Endothelial function and hemodynamic responses during mental stress.

OBJECTIVE: The hemodynamic basis of blood pressure responses during psychological stress shows striking individual differences that share an interesting similarity with risk for cardiovascular disease. Factors accounting for these individual differences are poorly understood. The present study examined the relationship of vascular endothelial function to stress-induced hemodynamic responses. METHODS: Subjects were 40 healthy men and women, aged 25 to 44 years. Hemodynamic responses were assessed during exposure to a battery of four diverse laboratory stressors. Endothelium-dependent arterial dilation (EDAD) was measured by ultrasound imaging of the brachial artery in response to reactive hyperemia. RESULTS: High EDAD response was associated with lower resting systolic (p < .01) and diastolic blood pressure (p < .05). EDAD response was unrelated to blood pressure responses during stress. However, systemic vascular resistance responses during laboratory stress were significantly greater (p < .02) for individuals with low EDAD responses. CONCLUSIONS: Exaggerated systemic vascular resistance responses during stress may reflect endothelial dysfunction. This association may help explain the growing evidence of a relationship between stress hemodynamics and cardiovascular disease risk. The nature of this association is discussed in terms of a possible interplay between the sympathetic nervous system and the endothelium in regulation of vascular tone.     

Laboratory-based blood pressure recovery is a predictor of ambulatory blood pressure

The recovery phase of the stress response is an individual difference characteristic that may predict cardiovascular risk. The purpose of this study was to examine whether laboratory-based blood pressure (BP) recovery predicts ambulatory BP (ABP). One hundred and eighty-two participants underwent a standard laboratory stress protocol, involving a 20-min baseline rest period, and four stressors presented in a counterbalanced order, each followed by a 10-min recovery period. Participants also wore an ABP monitor for 24h during a typical workday. Hierarchical regression analyses showed that BP recovery accounted for significant additional variance for daytime SBP (p<0.001), nighttime SBP (p<0.001), daytime DBP (p<0.001), and nighttime DBP (p<0.001), after controlling for baseline and reactivity BP. Results suggest that persistence of the BP response following stress may be a more salient characteristic of the stress response in understanding its potential impact on longer term cardiovascular regulation.     

Vascular profile, delayed recovery, inflammatory process, and ambulatory blood pressure: laboratory-to-life generalizability.

Impaired recovery and plasma concentration of intercellular adhesion molecule-1 (sICAM-1) were both highlighted as plausible and more established markers of cardiovascular disease, respectively. Hemodynamic patterns during recovery and their link with circulating levels of sICAM-1 were examined as predictors of 24-h blood pressure (ABP). Impedance cardiography measures and beat-to-beat BP were recorded in 45 healthy subjects during a 10-min baseline, four tasks, and four 10-min recovery periods. sICAM-1 levels at rest were determined by ELISA. ABP measures were obtained combining data from a work and an off day. Hierarchical regressions showed that patterns of compensatory changes in cardiac output and total peripheral resistance during recovery improved the prediction of ABP above and beyond resting and recovery BP, or reactivity hemodynamic patterns. Stress-induced recovery was essentially vascular in nature and a more vascular profile was associated with higher ABP and higher circulating levels of sICAM-1. The results suggest a link between recovery hemodynamics and cardiovascular risk.     

Exaggerated Sympathetic Nervous System Response to Extended Psychological Stress in Offspring of Hypertensives

The cardiovascular responses of 24 healthy young adult males with a parental history of hypertension and 24 males without a parental history of hypertension to an extended active-coping psychological stressor were compared under three drug conditions: placebo, the beta 1-blocking agent metoprolol, and the alpha 1-blocking agent prazosin. In the placebo condition, offspring of hypertensives exhibited significantly greater heart rate, blood volume pulse, and forearm blood flow responses to the task. They also exhibited a significantly greater initial decrease in forearm vascular resistance, which, in contrast to the offspring of normotensives, was no longer significantly different from baseline levels by the end of the session. No group differences in blood pressure response were observed. Metoprolol eliminated the differences in heart rate and forearm vascular resistance responses. Prazosin eliminated the difference in blood volume pulse response and elicited a sustained group difference in forearm vascular resistance. These results implicate the sympathetic nervous system in the exaggerated cardiovascular responsivity to psychological stress in individuals with a family history of essential hypertension. They also suggest that the pattern of increasing vascular resistance in response to this stressor observed in this and other studies in this laboratory reflects alpha-adrenergic activity and not neurohumorally independent autoregulation.     

