Depression and markers of inflammation as predictors of all-cause mortality in heart failure

BackgroundIn patients with heart failure (HF) depressive symptoms have been associated with mortality, as well as biological risk factors, including inflammation, nitric oxide (NO) regulation, and oxidative stress. We investigated the joint predictive value of depressive symptoms, inflammation and NO regulation on all-cause mortality in patients with HF, adjusted for covariates.MethodsSerum levels of inflammation (TNFα, sTNFr1, sTNFr2, IL-6, hsCRP, NGAL), NO regulation (l-arginine, ADMA, and SDMA), and oxidative stress (isoprostane 8-Epi Prostaglandin F2 Alpha) were measured in 104 patients with HF (mean age 65.7 ± SD 8.4 years, 28% women). Depressive symptoms (Beck Depression Inventory, BDI) were measured as continuous total, cognitive, and somatic symptoms, as well as categorized presence of mild/moderate depression (cut-off BDI ⩾10). In Cox proportional hazard models we adjusted for age, sex, poor exercise tolerance and comorbidity.ResultsAfter on average 6.1 years follow-up (SD = 2.9, range 0.4–9.2), 49 patients died. Total and somatic depressive symptoms, mild/moderate depression, higher NGAL, sTNFr2, IL-6, hsCRP and SDMA serum levels were significantly associated with a higher all-cause mortality rate, adjusted for covariates. The findings were most consistent for CRP level and somatic depressive symptoms. When combined, both depressive symptoms and markers of inflammation and NO regulation remained significantly associated with all-cause mortality. These associations were not confounded by age, sex, poor exercise tolerance and comorbidity.ConclusionDepressive symptoms and markers of inflammation and NO regulation are codominant risk factors for all-cause mortality in heart failure.     

Genetic and serum biomarker evidence for a relationship between TNFα and PTSD in Vietnam war combat veterans

BackgroundPosttraumatic stress disorder (PTSD) is associated with increased inflammation and comorbid medical conditions. However, study findings for individual inflammatory marker levels have been inconsistent. Some research suggests that resilience may play a role in decreased inflammation. A polymorphism in the promoter region of the tumor necrosis factor α gene (TNFα), TNFA −308 (rs1800629) is associated with psychiatric illness but its role in PTSD is yet to be elucidated.ObjectiveThis study investigates a key inflammatory marker, TNFα, for its role in PTSD severity.MethodIn a cohort of trauma-exposed Vietnam War veterans (n = 299; 159 cases, 140 controls) TNF α serum levels and TNFα polymorphism rs1800629 were correlated with PTSD severity and resilience scores.ResultsThe polymorphism was associated with PTSD severity (p = 0.045). There were significant group differences between cases and controls with regards to serum TNFα levels (p = 0.036). Significant correlations were found between PTSD severity and elevated TNFα levels (r = 0.153; p = 0.009), and between resilience and decreased TNFα levels at a trend level (p = 0.08) across the entire cohort. These relationships were non-significant after controlling for covariates. In the PTSD diagnostic group, a correlation of TNFα and PTSD severity was observed on a trend level (p = 0.06), the relationship between TNFα and resilience remained non-significant.ConclusionsTo our knowledge, this is the first time rs1800629 has been investigated in PTSD contributing to a growing body of literature that identifies the GG as a risk genotype for psychiatric disorders in Caucasian cohorts. However, more research is needed to replicate our results in larger, equally well-characterized cohorts. The relationship between serum TNFα levels and PTSD severity and resilience requires further investigation.     

Acute phase protein and cytokine levels in serum and saliva: A comparison of detectable levels and correlations in a depressed and healthy adolescent sample

Recent research has examined associations between inflammation and mental health, and has increasingly focused on utilising younger samples to characterise the temporal relationship between inflammatory responses and the emergence of other symptoms. These studies have typically used blood to measure inflammation, although rates of detection for many inflammatory markers appear to be low. Saliva is a safe and low-cost alternative, and adult research has shown that levels of some salivary markers correlate well with those in serum. However, no research has examined this association in young people. This study examined 16 inflammatory markers in serum and saliva in 17 depressed adolescents and 18 healthy controls, aged 13–18 years. In general, detection rates were higher in saliva compared to in serum. When non-detectable levels were excluded, serum levels of C-reactive protein (CRP) correlated with salivary CRP (r = 0.424, p = 0.015), and this correlation appeared to only exist for those individuals with high levels of serum CRP (r = 0.599, p = 0.014). However, when non-detectable levels were included as zero, salivary levels of CRP, interleukin (IL)-2, IL-12p70, and interferon (IFN)-γ correlated with their serum counterparts. No significant clinical group differences in any acute phase proteins or cytokines were present. This study suggests that saliva can be used to measure inflammation in studies with adolescent participants, especially CRP, as it appears to correlate with systemic inflammation for those individuals who are expected to have high levels of inflammation. Implications for future directions in research on salivary inflammatory markers are discussed.     

