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OBJECTIVES: Neuropeptide Y is associated with stress in animal and human laboratory studies. However, data from clinical studies are scarce and no clinical longitudinal studies have been published. The aim of this clinical study was to assess the possible association between changes in the levels of pain, depression, and stress measures, on the one hand, and plasma neuropeptide Y levels, on the other.

METHODS: Forty-four women with the fibromyalgia syndrome were exposed to a Cognitive Behavioral Therapy intervention. Levels of the plasma neuropeptide Y as well as pain, depression, and stress measures were obtained at the start and at the end of the intervention, and after a further six month follow-up. Based on these data, a before-and-after analysis was performed.

RESULTS: Almost all measures of pain, depression, and stress improved during the study; specifically, variables measuring life control (coping), depression, and stress-related time urgency improved significantly. Moreover, during the same time period, the mean plasma neuropeptide Y level was reduced from 93.2 ± 38.8 fmol/mL before the Cognitive Behavioral Therapy to 75.6 ± 42.9 fmol/mL (p<0.001) at the end of the study.

CONCLUSIONS: After exposure to a Cognitive Behavioral Therapy intervention, levels of most of the pain, depression, and stress measures improved, half of them significantly, as did the levels of neuropeptide Y. This circumstance indicates a possible functional relationship between pain-depression-stress and neuropeptide Y.

Background: The U-CARE Heart trial was one of the first randomized controlled trials to evaluate the effect of internet-based cognitive behavioral therapy on self-reported symptoms of anxiety or depression for patients with a recent myocardial infarction. While the effects of internet-based cognitive behavioral therapy on Hospital Anxiety and Depression Scale (HADS) scores at 14 weeks postbaseline were not significant, in this study, we investigated possible long-term effects of treatment.

Objective: The aim of this study was to evaluate the long-term effectiveness of internet-based cognitive behavioral therapy on self-reported symptoms of anxiety and depression in patients 12 months after a myocardial infarction and to explore subsequent occurrences of cardiovascular disease events.

Methods: Shortly after acute myocardial infarction, 239 patients (33% female, mean age 59.6 years) reporting mild-to-moderate symptoms of anxiety or depression were randomized to 14 weeks of therapist-guided internet-based cognitive behavioral therapy (n=117) or treatment as usual (n=122). Data from national registries were used to explore group differences in clinical outcomes such as cardiovascular disease and cardiovascular-related mortality for a follow-up period of up to 5 years: group differences in HADS total score 1 year post-myocardial infarction, the primary outcome, was analyzed using multiple linear regression. Secondary outcomes, such as HADS anxiety and depression subscales and the Cardiac Anxiety Questionnaire total score (CAQ), which measures heart-focused anxiety, were analyzed in the same way. Multiple imputation was used to account for missing data, and a pooled treatment effect was estimated. Adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs) for data pertaining to registry outcomes.

Results: Both groups reported lower HADS total scores 1 year after myocardial infarction than those at baseline. HADS total scores were not significantly different between the treatment and control groups 1 year after myocardial infarction (beta=-1.14, 95% CI -2.73 to 0.45, P=.16). CAQ was the only measure improved significantly by internet-based cognitive behavioral therapy when compared with treatment as usual ( beta=-2.58, 95% CI -4.75 to -0.42, P=.02) before adjusting for multiple comparisons. The composite outcome of nonfatal cardiovascular events and cardiovascular-related mortality did not differ between groups but was numerically higher in the internet-based cognitive behavioral therapy group, who were at slightly greater risk (HR 1.8, 95% CI 0.96 to 3.4, P=.07). Adjusting for previous myocardial infarction and diabetes attenuated this estimate (HR 1.5, 95% CI 0.8 to 2.8, P=.25).

Conclusions: Internet-based cognitive behavioral therapy was not superior in reducing self-reported symptoms of depression or anxiety compared to treatment as usual at the 1-year follow-up after myocardial infarction. A reduction in cardiac-related anxiety was observed but was not significant after adjusting for multiple comparisons. There was no difference in risk of cardiovascular events between the treatment groups. Low treatment adherence, which might have affected treatment engagement and outcomes, should be considered when interpreting these results.

BACKGROUND: The Heart School is a standard component of cardiac rehabilitation after myocardial infarction in Sweden. The group-based educational intervention aims to improve modifiable risks, in turn reducing subsequent morbidity and mortality. However, an evaluation with respect to mortality is lacking.

AIMS: Using linked population registries, we estimated the association of attending Heart School with both all-cause and cardiovascular mortality, two and five years after admission for first-time myocardial infarction.

METHODS: Patients with first-time myocardial infarction (<75 years) were identified as consecutively registered in the nationwide heart registry, SWEDEHEART (2006-2015), with >99% complete follow-up in the Causes of Death registry for outcome events. Of 192,059 myocardial infarction admissions, 47,907 unique patients with first-time myocardial infarction surviving to the first cardiac rehabilitation visit constituted the study population. The exposure was attending Heart School at the first cardiac rehabilitation visit 6-10 weeks post-myocardial infarction. Data on socioeconomic status was acquired from Statistics Sweden. After multiple imputation, propensity score matching was performed. The association of exposure with mortality was estimated with Cox regression and survival curves.

