Effects of aerobic conditioning on cardiovascular sympathetic response to and recovery from challenge.

Exercise has widely documented cardioprotective effects, but the mechanisms behind these effects are still poorly understood. Here, we test the hypothesis that aerobic training lowers cardiovascular sympathetic responses to and speeds recovery from challenge. We conducted a randomized, controlled trial contrasting aerobic versus strength training on indices of cardiac (pre-ejection period, PEP) and vascular (low-frequency blood pressure variability, LF-BPV) sympathetic responses to and recovery from psychological and orthostatic challenge in 149 young, healthy, sedentary adults. Aerobic and strength training did not alter PEP or LF-BPV reactivity to or recovery from challenge. These findings, from a large randomized, controlled trial using an intent-to-treat design, show that moderate aerobic exercise training has no effect on PEP and LF-BPV reactivity to or recovery from psychological or orthostatic challenge. In healthy young adults, the cardioprotective effects of exercise training are unlikely to be mediated by changes in sympathetic activity.

The association of cardiac vagal control and executive functioning--findings from the MIDUS study.

Cardiac vagal control (CVC), an index of parasympathetic contribution to cardiac regulation, has been linked to enhanced executive functioning (EF). However, findings to date have been based on small or unique samples. Additionally, previous studies assessed the CVC-EF link only during rest or recovery period from a cognitive challenge, but not during both states. In the present study, data on 817 socioeconomically diverse participants were obtained from the Midlife Development in the United States (MIDUS) study. As part of this study, participants completed cognitive tests, including EF, along with laboratory-based measures of CVC during rest and following recovery from a cognitive challenge. Regression analyses adjusting for respiratory rate revealed no effect of CVC at rest or during recovery on a global index of EF. However, exploratory post-hoc analyses of the components of the global EF index revealed a significant association between faster vagal recovery and better attention-switching and response inhibition abilities, as indexed by faster reaction time to the mixed SGST. This association remained significant after controlling for demographic, clinical (BMI, diseases and medications altering cardiac autonomic functioning, etc.), and health behavior covariates (Beta = .148, p = .010). Our findings suggest that future studies may need to investigate the links of CVC to specific EF abilities, rather than global measures of EF. Additionally, our results highlight the importance of assessing CVC during both rest and recovery from a cognitive challenge. The authors discuss the putative neurobiological underpinning of this link, as well as suggestions for future basic and clinical research.

Sex-specific impact of maternal-fetal risk factors on depression and cardiovascular risk 40 years later.

Major depressive disorder (MDD) and cardiovascular disease (CVD) represent leading causes of morbidity and mortality worldwide. We tested the hypothesis that growth restriction and preeclampsia (referred to as fetal risk) are significant predictors of these conditions, with women at higher risk in adulthood. Adult offspring exposed to fetal risk factors and their discordant siblings were from two prenatal cohorts, whose mothers were followed through pregnancy and whom we recruited as adults 40 years later (n = 538; 250 males and 288 females). Subjects were psychiatrically diagnosed and underwent a stress challenge during which parasympathetic regulation was assessed by electrocardiogram, operationalized as high-frequency R-R interval variability (HF-RRV). Linear mixed models and generalized estimating equations were used to examine the relationship of fetal risk on HF-RRV, MDD and comorbidity of low HF-RRV (lowest 25th percentile) and MDD, including interactions with sex and socioeconomic status (SES). Fetal risk was significantly associated with low HF-RRV response (F = 3.64, P = 0.05), particularly among low SES (interaction: F = 4.31, P < 0.04). When stratified by MDD, the fetal risk impact was three times greater among MDD compared with non-MDD subjects (effect size: 0.21 v. 0.06). Females had a significantly higher risk for the comorbidity of MDD and low HF-RRV than males (relative risk (RR) = 1.36, 95% CI: 1.07-1.73), an association only seen among those exposed to fetal risk (RR = 1.38, 95% CI: 1.04-1.83). Findings suggest that these are shared fetal antecedents to the comorbidity of MDD and CVD risk 40 years later, an association stronger in females than in males.

Exercise training favourably affects autonomic and blood pressure responses during mental and physical stressors in African-American men.