Inflammation and metabolic changes in first episode psychosis: Preliminary results from a longitudinal study

Metabolic abnormalities are commonly observed in patients with psychosis, and may confer greater risk of developing cardiovascular disease later in life. Such abnormalities are associated with inflammation in the general population, and there is increasing evidence for elevated inflammation in patients with first episode psychosis (FEP). The aim of this preliminary study is to examine the effect of changes in inflammation, as measured by high-sensitivity C-reactive protein (hsCRP), on metabolic changes in a three-month longitudinal study in a FEP sample.Fifty-three FEP patients from in- and out-patient services in South London, England, were included in this longitudinal study. Social and clinical data were collected, and fasting blood samples and anthropometric measurements (weight, Body Mass Index (BMI), lipid profile and gluco-metabolic parameters) were obtained at baseline and at three-month follow-up.Correlation analyses showed that those with increases in hsCRP over the three-month period also had increases in triglyceride levels (r = 0.49, p = 0.02). No association was observed with other lipid profile, or gluco-metabolic parameters, across the whole sample. Increases in weight and BMI were also associated with increases in triglyceride levels (r = 0.33, p = 0.02; and r = 0.31, p = 0.03, respectively); however, a multiple linear regression analysis found that the effects of inflammation on triglycerides were independent from the effect of changes in weight, and from the baseline inflammatory state.Our preliminary findings suggest that those patients experiencing greater increases in inflammation early on in the course of their illness may be at greater risk of developing short-term metabolic abnormalities, in particular dyslipidaemia, independent of weight-gain. Future work should investigate the use of inflammatory markers to identify patients in greater need of physical health interventions.     

Inflammatory biomarkers and emotional approach coping in men with prostate cancer

ObjectiveEmotion-regulating coping is associated with improvements in psychological and physical health outcomes. Yet in the context of prostate cancer-related stressors, limited research has characterized associations of emotion-regulating coping processes (emotional expression, emotional processing) and inflammatory processes that are related to disease risk. This investigation examined the relation of Emotional Approach Coping (EAC) with markers of inflammation to test the hypothesis that higher EAC scores at study entry (T1) would be associated with lower proinflammatory markers four months later (T2), specifically sTNF-RII, CRP, and IL-6.MethodsForty-one men (M age = 66.62 years; SD = 9.62) who had undergone radical prostatectomy or radiation therapy for localized prostate cancer within two years completed questionnaires, including assessments of EAC, at T1, and provided blood samples for immune assessments at T2.ResultsWhen controlling for relevant biobehavioral controls, emotional processing predicted lower IL-6 (B = −.66, p < .01), sTNF-RII (B = −.43, p < .05), and CRP (B = −.43, p < .10), whereas emotional expression was significantly associated with higher levels of sTNF-RII (B = .55, p < .05). Associations of emotional expression and IL-6 (B = .38, p < .10), and CRP (B = .44, p < .10) approached significance. Probing interactions of emotional processing and expression (though only approaching significance) suggested that expression of emotion is associated with higher inflammation (CRP and sTNF-RII) only in the context of low emotional processing.ConclusionsAttempts at emotion regulation via emotional processing appear to modulate inflammatory processes. Understanding, making meaning of, and working through emotional experience may be a promising target of intervention to reduce inflammation with potential effects on psychological and cancer outcomes in men with prostate cancer.     

