Daisy L. Whitehead

Synergistic effects of psychological and immune stressors on inflammatory cytokine and sickness responses in humans

Activation of the innate immune system is commonly accompanied by a set of behavioural, psychological and physiological changes known as ‘sickness behaviour’. In animals, infection-related sickness symptoms are significantly increased by exposure to psychosocial stress, suggesting that psychological and immune stressors may operate through similar pathways to induce sickness. We used a double-blind, randomised, placebo-controlled design to examine the effect of acute psychological stress on immune and subjective mood responses to typhoid vaccination in 59 men. Volunteers were assigned to one of four experimental conditions in which they were either injected with typhoid vaccine or saline placebo, and then either rested or completed two challenging behavioural tasks. Typhoid vaccine induced a significant rise in participants’ serum levels of interleukin-6 (IL-6) and this response was significantly larger in the stress versus rest conditions. Negative mood increased immediately post-tasks, an effect also more pronounced in the vaccine/stress condition. In the vaccine/stress group, participants with larger IL-6 responses had heightened systolic blood pressure responses to tasks and elevated post-stress salivary levels of the noradrenaline metabolite 3-methoxy-phenyl glycol (MHPG) and cortisol. Our findings suggest that, as seen in animals, psychological and immune stressors may act synergistically to promote inflammation and sickness behaviour in humans.

Triggering of acute coronary syndromes by physical exertion and anger: clinical and sociodemographic characteristics

Objective: To investigate the role of vigorous physical exertion and anger as triggers of acute coronary syndromes (ACS) and to identify the clinical and sociodemographic correlates of triggering. Design: Prospective observational clinical cohort study. Setting: Four coronary care units in the London area. Patients: 295 men and women with electrocardiographically and biochemically verified ACS. Main outcome measures: Physical exertion in the 1 h and anger in the 2 h before symptom onset were assessed with structured interviews. Control periods were the equivalent hours one day earlier and usual rates over the past six months. Data were analysed by case-crossover methods. Results: Physical exertion was reported by 10% and anger by 17.4% of patients in the hazard period. The risk of ACS onset after physical exertion compared with light or no activity was 3.50 (95% confidence interval (CI) 1.37 to 10.6). The risk of onset with anger was 2.06 (95% CI 1.12 to 3.92). Physical exertion during the hazard period was related to an absence of premonitory symptoms, presentation with an ST elevation myocardial infarction (STEMI), low socioeconomic deprivation and higher future cardiovascular risk. Anger during the hazard period was more common in younger, socioeconomically deprived patients who presented with a STEMI. Conclusions: Triggers are relevant across the spectrum of ACS. The distinct clinical and sociodemographic factors associated with physical exertion and anger suggest that different pathophysiological processes may be involved.

Pre-hospital delay in patients with acute coronary syndrome: Factors associated with patient decision time and home-to-hospital delay

Background: Pre-hospital delays in patients experiencing acute coronary syndromes (ACS) remain unacceptably long. Aims: To examine simultaneously a wide range of clinical, sociodemographic and situational factors associated with total pre-hospital delay and its two components. Methods: Pre-hospital delay data were collected from 228 patients with ACS using patients medical notes and semi-structured interviews. Total pre-hospital delay (symptom onset to hospital admission) was divided into 2 components: decision time (symptom onset to call for medical help), and home-to-hospital delay (call for help to hospital admission). Results: Shorter total pre-hospital delays and decision times were associated with ST segment myocardial infarction (STEMI), recognizing symptoms as cardiac in origin, being married, symptom onset outside the home and the presence of a bystander. Shorter home-to-hospital delays were more likely among younger patients, those experiencing an STEMI, and patients reporting a greater number of symptoms. Initial contact with emergency medical services was related to shorter total delays and decision times. Conclusions: Different factors were associated with shorter times in the 2 component phases. Greater understanding of the factors impacting on the component phases may help target interventions more effectively and reduce pre-hospital delays.

Acute depressed mood as a trigger of acute coronary syndromes.

BACKGROUND Some cases of acute coronary syndrome (ACS) may be triggered by emotional states such as anger, but it is not known if acute depressed mood can act as a trigger. METHODS 295 men and women with a verified ACS were studied. Depressed mood in the two hours before ACS symptom onset was compared with the same period 24 hours earlier (pair-matched analysis), and with usual levels of depressed mood, using case-crossover methods. RESULTS 46 (18.2%) patients experienced depressed mood in the two hours before ACS onset. The odds of ACS following depressed mood were 2.50 (95% confidence intervals 1.05 to 6.56) in the pair-matched analysis, while the relative risk of ACS onset following depressed mood was 4.33 (95% confidence intervals 3.39 to 6.11) compared with usual levels of depressed mood. Depressed mood preceding ACS onset was more common in lower income patients (p = .032), and was associated with recent life stress, but was not related to psychiatric status. CONCLUSIONS Acute depressed mood may elicit biological responses that contribute to ACS, including vascular endothelial dysfunction, inflammatory cytokine release and platelet activation. Acute depressed mood may trigger potentially life-threatening cardiac events.

