Psychological Stress and Cardiovascular Disease

There is an enormous amount of literature on psychological stress and cardiovascular disease. This report reviews conceptual issues in defining stress and then explores the ramifications of stress in terms of the effects of acute versus long-term stressors on cardiac functioning. Examples of acute stressor studies are discussed in terms of disasters (earthquakes) and in the context of experimental stress physiology studies, which offer a more detailed perspective on underlying physiology. Studies of chronic stressors are discussed in terms of job stress, marital unhappiness, and burden of caregiving. From all of these studies there are extensive data concerning stressors’ contributions to diverse pathophysiological changes including sudden death, myocardial infarction, myocardial ischemia, and wall motion abnormalities, as well as to alterations in cardiac regulation as indexed by changes in sympathetic nervous system activity and hemostasis. Although stressors trigger events, it is less clear that stress “causes” the events. There is nonetheless overwhelming evidence both for the deleterious effects of stress on the heart and for the fact that vulnerability and resilience factors play a role in amplifying or dampening those effects. Numerous approaches are available for stress management that can decrease patients’ suffering and enhance their quality of life

The roles of TNF-α and the soluble TNF receptor I on sleep architecture in OSA

Patients with obstructive sleep apnea (OSA) have been described to have increased levels of inflammatory cytokines (particularly TNF-α) and have severely disturbed sleep architecture. Serum inflammatory markers, even in normal individuals, have been associated with abnormal sleep architecture. Not much is known about the role the TNF receptor plays in the inflammation of OSA nor if it is associated with changes in sleep architecture or arousals during the night. We hypothesized that the TNF receptor might play an important role in the inflammation as well as sleep architecture changes in patients with OSA. Thirty-six patients with diagnosed (AHI > 15) but untreated OSA were enrolled in this study. Baseline polysomnograms as well as TNF-α and soluble TNF receptor I (sTNF-RI) serum levels were obtained on all patients. We evaluated the association between serum levels of TNF-α and sTNF-RI with various polysomongraphic characteristics, including sleep stages and EEG arousals. sTNF-RI levels were significantly correlated with snore arousals (r value 0.449, p value 0.009), spontaneous movement arousals (r value 0.378, p value 0.025), and periodic limb movement arousals (r value 0.460, p value 0.008). No statistically significant correlations were observed with TNF-α to any polysomnographic variables. To control for statistical significance with multiple comparisons, a MANOVA was performed with TNF-α and sTNF-RI as dependent variables and sleep architecture measures and arousals as independent variables. The model for sTNF-RI was statistically significant (F value 2.604, p value 0.03), whereas the model for TNF-α was not, suggesting sleep quality significantly affects sTNF-RI. Hierarchal linear regression analysis demonstrated that sTNF-RI was independently associated with spontaneous movement arousal index scores after controlling for age, body mass index, and sleep apnea severity. These findings suggest that sTNF-RI is associated with arousals during sleep, but not with other measures in patients with OSA

Effect of Alzheimer Caregiving Stress and Age on Frailty Markers Interleukin-6, C-Reactive Protein, and D-Dimer

Background. Elevated plasma levels of interleukin (IL)-6, C-reactive protein (CRP), and D-dimer belong to the biological alterations of the "frailty syndrome,” defining increased vulnerability for diseases and mortality with aging. We hypothesized that, compatible with premature frailty, chronic stress and age are related in predicting inflammation and coagulation activity in Alzheimer caregivers. Methods. Plasma IL-6, CRP, and D-dimer levels were measured in 170 individuals (mean age 73 ± 9 years; 116 caregivers, 54 noncaregiving controls). Demographic factors, diseases, drugs, and lifestyle variables potentially affecting inflammation and coagulation were obtained by history and adjusted for as covariates in statistical analyses. Results. Caregivers had higher mean levels of IL-6 (1.38 ± 1.42 vs 1.00 ± 0.92 pg/mL, p =.032) and of D-dimer (723 ± 530 vs 471 ± 211 ng/mL, p <.001) than controls had. CRP levels were similar between groups (p =.44). The relationship between caregiver status and D-dimer was independent of covariates (p =.037) but affected by role overload. Age accounted for much of the relationship with IL-6. After controlling for covariates, the interaction between caregiver status and age was significant for D-dimer (β =.20, p =.029) and of borderline significance for IL-6 (β =.17, p =.090). Post hoc regression analyses indicated that, among caregivers, age was significantly correlated with both D-dimer (β =.50, p <.001) and IL-6 (β =.38, p =.001). Among controls, however, no significant relationship was observed between age and either D-dimer or IL-6. Conclusions. The interaction between caregiving status and age for D-dimer and IL-6 suggests the possibility that older caregivers could be at risk of a more rapid transition to the frailty syndrome and clinical manifestations of cardiovascular disease

