Gerard J. Molloy

Psychological Distress as a Risk Factor for Cardiovascular Events: Pathophysiological and Behavioral Mechanisms

OBJECTIVES This study sought to estimate the extent to which behavioral and pathophysiological risk factors account for the association between psychological distress and incident cardiovascular events. BACKGROUND The intermediate processes through which psychological distress increases the risk of cardiovascular disease (CVD) are incompletely understood. An understanding of these processes is important for treating psychological distress in an attempt to reduce CVD risk. METHODS In a prospective study of 6,576 healthy men and women (ages 50.9 +/- 13.1 years), we measured psychological distress (using the 12-item version of the General Health Questionnaire >or=4) and behavioral (smoking, alcohol, physical activity) and pathophysiological (C-reactive protein, fibrinogen, total and high-density lipoprotein cholesterol, obesity, hypertension) risk factors at baseline. The main outcome was CVD events (hospitalization for nonfatal myocardial infarction, coronary artery bypass, angioplasty, stroke, heart failure, and CVD-related mortality). RESULTS Cigarette smoking, physical activity, alcohol intake, C-reactive protein, and hypertension were independently associated with psychological distress. There were 223 incident CVD events (63 fatal) over an average follow-up of 7.2 years. The risk of CVD increased in relation to presence of psychological distress in age- and sex-adjusted models (hazard ratio: 1.54, 95% confidence interval: 1.09 to 2.18, p = 0.013). In models that were adjusted for potential mediators, behavioral factors explained the largest proportion of variance ( approximately 65%), whereas pathophysiological factors accounted for a modest amount (C-reactive protein approximately 5.5%, hypertension, approximately 13%). CONCLUSIONS The association between psychological distress and CVD risk is largely explained by behavioral processes. Therefore, treatment of psychological distress that aims to reduce CVD risk should primarily focus on health behavior change.

Family caregiving and congestive heart failure. Review and analysis.

There is increasing evidence that discharge planning and post‐discharge support for CHF patients can contribute greatly to the medical management of heart failure (CHF) in the community and that the quality of the CHF patients close personal relationships can influence outcome in CHF. However, there has been little research on the impact of CHF on the family or the role of the family in the management of the condition. In this paper, we provide a review and analysis of studies that have explicitly investigated these issues in the informal carers of CHF patients.

Psychological distress and cancer mortality

BACKGROUND Psychological distress, such as ongoing depression and anxiety-related symptomatology, has been associated with a higher risk of incident cancer and poorer survival, although previous studies have not compared prognostic and etiological effects within the same sample. We examined the association between psychological distress and cancer mortality in a sample comprising participants with and without previous cancer admissions. METHODS Data were collected from a community-based sample of 15,453 men and women (including 295 people with cancer history) and prospectively linked to a patient-based database of cancer registry and deaths during an average follow-up of 7.0+/-3.3 years. Psychological distress was assessed using the 12-item version of the General Health Questionnaire (GHQ-12). RESULTS There were 425 incident cancer deaths. Psychological distress (GHQ-12 > or =4) was associated with increased cancer mortality in participants with cancer history [age, gender, social status, marital status, body mass index, smoking, alcohol, and physical activity; adjusted hazard ratio (HR)=1.97; 95% confidence interval (95% CI)=1.05-3.71; P=.035], but not in participants without cancer history. Among participants without cancer history, there was, however, an association between distress and lung cancer death (age- and gender-adjusted HR=2.04; 95% CI=1.36-3.06; P=.001), although adjustment for covariates attenuated this association. CONCLUSIONS Psychological distress was a predictor of cancer mortality, especially in lung cancer. The presence of participants with cancer history in community-based cohorts may overestimate the association between psychological distress and subsequent cancer mortality.

Fear of dying and inflammation following acute coronary syndrome

AIMS Many patients are afraid of dying during acute coronary syndrome (ACS), but the origins and biological correlates of these emotional responses are poorly understood. This study evaluated the prevalence of fear of dying, associations with inflammatory responses during ACS, and later heart rate variability (HRV) and cortisol secretion. METHODS AND RESULTS Two hundred and eight patients admitted with clinically verified ACS rated their fear of dying on interview in hospital. Plasma tumour necrosis factor (TNF)α was recorded on admission, and HRV and salivary cortisol were assessed 3 weeks later. Intense distress and fear of dying was experienced by 21.7%, with moderate levels in 66.1% patients. Fear of dying was more common in younger, lower socioeconomic status, and unmarried patients. It was positively associated with plasma TNFα on admission after controlling for sociodemographic factors, clinical risk, and pain intensity (adjusted odds = 4.67, 95% C.I. 1.66-12.65). TNFα was associated with reduced HRV 3 weeks later, adjusting for clinical and sociodemographic factors and medication (P = 0.019), while fear of dying was associated with reduced cortisol output (P = 0.004). CONCLUSIONS Intense distress and fear of dying and heightened inflammation may be related manifestations of an acute biobehavioural response to severe cardiac injury, and have implications for prognostically significant biological risk processes.

