Plasma legumain in familial hypercholesterolemia: associations with statin use and cardiovascular risk markers.

Legumain is known to be regulated in atherosclerotic disease and may have both pro- and anti-atherogenic properties. The study aimed to explore legumain in individuals with familial hypercholesterolemia (FH), a population with increased cardiovascular risk. Plasma legumain was measured in 251 subjects with mostly genetically verified FH, of which 166 were adults (≥18 years) and 85 were children and young adults (<18 years) and compared to 96 normolipidemic healthy controls. Plasma legumain was significantly increased in the total FH population compared to controls (median 4.9 versus 3.3 pg/mL, respectively, p < 0.001), whereof adult subjects with FH using statins had higher levels compared to non-statin users (5.7 versus 3.9 pg/mL, respectively, p < 0.001). Children and young adults with FH (p = 0.67) did not have plasma legumain different from controls at the same age. Further, in FH subjects, legumain showed a positive association with apoB, and markers of inflammation and platelet activation (i.e. fibrinogen, NAP2 and RANTES). In the current study, we show that legumain is increased in adult subjects with FH using statins, whereas there was no difference in legumain among children and young adults with FH compared to controls. Legumain was further associated with cardiovascular risk markers in the FH population. However the role of legumain in regulation of cardiovascular risk in these individuals is still to be determined.

Physical Exercise and Serum BDNF Levels: Accounting for the Val66Met Polymorphism in Older Adults.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) expression, which can be measured in blood serum, has been found to increase with aerobic exercise. The link between BDNF level, physical exercise, and genetic status (Val66Met polymorphism) has not been well researched in older adults. OBJECTIVE: To investigate the possible link between BDNF expression, acute aerobic exercise, and the Val66Met polymorphism in older adults. METHOD: Twenty-three healthy older adults participated in one session of acute aerobic exercise. Their serum BDNF levels were measured both at baseline and post exercise. Saliva samples were collected to identify each individual's genetic status. RESULTS: At baseline, the individuals' mean serum BDNF level was 16.03 ng/mL (Val66Val = 15.89 ng/mL; Val66Met = 16.34 ng/mL); post exercise, the individuals' mean serum BDNF level was 16.81 ng/mL (Val66Val = 16.14 ng/mL; Val66Met = 18.34 ng/mL). CONCLUSION: One session of acute aerobic exercise significantly increased the individuals' mean serum BDNF level. Males had higher BDNF levels than females. There was a significant interaction between gender and BDNF expression post exercise and a significant between-group effect of gender. The Val66Met carriers had a more positive response to the acute aerobic exercise compared with the Val66Val carriers, although without a significant difference between the two groups.

No effect of omega-3 polyunsaturated fatty acid supplementation on inflammatory markers in familial hypercholesterolemia: a randomized crossover trial.

Individuals with familial hypercholesterolemia (FH) have increased cardiovascular risk despite lipid-lowering therapy, and additional therapy is warranted. Omega-3 polyunsaturated fatty acid (n-3 PUFA) supplements have demonstrated an effect on cardiovascular endpoints in some clinical trials. Platelet-modifying and anti-inflammatory properties are among the proposed beneficial effects of n-3 PUFA. We investigated the effect of a high-dose n-3 PUFA supplement on platelet function and inflammatory markers in FH subjects. We performed a randomized, double-blind trial with a crossover design. Inclusion criteria were genetically verified heterozygous FH, stable disease, statin treatment >12 months, and age 18-75 years. Trial participants were allocated to two treatment periods in random order. The treatment periods (three months each) were separated by a three-month washout period. N-3 PUFA (1840 mg eicosapentaenoic acid and 1520 mg docosahexaenoic acid) and placebo (olive oil) were administered in four capsules daily. Endpoints were platelet function and inflammatory markers, assessed by platelet function analyzer, soluble markers P-selectin, vascular cell adhesion molecule (VCAM) and intercellular adhesion molecule (ICAM), 27 cytokines, and hematological parameters. Thirty-four heterozygous FH individuals completed the trial. No treatment effect (p = 0.93) from n-3 PUFA on the platelet function analyzer was found (2 s, 95% CI [-13, 6]). In our FH population, n-3 PUFA did not influence the levels of P-selectin (-2.0, 95% CI [-5.0, 2.0], p = 0.41), VCAM (0, 95% CI [-14.2, 14.2], p > 0.99), ICAM (-27.0, 95% CI [-70.1, 16.5]; p = 0.21), cytokine levels, or hematological parameters. In statin-treated FH individuals, high dose n-3 PUFA supplement did not affect platelet function and inflammatory markers.Trial registration number: EUDRACTNR 2012-000505-68; ClinicalTrials.gov NCT01813006HighlightsTrial studying the effect of omega-3 fatty acids supplements in familial hypercholesterolemia.High-dose omega-3 fatty acids supplements had no impact on platelet function.Cytokine levels were unchanged after three months of omega-3 fatty acid supplementation.No effect of omega-3 fatty acids on C-reactive protein was observed.