Hemodynamic effects of dietary caffeine, sleep restriction, and laboratory stress

This study examined the separate and interactive effects of caffeine, sleep restriction, and task-induced laboratory stress in 96 healthy male and female volunteers. Participants alternated weekly between ingesting placebo and caffeine (1.75 mg/kg) three times daily for 4 consecutive weeks, while being either rested or sleep restricted. Finapres measurements of blood pressure, cardiac output, and total peripheral resistance showed that caffeine produced persistent blood pressure increases with a vascular hemodynamic profile. Sleep restriction produced a pronounced vascular response not associated with appreciable changes in blood pressure, whereas blood pressure increases induced by cognitive activity showed mixed cardiac and vascular responses. The findings suggest that life-long dietary caffeine may contribute significantly to the development of cardiovascular disease.     

Behaviorally-evoked plasma catecholamine response and 24-hour excretion of urinary catecholamines among cardiac and vascular reactors

Individuals differ in the cardiac and vascular processes that underlie blood pressure elevations evoked by environmental stimuli; such differences may reflect variability in sympathoadrenal response. We separated 108 healthy, young-adult males into those with predominant elevations in either cardiac output or peripheral resistance when exposed to psychological challenges. We then asked if they differed on other measures of cardiovascular response, concomitant plasma catecholamine reactions or 24-h urinary excretion of catecholamines. Cardiac reactors, relative to vascular reactors, showed reduced cardiac pre-ejection period, a smaller reduction in stroke volume, and elevated plasma epinephrine response and 24-h urinary epinephrine excretion. Vascular reactors, relative to cardiac reactors, responded to mental stress with more elevated diastolic blood pressure, a rise in peripheral resistance and pulse wave velocity, and a greater reduction in stroke volume. Vascular reactors, however, did not show plasma norepinephrine response or 24-h urinary norepinephrine excretion that was greater than cardiac reactors. The results provide partial support for the hypothesis that variability in sympathoadrenal activity contributes to individual differences in cardiac and vascular reactivity, and extend prior observations by demonstrating covariation of behaviorally-elicited cardiac reactivity with the 24-h excretion of epinephrine.     

Menopause induced by oophorectomy reveals a role of ovarian estrogen on the maintenance of pressure homeostasis

OBJECTIVES: Following spontaneous menopause women show a greater increase in systolic and diastolic blood pressure than men of the same age. The aim of the present study was to assess the effect of acute ovarian hormone withdrawal and replacement on blood pressure and forearm blood flow. METHODS: We studied 18 fertile middle-aged normotensive women (48 +/- 1.5 years, range 46-51 years) 1 week prior and 1 month subsequent to bilateral oophorectomy by means of 24-h blood pressure monitoring and strain-gauge venous occlusion plethysmography. Eighteen subjects who had undergone hysterectomy with ovarian sparing, matched for age and biophysical characteristics, were used as a control group. All women were free from cardiovascular risk factors or disease. RESULTS: Oophorectomy increased the mean values of 24 h (P < 0.001), daytime (P < 0.05), and nighttime (P < 0.01) diastolic blood pressure and nighttime systolic blood pressure (P < 0.01). Blood pressure increase was associated with a rise in forearm vascular resistance (P < 0.01). No significant changes in either blood pressure or forearm vascular resistance values were observed in hysterectomized women. In 16 oophorectomized women a 3-month estrogen replacement therapy (ERT) (17beta-estradiol, 100 mcg/day by transdermal patches) brought blood pressure and forearm vascular resistance values to a level comparable to that recorded before intervention. CONCLUSIONS: Surgically-induced menopause causes an increase in peripheral vascular resistance and blood pressure suggesting a role of ovarian hormones in the homeostatic pressure modulation. Recovery of the baseline condition after ERT suggests that the accelerated increase in blood pressure after menopause is due to ovarian and above all estrogen insufficiency.     