Marital status, gender and cardiovascular mortality: Behavioural, psychological distress and metabolic explanations

The intermediate processes through which the various unmarried states can increase the risk of subsequent cardiovascular disease mortality are incompletely understood. An understanding of these processes and how they may vary by gender is important for understanding why marital status is strongly and robustly associated with subsequent cardiovascular disease. In a prospective study of 13,889 Scottish men and women (mean age 52.3, Standard Deviation: 11.8 yrs, range 35–95, 56.1% female) without a history of clinically diagnosed cardiovascular disease, we examined the extent to which health behaviours (smoking, alcohol, physical activity), psychological distress (General Health Questionnaire-12 item) and metabolic dysregulation (obesity levels, and the presence of hypertension and diabetes) account for the association between marital status and cardiovascular mortality. There were 258 cardiovascular deaths over an average follow up of 7.1 (Standard Deviation = 3.3) years. The risk of cardiovascular mortality was greatest in single, never married men and separated/divorced women compared with those that were married in gender stratified models that were adjusted for age and socio-economic group. In models that were separately adjusted, behavioural factors explained up to 33%, psychological distress explained up to 10% and metabolic dysregulation up to 16% of the relative change in the hazard ratios in the observed significant associations between marital status and cardiovascular mortality. Behavioural factors were particularly important in accounting for the relationship between being separated/divorced and cardiovascular mortality in both men and women (33% and 21% of the relative change in the hazard ratios, respectively). The findings suggest that health behaviour, psychological distress and metabolic dysregulation data have varying explanatory power for understanding the observed relationship between cardiovascular disease mortality and unmarried states.

Type-D personality and cortisol in survivors of acute coronary syndrome.

Objective: To test the hypothesis that Type-D personality is associated with elevated cortisol levels in patients 4 months after an acute coronary syndrome (ACS). Methods: Salivary cortisol profiles were measured at home in 70 coronary heart disease patients (Mean age = 60.90 years, SD = 10.7, 17% female) 4 months after hospitalization for ACS. Eight saliva samples were taken over the course of 1 day. Results: Thirty eight percent of the ACS patients were defined as Type-D. Cortisol profiles showed a typical diurnal pattern, with low levels in the evening, high levels early in the day. Type-D was not related to the cortisol awakening response, but cortisol output the day was higher in Type-D (mean = 4443.3, SD = 2334.1 nmol/l) than non Type-D patients (mean = 3252.0, SD = 1810.2 nmol/l) after adjustment for age, gender, hypertension, Global Registry of Acute Coronary Events risk score, recurrence of cardiac symptoms, previous myocardial infarction, body mass index and concurrent depressed mood (p = .044). Type-D personality accounted for 6% over the variance in cortisol output over the day, after covariates had been taken into account. Conclusion: Type-D personality may be associated with prolonged disruption of the hypothalamic-pituitary-adrenal axis function in survivors of acute cardiac events and may contribute to biological responses influencing future cardiac morbidity. MI = myocardial infarction; BMI = body mass index; ACS = acute coronary syndrome; CAR = cortisol awakening response; HPA = hypothalamic-pituitary-adrenal axis; SD = standard deviation; GRACE = global registry of acute coronary events.

Leisure time physical activity, risk of depressive symptoms, and inflammatory mediators: The English Longitudinal Study of Ageing

OBJECTIVES To examine if inflammatory markers (CRP, fibrinogen) might partly explain the association between physical activity (PA) and risk of depression. DESIGN/SETTING The English Longitudinal Study of Ageing, a prospective study of community dwelling older adults. PARTICIPANTS 4323 men and women (aged 63.4+/-9.7 yrs) free from depression at baseline. MEASURES Self reported leisure time PA levels and depressive symptoms (a score of > or = 4 using the 8-item CES-D scale) were assessed at baseline and 4 yrs follow up. The inflammatory markers, CRP and fibrinogen, were assessed at a 2 yrs intermediate time point between baseline and follow up. RESULTS At follow up 8% of the sample reported depressive symptomatology. In comparison with participants reporting none or light PA, the odds of depressive symptomatology for those reporting moderate or vigorous PA were 0.71 (95% CI, 0.54-0.95) and 0.58 (0.41-0.81), respectively, after adjustments for baseline CES-D score, age, gender, social-occupational class, smoking, alcohol, and chronic illness. Each standard unit increase in log CRP was associated with higher odds of depressive symptomatology at follow up (1.32, 1.13-1.55) and CRP was inversely associated with physical activity. The association between PA and depressive symptomatology was not, however, substantially modified by further adjustment for CRP (odds for none vs. vigorous PA=0.60, 0.43-0.84). CONCLUSIONS These data suggest that low grade systemic inflammation, as indexed by CRP, is a risk marker for depressive symptomatology, although this mechanism explains only a modest (approximately 5%) amount of the association between PA and risk of depression.