Reduced gut microbial diversity in familial hypercholesterolemia with no effect of omega-3 polyunsaturated fatty acids intervention - a pilot trial.

Individuals with familial hypercholesterolemia (FH) undergo an aggressive treatment with cholesterol-lowering drugs to prevent coronary heart disease. Recent evidence suggests an interplay between the gut microbiota, blood lipid levels and lipid-lowering drugs, but this has yet to be studied in individuals with FH. The objective of the study was to characterize the gut microbiota of individuals with familial hypercholesterolemia and examine if effects of omega-3 polyunsaturated fatty acids (PUFAs) on blood lipids act through modification of the gut microbiome. The gut microbiota composition of individuals with FH (N = 21) and healthy controls (N = 144) was analyzed by extracting DNA from stool samples and sequencing of the V3-V4 region of the 16S rRNA gene. A subgroup (n = 15) of the participants received omega-3 polyunsaturated fatty acids (PUFAs) supplementation or placebo in a crossover manner, and the effect of PUFAs on the gut microbiota was also investigated. Individuals with FH had a different gut microbiota composition compared to healthy controls, characterized by reduced richness (p = .001) and reduction of several genera belonging to Clostridia and Coriobacteriia. Patients using ezetimibe in addition to statins appeared to have lower richness compared to those only using statins (p = .01). Intervention with omega-3 PUFAs had negligible impact on the microbiota composition. Positive effects on blood lipids after intervention with omega-3 PUFA were not associated with baseline gut microbiota composition or gut microbial changes during treatment. Further, patients with FH have an altered gut microbiota compared to healthy controls, possibly driven by the use of ezetimibe.

ICU nurses´ lived experience of caring for adult patients with a tracheostomy in ICU: a phenomenological-hermeneutic study.

BACKGROUND: The care of adult patients with a tracheostomy in intensive care unit is complex, challenging and requires skilled intensive care unit nurses. ICU nurses' live experience is scarcely known. This study aimed to describe the lived experience of intensive care unit nurses of caring for adult patients with a tracheostomy in intensive care unit. METHODS: This study employs a qualitative design. In-depth interviews were conducted with a purposive sampling of 6 intensive care unit nurses from a medical-surgical ICU of a university hospital in Norway who were interviewed. Data was analyzed and interpreted using a phenomenological-hermeneutic approach. This study was reported according to the Consolidated Criteria for Reporting Qualitative Research (COREQ). RESULTS: The interpretation yielded the following themes and subthemes: 1) theme: 'challenges of caring for patients with a tracheostomy' consisted of the sub-themes: 'difficult to communicate/interpret and understand the patient's different forms of expression', 'complicated professional assessments', 'caring with patience', and 'collaborating with patient regarding challenges. 2) theme: 'the satisfaction from providing care to patients with a tracheostomy' consisted of the sub-themes: 'working with intensive care patients is instructive' and 'importance to motivate'. CONCLUSIONS: ICU nurses experienced ambivalent feelings while caring for adult patients with a tracheostomy in ICU. They perceived caring as demanding owing to communication and collaboration at the same time, they experienced satisfaction while they strived to provide proper care and motivation. The identified challenges would lead to further improvement in nurses' experiences and, in turn, the quality-of-care for patients with a tracheostomy. Awareness of these challenges is crucial to understand the need for an effective communication strategy to improve the quality and safety of adult patients with tracheostomy in ICU.

