Essential hypertension is typically thought to attack the brain late in its course, primarily through stroke. Accumulating evidence from both human and animal studies, though, shows that essential hypertension is associated with mild cognitive deficits, altered cerebral blood flow, decreases in grey matter volume, altered sympathetic nervous system function, and signs of premature brain aging. This evidence suggests that the brain is an early target of the disease, and, perhaps, the initial target. We propose to establish this point by examining pre-hypertensive individuals to establish that the brain sequelae of the disease are present prior to diagnostic levels of high blood pressure. We propose a cross sectional study of 250 participants followed by a 2 year longitudinal study of 200 participants with initial blood pressures in the pre-hypertensive range. Presence of brain sequelae in pre-hypertensive individuals will suggest that the currently accepted view is no longer tenable, the view that the brain is only affected late in the disease. Longitudinal results should indicate whether brain alterations predict later blood pressure or both brain and vascular effects of the disease occur in parallel. Risk factors associated with hypertension will be closely examined to see if such factors may implicate co-occurring pathology rather than hypertension in the induction of brain alterations. Successful completion of the project should direct clinical attention toward early sequelae of essential hypertension in both the brain and vasculature.

Public Health Relevance

This project is designed to show that brain structure and function is altered by essential hypertension even prior to the appearance of hypertensive levels of blood pressure. Current medical thought suggests that essential hypertension is a vascular disease that late in its course can interact with atherosclerosis to pose a high risk for stroke. Current evidence and that proposed in this project suggest in contrast that the brain is altered early in the course of the disease. Recognition of this should direct clinical intervention to the reversal of these brain effects in addition to the reduction of peripheral blood pressure. The significance of such a re-orientation is clear given the pandemic proportions of essential hypertension.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Biobehavioral Mechanisms of Emotion, Stress and Health Study Section (MESH)
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Maric-Bilkan, Christine
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University of Pittsburgh
Schools of Medicine
United States
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Gianaros, Peter J; Jennings, J Richard (2018) Host in the machine: A neurobiological perspective on psychological stress and cardiovascular disease. Am Psychol 73:1031-1044
Jennings, J Richard; Matthews, Karen A; Pardini, Dustin et al. (2018) Heart rate and hurtful behavior from teens to adults: Paths to adult health. Dev Psychopathol :1-13
Jennings, J Richard; Heim, Alicia F; Sheu, Lei K et al. (2017) Brain Regional Blood Flow and Working Memory Performance Predict Change in Blood Pressure Over 2 Years. Hypertension 70:1132-1141
Nunley, Karen A; Ryan, Christopher M; Aizenstein, Howard J et al. (2017) Regional Gray Matter Volumes as Related to Psychomotor Slowing in Adults with Type 1 Diabetes. Psychosom Med 79:533-540
Boylan, Jennifer Morozink; Jennings, J Richard; Matthews, Karen A (2016) Childhood socioeconomic status and cardiovascular reactivity and recovery among Black and White men: Mitigating effects of psychological resources. Health Psychol 35:957-66
Jennings, J Richard; Sheu, Lei K; Kuan, Dora C-H et al. (2016) Resting state connectivity of the medial prefrontal cortex covaries with individual differences in high-frequency heart rate variability. Psychophysiology 53:444-54
Jennings, J Richard; Allen, Ben; Gianaros, Peter J et al. (2015) Focusing neurovisceral integration: cognition, heart rate variability, and cerebral blood flow. Psychophysiology 52:214-224
Allen, Ben; Jennings, J Richard; Gianaros, Peter J et al. (2015) Resting high-frequency heart rate variability is related to resting brain perfusion. Psychophysiology 52:277-87
Jennings, J Richard; Heim, Alicia F; Kuan, Dora Chieh-Hsin et al. (2013) Use of total cerebral blood flow as an imaging biomarker of known cardiovascular risks. Stroke 44:2480-5
Heim, Alicia F; Coyne, Melissa J; Kamboh, M Ilyas et al. (2013) The catechol-o-methyltransferase Val158 Met polymorphism modulates organization of regional cerebral blood flow response to working memory in adults. Int J Psychophysiol 90:149-56

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