Cerebrospinal fluid inflammatory markers in Parkinson’s disease – Associations with depression,fatigue, and cognitive impairment

Neuroinflammation may be involved in the pathophysiology of Parkinson’s disease (PD) and specifically in non-motor symptoms such as depression, fatigue and cognitive impairment. The aim of this study was to measure inflammatory markers in cerebrospinal fluid (CSF) samples from PD patients and a reference group, and to investigate correlations between non-motor symptoms and inflammation.We quantified C-reactive protein (CRP), interleukin-6, tumor necrosis factor-alpha, eotaxin, interferon gamma-induced protein-10, monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein 1-β in CSF samples from PD patients (N = 87) and the reference group (N = 33). Sixteen of the PD patients had a dementia diagnosis (PDD). We assessed symptoms of fatigue, depression, anxiety and cognitive function using the Functional Assessment of Chronic Illness Therapy-Fatigue, the Hospital Anxiety and Depression Scale, and the Mini Mental State Examination, respectively.There were no significant differences in mean levels of inflammatory markers between PD patients and the reference group. After controlling for age, gender and somatic illness, patients with PDD had significantly higher levels of CRP compared to non-demented PD patients (p = 0.032) and the reference group (p = 0.026). Increased levels of inflammatory markers in CSF were significantly associated with more severe symptoms of depression, anxiety, fatigue, and cognition in the entire PD group. After controlling for PD duration, age, gender, somatic illness and dementia diagnosis, high CRP levels were significantly associated with more severe symptoms of depression (p = 0.010) and fatigue (p = 0.008), and high MCP-1 levels were significantly associated with more severe symptoms of depression (p = 0.032).Our results indicate that non-motor features of PD such as depression, fatigue, and cognitive impairment are associated with higher CSF levels of inflammatory markers.     

Exploratory associations with Tumor Necrosis Factor-α, disinhibition and suicidal endorsement after traumatic brain injury

PurposeTo examine the relationship of Tumor Necrosis Factor (TNF)-α to disinhibition and suicidal endorsement after traumatic brain injury (TBI).ParticipantsAdults with moderate to severe TBI (acute serum levels: n = 48, n = 543 samples; acute CSF levels: n = 37, n = 389 samples; chronic serum levels: n = 48, n = 326 samples).Main measuresTNFα levels (CSF, Serum) from time of injury to 12 months post-injury; Frontal Systems Behavior Scale – Disinhibition Subscale at 6 and 12 months post-injury; Patient Health Questionnaire at 6 and 12 months post-injury.ResultsParticipants with TBI had significantly higher CSF and serum TNFα levels than healthy controls (p < 0.05). Acute and chronic serum TNFα was significantly associated with disinhibition at 6 months post-injury (p = 0.009, p = 0.029 respectively), and 6 month disinhibition was associated with suicidal endorsement at both 6 and 12 months (p = 0.045, p = 0.033 respectively) and disinhibition at 12 months post-injury (p < 0.001).ConclusionThese preliminary data suggest a biological to behavioral pathway of suicidality after TBI, from TNFα to disinhibition to suicidal endorsement. Future investigation is warranted to validate these findings and clarify what biological mechanisms might underlie these relationships.     

Type D personality and course of health status over 18 months in outpatients with heart failure: multiple mediating inflammatory biomarkers

BackgroundThe distressed (Type D) personality is associated with poor health status (HS) and increased inflammatory activation in heart failure (HF). We tested whether multiple inflammatory biomarkers mediated the association between Type D personality and the course of self-reported HS over 18 months.MethodsHF outpatients (n = 228, 80% male, mean age 67.0 ± 8.7 years), filled out the Type D questionnaire (DS14) at inclusion and the Short Form-12 (SF12) and the Kansas City Cardiomyopathy Questionnaire (KCCQ) at 0, 6, 12, and 18 months. Blood samples at inclusion were analyzed for high sensitive C-reactive protein (hsCRP), interleukin (IL)-6, tumor necrosis factor (TNF)-α, and its soluble receptors (sTNFr1, sTNFr2). A multiple mediation latent growth model was tested using structural equation modeling.ResultsType D personality (prevalence = 21%) was associated with poorer HS (all scales p < 0.001), deterioration of mental HS (p < 0.001), and higher TNF-α and sTNFr2 levels in the full mediation model. A higher inflammatory burden was associated with a poorer baseline level and a deterioration of generic physical, mental and disease-specific HS. No mediating effects were found for the multiple inflammatory biomarkers on the association between Type D and baseline self-reported HS, whereas change in physical HS was significantly mediated by the group of five inflammatory biomarkers (p = 0.026).ConclusionsOnly the association between Type D personality and change in self-reported physical health status was significantly mediated by inflammatory biomarkers. Future research should investigate whether the association between Type D personality and poor health status may be explained by other biological or behavioral factors.     

