Serum Lipids,Neuroendocrine, and Cardiovascular Responses to Stress in Men and Women with Mild Hypertension

Abstract

In this study, we examined the relation between serum lipid levels, gender, and cardiovascular and neuroendocrine stress reactivity in patients with mild hypertension. Ninety-nine individuals (62 men, 37 women) with mild hypertension performed four mental stress tasks: mental arithmetic, public speaking, cold stress, and a computer videogame. Cardiovascular reactivity scores were computed by subtracting the minimum resting blood pressure (BP) and heart rate (HR) values from the maximum values obtained during each task. Neuroendocrine reactivity was calculated as the change from epinephrine and norepinephrine values from mean rest to mean task. High and low reactors were identified on the basis of median splits of reactivity scores, averaged across all four stressors. High systolic blood pressure reactors had higher levels of total (TC), low-density lipoprotein cholesterol (LDL-C), and apo-B than did low reactors. High diastolic blood pressure reactors had lower levels of high-density lipoprotein cholesterol (HDL-C) and higher levels of LDL-C and apo-B than did low reactors. High HR reactors had higher apo-AI:apo-AII ratios than low reactors. Lipid levels were not different for high and low epinephrine and norepinephrine reactors. Although women were noted to have more favorable lipid profiles than men, both male and female hypertensive patients who were high reactors had less favorable lipid profiles than low reactors.     

Sex Differences in Lipid, Lipoprotein, Cardiovascular, and Neuroendocrine Responses to Acute Stress

This study had two objectives: (a) to examine whether or not lipids and lipoproteins change in response to acute behavioral stress in young adults; and (b) to test the extent of sex differences in the magnitude of the lipid, lipoprotein, neuroendocrine, and cardiovascular changes during stress. Nineteen women and 22 men participated in a serial subtraction task, a videotaped speech task, and a self-evaluation task. The cholesterol portions of low density and high density lipoproteins, triglycerides, free fatty acids, epinephrine, norepinephrine, heart rate, and blood pressure were examined at rest and during each stressor. Repeated measures analyses of variance indicated that stress-related levels of low density and high density lipoprotein-cholesterol, triglycerides, free fatty acids, norepinephrine, heart rate, and blood pressure were elevated, relative to baseline, and that these responses were partially task or order dependent. Subsequent analyses of sex differences showed that males had larger low density lipoprotein-cholesterol and blood pressure increases during all tasks, relative to those of females, and females had larger heart rate responses to the speech task, relative to those of males. There were no sex differences in plasma catecholamine adjustments. These data demonstrate that the cholesterol fractions of high and low density lipoproteins increase during acute psychological stress, and are the first to systematically examine male/female differences in those stress responses.     

Neuroendocrine and Cardiovascular Stress Reactivity in Middle-Aged Normotensive Adults with Parental History of Cardiovascular Disease

Neuroendocrine and cardiovascular stress reactivity was studied in healthy middle-aged individuals whose parental history included essential hypertension and/or myocardial infarction and a control group without parental history of cardiovascular disease. All subjects completed a rest session (1 hour) and a stress session (1 hour). The stress session included behavioral (mirror image tracing, mental arithmetic, and the Stroop color word conflict test) and physical stressors (the cold pressor test and isometric exercise). Systolic and diastolic blood pressures and heart rate were recorded at baseline before and during all stressors. Specimens for determination of urinary catecholamines and cortisol were sampled after the rest and stress sessions respectively. Generally, a parental history of hypertension but not of myocardial infarction influenced neuroendocrine and cardiovascular stress reactivity. A family history of hypertension was associated with exaggerated epinephrine, norepinephrine, and cortisol excretion during stress and with enhanced heart-rate reactivity to behavioral (mental arithmetic and mirror image tracing) but not to physical stressors (isometric exercise or the cold pressor test). We conclude that individuals with a family history of hypertension tend to display exaggerated cardiovascular and neuroendocrine reactivity to stress.     