Hemodynamic responses during psychological stress: Implications for studying disease processes

Investigation of the physiological correlates of psychological stress is of interest in relation to the putative impact of stress in the etiology of cardiovascular disease. Although the assessment of blood pressure and heart rate responses to psychological stress has been very informative, the addition of cardiac output measurement has added a further dimension to this research field. In recent studies, a more complete hemodynamic picture of the stress response has been documented in terms of cardiac output and systemic vascular resistance components of blood pressure changes. Different stressors have been shown to produce similar blood pressure increases due to quite different hemodynamic mechanisms. Furthermore, when faced with the same stressor, different individuals may exhibit pressor responses that are very different hemodynamically. There is growing evidence that these hemodynamic response patterns to psychological stress are stable individual traits. Response stability is a prerequisite for considering how stress-related hemodynamic changes may be implicated in the pathophysiology of cardiovascular diseases. Observations that hemodynamic response patterns in individuals at higher risk for the development of hypertension differ from those of lower risk individuals show that specific patterns of hemodynamic response are associated with disease processes. Although it is as yet unclear whether they represent markers or mechanisms. Overall. hemodynamic studies appear to he helping to refine our understanding of how stress can impact cardiovascular disease processes.     

Cardiovascular reactivity of younger and older adults to positive-, negative-, and mixed-emotion cognitive challenge

Although aging is associated with progressive increases in blood pressure level, previous research has been inconsistent as to whether older adults show greater or lesser cardiovascular reactivity (CVR) to emotion than do younger adults. There is reason to believe that these inconsistencies could be clarified by examining age-related differences in hemodynamic profile revealed by measuring the pattern of cardiac output and total peripheral resistance associated with changes in blood pressure reactivity. Accordingly, the present study examined the performance, CVR, and hemodynamic profile of younger and older adults during encoding and recognition of word pairs involving four valence types: positive, negative, mixed (positive/negative), and neutral word pairs. Results revealed higher baseline blood pressure, increased CVR characterized by a vascular hemodynamic profile, and more rapid recovery (especially during encoding) for older than for younger participants. Results are discussed in light of research and theory on the relationship between aging and cardiovascular health.     

Cardiovascular reactivity in real life settings: Measurement, mechanisms and meaning

Cardiovascular reactivity to stress is most commonly studied in the laboratory. Laboratory stressors may have limited ecological validity due to the many constraints, operating in controlled environments. This paper will focus on paradigms that involve the measurement of cardiovascular reactions to stress in real life using ambulatory monitors. Probably the most commonly used paradigm in this field is to measure the response to a specific real life stressor, such as sitting an exam or public speaking. A more general approach has been to derive a measure of CV variability testing the hypothesis that more reactive participants will have more variable heart rate or blood pressure. Alternatively, self-reports of the participants’ perceived stress, emotion or demands may be linked to simultaneously collected ambulatory measures of cardiovascular parameters.This paper examines the following four questions: (1) What is the form and what are the determinants of stress-induced CV reactivity in real life? (2) What are the psychophysiological processes underlying heart rate and blood pressure reactivity in real life? (3) Does CV reactivity determined in the laboratory predict CV reactivity in real life? (4) Are ambulatory cardiovascular measures predictive of cardiovascular disease?It is concluded that the hemodynamic processes that underlie the blood pressure response can reliably be measured in real life and the psychophysiological relationships seen in the laboratory have been obtained in real life as well. Studies examining the effects of specific real life stressors show that responses obtained in real life are often larger than those obtained in the laboratory. Subjective ratings of stress, emotion and cognitive determinants of real life stress (e.g. demand, reward and control) also relate to real life CV responses. Surprisingly, ambulatory studies on real life cardiovascular reactivity to stress as a predictor of cardiovascular disease are rare. Measuring the CV response to stress in real life may provide a better measure of the stress-related process that are hypothesized to cause disease than is possible in the laboratory. In addressing these questions, below we review the studies that we believe are representative of the field. Therefore, this review is not comprehensive.     

