2) are disturbed in people with untreated OSA compared to people treated with continuous positive airway pressure (CPAP) and matched controls. Dependent CV risk markers will include measures of hemodynamics, hemostasis, autonomic nervous system activity, endothelial function, and oxidative stress. To document circadian rhythms, subjects will spend 5 days in a laboratory in a constant environment including dim light. To test CV function at all phases of the internal clock while controlling for behaviors that precede the tests, such as meals or the duration of time awake, subjects will live on recurring 5 hour 20 minute `days' during which behavior is tightly controlled. In protocols like this, we have measured BP continuously during sleep. This technique will allow us to determine the causes of OSA-associated non-dipping BP in terms of effects from the internal body clock, sleep itself, or the sleep disruptions caused by apneas. We hypothesize that people with OSA will have: (i) abnormally advanced circadian phase in BP and its regulators including catecholamines and cortisol, and (ii) deleterious circadian amplitudes in key CV risk markers. These two effects are hypothesized to explain the increased vulnerability and earlier timing of adverse CV events in OSA. This study will provide the first evidence of the relative role of internal circadian rhythms and specific behavioral stressors on CV function in OSA. By pointing to novel mechanisms by which OSA is linked to its comorbidities, this study may shed better light on nocturnal myocardial infarction and sudden cardiac death, help lead to treatment strategies based on time of day, and ultimately lead to a reduction in CV-related deaths.