Caffeine effects on cardiovascular and neuroendocrine responses to acute psychosocial stress and their relationship to level of habitual caffeine consumption

The effects of a moderate dose of caffeine on cardiovascular and neuroendocrine stress reactivity were examined in 25 healthy male subjects selected as habitual or light consumers of caffeine. Measurements were taken under resting conditions before and after administration of caffeine (3.5 mg/kg) or placebo, during a stressful laboratory task, and in a post-stress recovery period. Caffeine elevated blood pressure and plasma norepinephrine levels at rest, effects which added significantly to the effects of stress. Caffeine potentiated stress-related increases in plasma epinephrine and cortisol stress, more than doubling the responses observed in the control condition. These effects were present in both habitual and light consumers and level of habitual caffeine consumption did not affect their magnitude. Results indicate that caffeine can potentiate both cardiovascular and neuroendocrine stress reactivity and that the habitual use of caffeine is not necessarily associated with the development of tolerance to these effects.     

Effects of hemoconcentration and sympathetic activation on serum lipid responses to brief mental stress

OBJECTIVE: Previous studies suggest that hemoconcentration may be one mechanism by which acute psychological stress causes elevations of serum total cholesterol and its subfractions. Alternatively, such elevations may result from sympathetically mediated changes in lipid metabolism. This study evaluated these two hypotheses by manipulation of sympathetically mediated responses to stress using a nonselective adrenoceptor antagonist, labetalol. METHOD: In a 2 x 2 factorial design, 52 healthy male participants were randomly assigned to a stress or no-stress condition and, within each condition, were administered either labetalol or saline. Participants assigned to stress completed three cognitive and evaluative tasks lasting a total of 18 minutes. Indices of hemoconcentration (hematocrit and hemoglobin), heart rate, blood pressure, and serum lipids (total, high-density lipoprotein (HDL), low-density lipoprotein (LDL), free fatty acids, and triglycerides) were assessed at preinfusion and infusion baselines and after mental stress (or rest). RESULTS: Labetalol reduced sympathetic activation, as shown by a substantial reduction in heart rate elevation during stress, but did not alter changes in blood pressure or in hemoconcentration, as indicated by equivalent increases in hematocrit and hemoglobin in the two stressed groups. Labetalol blocked stress-induced increases in free fatty acid concentrations and lowered triglyceride levels but did not influence rises in total, HDL, or LDL cholesterol among stressed subjects. However, arithmetic correction for hemoconcentration eliminated the increases in total, HDL, and LDL cholesterol. CONCLUSIONS: These findings suggest that elevations in total cholesterol and its HDL and LDL subfractions during acute stress are caused by accompanying hemoconcentration, whereas concomitant rises in free fatty acids and triglycerides result from the direct metabolic effects of sympathetic activation.     

Variations in plasma lipid concentration during examination stress

The effect of psychological stress on plasma lipids was studied in 40 law students (20 men and 20 women). Plasma cholesterol, triglyceride, and apolipoprotein concentrations were examined at the beginning of the quarter and during the week before final examinations. Cortisol, blood pressure, and heart rate, and self-reports of stress and workload were also measured to verify that examinations were associated with increased stress levels. Perceived stress, perceived workload, and cortisol increased before examinations. Low density lipoprotein cholesterol (LDL-C) increased 5.8 +/- 13.9 mg/dL, and apolipoprotein B (apo B) increased 2.9 +/- 4.0 mg/dL. High density lipoprotein cholesterol decreased in women only. These changes were not due to changes in dietary intake or indexes of plasma volume. However, changes in cortisol and changes in LDL-C and apo B were associated, suggesting a neuroendocrine component to the effects. These results suggest that episodic, stressful situations may lead to potentially atherogenic changes in lipid and lipoprotein concentrations.     