Transmural myocardial infarction with de Winter's sign on ECG. / Transmuralt hjerteinfarkt med de Winters tegn i EKG.

BACKGROUND: De Winter's sign represents a constellation of ECG changes including upward sloping ST depressions greater than 1 mm at the J-point, which end in tall, symmetrical T waves in the precordial leads and reciprocal ST elevation in aVR. The pattern is considered specific for acute occlusion of the LAD. CASE PRESENTATION: A previously healthy man in his forties was referred from urgent care with suspected non-ST-elevation myocardial infarction (NSTEMI) which presented with acute chest pain, ECG with ST depressions and positive troponin-T. Repeat ECG at the local hospital showed further changes, leading to echocardiogram which revealed pronounced cardiac hypokinesia both in the septum and apex. The patient was transferred to the closest interventional cardiology centre and underwent successful PCI. ECG findings were later interpreted as consistent with de Winter's sign. INTERPRETATION: This case illustrates the importance of recognising other ECG changes in addition to ST elevation as indicative of acute reperfusion therapy.

Physical exercise as an add-on treatment to cognitive behavioural therapy for anxiety: a systematic review.

BACKGROUND: Cognitive behavioural therapy (CBT) is currently the treatment of choice for most anxiety disorders. Yet, with recovery rates of approximately 50%, many patients fail to achieve complete remission. This has led to increased efforts to enhance treatment efficacy. Physical exercise (PE) has in recent years been advocated as means to augment the effects of CBT for anxiety disorders. PE appears to reduce anxiety through other mechanisms than CBT, some of which might also have the potential to augment the effects of psychological treatment. AIMS: The current review aimed to summarize and discuss the current research status on CBT augmented with PE for anxiety. METHOD: A systematic literature search was conducted in the databases PsychInfo, Medline and Web of Science to evaluate the potential augmentative effect of combining PE with CBT for anxiety disorders. These effects were intended to be evaluated in a meta-analysis, but findings from the few and diverse studies were better summarized in a systematic review. RESULTS: Eight articles were included in this review, of which two had no control group, while six had from two to four experimental arms. Six of the studies concluded in favour of benefits of add-on PE, while two studies found no added benefits of the combined interventions. CONCLUSIONS: The combination of PE and CBT appears feasible. Add-on PE seems to be more beneficial for clinical populations, when administered regularly several times per week, across several weeks. Future studies should investigate further how and for whom to best combine PE and CBT.

Anti-inflammatory effects of non-statin low-density lipoprotein cholesterol-lowering drugs: an unused potential?