Sex differences in the hemodynamic responses to mental stress: Effect of caffeine consumption

The effect of caffeine on stress responses was compared in 25 men and 22 women in a 2-week placebo-controlled, double-blind, randomized crossover trial. On each week, participants abstained from all dietary sources of caffeine before undergoing a 6-h laboratory protocol under placebo or caffeine exposure followed by a 30-min mental stressor with blood pressure (BP) and cardiovascular hemodynamic assessments. On the placebo session, men and women showed a significant BP increase to stress, although women had significant cardiac responses whereas men had vascular responses. Caffeine ingestion before stress caused both men and women to have enhanced hemodynamic responses to the stressor associated with an increase in cardiac index and a drop in the peripheral resistance index. Caffeine enhances the cardiovascular fight-or-flight response pattern to stress in men and women.     

Postural stability of hemodynamic responses during mental challenge

Laboratory stress testing is typically conducted while subjects are seated, whereas real-life stressors may often be encountered while standing. The present study of 20 healthy young men evaluated blood pressure and underlying hemodynamic adjustments to a standardized mental arithmetic task performed twice while seated and twice while standing. Blood pressure increased during mental arithmetic in both postures, but the underlying hemodynamic determinants of the pressor responses were different for the two postures. Augmented cardiac output was responsible for increasing blood pressure during seated task performance, whereas increased vascular resistance was the mechanism for the pressor response to the task performed while standing. Blood pressure and hemodynamic responses were reproducible subject characteristics for a given posture; test-retest correlations were significant for all cardiovascular measures. However, seated blood pressure responses were not significantly correlated with standing blood pressure responses. In contrast, significant between-posture correlations were found for cardiac output and vascular resistance responses. This preliminary evidence of postural stability of the hemodynamic determinants of blood pressure responses during stress is consistent with growing evidence that hemodynamic response tendencies are robust characteristics of reactivity. Ambulatory monitoring of hemodynamic response patterns during real-life stress may reveal more idiosyncratic profiles of stress reactivity than are displayed by blood pressure responses alone.     

Laboratory stress testing to assess real-life cardiovascular reactivity

Thirty-six normotensive adults received laboratory stress testing (mental arithmetic, short-term memory, isometric handgrip, cold pressor tests) and 24-hour ambulatory blood pressure monitoring on two work days separated by a month. Laboratory and ambulatory measures of cardiovascular reactivity had low test-retest reliability. Increases in blood pressure during the memory and cold pressor tests were related to measures of reactivity obtained outside the laboratory (waking blood pressure variability, responses to home and work environments). However, the portion of ambulatory reactivity accounted for by laboratory reactivity was small. In the best case (r = 0.43), cold pressor diastolic pressure explained only 19% of diastolic pressure variability in the natural environment. Laboratory-ambulatory disagreement in reactivity was related to interindividual variability in physical activity on the day of ambulatory monitoring.     

