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Hypertension is a presumptive risk factor for premature cognitive decline. However, lowering blood pressure (BP) does not uniformly reverse cognitive decline, suggesting that high BP per se may not cause cognitive decline. We hypothesized that essential hypertension has initial effects on the brain that, over time, manifest as cognitive dysfunction in conjunction with both brain vascular abnormalities and systemic BP elevation. Accordingly, we tested whether neuropsychological function and brain blood flow responses to cognitive challenges among prehypertensive individuals would predict subsequent progression of BP. Midlife adults (n=154; mean age, 49; 45% men) with prehypertensive BP underwent neuropsychological testing and assessment of regional cerebral blood flow (rCBF) response to cognitive challenges. Neuropsychological performance measures were derived for verbal and logical memory (memory), executive function, working memory, mental efficiency, and attention. A pseudo-continuous arterial spin labeling magnetic resonance imaging sequence compared rCBF responses with control and active phases of cognitive challenges. Brain areas previously associated with BP were grouped into composites for frontoparietal, frontostriatal, and insular-subcortical rCBF areas. Multiple regression models tested whether BP after 2 years was predicted by initial BP, initial neuropsychological scores, and initial rCBF responses to cognitive challenge. The neuropsychological composite of working memory (standardized beta, -0.276; se=0.116; P =0.02) and the frontostriatal rCBF response to cognitive challenge (standardized beta, 0.234; se=0.108; P =0.03) significantly predicted follow-up BP. Initial BP failed to significantly predict subsequent cognitive performance or rCBF. Changes in brain function may precede or co-occur with progression of BP toward hypertensive levels in midlife., (© 2017 American Heart Association, Inc.)

Individuals who express relatively large-magnitude or "exaggerated" blood pressure (BP) reactions to behavioral stressors are presumably at increased risk for cardiovascular disease. As shown by recent neuroimaging studies, individuals who express exaggerated stressor-evoked BP reactivity also express heightened neural activity in corticolimbic brain areas that centrally regulate the cardiovascular system. These studies, however, have exclusively examined BP reactivity and concomitant neural activity during stressor exposure. If exaggerated BP reactivity originates in part from a centrally regulated and dispositional cardiovascular response tendency, then heightened resting (prestressor) corticolimbic activity may predict the subsequent expression of exaggerated stressor-evoked BP reactivity. To test this hypothesis, perfusion MRI was used to quantify resting regional cerebral blood flow (an indirect metabolic measure of neural activity) in men (n=19) and women (n=20) aged 20 to 37 years who subsequently performed cognitive stressor tasks to evoke BP reactivity. Individuals who expressed larger task-induced rises in systolic and diastolic BP also expressed higher resting regional cerebral blood flow in 4 functionally related corticolimbic areas: the dorsal and perigenual anterior cingulate, medial prefrontal, and insular cortices. Specifically, resting regional cerebral blood flow in these areas accounted, respectively, for 40% and 31% of the variance in systolic (P=0.001) and diastolic (P=0.008) BP reactivity, after accounting for total resting cerebral blood flow, resting BP, task performance, and task-related ratings of unpleasantness, arousal, and perceived psychological control. Heightened resting corticolimbic activity may represent a neurobiological correlate of an individual's predisposition for exaggerated stressor-evoked BP reactivity and possibly related cardiovascular risk.

Individuals who show exaggerated blood pressure reactions to psychological stressors are at increased risk for hypertension, atherosclerosis, and stroke. We tested whether individuals who show exaggerated stressor-induced blood pressure reactivity also show heightened stressor-induced neural activation in brain areas involved in controlling the cardiovascular system. In a functional MRI study, 46 postmenopausal women (mean age: 68.04; SD: 1.35 years) performed a standardized Stroop color-word interference task that served as a stressor to increase blood pressure. Across individuals, a larger task-induced rise in blood pressure covaried with heightened and correlated patterns of activation in brain areas implicated previously in stress-related cardiovascular control: the perigenual and posterior cingulate cortex, bilateral prefrontal cortex, anterior insula, and cerebellum. Entered as a set in hierarchical regression analyses, activation values in these brain areas uniquely predicted the magnitude of task-induced changes in systolic (DeltaR(2)=0.54; P<0.001) and diastolic (DeltaR(2)=0.27; P<0.05) blood pressure after statistical control for task accuracy and subjective reports of task stress. Heightened stressor-induced activation of cingulate, prefrontal, insular, and cerebellar brain areas may represent a functional neural phenotype that characterizes individuals who are prone to show exaggerated cardiovascular reactivity.

Exaggerated cardiovascular reactivity to behavioral challenges among otherwise healthy individuals has been associated with carotid atherosclerosis. We evaluated whether a similar relationship exists among hypertensives, who are at a heightened atherosclerotic risk. Untreated, hypertensive men (n=251; age range, 40 to 70 years; 197 white, 54 black) completed a standardized battery of behavioral challenges while their blood pressure responses to the battery were measured. Mean and maximum carotid intima-media thickness and the occurrence of carotid plaques were subsequently determined using B-mode ultrasonography. Although greater systolic and diastolic responses to the battery were associated with greater mean and maximum intima-media thickness in univariate analyses (P<0.01), only diastolic reactivity showed a unique association with mean and maximum carotid intima-media thickness after multivariate adjustment for age, race, socioeconomic status, smoking and alcohol use, body mass index, lipid profile, glucose and insulin concentrations, and resting blood pressure (P<0.05). Carotid plaque occurrence was associated with greater systolic reactivity (P=0.05) and was marginally associated with greater diastolic reactivity (P=0.07) in univariate analyses, but neither systolic nor diastolic reactivity was uniquely associated with the presence of carotid plaques after multivariate risk-factor adjustment. Among hypertensives, exaggerated behaviorally evoked cardiovascular reactivity appears to be uniquely associated with greater carotid intima-media thickness but not with carotid plaque occurrence.