Aerobic exercise is a powerful mechanism by which cardiovascular and autonomic parameters may be improved. We sought to quantify the extent of benefit that could be achieved by a short-term monitored exercise regimen on several autonomic parameters during recognized mental and physical stressors in young normotensive African-American men matched for a family history of hypertension, a group at high risk for the development of hypertension. Autonomic modulations were derived using spectral decomposition of the electrocardiogram and beat-to-beat blood pressures (BPs). Arterial compliance was obtained using contour analysis of the radial artery pulse wave. The analysis of variance revealed that compared with a matched sedentary control group, aerobic capacity of the trained group significantly increased by 16%. Autonomic modulations, arterial compliance and BP responses significantly improved during some of the stressors, whereas no such improvements were seen in the control group. Attenuated responses, mediated through a favourable shift in sympathovagal balance and enhanced arterial compliance, provide mechanistic evidence of how certain variables may be improved due to aerobic conditioning in a population at high risk for the development of hypertension.

Relation between depression after coronary artery bypass surgery and 12-month outcome: a prospective study.

BACKGROUND: The association of depression with cardiac events has been investigated mainly in community cohorts, in patients undergoing catheterisation, or in patients who have had myocardial infarction. We have assessed the effect of depression on outcomes after coronary artery bypass graft (CABG) surgery. METHODS: In a prospective study, we followed up for 1 year 207 men and 102 women, who had undergone coronary artery bypass graft surgery. We assessed depression with a structured psychiatric interview (diagnostic interview schedule) and a questionnaire (Beck depression inventory) before discharge. Cardiac events included angina or heart failure that needed admission to hospital, myocardial infarction, cardiac arrest, percutaneous transluminal coronary angioplasty, repeat CABG, and cardiac mortality. Non-cardiac events consisted of all other reasons for mortality or readmission. FINDINGS: 63 patients (20%) met modified diagnostic statistical manual IV criteria for major depressive disorder. At 12 months, 17 (27%) of these patients had a cardiac event compared with 25 of 246 (10%) who were not depressed (p<0.0008). Five variables had significant univariate associations with cardiac events: sex, living alone, low ejection fraction (<0.35), length of hospital stay, and depression. In a Cox proportional-hazard model with these five and two other variables of cardiac severity, major depressive disorder (risk ratio 2.3 [95% CI 1.17-4.56]), low ejection fraction (2.3 [1.07-5.03]), and female sex (2.4 [1.24-4.44]) were associated with adverse outcomes. Depression did not predict deaths or admissions for non-cardiac events. INTERPRETATION: Depression is an important independent risk factor for cardiac events after CABG surgery.

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.

Enhanced stress reactivity in paediatric anxiety disorders: implications for future cardiovascular health.

The aim was to clarify the developmental nature of associations between psychiatric illness and risk for cardiovascular disease by investigating differences in cardiac functioning between youth with anxiety disorders and healthy controls. Twenty-two children meeting DSM-IV criteria for either separation anxiety disorder, overanxious disorder, panic disorder/panic attacks, or social phobia and 12 healthy controls underwent continuous electrocardiogram and respiration rate monitoring during a 15 min baseline period and 15 min of exposure to 5% CO(2). Heart rate (HR) and high frequency heart rate variability (HRV), a non-invasive measure of cardiac parasympathetic control, were calculated. Youth with anxiety disorders had higher and less fluctuating HR during baseline. Data also suggested that probands showed diminished overall changes in HRV during baseline and CO(2) inhalation relative to controls. However, as respiration rate affects HRV, these findings were confounded by changes in respiration elicited by CO(2) inhalation. The data suggest that youth with anxiety disorders experience an elevated and less fluctuating HR in the face of a novel situation, possibly due to a failure to appropriately modulate HRV. In adults, sustained elevations in HR in conjunction with deficient vagal modulation predicts risk for future cardiovascular disease. As such, the current data suggest that the presence of an anxiety disorder may identify youth who exhibit autonomic profiles that place them at risk for cardiac disease.

Hostility, gender, and cardiac autonomic control.