Objectives. Inflammatory responses are closely knit with low-density lipoprotein (LDL)-cholesterol in driving atherosclerosis. Even if LDL-cholesterol is causative to atherosclerotic diseases and LDL-cholesterol lowering reduces hard clinical endpoints, there is a residual risk for clinical events, possibly driven by inflammatory processes, in accordance with its role in autoimmune diseases. Design. As LDL-cholesterol treatment targets are reduced, the use of non-statin lipid-lowering drugs will probably increase. Atherosclerotic plaques evolve through lipid infiltration and modification in the intima, furthermore infiltration of cells including monocytes, macrophages, T-lymphocytes and neutrophils initiating inflammatory signaling. Here we briefly review inflammation in atherosclerosis and the effects of the non-statin lipid-lowering drugs on inflammation. The review is limited to the most common non-statin lipid lowering drugs, i.e. proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors, bile acid sequestrants (BAS) and cholesterol absorption inhibitors. Results. PCSK9 inhibition is mostly studied together with statins and is associated with a reduction of pro-inflammatory cytokines. Furthermore, PCSK9 inhibitors seem to have an effect on monocyte migration trough CCR2. They also have an interaction with sirtuins, possibly offering a therapeutic target. BAS have several interesting effects on inflammation, including reduction of pro-inflammatory cytokines and a reduction of the number of infiltrating macrophages, however there are relatively few reports considering that these drugs have been on the market for decades. Ezetimibe also has effects on inflammation including reduction of pro-inflammatory cytokines and adhesion molecules, however these effects are usually accomplished in tandem with statins. Conclusion. This topic adds an interesting piece to the puzzle of atherosclerosis, indicating that PCSK9 inhibition, BAS and ezetimibe all affect thromboinflammation.

Comparison of cytokine changes in three different lipoprotein apheresis systems in an ex vivo whole blood model.

INTRODUCTION: Even if proprotein convertase subtilisin/kexin type 9 inhibitors have replaced lipoprotein apheresis in many patients, lipoprotein apheresis still is an important option in homozygous familial hypercholesterolemia, progressive atherosclerosis or when removal of lipoprotein(a) is indicated. Additional possible favorable effects beyond lipid lowering could include changes in the concentration of cytokines and improvement of hemorheology. METHODS: We evaluated how whole blood adsorption, dextran sulfate plasma adsorption, and double filtration plasmapheresis lipoprotein apheresis systems affected cytokine concentrations, using a human whole blood ex vivo model differentiating the effect of the lipoprotein apheresis and plasma separation columns and describing temporal changes. RESULTS: Compared to the control bag, the whole blood adsorption system reduced Interferon-γ (IFN-γ), IL-8, IL-1ra, eotaxin, tumor necrosis factor (TNF), monocyte chemoattractant protein 1 (MCP-1), platelet derived growth factor (PDGF)-BB, regulated on activation T cell expressed and secreted (RANTES), macrophage inflammatory protein-1ß (MIP-1ß), and IP-10 (P < .05). The dextran sulfate plasma adsorption system reduced IFN-γ, IL-8, IL-1ra, eotaxin, TNF, MCP-1, PDGF-BB, MIP-1ß, and IP-10 (P < .05). Vascular endothelial growth factor (VEGF) and granulocyte macrophage colony stimulating factor (GM-CSF) were increased in the whole blood and dextran sulfate plasma adsorption systems (P < .05). The double filtration plasmapheresis system reduced IFN-γ, IL-1ra, TNF, MIP-1ß, and IP-10 (P < .05), while MCP-1,VEGF, GM-CSF, and RANTES were increased (P < .05). The plasma separation column increased concentration of RANTES, and was a barrier to reduction of eotaxin. Temporal patterns of concentration change indicated first pass increase of PDGF-BB and first pass reduction of IP-10. CONCLUSION: There were marked differences in how the three systems affected total and temporal cytokine concentration changes in this in vitro model, as well as compared to former in vivo studies.

Risk of Ischemic Stroke and Total Cerebrovascular Disease in Familial Hypercholesterolemia: A Register Study From Norway.