Cumulative meta-analysis of interleukins 6 and 1β, tumour necrosis factor α and C-reactive protein in patients with major depressive disorder

Cumulative meta-analyses are used to evaluate the extent to which further studies are needed to confirm or refute a hypothesis. We used this approach to assess observational evidence on systemic inflammation in individuals with major depressive disorder. We identified 58 studies of four common inflammatory markers in a literature search of PubMed, Embase and PsychInfo databases in May 2014. Pooled data from the earliest eight studies already showed an association between interleukin-6 concentrations and major depression; 23 more recent studies confirmed this finding (d = 0.54, p < 0.0001). A significant association between C-reactive protein levels and major depression was noted after 14 studies and this did not change after addition of six more studies (d = 0.47, p < 0.0001). For these two inflammatory markers, there was moderate heterogeneity in study-specific estimates, subgroup differences were small, and publication bias appeared to be an unlikely explanation for the findings. Sensitivity analyses including only high-quality studies and subjects free of antidepressant medication further verified the associations. While there was a link between tumour necrosis factor-α levels and major depression (d = 0.40, p = 0.002), the cumulative effect remained uncertain due to the extensive heterogeneity in study-specific estimates and inconsistencies between subgroups. No evidence was found for the association between interleukin-1β levels and major depression (d = −0.05, p = 0.86). In conclusion, this cumulative meta-analysis confirmed higher mean levels of interleukin-6 and C-reactive protein in patients with major depression compared to non-depressed controls. No consistent association between tumour necrosis factor-α, interleukin-1β and major depression was observed. Future studies should clarify the specific immune mechanisms involved as well as continue testing anti-inflammatory therapies in patients suffering from major depression.     

Gender differences in the association of sleep apnea and inflammation

Over the last 15 years, many studies have established an association of sleep apnea with inflammation and metabolic aberrations. However, no controlled studies have examined potential gender effects in this association. We recruited 120 middle-aged, predominantly non-obese mild-to-moderate sleep apneics and controls (62 males, 58 females). All participants underwent a clinical history, physical examination, and 1-night 8-h polysomnography recording and provided a single fasting blood sample for assessment of interleukin-6 (IL-6), tumor necrosis factor receptor 1 (TNFR1), C-reactive protein (CRP), leptin, and adiponectin levels. Among non-sleep apneics, females had higher levels of TNFR1 (p = 0.01), CRP (p = 0.005), leptin (p < 0.001), and adiponectin (p < 0.001) compared to males, independent of age and body mass index. When analyzed separately by gender, sleep apneic men had elevated TNFR1 (p = 0.04), CRP (p = 0.06) and IL-6 (p = 0.11) relative to control men; in sleep apneic females, only CRP was elevated (p = 0.04). Furthermore, CRP was associated with apnea severity in a dose–response manner (p-linear = 0.04 in both genders) and was independently associated with comorbid hypertension in apnea (p-linear = 0.005 for women; p-linear = 0.09 for men). In conclusion, although women have naturally higher levels of inflammatory and metabolic markers than men, sleep apneic men appear to have a more severe inflammatory profile compared to women. Our findings suggest that these markers should be analyzed and interpreted separately in men and women, and that a single measure of plasma CRP appears to be a clinically-useful marker of apnea severity and comorbid cardiovascular morbidity.     

An association between neuropeptide Y levels and leukocyte subsets in stress-exacerbated asthmatic mice

Neuropeptide Y (NPY) was recently proposed to be associated with stress and airway inflammation; however, this has rarely been studied in animal models of asthma. Twenty-four C57BL/6 mice were randomly divided into 3 groups of 8 each: naive control group, asthma group (with an established asthma model), and stressed asthma group (with established asthma and stress models). Bronchoalveolar lavage (BAL) fluid was collected for total cell counts using a hemocytometer and for cytological examinations by Wright stain. Differential inflammatory cell counts were performed to identify eosinophils, macrophages, neutrophils, and lymphocytes. NPY and corticosterone serum levels were determined with enzyme immunoassay kits. Stress was associated with increased airway inflammatory response, which was manifested by the accumulation of total leukocytes and eosinophils in the BAL fluid in comparison with the asthma and the control groups. The levels of NPY (p < 0.05) and corticosterone (p < 0.01) were elevated in the stressed asthma group in comparison with the control and asthma groups. The concentration of NPY and corticosterone positively correlated with the total leukocyte count (r = 0.892, p < 0.05 and r = 0.937, p < 0.01 respectively) and eosinophil numbers (r = 0.806, p = 0.053 and r = 0.885, p < 0.01 respectively).Stress may be associated with elevated peripheral NPY level, which was observed to be associated with exacerbated airway inflammation in asthmatic mice.     

