Osteoprotegerin predicts cardiovascular events in patients treated with haemodialysis.

BACKGROUND: Disturbances in bone mineral metabolism are associated with increased mortality and cardiovascular events (CVEs). However, the association between bone-associated protein biomarkers, mortality and CVEs independent of cytokine activation remains unknown. This study aimed to investigate bone-associated protein biomarkers and the association with inflammatory cytokines and cardiovascular (CV) outcomes. METHODS: This prospective study enrolled haemodialysis patients in Denmark between December 2010 and March 2011. Using a proximity extension proteomics assay, nine bone-associated proteins were examined: cathepsin D (CTSD), cathepsin L1 (CTSL1), dickkopf-related protein 1, fibroblast growth factor 23, leptin, osteoprotegerin (OPG), receptor activator of nuclear factor kappa-Β ligand, TNF-related apoptosis-inducing ligand (TRAIL) and TRAIL receptor 2 (TRAIL-R2). The importance of the bone-associated protein markers was evaluated by a random forest (RF) algorithm. The association between bone-associated proteins with all-cause death, CV death and CVEs was analysed in multivariable Cox models adjusted for age, gender, comorbidities, laboratory data and dialysis duration. RESULTS: We enrolled 331 patients [63.7% men; mean age, 65 years (standard deviation 14.6)] in a prospective cohort study with 5 years of follow-up. When adjusting for confounders, CTSL1 remained associated with all-cause death and four biomarkers were associated with CVEs. However, the association between bone markers and the outcomes was attenuated after adjusting for inflammatory proteins and only OPG remained associated with CVEs in the adjusted model. Evaluating the importance of bone markers by RF, OPG was the most important marker related to CVEs. OPG also improved the prediction of CVEs in integrated discrimination improvement and net reclassification improvement analyses. CONCLUSIONS: OPG, a well-known bone biomarker, was associated with CVEs independent of cytokine activity. In contrast, the association between CVEs and the remaining three bone-associated proteins (TRAIL-R2, CTSD and CTSL1) was affected by cytokine inflammation activity.

Are fatty acids associated with disease activity and biomarkers in patients with psoriatic arthritis? Data from a multicenter clinical trial.

The pathogenesis of psoriatic arthritis (PsA) involves inflammation and bone and soft tissue turnover. Dietary fatty acids have previously been associated with pro-inflammatory effects induced by saturated fatty acids (SFA) and anti-inflammatory effects achieved by at least some polyunsaturated fatty acids (PUFA). The aim of the study was to investigate the correlations between the content of fatty acids in granulocytes and clinical and biochemical markers of PsA. A total of 140 patients with PsA were included. Skin and joint disease activity were assessed. Fatty acid composition in granulocytes was determined by gas chromatography. Competitive enzyme-linked immunosorbent assays were used to assess bone and soft tissue turnover. The content of SFA, n-6 PUFA or n-3 PUFA in granulocytes was not associated with disease activity. Marine n-3 PUFA was significantly positively correlated with collagen degradation. In contrast, n-6 PUFA was significantly positively correlated with collagen formation and negatively correlated with collagen degradation. However, the correlations were all weak. No association was found between the content of fatty acids in granulocytes and disease activity in this population of patients with PsA. The correlation between fatty acids and biomarkers of bone and soft tissue turnover needs further investigation.

Effect of n-3 PUFA on extracellular matrix protein turnover in patients with psoriatic arthritis: a randomized, double-blind, placebo-controlled trial.

Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by involvement of skin, axial and peripheral skeleton. An altered balance between extracellular matrix (ECM) formation and breakdown is a key event in PsA, and changes in ECM protein metabolites may provide insight to tissue changes. Dietary fish oils (n-3 PUFA) might affect the inflammation driven tissue turnover. The aim was to evaluate ECM metabolites in patients with PsA compared to healthy individuals and investigate the effects of n-3 PUFA. The 24-week randomized, double-blind, placebo-controlled trial of PUFA included 142 patients with PsA. Fifty-seven healthy individuals were included for comparison. This study is a sub-study investigating biomarkers of tissue remodelling as secondary outcomes. Serum samples at baseline and 24 weeks and healthy individuals were obtained, while a panel of ECM metabolites reflecting bone and soft tissue turnover were measured by ELISAs: PRO-C1, PRO-C3, PRO-C4, C1M, C3M, C4M, CTX-I and Osteocalcin (OC). C1M, PRO-C3, PRO-C4 and C4M was found to be elevated in PsA patients compared to the healthy individuals (from 56 to 792%, all p < 0.0001), where no differences were found for OC, CTX-I, PRO-C1 and C3M. PRO-C3 was increased by 7% in patients receiving n-3 PUFA after 24 weeks compared to baseline levels (p = 0.002). None of the other biomarkers was changed with n-3 PUFA treatment. This indicates that tissue turnover is increased in PsA patients compared to healthy individuals, while n-3 PUFA treatment for 24 weeks did not have an effect on tissue turnover. Trial registration NCT01818804. Registered 27 March 2013-Completed 18 February 2016. https://clinicaltrials.gov/ct2/show/NCT01818804?term=NCT01818804&rank=1.

