Paula M.C. Mommersteeg

Mindfulness-based stress reduction and physiological activity during acute stress: a randomized controlled trial

OBJECTIVE The aim was to examine the effects of a Mindfulness-Based Stress Reduction (MBSR) intervention on cardiovascular and cortisol activity during acute stress. METHOD Eighty-eight healthy community-dwelling individuals reporting elevated stress levels were randomly assigned to the MBSR protocol or a waitlist control group. Before and after the intervention period they participated in a laboratory stress protocol consisting of mental arithmetic and speech tasks. Laboratory measurements included continuous cardiovascular parameters (heart period, heart rate variability, and systolic and diastolic blood pressure [SBP and DBP]), and salivary cortisol. RESULTS Compared to the control group and controlling for age, sex, body mass index, and beta-blockers, the MBSR group showed larger pre- to postintervention decreases in overall SBP (F(1, 58) = 4.99, p = .029, partial η² = .08) and DBP (F(1, 58) = 11.09, p = .002, partial η² = .16). In addition, the MBSR group exhibited smaller SBP and DBP stress-related changes from pre- to postintervention (F(2, 116) = 4.89, p = .012, partial η² = .08; F(2, 116) = 6.07, p = .007, partial η² = .10, respectively). No effects were obtained on other physiological measures. CONCLUSION MBSR may help reducing blood pressure levels and blood pressure reactivity to stress.

The association between diabetes and an episode of depressive symptoms in the 2002 World Health Survey: an analysis of 231 797 individuals from 47 countries

Depression is common in people with diabetes and increases the risk of poor health outcomes, including premature mortality. We explored the association between diabetes and an episode of depressive symptoms in a cross‐sectional multinational study, which included a large number of low‐ and middle‐income non‐Western countries.

Positive affect dimensions and their association with inflammatory biomarkers in patients with chronic heart failure

BACKGROUND In cardiac patients positive affect has found to be associated with improved clinical outcomes, with reduced inflammation being one of the potential mechanisms responsible. METHODS Positive affect was assessed using The Global Mood Scale (GMS), Positive and Negative Affect Schedule (PANAS), and Hospital Anxiety and Depression Scale (HADS) in patient with chronic heart failure (N=210; 67 ± 9 years, 79% men). Markers of inflammation (TNFα, sTNFr1, sTNFr2, IL-6 and CRP) were measured and averaged at three consecutive time points. RESULTS The positive affect dimensions of the GMS and PANAS were significantly associated with lower averaged levels of sTNFr2, TNFα and IL-6 (p<.1), even after adjustment for clinical and lifestyle confounders. Positive affect of the HADS was significantly associated with lower averaged levels of hsCRP (p<.1), but was no longer significant after correction for lifestyle confounders and depressive symptoms. CONCLUSION Positive affect is associated with reduced inflammation in patients with heart failure.

Higher levels of psychological distress are associated with a higher risk of incident diabetes during 18 year follow-up : Results from the British Household Panel Survey

BackgroundReviews have shown that depression is a risk factor for the development of type 2 diabetes. However, there is limited evidence for general psychological distress to be associated with incident diabetes. The aim of the present study was to test whether persons who report higher levels of psychological distress are at increased risk to develop type 2 diabetes during 18 years follow up, adjusted for confounders.MethodsA prospective analysis using data from 9,514 participants (41 years, SD=14; 44% men) of the British Household Panel Survey. The General Health Questionnaire 12 item version was used to assess general psychological distress, diabetes was measured by means of self-report. Cox proportional hazards regression models were used to calculate the multivariate-adjusted hazard ratio (HR) of incident diabetes during 18 years follow up, comparing participants with low versus high psychological distress at baseline (1991).ResultsA total of 472 participants developed diabetes 18 year follow up. Those with a high level of psychological distress had a 33% higher hazard of developing diabetes (HR=1.33, 95% CI 1.10–1.61), relative to those with a low level of psychological distress, adjusted for age, sex, education level and household income. After further adjustment for differences in level of energy, health status, health problems and activity level, higher psychological distress was no longer associated with incident diabetes (HR=1.10, 95% CI 0.91-1.34).ConclusionsHigher levels of psychological distress are a risk factor for the development of diabetes during an 18 year follow up period. This association may be potentially mediated by low energy level and impaired health status.