The effects of rofecoxib on 24-h ambulatory blood pressure and heart rate monitoring in patients with hypertension and osteoarthritis

The aim of the study was to investigate the effects of the cylooxygenase (COX)-2 specific inhibitor rofecoxib, on blood pressure (BP) and heart rate (HR) in patients with well-controlled hypertension and osteoarthritis via 24-h ambulatory monitoring. Thirty patients with well controlled hypertension were included. Fifteen patients had osteoarthritis and were recommended by their rheumatologists to take rofecoxib 12.5 mg/day (rofecoxib group). The control group consisted of 15 patients who had hypertension but no clinical osteoarthritis and did not receive any anti-inflammatory drugs. Twenty-four-hour ambulatory monitoring of BP and HR were performed on the day before initiation of rofecoxib therapy and on days 3 and 14 of COX-2 therapy. The control group underwent 24-h monitoring three times at similar intervals. Antihypertensive medications were continued. On day 3 of rofecoxib therapy, mean HR for both daytime and nighttime were lower than those at baseline. On day 14, the changes in mean HR did not differ from baseline values. Similarly, diastolic BP (daytime and nighttime) on day 3 appeared to be lower than at baseline. However this difference was not observed on day 14, and mean daytime and nighttime diastolic BP returned to baseline values. There was no statistically significant difference in the mean arterial pressure or systolic BP recordings on days 3 or 14 than at baseline. Rofecoxib 12.5 mg/day did not significantly increase BP during 24-h ambulatory BP monitoring in patients with well-controlled hypertension and osteoarthritis.     

Hemodynamic profile of stress-induced anticipation and recovery.

Systolic and diastolic blood pressure, heart rate, stroke volume, cardiac output, and total peripheral resistance were measured in 100 healthy men and women with the aim of investigating hemodynamic profile during anticipation of, and recovery from, exposure to active and passive laboratory stressors. A 5-min anticipatory period preceded two tasks, both of which lasted 2.5 min. The tasks were mental arithmetic ('beta-adrenergic' stress) and the cold pressor test ('alpha-adrenergic' stress). Each task was followed by a 5-min recovery period. Blood pressure and heart rate were measured with a FinaPres 2300e, and stroke volume, cardiac output, and total peripheral resistance were computed from these parameters. Salivary cortisol was measured in relation to both tasks, and participants completed tests of state and trait anxiety, locus of control, and hostility. As expected, mental arithmetic and the cold pressor test elicited myocardial and vascular patterns of reactivity, respectively. However, contrary to expectations, anticipatory and recovery hemodynamic profile involved essentially vascular responding for both stressors. Salivary cortisol increased in response to both tasks but only weakly correlated with hemodynamic changes. None of the subjective measurements was a strong predictor of physiological reactivity. The findings suggest that stress-induced anticipatory and recovery reactivity may be generally vascular rather than myocardial. This could have important implications in light of suggestions that anticipatory and recovery responses may be better predictors of subsequent cardiovascular disease than direct stress-induced reactivity.     

Noninvasive,automatic 24-h ambulatory blood pressure monitoring in normotensive subjects

Summary The reliability of noninvasive, automatic blood pressure monitoring is not yet clearly established. A 24-h ambulatory blood pressure profile was obtained in 9 healthy, normotensive subjects with an automatic, noninvasive device. The blood pressure profile showed the typical circadian pattern with lower systolic and diastolic values during sleep, although pulse pressure was fairly constant (about 40 mm Hg). The systolic blood pressure rose steeply in the early morning hours — before waking up. The results were compared with simultaneous hourly readings using the auscultatory method. There were no statistically significant differences between the automatic and auscultatory readings, 13 of the 18 mean values at. different time points being within 2 mm Hg of each other. All the auscultatory means fell within the 95% confidence limits of those measured hourly by the automatic method. Although the automatic method seemed to be reliable compared with the auscultatory method, its sensitivity to motion artifacts is a disadvantage in a truly ambulatory setting.     

Hypoxia disturbs fetal hemodynamics and growth.