Arrhythmias in Patients on Maintenance Dialysis: A Cross-sectional Study.

RATIONALE & OBJECTIVE: Patients with kidney failure treated with maintenance dialysis experience a high rate of mortality, in part due to sudden cardiac death caused by arrhythmias. The prevalence of arrhythmias, including the subset that are clinically significant, is not well known. This study sought to estimate the prevalence of arrhythmias, characterize the pattern of arrhythmic events in relation to dialysis treatments, and identify associated clinical characteristics. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: 152 patients with kidney failure treated with maintenance dialysis in Denmark. EXPOSURES: Dialysis treatment; clinical characteristics; cardiac output and preload defined using echocardiography. OUTCOMES: Prevalence and pattern of arrhythmias on 48-hour Holter monitoring; odds ratios for arrhythmias. ANALYTICAL APPROACH: Descriptive analysis of the prevalence of arrhythmias. Pattern of arrhythmias described using a repeated-measures negative binomial regression model. Associations between clinical characteristics and echocardiographic findings with arrhythmias were assessed using logistic regression. RESULTS: Among the 152 patients studied, 83.6% were treated with in-center dialysis; 10.5%, with home hemodialysis; and 5.9%, with peritoneal dialysis. Premature atrial and ventricular complexes were seen in nearly all patients and 41% had paroxysmal supraventricular tachycardia. Clinically significant arrhythmias included persistent atrial fibrillation observed among 8.6% of patients, paroxysmal atrial fibrillation among 3.9%, nonsustained ventricular tachycardia among 19.7%, bradycardia among 4.6%, advanced second-degree atrioventricular block among 1.3%, and third-degree atrioventricular block among 2.6%. Premature ventricular complexes were more common on dialysis days, while tachyarrhythmias were more often observed during dialysis and in the immediate postdialytic period. Older age (OR per 10 years older, 1.53; 95% CI, 1.15-2.03; P=0.003), elevated preload (OR, 4.02; 95% CI, 1.05-15.35; P=0.04), and lower cardiac output (OR per 1L/min greater, 0.66; 95% CI, 0.44-1.00; P=0.05) were independently associated with clinically significant arrhythmias. LIMITATIONS: Arrhythmia monitoring limited to 48 hours; small sample size; heterogeneous nature of the population, risk for residual confounding. CONCLUSIONS: Arrhythmias, including clinically significant abnormal rhythms, were common. Tachyarrhythmias were more frequent during dialysis and the immediate postdialytic period. The relevance of these findings to clinical outcomes requires additional study.

Haptoglobin 2-2 Genotype, Patient, and Graft Survival in Renal Transplant Recipients.

BACKGROUND: Cardiovascular disease is the leading cause of death in renal transplant recipients. An association between haptoglobin genotype 2-2 and cardiovascular disease has been found in patients with diabetes mellitus and liver transplant recipients. To date, the role of haptoglobin genotype after renal transplantation has not been studied. METHODS: In this single-center retrospective cohort study of 1975 adult Norwegian transplant recipients, who underwent transplantation between 1999 and 2011, we estimated the risk of all-cause and cardiovascular mortality and overall and death-censored graft loss for patients with haptoglobin genotype 2-2 compared to genotype 2-1 or 1-1, after adjustment for confounders and competing risks. RESULTS: We found no associations between haptoglobin genotype 2-2 and cardiovascular mortality (subdistributional hazard ratio 1.08, 95% confidence interval 0.78-1.49; P = .63). We also failed to detect any association between haptoglobin 2-2 genotype and all-cause mortality, overall graft loss, and death-censored graft loss. Similar results were found in the subpopulation of transplant recipients with diabetes. CONCLUSION: In this large cohort of kidney transplant recipients, we could not demonstrate any association between haptoglobin 2-2 genotype and patient or graft survival after renal transplantation.