Depression is associated with flatter cortisol rhythms in patients with coronary artery disease

OBJECTIVE Depression is associated with coronary heart disease, but the underlying mechanisms are not fully understood. Cortisol is involved in the development of coronary artery disease (CAD), but evidence directly linking depression with cortisol in patients with CAD is limited. This study evaluated cortisol output over the day in patients with suspected CAD in relation to depressive symptoms. METHODS Eighty-eight patients who were being investigated for suspected CAD (defined by clinical symptoms plus positive exercise tests or myocardial perfusion scans) took eight saliva samples over the day and evening. Depressed mood was assessed with the Beck Depression Inventory. Actigraphy was used to define time of waking objectively. RESULTS The cortisol awakening response and cortisol rhythm over the remainder of the day and evening were analyzed separately. Fifty-two (61.9%) patients were later found to have definite CAD on angiography, while the remainder did not. The cortisol slope over the day was flatter in more depressed patients with CAD (P<.001) but was not related to depression in patients without CAD (P=.68). This effect was due to the combination of lower cortisol early in the day and higher cortisol in the evening in more depressed CAD patients, independent of age, gender, medication, and times of waking and sleeping (P=.003). Additionally, cortisol measured on waking and 15 and 30 min after waking was greater in CAD than in non-CAD patients (P=.04), but was not related to depression. CONCLUSIONS The flatter cortisol rhythms of more depressed CAD patients may contribute to the progression of coronary atherosclerosis.

Persistent depressive symptomatology and inflammation: to what extent do health behaviours and weight control mediate this relationship?

We examined if persistent depressive symptoms are associated with markers of inflammation (C-Reactive Protein-CRP) and coagulation (fibrinogen), and if this association can be partly explained by weight control and behavioural risk factors (smoking, alcohol, physical activity). The study sample included 3609 men and women (aged 60.5+/-9.2 years) from The English Longitudinal Study of Ageing, a prospective study of community dwelling older adults. Depressive symptoms (using the 8-item CES-D scale), health behaviours (smoking, alcohol, physical activity), body weight, and central adiposity were assessed at baseline and 2 years follow up. CRP and fibrinogen were assessed at follow up. At baseline 12.7% of the sample reported elevated depressive symptomatology, which persisted in 6.1% of participants at follow up. Baseline CES-D score was associated with CRP (beta=.035, SE=.0066) and fibrinogen (beta=.023, SE=.0060) measured 2 years later. Using simple mediation analysis we observed both a direct association of depressive symptoms on CRP (beta=.013, SE=.0066) and indirect mediating effects through behavioural risk factors (beta for total indirect effect beta=.022, SE=.0023). For fibrinogen there were no direct effects of depression, and the association was entirely explained through indirect mediating effects of health behaviours. The presence of recurrent elevated depressive symptomatology at both time points was more strongly associated with CRP and fibrinogen. In summary, the association between depressive symptoms and low grade inflammation can be partly explained by behavioural risk factors. The presence of persistent depression appears to be associated with the greatest risk of elevated inflammation.

Social networks and partner stress as predictors of adherence to medication, rehabilitation attendance, and quality of life following acute coronary syndrome.

OBJECTIVE This study examined whether social network size and partner stress predicted medication adherence, cardiac rehabilitation attendance, and quality of life 12 months following hospitalization for an acute coronary syndrome (ACS). DESIGN ACS patients (N = 193, M age = 60.6 years, SD = 11.4 years, 23% female) were recruited shortly following admission to 4 local hospitals. A prospective design was employed with follow-up data collected 12 months following hospital admission. MAIN OUTCOME MEASURES Data were gathered on social network size and partner stress. The main outcomes assessed at 12 months were medication adherence, cardiac rehabilitation attendance, and quality of life (Short Form 36). RESULTS Partner stress predicted medication nonadherence, odds ratio: 2.89, (95% CI = 1.21, 6.95). ACS patients with large social networks were more likely to attend rehabilitation, odds ratio: 3.42, (95% CI = 1.42, 8.25). Analyses were adjusted for age, gender, clinical risk scores, readmission/recurrence, and negative affectivity. Both partner stress and smaller social network size were associated with poorer quality of life. CONCLUSION Social network size and partner stress may partly exert their influence on coronary heart disease morbidity and mortality through recovery behaviors and maintenance of quality of life.