Impact of sleeping position on central sleep apnea/Cheyne–Stokes respiration in patients with heart failure

BackgroundThe present study determines the influence of sleeping position on central sleep apnea (CSA) in patients with heart failure (HF).MethodsThe apnea/hypopnea index (AHI) during different body positions while asleep was examined by cardiorespiratory polygraphy in 71 patients with HF (ejection fraction <45%).ResultsTwenty-five of the patients having predominantly CSA (central apnea index ?10/h) with a lower obstructive apnea index (<5/h) were assigned to groups with positional (lateral to supine ratio of AHI <50%, n = 12) or non-positional (ratio ?50%, n = 13) CSA. In the non-positional group the BNP level was higher, the ejection fraction was lower and the trans-tricuspid pressure gradient was higher than in the positional group. Multiple regression analysis revealed more advanced age (p = 0.006), log₁₀ BNP (p = 0.017) and lung-to-finger circulation time (p = 0.020) as independent factors of the degree of positional CSA. Intensive treatment for HF changed CSA from non-positional to positional in all eight patients tested. Single night of positional therapy reduced CSA (p < 0.05) and BNP level (p = 0.07) in seven positional patients.ConclusionAs cardiac dysfunction progresses, severity of CSA also increases and positional CSA becomes position-independent. Positional therapy could decrease CSA, thereby having a valuable effect on HF.     

Plasma brain natriuretic peptide is elevated in the acute phase of intracerebral hemorrhage

Previous reports have shown that plasma brain natriuretic peptide (BNP) levels are increased in patients with subarachnoid hemorrhage and ischemic stroke. We examined BNP in patients with intracerebral hemorrhage (ICH). Between June 2006 and February 2010, we prospectively enrolled consecutive patients with acute ICH within 24 hours of onset. The plasma BNP level was measured twice, on admission and 4 weeks after onset or at discharge. We investigated whether plasma BNP was elevated in the acute phase of ICH and associated factors. The mean ± standard deviation (SD) plasma BNP level of all patients was 71.1 ± 104.1 pg/mL. The log BNP level positively correlated with the cardio–thoracic ratio (r = 0.240, p = 0.0001). Moreover, BNP was significantly associated with intraventricular extension (p = 0.0039) and hydrocephalus (p = 0.0046). The mean ± SD BNP level of patients with cerebellar hemorrhage was the highest (130.2 ± 152.0 pg/mL), followed by brainstem (84.5 ± 170.6 pg/mL), lobar (72.4 ± 148.1 pg/mL), thalamus (64.8 ± 72.1 pg/mL), and putamen (59.9 ± 62.6 pg/mL) hemorrhages. In 185 patients, BNP was measured in the subacute phase of ICH. The BNP level in the acute phase of ICH was significantly higher than that in the subacute phase of ICH (69.3 ± 108.1 versus 21.7 ± 23.5 pg/mL, p < 0.0001). In conclusion, plasma BNP appears to be elevated in the acute phase of ICH, particularly in those with cerebellar lesions.     

Cytokine-induced depression during IFN-α treatment: The role of IL-6 and sleep quality