The effect of marine n-3 polyunsaturated fatty acids on cardiac autonomic and hemodynamic function in patients with psoriatic arthritis: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: The aim of this study was to investigate the effect of marine n-3 polyunsaturated fatty acids (PUFA) on cardiac autonomic function and vascular function in patients with psoriatic arthritis. METHODS: The study was conducted as a randomized, double-blind, placebo-controlled trial, where 145 patients with psoriatic arthritis were supplemented with 3 g of n-3 PUFA or olive oil (control) daily for 24 weeks. Blood pressure, heart rate, heart rate variability (HRV), central blood pressure, pulse wave velocity (PWV) and fatty acid composition of granulocytes, were determined at baseline and after supplementation. RESULTS: At baseline we found a significant difference in the mean of all normal RR intervals (inverse of heart rate, vary from beat to beat) when comparing subjects with the highest vs the lowest fish intake (p = 0.03). After supplementation for 24 weeks there was a trend towards an increase in RR (p = 0.13) and decrease in heart rate (p = 0.12) comparing the n-3 PUFA group with the control group. However, per-protocol analysis showed significantly increased RR (p = 0.01) and lowered heart rate (p = 0.01) in the n-3 PUFA supplemented patients compared with controls. Blood pressure, PWV and Central blood pressure did not change after supplementation with n-3 PUFA. Adjustment for disease activity and conventional cardiovascular risk factors did not change the results. CONCLUSIONS: Marine n-3 PUFA increased RR intervals in patients with psoriatic arthritis which may suggest a protective effect of n-3 PUFA against cardiovascular disease in this population. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT01818804.

Plasma n-3 Polyunsaturated Fatty Acids and Bone Mineral Density in Renal Transplant Recipients.

OBJECTIVE: Renal transplant recipients (RTR) suffer high rates of bone loss and increased risk of fracture. Marine n-3 polyunsaturated fatty acids (n-3 PUFA), found mainly in fish and seafood, may have beneficial effects on bone and are positively associated with bone mineral density (BMD) in healthy elderly. The aim of this study was to investigate if this association prevails despite the more complex causes of bone loss in RTR. DESIGN, SUBJECTS, AND METHODS: A total of 701 RTR were included in a cross-sectional analysis. BMD of lumbar spine, proximal femur, and distal forearm were measured by dual energy x-ray absorptiometry scan, and blood samples were drawn in the fasting state for measurement of plasma fatty acid composition 10 weeks posttransplant. Multiple linear regression analysis was used to assess the association between plasma marine n-3 PUFA levels and BMD. RESULTS: Mean age was 52.2 years, and two-thirds were men. Based on femoral neck T-scores, 26% of patients were osteoporotic and 52% osteopenic. Z-scores increased significantly across quartiles of marine n-3 PUFA levels, and marine n-3 PUFA was a positive predictor of BMD at total hip and lumbar spine after multivariate adjustment. No association was found between n-6 PUFA content and BMD. CONCLUSIONS: Plasma marine n-3 PUFA levels were positively associated with BMD at the hip and lumbar spine 10 weeks posttransplant.

Osteoprotegerin and mortality in hemodialysis patients with cardiovascular disease.

BACKGROUND: Patients treated with hemodialysis (HD) have an increased mortality, mainly caused by cardiovascular disease (CVD). Osteoprotegerin (OPG) is a glycoprotein involved in the regulation of the vascular calcification process. Previous studies have demonstrated that OPG is a prognostic marker of mortality. The aim of this study was to investigate if OPG was a prognostic marker of all-cause mortality in high-risk patients with end-stage renal disease and CVD. METHODS: We prospectively followed 206 HD patients with CVD. OPG was measured at baseline and the patients were followed for 2 years or until reaching the primary endpoint, i.e., all-cause mortality. RESULTS: All-cause mortality during follow-up was 44% (90/206). High OPG was associated with increased mortality, using the first tertile as reference, with an unadjusted HR of 1.70 (CI 1.00 - 2.88) for the second tertile and HR of 1.63 (CI 0.96 - 2.78) for the third tertile. In a multivariate Cox-regression analysis age, CRP and OPG in both the second and third tertile were significantly associated with increased mortality In the unadjusted survival analysis, a test for trend of OPG yielded a p-value of 0.08; in the adjusted analyses, the p-value for trend was 0.03. CONCLUSIONS: In a high-risk population of hemodialysis patients with previously documented cardiovascular disease, a high level of OPG was an independent risk marker of all-cause mortality.

Marine n-3 fatty acids, atrial fibrillation and QT interval in haemodialysis patients.