Low-birth-weight babies have an increased risk of cardiovascular disease (CVD) in later life. The authors hypothesize that fetal hypoxia alters the structure and function of the developing cardiovascular system resulting in CVD. They investigated the effects of chronic hypoxia on cardiac performance, hemodynamic control, and growth during the second half of embryonic chick development. Three stages of hemodynamic adaptations were identified in hypoxic chick embryos. At embryonic day 13 (E13), heart rate and blood pressure were higher in hypoxic embryos. At E17, this was followed by sympathetic hyperinnervation of peripheral arteries, resulting in increased vasoconstriction during a chemoreflex. This was accompanied by dilatation of the left ventricle and a 50% reduction in cardiac contractility. E19 hypoxic embryos had a 33% higher baseline vascular tone, but failed to maintain blood pressure during acute stress, indicating cardiac failure. Reduced body, heart, and liver weights followed the hemodynamic changes. Chronic hypoxia induces dilated cardiomyopathy and sympathetic hyperinnervation of the peripheral vasculature leading to aberrant fetal hemodynamics and fetal growth restriction. This study identifies that alterations in fetal hemodynamic regulation are in the causal pathway between disturbances in fetal environment, restricted fetal growth and CVD, and establishes fetal hypoxia as a novel risk factor for cardiovascular disease.     

Time course and mechanisms of hemoconcentration in response to mental stress

Hemoconcentration with mental stress exposure may be involved in the triggering of acute cardiovascular events. In the present study, hematocrit was measured repeatedly at baseline, during a 4 min mental stress task and during 20 min of recovery. Blood was sampled every 1-2 min throughout. Blood pressure, heart rate and R-wave to pulse interval, a measure of cardiac contractility, were measured with the same periodicity. The stress task elicited a 1.3% increase in hematocrit, which was sustained with full return to baseline level occurring only after 16 min of recovery. Between-subject correlations between hematocrit and hemodynamic activity were low. Aggregate within-subject coefficients were more impressive; the temporal profile of hematocrit correlated significantly with all hemodynamic variables. Similar within-subject analyses indicated that whereas cardiac contractility was correlated with hematocrit both during stress-related increase and subsequent recovery, blood pressure was related to hematocrit only during the increase. This suggests that stress-induced hemoconcentration may driven by different mechanisms than those which underlie its recovery.     

Predicting Home and Work Blood Pressure Measurements from Resting Baselines and Laboratory Reactivity in Black and White Americans

The relationship between blood pressure in the laboratory (both at rest and in response to laboratory tasks) and ambulatory blood pressure at home and at work was evaluated. One hundred nineteen normotensive and unmedicated mild-moderate hypertensive black and white females and males participated in laboratory blood pressure monitoring at rest and during four challenging tasks (structured interview, video game, bicycle exercise, and cold pressor test) as well as ambulatory blood pressure monitoring while at home and at work. Baseline blood pressure taken while subjects were at rest was the strongest predictor of ambulatory systolic blood pressure (r = .64) and diastolic blood pressure (r = .77) at work. Among reactivity tasks the strongest predictors of ambulatory blood pressure in the total population were the structured interview and the video game (both psychological tasks) followed by the cold pressor test. Racial comparisons, however, determined that the cold pressor test predicted diastolic blood pressure significantly better for blacks (r = .73) than for whites (r = .40), suggesting a possible difference in blood pressure regulation.     

Systemic lupus erythematosus and hypertension

Systemic lupus erythematosus (SLE) is associated with a high burden of cardiovascular disease (CVD), which is in part imputed to classical vascular risk factors such as hypertension. Hypertension is frequent among patients with SLE and studies show it is more prevalent in SLE patients than in people without SLE. Despite the high frequency of hypertension in SLE patients, the pathophysiological mechanisms underlying the development of hypertension remain poorly understood. 24-h ambulatory blood pressure monitoring has emerged as a valuable tool in determining blood pressure (BP) in SLE patients in whom hypertension has been associated with damage accrual, stroke and cognitive dysfunction. Although prevalent, current guidelines neglect the specific management of hypertension in SLE patients in their recommendations. This review discusses the mechanisms that may lead to hypertension and the literature evaluating hypertension screening and management in SLE patients.