Brief report: Characteristics of antidepressant use in patients with heart failure

Paul J Mills1, Joel E Dimsdale1, Suzi Hong1, Geoffrey Van Den Brande2, Laura Redwine2, Barry H Greenberg2, Thomas Rutledge11Department of Psychiatry; 2Department of Medicine, University of California San Diego, La Jolla, CA, USABackground: Depression is common in heart failure (HF), but there is little data on the characteristics of antidepressant use in patients with HF.Objective: To survey basic information on antidepressant prescription characteristics, use, effectiveness, and follow-up.Methods: Observational study in two outpatient cardiology clinics of 37 NYHA class I&amp;ndash;IV HF patients taking antidepressant medication.Results: Thirty-one percent of prescriptions for antidepressants were obtained from psychiatrists, 58% from primary care physicians, and 8% from cardiologists. The majority of patients (87%) reported regularly taking their antidepressant medication as prescribed, however 48% reported never having had the dosage of their antidepressant medication adjusted. Only 53% of the patients reported that the medication had helped their mood &amp;ldquo;almost entirely&amp;rdquo; or &amp;ldquo;mostly&amp;rdquo; back to normal since starting their antidepressants, while the remaining patients reported that their mood was only &amp;ldquo;halfway&amp;rdquo; or &amp;ldquo;somewhat&amp;rdquo; back to normal or that the medication had not helped their depression at all. Among a subset of 10 patients who completed the Beck Depression (BDI) inventory, 6 still had depressed mood (BDI&amp;nbsp;&amp;ge; 10).Conclusion: The findings from this survey study provide insight into the characteristics of antidepressant use in patients with HF and argue for better follow up of HF patients who are prescribed antidepressants.Keywords: heart failure, antidepressant medication, adherence, effectivenes

Longitudinal Relationship of Low Leisure Satisfaction but not Depressive Symptoms With Systemic Low-Grade Inflammation in Dementia Caregivers

Objectives. This study aimed to further elucidate the biobehavioral mechanisms linking dementia caregiving with an increased cardiovascular disease risk. We hypothesized that both elevated depressive symptoms and a behavioral correlate of depression, low leisure satisfaction, are associated with systemic inflammation. Method. We studied 121 elderly Alzheimer's disease caregivers who underwent 4 annual assessments for depressive symptoms, leisure satisfaction, and circulating levels of inflammatory markers. We used mixed-regression analyses controlling for sociodemographic and health-relevant covariates to examine longitudinal relationships between constructs of interest. Results. There were inverse relationships between total leisure satisfaction and tumor necrosis factor-α (TNF-α; p = .047), interleukin-8 (IL-8; p .17). Depressive symptoms did not mediate the relationship between leisure satisfaction and inflammation. Discussion. Lower satisfaction with leisure activities is related to higher low-grade systemic inflammation. This knowledge may provide a promising way of improving cardiovascular health in dementia caregivers through behavioral activation treatments targeting low leisure satisfactio

Problem Behavior of Dementia Patients Predicts Low-Grade Hypercoagulability in Spousal Caregivers