Patients treated with haemodialysis are at high risk of sudden cardiac death (SCD) often caused by arrhythmias. Atrial fibrillation (AF) is frequent among haemodialysis patients and is associated with increased mortality. Prolonged QTc is a risk marker of ventricular arrhythmia and is thereby associated with SCD. Studies have suggested that n-3 PUFA may have an antiarrhythmic effect, but the exact mechanism is not clear. The aim of this study was to examine whether AF was associated with n-3 PUFA in plasma phospholipids and whether supplementation with n-3 PUFA would shorten the QTc interval in haemodialysis patients compared to placebo. In a double-blinded randomised, placebo-controlled intervention trial 206 haemodialysis patients with CVD were treated with 1·7 g n-3 PUFA or placebo (olive oil) daily for 3 months. Blood samples and electrocardiogram evaluations were carried out at baseline and after 3 months. The QT interval, PQ interval and heart rate were measured in all patients with sinus rhythm (SR). At baseline 13 % of patients had AF. The content of the n-3 PUFA, DHA, was significantly lower (P < 0·05) in serum of patients with AF compared with patients with SR. Thus, the DHA content was independently negatively associated with AF. Supplementation with n-3 PUFA did not shorten the QT interval significantly compared to the placebo group (P = 0·42), although subgroup analysis within the n-3 PUFA group revealed a shortening effects on QTc (P = 0·01). In conclusion, an inverse association was found between the presence of AF and the plasma DHA in haemodialysis patients. Intervention with n-3 PUFA did not shorten the QTc interval compared to placebo.

Can patiromer allow for intensified renin-angiotensin-aldosterone system blockade with losartan and spironolactone leading to decreased albuminuria in patients with chronic kidney disease, albuminuria and hyperkalaemia? An open-label randomised controlled trial: MorphCKD.

INTRODUCTION: Chronic kidney disease (CKD) is associated with significantly increased morbidity and mortality. No specific treatment of the underlying condition is available for the majority of patients, but ACE-inhibitors (ACE-I) and angiotensin II-receptor blockers (ARB) slows progression in albuminuric CKD. Adding a mineralocorticoid receptor-antagonist (MRA) like spironolactone has an additive effect. However, renin-angiotensin-aldosterone system (RAAS)-blockade increases the risk of hyperkalaemia which is exacerbated by the presence of CKD. Thus, hyperkalaemia may prevent optimal use of RAAS-blockade in some patients.This project hypothesises that adding a potassium binder (patiromer) allows for improved RAAS-blockade including the use of MRA, thereby reducing albuminuria in patients with albuminuric CKD where full treatment is limited by hyperkalaemia.If successful, the study may lead to improved treatment of this subgroup of patients with CKD. Furthermore, the study will examine the feasibility of potassium binders in patients with CKD. METHODS AND ANALYSIS: An open-label, randomised controlled trial including 140 patients with estimated glomerular filtration rate (eGFR) 25-60 mL/min/1.73 m2, a urinary albumin/creatinine ratio (UACR) >500 mg/g (or 200 mg/g if diabetes mellitus) and a current or two previous plasma-potassium >4.5 mmol/L. Patients who develop hyperkaliaemia >5.5 mmol/L during a run-in phase, in which RAAS-blockade is intesified with the possible addition of spironolactone, are randomised to 12-month treatment with maximal tolerated ACE-I/ARB and spironolactone with or without patiromer.The primary endpoint is the difference in UACR measured at randomisation and 12 months compared between the two groups. Secondary endpoints include CKD progression, episodes of hyperkalaemia, blood pressure, eGFR, markers of cardiovascular disease, diet and quality of life. ETHICS AND DISSEMINATION: This study is approved by The Central Denmark Region Committees on Health Research Ethics (REFNO 1-10-72-110-20) and is registered in the EudraCT database (REFNO 2020-001595-15). Results will be presented in peer-reviewed journals, at meetings and at international conferences.

The Physiological and Cardiologic Effects of Long Video Gaming Sessions in Adult Males.