OBJECTIVE: Although considerable evidence implicates hostility in the development of coronary artery disease (CAD), the pathogenic mechanisms remain poorly understood. We have developed a psychophysiological model that holds that altered autonomic nervous system function links psychological traits with CAD outcomes. In laboratory studies, stressors reduce high-frequency (HF) heart period variability, an index of cardiac vagal modulation. With ambulatory electrocardiographic recording, we demonstrated in a predominantly male sample that hostility was inversely associated with HF power, but only during waking hours. These findings are consistent with the hypothesis that hostile individuals experience multiple stressful interpersonal transactions each day, resulting in overall lower HF power during the day but not at night. METHODS: To further evaluate this hypothesis, we screened 96 subjects using the Cook-Medley Hostility Scale and selected 15 men and 15 women representing a wide distribution of hostility. These subjects were studied in a laboratory session assessing reactivity to psychological and orthostatic challenges with continuous electrocardiographic, blood pressure, and respiration monitoring. We predicted that for men and women, hostility would be inversely related to reductions in HF power in response to challenge. RESULTS: In response to mental stressors, all measures of heart period variability change were inversely related to hostility as predicted. No such relationships were found for responses to tilt. The data suggested a possible effect of gender on these relationships. CONCLUSIONS: These data add to the growing body of evidence showing that hostility influences vagal modulation of the cardiovascular system and suggest that altered autonomic control is a pathogenic mechanism linking hostility and CAD.

Physiologic responses to cognitive challenge during pregnancy: effects of task and repeat testing.

Physiological responses to stress during pregnancy are believed to influence birth outcomes. Researchers have studied pregnant women in laboratory stressor paradigms to investigate these associations, yet normative data on cardiovascular and respiratory responses to laboratory challenge during pregnancy are not yet established. To begin to establish such normative data, this study examined the effects of task and repeat stressor exposure on reactivity in third-trimester pregnant women. Thirty-one healthy pregnant women (mean age=27 years; range 18-36) between the 33rd and 39th week of pregnancy, were instrumented for continuous electrocardiography, blood pressure (BP), and respiration data. Subjects rested quietly for a 5-min baseline and then performed both a mental arithmetic stressor and a Stroop color-word-matching task, each 5 min in length and each followed by a 5-min recovery period. The order of the tasks was counterbalanced. After each 5-min period, subjects rated the period on a 10-point stress scale. Averaged across task type and challenge period, systolic and diastolic BP and respiration rate increased significantly in response to cognitive challenge, but heart rate (HR) did not. When data were examined for task and period effects, the following results emerged: the Stroop task elicited significantly greater systolic BP and HR reactivity than the arithmetic task, yet subjects rated the arithmetic task as more stressful. Averaged across task type, subjects showed greater systolic BP reactivity during the second challenge period compared to the first. Finally, women's BP tended to drift upward and did not return to baseline during the first recovery period. These findings indicate that averaging data across tasks and periods can obscure the time course of response patterns that may be important in the study of associations between maternal stress and perinatal development, as well as in other research on reactivity to repeat stress exposure.

Heart rate variability in depressive and anxiety disorders.

Loss of normal autonomic nervous system control of heart rate and rhythm is an important risk factor for adverse cardiovascular events. After myocardial infarction, reduction in beat-to-beat heart rate variability, a measure of cardiac autonomic innervation by the brain, is a strong predictor of death. With loss of vagal innervation, as is noted in patients with severe neuropathy and in heart transplant recipients, there is loss of heart rate variability. It is speculated that decreased parasympathetic innervation exposes the heart to unopposed stimulation by sympathetic nerves. Individuals with high hostility scores and patients with anxiety or depressive disorders have low heart rate variability and may be at increased risk for cardiovascular death associated with coronary heart disease and arrhythmias. After myocardial infarction, depressed patients exhibit higher mortality rates compared with nondepressed patients. Men with "phobic anxiety," a construct that appears to overlap substantially with panic disorder, also have higher rates of sudden cardiac death and coronary artery disease than control populations. The reduction in autonomic nervous system control to the heart may be one link between psychopathology and heart disease. Although tricyclic antidepressants reduce heart rate variability, at least one study has suggested that, in patients with panic disorder, treatment with the selective serotonin reuptake inhibitor paroxetine normalizes heart rate variability. Hence there is potential for the treatment of psychiatric disorders to affect positively the development and course of cardiovascular disease.