Background and Purpose- Familial hypercholesterolemia (FH) is a common autosomal dominant disease leading to increased level of serum LDL (low-density lipoprotein) cholesterol and risk of coronary heart disease. Whether FH increases the risk of cerebrovascular disease, including ischemic stroke, is debated. Accordingly, we studied the incidence of cerebrovascular disease in a cohort of people with genetically verified FH compared with the entire Norwegian population and examined whether people in this cohort with previous cohort had increased risk of cerebrovascular disease. Methods- Incidence rates of hospitalization for cerebrovascular disease (among 3144 people with FH) and ischemic stroke (among 3166 people with FH) were estimated by linkage of FH people to Cardiovascular Disease in Norway-a nationwide database of cardiovascular disease hospitalizations (2001-2009). We calculated standardized incidence ratios and used Cox regression to estimate hazard ratios. Results- A total of 46 cases (19 women and 27 men) of cerebrovascular disease were observed in the cohort of people with FH, with no increased risk of cerebrovascular disease compared with the general population (standardized incidence ratio, 1.0; 95% CI, 0.8-1.4). Total number of ischemic strokes in the cohort of people with FH was 26 (9 women and 17 men), with no increased risk compared with the general population (standardized incidence ratio, 1.0; 95% CI, 0.7-1.5). Prior coronary heart disease significantly increased cerebrovascular disease risk in women (hazard ratio, 3.29; 95% CI, 1.20-9.00) but not in men (hazard ratio, 1.03; 95% CI, 0.45-2.37; Pinteraction=0.04). Conclusions- In a large cohort of genetically verified FH, risks of cerebrovascular disease and ischemic stroke were not increased compared with the total Norwegian population.

Lipoprotein apheresis affects lipoprotein particle subclasses more efficiently compared to the PCSK9 inhibitor evolocumab, a pilot study.

Lipoprotein apheresis and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are last therapeutic resorts in patients with familial hypercholesterolemia (FH). We explored changes in lipoprotein subclasses and high-density lipoprotein (HDL) function when changing treatment from lipoprotein apheresis to PCSK9 inhibition. We measured the levels of low-density lipoprotein (LDL) and HDL particle subclasses, serum amyloid A1 (SAA1), paraoxonase-1 (PON1) activity and cholesterol efflux capacity (CEC) in three heterozygous FH patients. Concentrations of all LDL particle subclasses were reduced during apheresis (large 68.0 ±â€¯17.5 to 16.3 ±â€¯2.1 mg/dL, (p = 0.03), intermediate 38.3 ±â€¯0.6 to 5.0 ±â€¯3.5 mg/dL (p = 0.004) and small 5.0 ±â€¯2.6 to 0.2 ±â€¯0.1 mg/dL (p = 0.08)). There were non-significant reductions in the LDL subclasses during evolocumab treatment. There were non-significant reductions in subclasses of HDL particles during apheresis, and no changes during evolocumab treatment. CEC was unchanged throughout the study, while the SAA1/PON1 ratio was unchanged during apheresis but decreased during evolocumab treatment. In conclusion, there were significant reductions in large and intermediate size LDL particles during apheresis, and a non-significant reduction in small LDL particles. There were only non-significant reductions in the LDL subclasses during evolocumab treatment.

Bariatric surgery reduces fasting total fatty acids and increases n-3 polyunsaturated fatty acids in morbidly obese individuals.

BACKGROUND: Obesity is a global pandemic leading to increased mortality and increased risk of cardiovascular disease. Bariatric surgery is an established treatment of obesity leading to weight loss and reduction of mortality. To further elucidate how bariatric surgery improves metabolic control, we explored the fatty acid (FA) profiles in morbidly obese subjects treated with lifestyle intervention and subsequent bariatric surgery. METHODS: The intervention group consisted of 34 morbidly obese patients scheduled for bariatric surgery and the control group of 17 non-obese patients scheduled for elective laparoscopic procedures. The intervention group had to undergo lifestyle changes preoperatively. Fasting blood samples were drawn at admission, after lifestyle intervention and 1 year after bariatric surgery. RESULTS: At admission, the morbidly obese patients had significantly higher levels of monounsaturated FAs (MUFAs) and lower levels of n-6 polyunsaturated FAs (PUFAs) and n-3 PUFAs than healthy controls (all p-values <.05). In the intervention group, there was a significantly lower level of total FAs after lifestyle intervention, and from admission to 1 year after surgical intervention (both, p < .05), primarily reflecting a lower proportion of saturated FAs (SFAs). Following bariatric surgery, but not after lifestyle changes, there was an increase in the proportion of n-3 PUFA (p < .05) reaching levels not significantly different from healthy controls. CONCLUSIONS: Our findings suggest that a reduced proportion of the proposed anti-atherogenic n-3 PUFAs characterizes morbidly obese individuals, and that this FA profile is reversed by bariatric surgery, but not by lifestyle intervention.