Beta-blocker induced changes in the cholesterol: High-density lipoprotein cholesterol ratio and risk of coronary heart disease

Summary The lowering of blood pressure with beta-blocking drugs has had a low impact on coronary heart disease (CHD) mortality and the question has been raised whether adverse changes in plasma lipoproteins offset the benefits of blood pressure reduction. Comparison of plasma lipoprotein concentrations in hypertensive patients treated with commonly used beta-blockers with lipoprotein concentrations in patients with coronary heart disease shows that these drugs cause clinically important shifts in the cholesterol ratio [total cholesterol (TC): high-density lipoprotein cholesterol (HDLC)] and reductions in the atheroprotective lipoprotein HDLC. The magnitude of these changes is sufficient to increase the risk of heart attack two- to four-fold depending on the initial cholesterol ratio and the duration of treatment. Only beta-blockers with marked intrinsic sympathomimetic agonist activity (pindolol) or combined alpha-beta-blocking properties (Labetalol) appear free of adverse effects on plasma lipoproteins and triglycerides. Chronic treatment with other betablockers should be accompanied by cholesterol and HDLC measurements at the beginning of therapy. Plasma lipoprotein measurements at 3–6 month intervals seem mandatory in patients with cholesterol values greater than 6 mmol/l (230 mg/dl) and (TC):HDLC ratios above 5 at the start of treatment. The risk of a coronary event must be regarded as unacceptable when the cholesterol ratio exceeds a critical value of about 6. Further controlled studies are needed to evaluate the effects of beta-blockers in hypertension when administered for periods of up to a year or more. More information is required on the behaviour of lipoprotein subspecies and apoproteins. Since the changes in lipoproteins reported in studies referred to in this review may have been submaximal the risks and the benefits from beta-blocker therapy must be carefully considered.     

Lipid reactivity among men with a parental history of myocardial infarction.

In the current study, we examined lipid and cardiovascular responses to an acute stressor among men with and without a parental history of myocardial infarction. 37 men were selected from a large group who completed medical history questionnaires and interviews. Twenty-two men who denied parental history of heart disease (negative parental history) were compared with 15 men with one or both parents who had suffered a myocardial infarction (positive parental history). Total cholesterol, high- and low-density lipoprotein cholesterol, triglycerides, heart rate, and blood pressure were measured at rest and during a videotaped speech stressor. Positive parental history men had significantly higher low-density lipoprotein cholesterol levels and blood pressure at baseline, significantly lower high-density lipoprotein cholesterol levels at baseline, and significantly larger total cholesterol and low-density lipoprotein cholesterol reactivity, relative to negative parental history men. Because parental history is a risk factor for subsequent cardiovascular morbidity and mortality, these data suggest that lipid reactivity to stress may be biologically important.     

Differential impact of the first and second wave of a stress response on subsequent fear conditioning in healthy men

Stress is a process of multiple neuroendocrine changes over time. We examined effects of the first-wave and second-wave stress response on acquisition and immediate extinction of differential fear conditioning, assessed by skin conductance responses. In Experiment 1, we placed acquisition either close to the (second-wave) salivary cortisol peak, induced by a psychosocial stressor (experimental group, EG), or after non-stressful pretreatment (control group, CG). Contrary to predictions, groups did not differ in differential responding. In the EG only, mean differential responding was negatively correlated with cortisol increases. In Experiment 2, we placed conditioning near the first-wave stress response, induced by a cold pressor test (CPT), or after a warm-water condition (CG). CPT-stress increased extinction resistance. Moreover, acquisition performance after CPT was positively correlated with first-wave blood pressure increases. Data suggest that mediators of the first-wave stress response enhance fear maintenance whereas second-wave cortisol responsivity to stress might attenuate fear learning.     