Type D personality, depressive symptoms and work-related health outcomes.

Aims: Personality may play a decisive role in perceiving work-related characteristics as stressful, leading to adverse health outcomes. Persons with a Distressed personality (Type D) experience increased negative emotions while inhibiting these emotions in social situations. We investigated the role of Type D personality on adverse health outcomes, sick leave, burnout and disability pension. The mediating role of depressive symptoms on this relation was assessed because Type D represents a vulnerability factor for depression. Methods: In a cross-sectional community sample of the Dutch population (n = 1,172) Type D personality was related to sick-leave (five categories of days per year), burnout, and disability pension, controlling for confounders. Results: Individuals with Type D personality reported more burnout (27% vs 8%), disability pension (32% vs 11%), and had an increased incidence of short-term sick leave (χ2 = 13.1, p = 0.011) as compared to non-Type D’s. Type D was significantly related to burnout (odds ratio (OR) = 4.16) and disability pension (OR = 2.62) independent of confounders. The Sobel test indicated significant mediation of depression on the relation between Type D personality and the work-related health outcomes. After mediation Type D personality remained significantly related to burnout, indicating a unique unshared effect. Conclusions: Type D personality is related to adverse health outcomes in the working population, mediated by depression, which warrants further research for this personality type.

Neutrophil Gelatinase-Associated Lipocalin and depression in patients with chronic heart failure.

Depression adversely affects prognosis in heart failure (HF) patients. Inflammation is indicated as potential biological pathway in this co-morbidity. Since increased levels of the cytokine Neutrophil Gelatinase-Associated Lipocalin (NGAL) are predictive for HF prognosis, and recently indicated in patients with major depression, this study examined the association of serum NGAL levels with symptoms of depression in patients with HF. Serum NGAL levels were measured in 104 patients with HF (left ventricular ejection fraction, LVEF⩽40). Depression, evaluated using the Beck Depression Inventory (BDI; total score, somatic and cognitive component), and the Hamilton Depression Rating scale (HAMD), at baseline and 12months follow-up, was associated with NGAL levels using mixed model analysis. Analyses were adjusted for demographics measures, disease severity indicators, inflammation, comorbidity and medication. Increased serum NGAL levels were significantly associated with depression measured by HAMD (baseline: r=0.25, p<.05) and BDI (baseline: r=0.22, p<.05; 12months: r=0.37, p<.01). This association remained significant after adjustment for covariates; age, sex, time, LVEF, and creatinine (HAMD, t=2.01, p=.047; BDI, t=2.28, p=.024). NGAL was significantly associated with somatic- (p=0.004), but not cognitive depressive symptoms (p=0.32). NGAL levels were associated with the experienced HF-related functional limitations (6min walk test), rather than the severity of cardiac dysfunction (LVEF). This study indicates that depression in patients with chronic HF is associated with elevated NGAL levels, independent of clinical severity of the underlying disease.

Health-related quality of life is related to cytokine levels at 12 months in patients with chronic heart failure.

Chronic heart failure (CHF) is a condition with a high mortality risk. Besides traditional risk factors, poor health-related quality of life (HRQoL) is also associated with poor prognosis in CHF. Immunological functioning might serve as a biological pathway underlying this association, since pro and anti-inflammatory cytokines are independent predictors of prognosis. The aim of this study was to examine the association between HRQoL at inclusion (baseline) and pro and anti-inflammatory cytokine levels both at baseline and 12months, using a prospective study design. CHF outpatients completed the Minnesota Living with Heart Failure Questionnaire (MLHFQ) and the Short Form Health Survey 36 (SF-36). Blood samples were drawn at baseline (n=111) and 12months (n=127) to measure pro (IL-6, TNFalpha, sTNFR1, sTNFR2) and anti- (IL1ra, IL-10) inflammatory markers. Linear regression analysis were run for the MLHFQ, the SF-36 mental component summary (MCS) and the physical component summary (PCS), controlling for age, sex, BMI, smoking, co morbidity, NYHA-class and 6min walk test. Baseline MLHFQ was associated with increased levels of baseline sTNFR2, and 12-month sTNFR1 12month sTNFR2. Baseline MCS and change in MCS were related to increased 12-month sTNFR1 levels. All significant findings relate a worse HRQoL at baseline or a deterioration over time to increased sTNFR1/2 levels. These findings suggest that immune activation may be one of the pathways underlying the relationship between poor HRQoL and mortality and morbidity in CHF patients. Future studies are warranted to replicate these findings in larger samples.