A Feasibility study on Combining Internet-Based Cognitive Behaviour Therapy with Physical Exercise as Treatment for Panic Disorder--Treatment Protocol and Preliminary Results.

Internet-based cognitive behaviour therapy (ICBT) is a recommended, cost-effective and efficacious treatment for panic disorder (PD). However, treatment effects in psychiatric settings indicate that a substantial proportion fail to achieve remission. Physical exercise improves symptoms in patients with PD, and acts through mechanisms that can augment the effect of ICBT. The feasibility of combining these two interventions has not previously been investigated, and this was the aim of this study. The intervention comprised guided ICBT combined with one weekly session of supervised and two weekly sessions of unsupervised physical exercise for a total of 12 weeks. Treatment rationale, procedures and protocols are presented together with preliminary results for four patients with PD who have currently finished treatment. Quantitative and qualitative results are reported on the feasibility of adhering to the treatments, treatment outcome as assessed by clinician rating and estimation of reliable and clinically significant change for outcome measures, and participants' satisfactions with the combined treatment. The preliminary results indicate that the combined treatment is feasible to complete, and that the combination is perceived by the participants as beneficial.

Comparing physical exercise in groups to group cognitive behaviour therapy for the treatment of panic disorder in a randomized controlled trial.

BACKGROUND: Previous studies have suggested that physical exercise can reduce symptoms for subjects suffering from panic disorder (PD). The efficacy of this intervention has so far not been compared to an established psychotherapy, such as cognitive behaviour therapy (CBT). Assessment of controlled long-term effects and the clinical significance of the treatment are also lacking. AIM: To compare physical exercise to CBT as treatment for PD, and assess controlled long-term and clinically significant effects. METHOD: PD-patients were randomized to either three weekly sessions of physical exercise (n = 17), or one weekly session of CBT (n = 19). Both treatments ran for 12 weeks, were manualized and administered in groups. Patients were assessed twice before the start of treatment, at post-treatment and at 6 and 12 months thereafter. Primary outcome-measures consisted of the Mobility Inventory (MI), the Agoraphobia Cognitions Questionnaire (ACQ) and the Body Sensations Questionnaire (BSQ). RESULTS: A two-way repeated measures MANOVA of these measures demonstrated a significant effect of time, F(16, 544) = 7.28, p < .01, as well as a significant interaction effect, F(16, 544) = 1.71, p < .05, in favour of CBT. This finding was supported by the assessment of clinically significant changes of avoidant behaviour and of treatment-seeking one year later. CONCLUSION: Group CBT is more effective than group physical exercise as treatment of panic disorder, both immediately following treatment and at follow-up assessments.

Registered nurses' experience of care for adult patients with a temporary tracheostomy at general hospital wards. A phenomenological-hermeneutic explorative study.

BACKGROUND: Caring for adult patients with a temporary tracheostomy in general wards can be challenging and complex. Little research has explored registered nurses' experiences with caring for these groups of patients. OBJECTIVES: This study sought to interpret and describe registered nurses' lived experiences of caring for adult patients with a tracheostomy in general wards. RESEARCH DESIGN/METHODOLOGY: Six registered nurses were interviewed in this study. The interviews were analysed to gain comprehensive knowledge about caring for adult patients with a temporary tracheostomy. The interviews were transcribed, analysed, and interpreted by using Gadamers philosophical hermeneutics and Kvale and Brinkmann's three steps of understanding. SETTING: Three different wards medical, surgical, and neurological of a teaching hospital in Norway. FINDINGS: Three themes emerged from data analysis. These included experiencing clinically challenging patients, a lack of clinical support from the intensive care nurses, and a lack of professional confidence. CONCLUSION: This study highlighted the challenges surrounding the care of an adult patient with a tracheostomy in the general wards. Identifying these challenges would lead to further improvement in registered nurses' experiences and, in turn, in the quality of competent care for adult patients with a tracheostomy in the general ward. IMPLICATIONS FOR CLINICAL PRACTICE: Understanding the registered nurses' experiences will assist the head nurses in planning and providing relevant information and education to provide safe and holistic patient care. Adequate support from intensive care unit nurses and professional development are required to ensure high-quality care. This study recommends that healthcare managers focus on establishing step-down units to improve patient outcomes, especially for high-risk patients and to increase the competencies of registered nurses in caring for adult patients with a tracheostomy as a whole person.