Changes in lipid profile variables in response to submaximal and maximal exercise in trained cyclists

This study examined the effect of prolonged submaximal exercise followed by a self-paced maximal performance test on cholesterol (T-Chol), triglycerides (TG), and high-density lipoprotein cholesterol (HDLC). Nine trained male athletes cycled at 70% of maximal oxygen consumption for 60 min, followed by a selfpaced maximal ride for 10 min. Venous blood samples were obtained at rest, at 30 and 60 min during submaximal exercise, and immediately after the performance test. Lactic acid, haematocrit (Hct), haemoglobin (Hb), T-Chol and TG were measured in the blood, while plasma was assayed for HDL-C. Plasma volume changes in response to exercise were calculated from Hct and Hb values and all lipid measurements were corrected accordingly. In order to ascertain the repeatability of lipid responses to exercise, all subjects were re-tested under identical testing conditions and experimental protocols. When data obtained during the two exercise trials were analysed by two-way ANOVA no significant differences (P > 0.05) between tests were observed. Consequently the data obtained during the two testing trials were pooled and analysed by one-way ANOVA. Blood lactic acid increased non-significantly (P > 0.05) during the prolonged submaximal test, but rose markedly (P < 0.05) following the performance ride. Lipid variables ascertained at rest were within the normal range for healthy subjects. ANOVA showed that blood T-Chol and TG were unchanged (P > 0.05), whereas HDL-C rose significantly (P < 0.05) in response to exercise. Post hoc analyses indicated that the latter change was due to a significant rise in HDL-C after the performance ride. It is concluded that apparent favourable changes in lipid profile variables occur in response to prolonged submaximal exercise followed by maximal effort, and these changes showed a good level of agreement over the two testing occasions.     

Augmented sympathetic nerve activity in response to stressors in young borderline hypertensive men

To determine whether there may be an abnormality in sympathetic nerve activity in response to physical and psychological stressors, we microneurologically recorded muscle sympathetic nerve activity in 11 normotensive and 9 borderline hypertensive, age-matched men. Supine blood pressure, plasma levels of epinephrine and norepinephrine and muscle sympathetic nerve activity were measured before and during a cold pressor test or a mental arithmetic test. The resting basal values of muscle sympathetic nerve activity, blood pressure and plasma epinephrine were significantly higher in the borderline hypertensives than in the normotensives (P less than 0.05). Plasma norepinephrine levels tended to be higher in the borderline hypertensives than in the normotensives but not to a significant extent (P less than 0.10). The cold test produced significantly exaggerated pressor and muscle sympathetic nerve responses (P less than 0.05) with a trend towards an increase in plasma norepinephrine (P less than 0.10) in the borderline hypertensives as compared with normotensives. The mental arithmetic test produced significantly enhanced pressor and plasma epinephrine responses in the borderline hypertensives as compared with the normotensives (P less than 0.05). During the mental arithmetic test the muscle sympathetic nerve activity decreased significantly in the normotensives (P less than 0.05) but not in the borderline hypertensives. These findings indicate that in people with borderline hypertension an abnormality exists in sympathetic nerve activity at rest and in response to stressors.     

Vagal rebound and recovery from psychological stress

OBJECTIVE: To characterize cardiovascular recovery and examine the possible relationship of vagal activity and reflexes to risk for heart disease. METHODS: Subjects performed cold pressor and mental arithmetic tasks. Heart rate, heart period variability, and pre-ejection period were obtained for 1 minute before, during, and after each task (Experiment 1). In the second experiment, subjects performed a Stroop color-word task and a mental arithmetic task. Heart rate, heart period variability, blood pressure, and baroreflex sensitivity were obtained during the 5-minute baseline, task, and recovery periods (Experiment 2). RESULTS: In Experiment 1, heart rate during recovery was lower than baseline despite continued pre-ejection period shortening, whereas recovery heart period variability was higher than baseline. In Experiment 2, blood pressure increased throughout the session. However, recovery heart rate after mental arithmetic was lower than baseline heart rate, and heart period variability was higher during both recovery periods than during baseline. Vagal rebound, a sharp increase in variability in the first minute of recovery, was reduced in men in Experiment 1 and in individuals with a family history of cardiovascular disease in Experiment 2 and was associated with degree of change in baroreflex sensitivity between task and rest. CONCLUSIONS: Cardiovascular recovery from stress is associated with increased vagal modulation despite residual sympathetic activation. Vagal rebound may be involved in mechanisms resetting the baroreflex sensitivity at the onset and offset of stress. Diminished vagal rebound during recovery from stress is associated with standard risk factors for cardiovascular disease. The results support an association between attenuated vagal reflexes and risk for cardiovascular disease.     