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

BACKGROUND The 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. METHODS HF 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. RESULTS Type 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). CONCLUSIONS Only 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.

Nitric Oxide Dysregulation in Patients With Heart Failure: The Association of Depressive Symptoms With L-Arginine, Asymmetric Dimethylarginine, Symmetric Dimethylarginine, and Isoprostane

Objective Nitric oxide (NO) regulation plays a critical role in cardiovascular diseases including heart failure (HF). Markers of NO dysregulation have been found in individuals with depression without cardiovascular disease. Because depression is associated with poor HF outcomes, the present study tested the hypothesis that depression is associated with a dysregulated NO pathway in patients with HF. Methods Serum levels of NO regulation (L-arginine, asymmetric dimethylarginine [ADMA], and symmetric dimethylarginine [SDMA]) and oxidative stress (isoprostane 8-epi prostaglandin F2&agr;) were measured in 104 patients with HF (mean [standard deviation] age = 65.7 [8.4] years, 28% women) at baseline and 12 months. Depressive symptoms were measured using the Beck Depression Inventory. The associations between depressive symptoms with markers of NO regulation were examined with mixed-model analysis, adjusted for age, sex, time of assessment, left ventricular ejection fraction, creatinine, and hypertension. Results Depressive symptoms were correlated with a lower L-arginine/ADMA ratio (r = −0.22, p = .003) and higher SDMA levels (r = 0.28, p < .001). Associations were similar for somatic depressive symptoms and cognitive-affective symptoms (L-arginine/ADMA ratio: r = −0.20 [p = .009] versus r = −0.19 [p = .013]; ADMA: r = 0.16 [p = .043] versus r = 0.10 [p = .20]; SDMA: r = 0.27 [p < .001] versus r = 0.22 [p = .005], respectively). No associations were found between depressive symptoms and isoprostane. The association between depression and the L-arginine/ADMA ratio remained significant in multivariate adjusted models. Conclusions Depressive symptoms were associated with markers of NO dysregulation, particularly the L-arginine/ADMA ratio and SDMA, in patients with HF. The lower L-arginine/ADMA ratio indicates less available NO, suggesting that NO-related endothelial dysfunction may play a role in the adverse risk of HF progression associated with depression.

Association between brain natriuretic peptide, markers of inflammation and the objective and subjective response to cardiac resynchronization therapy.

INTRODUCTION Studies suggest that cardiac resynchronization therapy (CRT) can induce a decrease in brain natriuretic peptide (BNP) and systemic inflammation, which may be associated with CRT-response. However, the evidence is inconclusive. We examined levels of BNP and inflammatory markers from pre-CRT implantation to 14months follow-up in CRT-responders and nonresponders, defined by two response criteria. METHODS We studied 105 heart failure patients implanted with a CRT-defibrillator (68% men; age=65.4±10.1years). The objective CRT-response was defined as a reduction of ⩾15% in left ventricular end systolic volume; subjective CRT-response was defined as an improvement of ⩾10 points in patient-reported health status assessed with the Kansas City Cardiomyopathy Questionnaire. Plasma BNP and markers of inflammation (CRP, IL-6, TNFα, sTNFr1 and sTNFr2) were measured at three time points. RESULTS Pre-implantation concentrations of TNFα were significantly lower for subjective responders compared to nonresponders (p=.05), but there was no difference in BNP and the other inflammatory markers at baseline. Objective CRT-response was significantly associated with lower BNP levels over time (F=27.31, p<.001), and subjective CRT-response with lower TNFα levels (F=5.67, p=.019). CONCLUSION Objective and subjective response to CRT was associated with lower levels of BNP and TNFα, respectively, but not with other markers of inflammation. This indicates that response to CRT is not automatically related to a stronger overall decrease in inflammation. Large-scale studies are warranted that further examine the relation between the clinical effects of CRT on inflammatory markers, as the latter have been associated with poor prognosis in heart failure.