RESULTS: After matching, attending Heart School was associated (hazard ratio (95% confidence interval)) with a markedly lower risk of both all-cause (two-year hazard ratio = 0.53 (0.44-0.64); five-year hazard ratio = 0.62 (0.55-0.69)) and cardiovascular (0.50 (0.38-0.65); 0.57 (0.47-0.69)) mortality. The results were robust in several sensitivity analyses.

CONCLUSIONS: Attending Heart School during cardiac rehabilitation is associated with almost halved all-cause and cardiovascular mortality after first-time myocardial infarction. The result warrants further investigation through adequately powered randomised trials.

Background and aims: Substance P (CSF-SP) is known to be elevated in females with fibromyalgia syndrome (FMS). The aims of this study were to evaluate the effect of cognitive behaviour therapy (CBT) on plasma SP levels in women with FMS and to find possible clinical behavioural correlates to plasma SP level changes. Methods: Forty-eight women with FMS were randomly allocated into two groups. Group 1 received the CBT treatment intervention over the course of 6 months while group 2 was waitlisted. CBT was given with a protocol developed to diminish stress and pain. After 6 months, group 2 was given the same CBT treatment as well. All were followed up 1 year after the start of CBT treatment. This approach allowed for two analytical designs a randomised controlled trial (RCT) (n=24 vs. n=24) and a before-and-after treatment design (n=48). All women were repeatedly evaluated by the West Haven-Yale Multidimensional Pain Inventory (MPI) and three other psychometric questionnaires and plasma SP was analysed. Results: In the RCT design, the plasma SP level was 8.79 fmol/mL in both groups at the start of the trial, after adjustment for initial differences. At the end of the RCT, the plasma SP level was 5.25 fmol/mL in the CBT intervention group compared to 8.39 fmol/mL in the control group (p=0.02). In the before-and-after design, the plasma SP was reduced by 33% (p <0.01) after CBT, but returned to the pre-treatment level at follow-up 1 year after the start of CBT treatment. Plasma SP was associated with the MPI dimensions experienced "support from spouses or significant others" and "life control". Conclusions: Plasma SP might be a marker of the effect of CBT in FMS associated with better coping strategies and reduced stress rather than a biochemical marker of pain.

Background: Symptoms of depression and anxiety are common after a myocardial infarction (MI). Internet-based cognitivebehavioral therapy (iCBT) has shown good results in other patient groups.

Objective: The aim of this study was to evaluate the effectiveness of an iCBT treatment to reduce self-reported symptoms ofdepression and anxiety among patients with a recent MI.

Methods: In total, 3928 patients were screened for eligibility in 25 Swedish hospitals. Of these, 239 patients (33.5%, 80/239women, mean age 60 years) with a recent MI and symptoms of depression or anxiety were randomly allocated to a therapist-guided,14-week iCBT treatment (n=117), or treatment as usual (TAU; n=122). The iCBT treatment was designed for post-MI patients.The primary outcome was the total score of the Hospital Anxiety and Depression Scale (HADS) 14 weeks post baseline, assessedover the internet. Treatment effect was evaluated according to the intention-to-treat principle, with multiple imputations. For themain analysis, a pooled treatment effect was estimated, controlling for age, sex, and baseline HADS.

Results: There was a reduction in HADS scores over time in the total study sample (mean delta=−5.1, P<.001) but no differencebetween the study groups at follow-up (beta=−0.47, 95% CI −1.95 to 1.00, P=.53). Treatment adherence was low. A total of46.2% (54/117) of the iCBT group did not complete the introductory module.

Conclusions: iCBT treatment for an MI population did not result in lower levels of symptoms of depression or anxiety comparedwith TAU. Low treatment adherence might have influenced the result.

Trial Registration: ClinicalTrials.gov NCT01504191; https://clinicaltrials.gov/ct2/show/NCT01504191 (Archived at Webciteat http://www.webcitation.org/6xWWSEQ22)

Background: The Secondary Prevention in Uppsala Primary Healthcare Project (SUPRIM) is a prospective randomized controlled trial of a group-based cognitive behavioral therapy (CBT) stress management program for coronary heart disease (CHD) patients. The intervention reduced the risk of fatal or non-fatal first recurrent cardiovascular (CV) events. The aim of the present study was to analyze if the positive effects of the CBT program on clinical outcomes could have been mediated by changes in biomarkers for inflammation.

Methods: Altogether 362 patients with CHD were randomly assigned to intervention or usual care. The inflammatory biomarkers (VCAM-1, TNF-R1, TNF-R2, PTX3, and hs-CRP) were serially assessed at five time points every six months from study start until 24 months later, and analyzed with linear mixed models.

Results: Baseline levels of the inflammatory markers were near normal, indicating a stable phase. The group-based CBT stress management program did not significantly affect the levels of inflammatory biomarkers in patients with CHD. Three out of five (VCAM-1, TNF-R2, and PTX3) inflammatory biomarkers showed a slight increase over time in both study groups, and all were positively associated with age.

Conclusion: Group-based CBT stress management did not affect biomarkers for inflammation in patients with CHD. It is therefore unlikely that inflammatory processes including these biomarkers were mediating the effect the CBT program had on the reduction in CV events. The close to normal baseline levels of the biomarkers and the lack of elevated psychological distress symptoms indicate a possible floor effect which may have influenced the results.

Keywords: Biomarkers, CBT, CHD, inflammation, stress management