Increases in lipids and immune cells in response to exercise and mental stress in patients with suspected coronary artery disease: effects of adjustment for shifts in plasma volume

This study examined the role of shifts in plasma volume on lipid and immune reactions to stress. Lipid, immune, rheological, and cardiovascular reactions to exercise and mental stress in 51 patients with suspected coronary artery disease were determined. Blood pressure and heart rate were measured during and blood samples taken at the end of each rest and task. Lipids (total cholesterol, triglycerides, HDL, LDL) and immune cells (lymphocytes, monocytes, granulocytes) increased with exercise, whereas cholesterol, LDL, and lymphocytes increased with mental stress. Plasma volume decreased by 1 and 5% following mental and exercise stress, respectively. The task-induced increases in lipids were no longer statistically significant following adjustment for changes in plasma volume, whereas the increases in immune cell numbers survived such correction. This study provides evidence that, in coronary artery disease patients, exercise and mental stress-induced increases in lipids but not immune cells can be largely accounted for by shifts in plasma volume.     

Plasma beta-amyloid (A beta) 40 concentration, lipid status and age in humans

The circulation constitutes a potential source of the beta-amyloid (A beta) protein deposited cerebrally in Alzheimer's disease (AD). Cardiovascular risk factors, including hyperlipidaemia, may be involved in the pathogenesis of AD. Plasma A beta 40 was measured by radioimmunoassay in normal and hyperlipidaemic subjects with the aim of determining if plasma lipid content and/or age correlated with circulating A beta 40 concentration. Plasma A beta 40 levels in hyperlipidaemics were elevated by 20.3% compared to normal subjects. A beta 40 did not correlate with plasma lipids in normal subjects. Age, however, correlated positively with A beta 40 in these individuals and with total cholesterol, low-density lipoprotein (LDL) and triglycerides. No correlations were observed in hyperlipidaemic patients or when the data for the two groups were combined. These data are consistent with ageing, the primary risk factor for AD, but not hyperlipidaemia influencing circulating A beta 40 levels.     

Reactivity of immune, endocrine and cardiovascular parameters to active and passive acute stress

This study clarified associations among immune, autonomic, and endocrine activities during mental arithmetic and cold pressor stress tasks in 26 women in the follicular phase. Both tasks decreased CD3+ T cells, CD4+ T cells, and CD19+ B cells, whereas they increased lymphocytes, granulocytes, NK cells, and NK cell activity (NKCA). The mental arithmetic task had a greater impact than the cold pressor task on changes in CD3+ T cells and in NK cells. Cardiovascular reactivity to active stress was associated with increased NK cells and decreased CD3+ T cells. Reduced cortisol levels during passive stress were associated with decreased CD19+ B cells and with increased NK cells. The merits of this study are that it controlled the following factors. Perceived stress during the two tasks was matched; both tasks lasted long enough to elicit high-magnitude responses; and the length of the intervening rest period minimized probable carryover effects between tasks.     