Depressive symptoms, poor sleep quality, and systemic markers of inflammation (e.g., interleukin (IL)-6) are frequently associated. Interferon-alpha (IFN-α) therapy results in Major Depressive Disorder (MDD) in some people, offering the possibility to elucidate the relationship of MDD to sleep and inflammation during treatment. In particular, delineating the temporal relations among these factors could help inform their causal relationships. To this end, a cohort of 95 non-depressed hepatitis C patients was followed prospectively for four consecutive months during IFN-α therapy. We found that higher pre-treatment levels of circulating IL-6 predicted incidence of MDD (X²(1) = 7.7; p < 0.05). Time-lagged mixed-effect analyses supported uni-directional associations in which IL-6 predicted next month’s PSQI scores (F(47, 11.6) = 78.4; p < 0.0005), and PSQI scores predicted next month’s depressive Beck Depression Inventory-II (BDI) scores (F(16, 22.6) = 3.4; p < 0.005). In addition, on any given month of treatment, IL-6 levels predicted BDI symptoms the following month (F(16, 97.5) = 7.3; p < 0.0005), and conversely BDI predicted next month’s IL-6 (F(14, 7.4) = 5.2; p < 0.05) – providing evidence for a positive feedback relationship between depressive symptoms and systemic inflammation. These data provide further evidence that high levels of inflammation and poor sleep quality may be risk factors for IFN-α induced depression. Furthermore, these findings highlight the complex temporal relationships that exist among sleep, depression, and inflammation, and support the need for further prospective investigations to elucidate the dynamics that underlie depression during IFN-α treatment.     

The mediation effect of health literacy between subjective social status and depressive symptoms in patients with heart failure

ObjectivesDepressive symptoms are prevalent and cause adverse outcomes in heart failure. Previous studies have linked depressive symptoms with socioeconomic status. However, little is known about the mechanisms underlying this relationship. This study aimed to evaluate the association between socioeconomic status and depressive symptoms, and to examine whether access to healthcare, health literacy and social support mediated this relationship in patients with heart failure.MethodsCross-sectional design was used to study 321 patients with heart failure recruited from a general hospital. Demographics, clinical data, depressive symptoms, socioeconomic status (i.e., education, employment, income, and subjective social status), access to healthcare, health literacy, and social support were collected by patient interview, medical record review or questionnaires. A series of logistic regressions and linear regressions were conducted to examine mediation.ResultsThe mean age of patients with heart failure was 63.6 ± 10.6 years. Fifty-eight patients (18%) had depressive symptoms. Lower subjective social status (OR = 1.321, p = 0.012) and lower health literacy (OR = 1.065, p < 0.001) were separately associated with depressive symptoms. When subjective social status and health literacy were entered simultaneously, the relationship between subjective social status and depressive symptoms became non-significant (OR = 1.208, p = 0.113), demonstrating mediation. Additionally, lower social support was associated with depressive symptoms (OR = 1.062, p = 0.007).ConclusionsIn patients with heart failure, health literacy mediated the relationship between subjective social status and depressive symptoms. Lower social support was associated with depressive symptoms. Interventions should take these factors into account.     

Radiotherapy and chemotherapy plus radiation in the treatment of patients with pure intracranial germinoma: A meta-analysis

ObjectiveTo evaluate the efficiency of radiotherapy (RT) only and chemotherapy plus radiotherapy (CRT) strategy in the treatment of pure intracranial germinoma.MethodsWe searched PUBMED, EMBASE, Medline and Cochrane library up to May 2016 for studies that enrolled patients with pure intracranial germinoma receiving either RT only or CRT treatment as their first-line treatment. The meta-analysis was conducted on the overall survival rate (OS) and disease free survival (DFS) at 3 years and 5 years. The outcomes were pooled using a random-effect model.ResultsThe final search included 15 studies with 310 patients. The pooled 3-year OS (97% vs. 94%, p = .000) and 3-year DFS (96% vs. 93%, p = 0.043) of CRT group was significantly higher than that of RT only group. However, at 5 years, the OS was 94% in RT only group and 92% in the combined group (p = 0.29) . For DFS, the RT only group was higher than the combined group (94% vs.89%, p = .000).ConclusionsBoth RT and CRT for intracranial pure germinoma gain satisfying outcomes, and the CRT strategy has a higher overall survival rate and disease free survival rate at 3 years than RT regimen. At 5 years in the postoperative period, the advantage of survival rates for CRT is eliminated or even reversed. For patients with pure intracranial germinoma, especially those with acute and severer condition and poorer prognosis, CRT strategy would be a better choice.     