Three different LDL apheresis columns efficiently and equally reduce lipoprotein(a) concentrations in patients with familial hypercholesterolemia and small apolipoprotein(a) particles.

INTRODUCTION: High levels of lipoprotein(a) [Lp(a)] and apolipoprotein(a) [apo(a)] are associated with cardiovascular disease. In this study we determined apo(a) particle size and compared the Lp(a) reducing efficacy of three different LDL apheresis columns; DL-75, LA-15 and EC-50W in patients with familial hypercholesterolemia (FH). RESULTS: Average Lp(a) concentration was reduced by 70%, 74% and 75% (all p<0.0001) for DL-75, LA-15 and EC-50W, respectively. No significant changes in the relative proportion of the isoforms of 14 and 32K 4 domains were observed after apheresis. CONCLUSION: Three different LDL apheresis columns reduced Lp(a) efficiently with preserved ratio between apo(a) isoforms.

[Physical activity has an acute effect on depression and anxiety syndromes]. / Fysisk aktivitet kan ha omedelbar effekt på depression och ångest.

Physical activity has a preventive and an acute effect on both depression and anxiety syndromes. The effect of just physical activity, usually 3 times/week for 8-12 weeks, is equal to treatment with psychotherapy or antidepressants for mild to moderate depression, according to several meta-analyses. Addition of physical exercise to psychotherapy has a significantly greater effect than psychotherapy alone. Few high-quality studies on anxiety syndromes have been performed regarding the treatment effect of physical activity. In anxiety syndromes, physical activity for 10-12 weeks has a better effect than no treatment. Yet, psychotherapy or pharmacological treatment has a better effect than physical exercise in panic disorder. The article describes a variety of positive physiological, neurobiological and psychological mechanisms of physical activity.

Self-Reported Measures Have a Stronger Association With Dizziness-Related Handicap Compared With Physical Tests in Persons With Persistent Dizziness.

Background: Associations between dizziness-related handicap and a variety of self-reported measures have been reported. However, research regarding associations between dizziness-related handicap and aspects of functioning that includes both physical tests and self-reported measures is scarce. Objective: The purpose of the study was to describe the variations in signs and symptoms in people with persistent dizziness using physical tests and self-reported outcomes across three severity levels of the Dizziness Handicap Inventory (DHI) and investigate their associations with the DHI. Method: Participants with persistent dizziness (n = 107) were included in this cross-sectional study. The participants underwent (1) physical tests (gait tests, grip strength, body flexibility, and movement-induced dizziness) and completed questionnaires regarding (2) psychological measures (Mobility Inventory of Agoraphobia, Body Sensation Questionnaire, Agoraphobic Cognitions Questionnaire, and Hospital Depression and Anxiety Questionnaire), and (3) fatigue, dizziness severity, and quality of life (Chalders Fatigue Scale, Vertigo Symptom Scale-Short Form, and EQ visual analog scale), in addition to the DHI. Data were presented by descriptive statistics for three DHI severity levels (mild, moderate, and severe). A multiple linear backward regression analysis was conducted for each group of measures in relation to the DHI total score, with additional analyses adjusting for age and sex. Based on these results, significant associations were tested in a final regression model. Results: With increasing severity levels of DHI, the participants demonstrated worse performance on most of the physical tests (preferred and fast gait velocity, dizziness intensity after head movements), presented with worse scores on the self-reported measures (avoidance behavior, fear of bodily sensation, fear of fear itself, psychological distress, fatigue, dizziness severity, quality of life). After adjusting for age and sex, significant associations were found between total DHI and avoidance behavior, psychological distress, dizziness severity, and quality of life, but not with any of the physical tests, explaining almost 56% of the variance of the DHI total score. Conclusion: There was a trend toward worse scores on physical tests and self-reported measurements with increasing DHI severity level. The DHI seems to be a valuable tool in relation to several self-reported outcomes; however, several signs and symptoms may not be detected by the DHI, and thus, a combination of outcomes should be utilized when examining patients with persistent dizziness.