Cerebral activation, hostility, and cardiovascular control during mental stress.

OBJECTIVE: Hostility has been established as a risk factor for the development of coronary artery disease. Putatively pathogenic hemodynamic and neuroendocrine responses to psychological stressors are associated with hostility, but the cerebral effects of hostility and their relationship to these responses are unknown. This pilot study examined cardiovascular and cerebral blood flow responses to stress in subjects with high and low levels of trait hostility. METHODS: Regional cerebral blood flow was measured by single-photon emission computed tomography (SPECT) during a control condition and in response to mental arithmetic stress. RESULTS: The stressor was associated with reduced blood flow to the prefrontal cortex, and this reduction was greater in the high hostility subjects. CONCLUSION: These preliminary findings support the hypothesis that mental arithmetic stress is associated with reduced blood flow to prefrontal cortex, and that trait hostility is associated with a stronger effect.

Mixed-effects models in psychophysiology.

The current methodological policy in Psychophysiology stipulates that repeated-measures designs be analyzed using either multivariate analysis of variance (ANOVA) or repeated-measures ANOVA with the Greenhouse-Geisser or Huynh-Feldt correction. Both techniques lead to appropriate type I error probabilities under general assumptions about the variance-covariance matrix of the data. This report introduces mixed-effects models as an alternative procedure for the analysis of repeated-measures data in Psychophysiology. Mixed-effects models have many advantages over the traditional methods: They handle missing data more effectively and are more efficient, parsimonious, and flexible. We described mixed-effects modeling and illustrated its applicability with a simple example.

Maternal stress responses and anxiety during pregnancy: effects on fetal heart rate.

This study examined the effect of an acute maternal stress response and anxiety on fetal heart rate. Seventeen healthy, 3rd-trimester pregnant women (mean age = 26 +/- 6 years) were instrumented for continuous electrocardiography, blood pressure (BP), respiration, and fetal heart rate (HR). Subjects completed the state anxiety subscale of the State Trait Personality Inventory (STPI), then rested quietly in a semirecumbent position for a 5-min baseline period, followed by either a 5-min arithmetic or Stroop color-word task. Over the entire 5-min stress period and when averaged across all subjects, the stressors led to significant increases in maternal systolic BP and respiratory rate but changes in maternal HR, diastolic BP, and fetal HR were not significant. However, when subjects were dichotomized into groups that had above or below average anxiety scores [ANX(+) and ANX(-)], both groups had similar respiration rate increases to the stressors, but the BP and fetal heart rate (FHR) responses were significantly different. Women in the ANX(-) group had significantly greater BP responses compared to women in the ANX(+) group whereas the fetuses of ANX(+) women showed significant HR increases and the fetuses of ANX(-) women exhibited nonsignificant decreases. These findings suggest that women's acute emotional reactivity during pregnancy can influence fetal HR patterns and that a stress-induced increase in maternal BP is not the primary signal by which a women's stress response is transduced to her fetus. The results are consistent with the hypothesis that maternal psychological variables may shape the neurobehavioral development of the fetus.

Effects of desipramine on autonomic input to the heart.

OBJECTIVE: To examine the impact of age on the effects of desipramine (DMI) on autonomic input to the heart. METHOD: Twenty-four-hour electrocardiograms were obtained from 42 subjects, aged 7 to 66 years, while off and on DMI. To obtain measures of autonomic input to the heart, heart rate variability was assessed via spectral analysis of RR interval variability. RESULTS: DMI treatment was associated with a significant increase in 24-hour mean heart rate and significant decreases in RR interval variability in all spectral bands, including in the high-frequency band, which provides a measure of parasympathetic input to the heart. RR interval variability was greater in younger individuals both off and on DMI. CONCLUSIONS: DMI treatment was associated with a marked decline in RR interval variability, indicating that DMI affects autonomic input to the heart. Specifically, DMI reduced parasympathetic input, which, in theory, may increase vulnerability to arrhythmias. However, the magnitude of DMI's impact on RR interval variability did not vary with age.