Temporal stability of lipid responses to acute psychological stress in middle-aged men

The purpose of this study was to establish the temporal stability of lipid responses to acute psychological stress. Eighteen men were tested twice an average of 16.2 months apart in identical laboratory reactivity protocols. Total cholesterol, triglycerides, high- and low-density lipoprotein-cholesterol, plasma volume, heart rate, and blood pressure were assessed during rest, serial subtraction, and speech. After correction for changes in plasma volume, significant elevations were recorded for all variables during the speech task, but fewer variables showed changes during the serial subtraction task. Strong intersession associations were found when considering levels of the variables during baseline and stress (rs≥58). Correlations for the change scores ranged from .36 to .52 for the atherogenic lipids and from .39 to .87 for the cardiovascular variables. Little evidence was found for stability of plasma volume changes. There is moderate to high temporal stability of the atherogenic lipids when considering rest and stress levels and small to moderate temporal stability when considering change scores.     

Cardiovascular recovery from stress predicts longitudinal changes in blood pressure

Cardiovascular reactivity and recovery were examined as predictors of blood pressure changes over 3 years. Blood pressure and heart rate readings were obtained from 73 men and women aged 18-20 years during cold pressor, mental arithmetic, tourniquet ischemia, cycle exercise and step exercise tasks. Regression analyses indicated that after adjustment for initial blood pressure, initial age, initial body-mass index, sex, parental history of hypertension, and length of follow-up, heightened heart rate reactivity to mental arithmetic was associated with increased follow-up systolic blood pressure (DeltaR(2)=0.04, P<0.05). Systolic blood pressure recovery from cold pressor and tourniquet ischemia were also positively related to follow-up systolic blood pressure (DeltaR(2)=0.04 and 0.04, respectively, P<0.05) and remained so even after adjustment for the corresponding cardiovascular reactivity measures. These findings suggest that cardiovascular reactivity and recovery measures are modest predictors of longitudinal changes in blood pressure.     

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.     

Cholesterol Concentrations and Cardiovascular Reactivity to Stress in African American College Volunteers

Cholesterol levels and cardiovascular responses to emotionally arousing stimuli were examined in 60 healthy African American males and females. Cardiac output, stroke volume, contractile force, heart rate, and blood pressure were measured as the participants viewed two racially noxious scenes on videotape. Total serum cholesterol, high-density lipoproteins (HDL), low-density lipoproteins (LDL), and triglycerides were measured within 2 weeks of viewing the scenes. Multiple regression analysis showed that LDL and HDL were significant predictors of blood pressure responses. A correlation analysis revealed that total serum cholesterol and LDL were positively correlated with stroke volume, contractile force, and blood pressure reactivity. A possible relationship among stress, -adrenergic activity, and nonmetabolized free fatty acids is discussed. These findings suggest that cardiovascular reactivity to stress may be a new risk factor for heart and vascular diseases.     

Variable neuroendocrine responses to ecologically-relevant challenges in sticklebacks

Variable neuroendocrine responses to ecologically-relevant challenges in sticklebacks. PHYSIOL BEHAV 00(0) 000-000, 2006. Here, we compare the behavioral, endocrine and neuroendocrine responses of individual sticklebacks exposed to either an unfamiliar conspecific or to a predator. We found that the two stressors elicited a similar hypothalamic-pituitary-interrenal response as assessed by whole-body concentrations of cortisol, but produced quite different patterns of change in brain monoamine and monoamine metabolite content as assessed by concentrations of serotonin (5-HT), dopamine (DA), norepinephrine (NE) and the monoamine metabolites 5-hydroxyindole acetic acid (5-HIAA), homovanillic acid (HVA) and 3-4-dihydroxyphenylacetic acid (DOPAC). For example, relative to baseline levels, NE levels were elevated in individuals exposed to a predator but were lower in individuals confronted by a challenging conspecific. Levels of monoamine neurotransmitters in specific regions of the brain showed extremely close links with behavioral characteristics. Frequency of attacking a conspecific and inspecting a predator were both positively correlated with concentrations of NE. However, whereas serotonin was negatively correlated with frequency of attacking a conspecific, it was positively associated with predator inspection. The data indicate that the qualitative and quantitative nature of the neuroendocrine stress response of sticklebacks varies according to the nature of the stressor, and that interindividual variation in behavioural responses to challenge are reflected by neuroendocrine differences.