Effect of N-3 Polyunsaturated Fatty Acids on Lipid Composition in Familial Hypercholesterolemia: A Randomized Crossover Trial.

Individuals with familial hypercholesterolemia (FH) have an increased risk of cardiovascular disease. Treatment is mainly low-density lipoprotein cholesterol (LDL-C) reduction. How omega-3 polyunsaturated fatty acids (n-3 PUFAs) supplements affect lipoproteins in FH subjects is unknown. We hypothesized that a high-dose n-3 PUFA supplement would reduce atherogenic lipoproteins and influence the high-density lipoprotein cholesterol (HDL-C) function. We performed a randomized, double-blinded crossover study with 34 genetically verified FH individuals (18−75 years, clinically stable, statin treatment > 12 months). Treatment was 4 g n-3 PUFAs (1840 mg eicosapentaenoic acid and 1520 mg docosahexaenoic acid daily) or four capsules of olive oil for three months in a crossover design with a washout period of three months. The defined outcomes were changes in triglycerides, lipoproteins, lipoprotein subfractions, apolipoproteins, and HDL-C function. After treatment with n-3 PUFAs, total cholesterol, LDL-C, and triglycerides were reduced compared to placebo (p ≤ 0.01 for all). Total HDL-C levels were unchanged, but the subfraction of large HDL-C was higher (p ≤ 0.0001) after n-3 PUFAs than after placebo, and intermediate HDL-C and small HDL-C were reduced after n-3 PUFAs compared to placebo (p = 0.02 and p ≤ 0.001, respectively). No changes were found in apolipoproteins and HDL-C function. N-3 PUFAs supplements reduced atherogenic lipoproteins in FH subjects, leaving HDL-C function unaffected.

The risk of various types of cardiovascular diseases in mutation positive familial hypercholesterolemia; a review.

Familial hypercholesterolemia (FH) is a common, inherited disease characterized by high levels of low-density lipoprotein Cholesterol (LDL-C) from birth. Any diseases associated with increased LDL-C levels including atherosclerotic cardiovascular diseases (ASCVDs) would be expected to be overrepresented among FH patients. There are several clinical scoring systems aiming to diagnose FH, however; most individuals who meet the clinical criteria for a FH diagnosis do not have a mutation causing FH. In this review, we aim to summarize the literature on the risk for the various forms of ASCVD in subjects with a proven FH-mutation (FH+). We searched for studies on FH+ and cardiovascular diseases and also included our and other groups published papers on FH + on a wide range of cardiovascular and other diseases of the heart and vessels. FH + patients are at a markedly increased risk of a broad range of ASCVD. Acute myocardial infarction (AMI) is the most common in absolute numbers, but also aortic valve stenosis is by far associated with the highest excess risk. Per thousand patients, we observed 3.6 incident AMI per year compared to 1.9 incident aortic valve stenosis, however, standardized incidence ratio (SIR) for incident AMI was 2.3 compared to 7.9 for incident aortic valve stenosis. Further, occurrence of ischemic stroke seems not to be associated with increased risk in FH+. Clinicians should be aware of the excess risk of almost all kind of ASCVD in FH+, and the neutral risk of stroke need to be studied further in FH + patients.