Project Grant R01HL169320

EFFECTS OF EXPERIMENTAL SLEEP RESTRICTION IN OFFSPRING OF HYPERTENSIVE PARENTS - PROJECT SUMMARY HYPERTENSION IS THE CHIEF RISK FACTOR FOR CARDIOVASCULAR (CV) DISEASE AND A MAJOR THREAT TO POPULATION HEALTH. GIVEN THE BURDEN OF HYPERTENSION, IT IS CRITICAL TO IDENTIFY RISK ENHANCERS IN POPULATIONS SUSCEPTIBLE TO CV DISEASE, FOR RISK STRATIFICATION. WHILE FAMILY HISTORY OF HYPERTENSION, ESPECIALLY PARENTAL HYPERTENSION, IS WELL- KNOWN AS A ROBUST PREDICTOR OF HIGH BLOOD PRESSURE (BP) AND CV DISEASE IN THE OFFSPRING, THE ROLE OF CHRONIC SLEEP DEFICIENCY IS BEING INCREASINGLY RECOGNIZED. EVIDENCE FROM EPIDEMIOLOGICAL AND LABORATORY-BASED STUDIES CONVERGES TO INDICATE THAT INSUFFICIENT SLEEP INCREASES BP AND ALTERS CV DISEASE MECHANISMS, THUS PREDISPOSING TO ADVERSE OUTCOMES. WHETHER THE DETRIMENTAL IMPACT OF INSUFFICIENT SLEEP ON CV RISK IS POTENTIATED IN POPULATIONS WITH PREEXISTING VULNERABILITIES, SUCH AS THE OFFSPRING OF HYPERTENSIVE FAMILIES, IS PLAUSIBLE YET UNKNOWN. TO BRIDGE THIS GAP, WE PROPOSE A RANDOMIZED, CONTROLLED, CROSSOVER, 10-DAY INPATIENT STUDY TO INVESTIGATE WHETHER EXPERIMENTAL SLEEP RESTRICTION INCREASES BP AND IMPAIRS CV FUNCTION IN INDIVIDUALS WITH A POSITIVE PARENTAL HISTORY OF HYPERTENSION (+PHH), AND WHETHER THE HYPOTHESIZED ADVERSE IMPACT OF SHORTENED SLEEP IS GREATER IN THIS GROUP COMPARED TO INDIVIDUALS WITH A NEGATIVE PHH (PHH). WE PROPOSE THE FOLLOWING SPECIFIC AIMS COMPARING SLEEP RESTRICTION TO NORMAL SLEEP IN THE OFFSPRING OF HYPERTENSIVE PARENTS RELATIVE TO THE OFFSPRING OF NORMOTENSIVE PARENTS. AIM 1. TO COMPARE THE EFFECTS OF SLEEP RESTRICTION ON AMBULATORY BP IN INDIVIDUALS WITH A +PHH COMPARED TO THOSE WITH A PHH. AIM 2. TO DETERMINE THE IMPACT OF SLEEP RESTRICTION ON NEURAL CIRCULATORY CONTROL AND VASCULAR FUNCTION IN INDIVIDUALS WITH A +PHH COMPARED TO THOSE WITH A PHH. AIM 3. TO EXPLORE EPIGENETIC AND TRANSCRIPTOMIC MODIFICATIONS IN RESPONSE TO SLEEP RESTRICTION IN INDIVIDUALS WITH A +PHH COMPARED TO THOSE WITH A PHH. THIS PROPOSAL BUILDS UPON IMPORTANT STRENGTHS, INCLUDING AN INTERDISCIPLINARY TEAM OF INVESTIGATORS WITH UNIQUE EXPERIENCE AND EXPERTISE; SUPPORTING PRELIMINARY DATA; A ROBUST STUDY DESIGN WHICH WILL ENSURE RIGOROUS AND UNBIASED RESEARCH; AND INTEGRATION OF PHYSIOLOGICAL, BEHAVIORAL, AND OMICS VARIABLES IN A TRANSLATIONAL FRAMEWORK. THIS MECHANISTIC STUDY WILL INFORM ON THE ROLE OF SLEEP DEFICIENCY AS A CV RISK ENHANCER IN INDIVIDUALS WITH FAMILIAL PREDISPOSITION TO HYPERTENSION, AND GUIDE FUTURE PREVENTATIVE STRATEGIES TARGETING SLEEP TO AMELIORATE CV RISK IN VULNERABLE POPULATIONS.