Research completed under this Program Project Grant has identified """"""""masked hypertension"""""""" (MHT), a condition associated with target organ damage and significantly increased cardiovascular risk. MHT is defined by BP that is normal in the clinic but hypertensive (HT) during the day, possibly the result of higher psychological stress, delayed recovery from this pressor stimulus, or both. Functional changes in cardiovascular (CV) regulation may characterize MHT, and in turn contribute to the development of essential HT. We view MHT as an intermediate phase between NT and HT, and a potentially invaluable focus for revealing the developmental pathophysiology of HT.
The Specific Aim of Project 2 is to examine physiological and psychological factors associated with delayed post-stress BP recovery, the process we hypothesize contribute to the high daytime BP that is characteristic of MHT. In the laboratory we will study the reactivity to and recovery from anger recall stress in equal numbers of subjects with MHT and sustained normotension (SNT) (n=85/group, selected from Project 1). We will obtain physiological measures of CV regulation, and psychological measures of emotion and rumination during baseline, stress, and extended recovery periods. We hypothesize that compared to individuals with SNT, those with MHT, 1) will demonstrate a greater increase from baseline to the anger recall task in cardiac output (CO) and total peripheral resistance (TPR), and endothelial dysfunction, the primary contributors to BP, and hence also in BP;2) will demonstrate slower return of these indices to baseline levels during extended observation;and; 3) this slower return to baseline among MHT subjects during extended observation will be partially mediated by the occurrence of angry rumination during that period. We will also examine whether autonomic (BP variability, RR interval variability [RRV], catecholamines) and associated biological (Cortisol, endothelin-1, inflammation, oxidative stress) indices of vascular integrity and function demonstrate a comparable pattern of reactivity to and recovery from anger recall as that seen for BP, CO, TPR, and endothelial function.
Significance. Over 28% of US adults have a diagnosis of essential HT. Despite best efforts using current research models, it remains a leading cause of death and disability. In this application, we propose to use the model of MHT, an intermediate condition that afflicts upwards of an additional 20 million people, to identify the pathophysiological processes that distinguish MHT from SNT. We believe that this approach will identify key factors that are dysregulated in MHT and in so doing will contribute to the eariier identification and improved prognosis of individuals who are on a trajectory to essential HT.
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