Depressed Mood, Positive Affect, and Heart Rate Variability in Patients With Suspected Coronary Artery Disease

Objective: To test associations between heart rate variability (HRV), depressed mood, and positive affect in patients with suspected coronary artery disease (CAD). Depression is associated with impaired HRV post acute cardiac events, but evidence in patients with stable coronary artery disease (CAD) is inconsistent. Methods: Seventy-six patients (52 men, 24 women; mean age = 61.1 years) being investigated for suspected CAD on the basis of symptomatology and positive noninvasive tests, completed 24-hour electrocardiograms. The Beck Depression Inventory (BDI) was administered, and positive and depressed affect was measured over the study period with the Day Reconstruction Method (DRM). A total of 46 (60.5%) patients were later found to have definite CAD. HRV was analyzed, using spectral analysis. Results: Typical diurnal profiles of HRV were observed, with greater normalized high frequency (HF) and lower normalized low frequency (LF) power in the night compared with the day. BDI depression scores were not consistently associated with HRV. But positive affect was associated with greater normalized HF power (p = .039) and reduced normalized LF power (p = .007) independently of age, gender, medication with β blockers, CAD status, body mass index, smoking, and habitual physical activity level. In patients with definite CAD, depressed affect assessed using the DRM was associated with reduced normalized HF power and heightened normalized LF power (p = .007) independently of covariates. Conclusions: Relationships between depression and HRV in patients with CAD may depend on affective experience over the monitoring period. Enhanced parasympathetic cardiac control may be a process through which positive affect protects against cardiovascular disease. BDI = Beck Depression Inventory; CAD = coronary artery disease; CHD = coronary heart disease; DRM = Day Reconstruction Method; ENRICHD = Enhancing Recovery in Coronary Heart Disease; HRV = heart rate variability; HF = high frequency; LF = low frequency; MI = myocardial infarction; pNN50 = the number of pairs of adjacent NN intervals differing by >50 ms, divided by the total number of NN intervals; RMSSD = square root of the mean of the sum of the squares of successive NN differences; VLF = very low frequency.

Hostility and physiological responses to laboratory stress in acute coronary syndrome patients

Objective Evidence suggests that emotional stress can trigger acute coronary syndromes in patients with advanced coronary artery disease (CAD), although the mechanisms involved remain unclear. Hostility is associated with heightened reactivity to stress in healthy individuals, and with an elevated risk of adverse cardiac events in CAD patients. This study set out to test whether hostile individuals with advanced CAD were also more stress responsive. Methods Thirty-four men (aged 55.9±9.3 years) who had recently survived an acute coronary syndrome took part in laboratory testing. Trait hostility was assessed by the Cook Medley Hostility Scale, and cardiovascular activity, salivary cortisol, and plasma concentrations of interleukin-6 were assessed at baseline, during performance of two mental tasks, and during a 2-h recovery. Results Participants with higher hostility scores had heightened systolic and diastolic blood pressure (BP) reactivity to tasks (both P<.05), as well as a more sustained increase in systolic BP at 2 h post-task (P=.024), independent of age, BMI, smoking status, medication, and baseline BP. Hostility was also associated with elevated plasma interleukin-6 (IL-6) levels at 75 min (P=.023) and 2 h (P=.016) poststress and was negatively correlated with salivary cortisol at 75 min (P=.034). Conclusion Hostile individuals with advanced cardiovascular disease may be particularly susceptible to stress-induced increases in sympathetic activity and inflammation. These mechanisms may contribute to an elevated risk of emotionally triggered cardiac events in such patients.

Post-traumatic stress disorder in patients with cardiac disease: predicting vulnerability from emotional responses during admission for acute coronary syndromes

Objectives: To assess frequency and predictors of post-traumatic stress disorder (PTSD), measured by the Post Traumatic Stress–self report version, at three months after admission for acute coronary syndromes (ACS). Design: Two-phase prospective study. Setting: Four coronary care units. Patients: 135 patients admitted to hospital with ACS confirmed by ECG and cardiac enzyme changes. Results: 20 patients (14.8%) showed a symptom pattern characteristic of PTSD at three months assessed by a conservative scoring criterion. Severity of chest pain and psychological factors during admission were predictive of PTSD severity. Acute stress symptoms, depression, negative affect, hostility, and pain scores were independent predictors of three-month PTSD symptoms (R2  =  0.495, p < 0.001). In contrast, demographic factors (age, sex, education level and income) were unrelated to post-traumatic symptoms, as were markers of clinical disease severity. Conclusions: Patient vulnerability to PTSD three months after ACS is predictable on the basis of psychological state and chest pain at the time of admission. This may be valuable to the clinician, as PTSD after myocardial infarction is associated with poorer quality of life, reduced adherence to drug treatment and increased likelihood of cardiovascular morbidity.

76. Optimism is associated with attenuated stressor-induced increases in inflammatory cytokines and negative mood states

cancer diagnosis, which persisted after treatment. The purpose of this study was to determine whether adiposity contributed to IL-6 elevations in women diagnosed with breast cancer. Early stage breast cancer patients were evaluated prior to treatment and compared to women without breast cancer. Plasma IL-6, PBMC production of IL-6 and body mass index (BMI) were measured. Fifty-one percent of women with breast cancer and 58% of women without breast cancer were overweight (BMI >25 kg/m); while 23% of women with breast cancer versus 28% of women without breast cancer met obesity criteria (BMI > 30 kg/m). Women with breast cancer had greater plasma IL-6 levels than women without breast cancer. When plasma IL-6 levels were stratified by BMI, both overweight and obese women with breast cancer had higher plasma IL-6 than women with breast cancer with lower BMI (<25 kg/m2). IL-6 production significantly correlated (r = 0.461; p < 0.01) with BMI in women with breast cancer but no correlation was found in women without breast cancer. Thus, adipose tissue likely contributes to IL-6 elevations in breast cancer patients. Given the potential of IL-6 to stimulate breast cancer cell proliferation, adipose-tissue-driven inflammatory pathways may negatively impact cancer prognosis.