Association between depressive symptoms and fibrosis markers: The Cardiovascular Health Study

ObjectiveFibrosis plays an important role in heart failure (HF) and other diseases that occur more frequently with increasing age. Depression is associated with an increased risk of heart failure and other age-related diseases. This study examined the association between depressive symptoms and fibrosis markers in adults aged 65 years and above.MethodsFibrosis markers and depressive symptoms were assessed in 870 participants (age = 80.9 ± 5.9 yrs, 49% women) using a case-control design based on heart failure status (307 HF patients and 563 age- and sex-matched controls, of whom 284 with CVD risk factors (hypertension, diabetes mellitus, or hypercholesterolemia) and 279 controls without these CVD risk factors). Fibrosis markers were procollagen type I (PIP), type I collagen (CITP), and procollagen type III (PIIINP). Inflammation markers included C-reactive protein, white blood cell counts and fibrinogen. Depression was assessed using the Center for Epidemiological Studies-Depression (CES-D) scale using a previously validated cut-off point for depression (CES-D ? 8). Covariates included demographic and clinical variables.ResultsDepression was associated with higher levels of PIP (median = 411.0, inter-quartile range (IQR) = 324.4–472.7 ng/mL vs. 387.6, IQR = 342.0–512.5 ng/mL, p = 0.006) and CITP (4.99, IQR = 3.53–6.85 vs. 4.53, IQR = 3.26–6.22 μg/L, p = 0.024), but not PIIIINP (4.07, IQR = 2.75–5.54 μg/L vs. 3.58, IQR = 2.71–5.01 μg/L, p = 0.29) compared to individuals without depression. Inflammation markers were also elevated in depressed participants (CRP, p = 0.014; WBC, p = 0.075; fibrinogen, p = 0.074), but these inflammation markers did not account for the relationship between depression and fibrosis markers.ConclusionsDepression is associated with elevated fibrosis markers and may therefore adversely affect heart failure and other age-related diseases in which extra-cellular matrix formation plays a pathophysiological role.     

Sex differences in the association between stressor-evoked interleukin-6 reactivity and C-reactive protein

Individuals differ consistently in the magnitude of their inflammatory responses to acute stressors, with females often showing larger responses than males. While the clinical significance of these individual differences remains unclear, it may be that greater inflammatory responses relate to increased systemic inflammation and thereby risk for chronic inflammatory disease. Here, we examined whether acute stressor-evoked interleukin (IL)-6 responses associate with resting levels of C-reactive protein (CRP), a marker of systemic inflammation, and whether this association differs by sex. Subjects were 57 healthy midlife adults (30–51 years; 33% female; 68% white). Blood was drawn before and 30-min after two mental stress tasks: a multisource interference task and a Stroop color word task. Hierarchical regressions controlling for age, sex, race, and BMI tested whether stressor-evoked IL-6 responses were associated with resting CRP and whether this association differed by sex. Results indicated that sex and stressor-evoked IL-6 responses interacted to predict CRP (ΔR² = 0.08, B = −1.33, β = −0.39, p = 0.02). In males, larger stressor-evoked IL-6 responses associated with higher CRP, whereas in females, stressor-evoked IL-6 responses showed a non-significant negative association with CRP. These findings indicate that inflammatory responses to acute stressors associate with resting levels of CRP; however, this association differs by sex. Previous literature suggests that there are sex differences in stressor-evoked IL-6 responses, but this is the first study to show sex differences in the relationship between acute inflammatory responses and systemic inflammation. The contribution of these sex differences to inflammatory disease risk warrants further investigation.     

Influence of repeated maximal exercise testing on biomarkers and fatigue in sarcoidosis

Fatigue in the immune mediated inflammatory disease sarcoidosis is thought to be associated with impaired exercise tolerance. This prospective study assessed fatigue and recuperative capacity after repeated exercise, and examined whether changing concentrations in biomarkers upon exercise are associated with fatigue.Twenty sarcoidosis patients and 10 healthy volunteers performed maximal cardiopulmonary exercise tests on two successive days. Concentrations of cytokines, stress hormones, ACE and CK were assessed before and after the two exercise tests, and 3 days thereafter. All participants completed a sleep diary.Severely fatigued patients showed significant lower VO₂ max (p = 0.038, p = 0.022) and maximal workload (p = 0.034, p = 0.028) on both exercise tests compared to healthy controls. No impairment of maximal exercise testing was demonstrated during the second cycling test in any group. Fatigue was not correlated with changes in concentrations of biomarkers upon exercise. Severely fatigued patients rated both tests as significantly more fatiguing, and reported significant lower mean subjective night sleeping time during the testing period.Fatigue in sarcoidosis patients cannot be objectified by reduction of exercise capacity after repeated maximal exercise testing, and is not correlated with significant changes in biomarkers. Severe fatigue is only and consistently featured by patient reported outcomes.