Background. Low-grade hypercoagulability might be one pathway to explain how the chronic stress of dementia caregiving increases cardiovascular disease risk, but the specific aspects of caregiver stress that elicit hypercoagulability are elusive. We hypothesized that dementia patients' problem behaviors and negative reactions of caregivers to these behaviors would relate to hypercoagulability in caregivers. Methods. One hundred and eight participants (mean age 74 ± 8 years, 70% women) providing in-home care for their spouse with Alzheimer's disease were examined. Caregivers were interviewed about the number of 24 predefined patient problem behaviors in the previous week (range 0-24) and how upset or bothered they felt in response to these behaviors (total score 0-96). Von Willebrand factor, plasminogen activator inhibitor-1, and D-dimer were determined in plasma and standardized z-scores of their concentrations summed into a procoagulant index. Results. Greater number of problem behaviors (ΔR2 = 0.046, p = .014) and negative reactions of caregivers to these behaviors (ΔR2 = 0.044, p = .017) were associated with greater procoagulant index after controlling for sociodemographic factors, major cardiovascular risk factors, health habits, and health problems. However, the number of and reaction to problem behaviors did not significantly predict procoagulant activity independent from each other. Post hoc analysis revealed a positive association between the number of problem behaviors and D-dimer (p = .010, ΔR2 = 0.053), even when controlling for negative reactions (p = .033, ΔR2 = 0.036). Caregiver reaction to problem behaviors was not significantly associated with any procoagulant factor individually. Conclusion. Alzheimer patients' problem behavior and their negative appraisal by the caregiver may contribute to the chronic low-grade hypercoagulable state in dementia caregiver

Arousal frequency is associated with increased fatigue in obstructive sleep apnea

Fatigue is an important and often underemphasized symptom in patients with obstructive sleep apnea (OSA). Sleep fragmentation, i.e., arousals and disruptions in sleep architecture, is common in patients with OSA and may potentially contribute to their fatigue. We hypothesized that arousal frequency and changes in sleep architecture contribute to the fatigue experienced by patients with OSA. Seventy-three patients with diagnosed but untreated OSA (AHI ≥ 15) were enrolled in this study. A baseline polysomnogram was obtained, and fatigue was measured with the Multidimensional Fatigue Symptom Inventory-short form (MFSI-sf). We evaluated the association between fatigue and arousals and various polysomongraphic variables, including sleep stages and sleep efficiency. Significant correlations between MFSI-sf subscale scores and various arousal indices were noted. Emotional fatigue scores were associated with total arousal index (r = 0.416, p = .021), respiratory movement arousal index (r = 0.346, p = .025), and spontaneous movement arousal index (r = 0.378, p = .025). Physical fatigue scores were associated with total arousal index (r = 0.360, p = .033) and respiratory movement arousal index (r = 0.304, p = .040). Percent of stage 1 sleep and REM sleep were also associated with physical and emotional fatigue scores. Hierarchal linear regression analysis demonstrated that emotional fatigue scores were independently associated with spontaneous movement arousals after controlling for age, body mass index, depression, and sleep apnea severity. These findings suggest that arousals may contribute to the fatigue seen in patients with OSA

Longitudinal Relationship of Low Leisure Satisfaction but not Depressive Symptoms With Systemic Low-Grade Inflammation in Dementia Caregivers.

Objectives.This study aimed to further elucidate the biobehavioral mechanisms linking dementia caregiving with an increased cardiovascular disease risk. We hypothesized that both elevated depressive symptoms and a behavioral correlate of depression, low leisure satisfaction, are associated with systemic inflammation.Method.We studied 121 elderly Alzheimer's disease caregivers who underwent 4 annual assessments for depressive symptoms, leisure satisfaction, and circulating levels of inflammatory markers. We used mixed-regression analyses controlling for sociodemographic and health-relevant covariates to examine longitudinal relationships between constructs of interest. RESULTS: There were inverse relationships between total leisure satisfaction and tumor necrosis factor-α (TNF-α; p = .047), interleukin-8 (IL-8; p .17). Depressive symptoms did not mediate the relationship between leisure satisfaction and inflammation.Discussion.Lower satisfaction with leisure activities is related to higher low-grade systemic inflammation. This knowledge may provide a promising way of improving cardiovascular health in dementia caregivers through behavioral activation treatments targeting low leisure satisfaction