The effect of long gaming sessions on energy intake, caffeine intake, blood pressure, heart rate, heart rate variability, and biochemical cardiac injury markers is unknown. The objective of this exploratory study was to investigate the changes in healthy male adults during two consecutive 18-hour sedentary video gaming sessions. Nine participants were enrolled in the study. Energy intake was noted in food diaries. Heart rate variability was monitored continuously; blood pressure and cardiac injury markers were measured every three to six hours. During the 42-hour study, the participants had an energy and caffeine intake of 8004.9 kcal and 1354.4 mg, respectively. The participants had a significant decrease in energy intake in the second session (p=0.01). A strong, negative correlation was found between body mass index and total energy intake (R=-0.84, p=0.005) and waist circumference and total energy intake (R=-0.70, p=0.036) in the first session. No nightly dip in blood pressure or heart rate was observed. Based on this study, long-term adverse effects of gaming cannot be ruled out. The non-dip of HR and BP suggests that long gaming sessions could be detrimental to cardiovascular health long term.

Novel Biomarkers Detected by Proteomics Predict Death and Cardiovascular Events in Hemodialysis Patients.

End-stage kidney disease increases mortality and the risk of cardiovascular (CV) disease. It is crucial to explore novel biomarkers to predict CV disease in the complex setting of patients receiving hemodialysis (HD). This study investigated the association between 92 targeted proteins with all-cause death, CV death, and composite vascular events (CVEs) in HD patients. From December 2010 to March 2011, 331 HD patients were included and followed prospectively for 5 years. Serum was analyzed for 92 CV-related proteins using Proseek Multiplex Cardiovascular I panel, a high-sensitivity assay based on proximity extension assay (PEA) technology. The association between biomarkers and all-cause death, CV death, and CVEs was evaluated using Cox-regression analyses. Of the PEA-based proteins, we identified 20 proteins associated with risk of all-cause death, 7 proteins associated with risk of CV death, and 17 proteins associated with risk of CVEs, independent of established risk factors. Interleukin-8 (IL-8), T-cell immunoglobulin and mucin domain 1 (TIM-1), and C-C motif chemokine 20 (CCL20) were associated with increased risk of all-cause death, CV death, and CVE in multivariable-adjusted models. Stem cell factor (SCF) and Galanin peptides (GAL) were associated with both decreased risk of all-cause death and CV death. In conclusion, IL-8, TIM-1, and CCL20 predicted death and CV outcomes in HD patients. Novel findings were that SCF and GAL were associated with a lower risk of all-cause death and CV death. The SCF warrants further study with regard to its possible biological effect in HD patients.

Intake of marine n-3 polyunsaturated fatty acids and the risk of rheumatoid arthritis: protocol for a cohort study using data from the Danish Diet, Cancer and Health cohort and Danish health registers.

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory joint disease with multifactorial aetiology. Smoking is a well-established lifestyle risk factor, but diet may also have an impact on the risk of RA. Intake of the major marine n-3 polyunsaturated fatty acids in particular eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been hypothesised to lower the risk of RA due to their anti-inflammatory effects, although based on limited knowledge. Therefore, we aim to investigate the associations between dietary intake of EPA and DHA and the risk of incident RA. METHODS AND ANALYSIS: A cohort study. The follow-up design will be based on data from the Danish Diet, Cancer and Health cohort, which was established between 1993 and 1997. The participants will be followed through record linkage using nationwide registers including the Danish Civil Registration System, the Danish National Patient Registry and the Danish National Prescription Registry using the unique Civil Personal Registration number. Time-to-event analyses will be conducted with RA as the outcome of interest. The participants will be followed from inclusion until date of RA diagnosis, death, emigration or end of follow-up. HRs with 95% CIs obtained using Cox proportional hazard regression models, with age as underlying time scale and adjustment for established and potential risk factors, will be used as measures of association. ETHICS AND DISSEMINATION: The study has been approved by the Data Protection Committee of Northern Jutland, Denmark (2019-87) and the North Denmark Region Committee on Health Research Ethics (N-20190031). Study results will be disseminated through peer-reviewed journals and presentations at international conferences.

Intravenous infusion of n-3 polyunsaturated fatty acids and inducibility of ventricular tachycardia in patients with implantable cardioverter defibrillator.

AIMS: Marine n-3 polyunsaturated fatty acids (PUFA) may have antiarrhythmic effects. The aim of this study was to investigate the effect of intravenously administered n-3 PUFA on the inducibility of ventricular tachycardia (VT) in patients with an implantable cardioverter defibrillator (ICD). METHODS AND RESULTS: In a randomized, placebo-controlled cross-over study, patients with an ICD underwent two electrophysiological studies using the stimulation possibilities in the ICD preceded by intravenous infusion of either a lipid emulsion delivering 3.9 g n-3 PUFA or placebo (0.9% saline). The level of stimulation required to induce sustained monomorphic VT was ranked in order from least to most aggressive, and non-inducibility was ranked highest. The content of n-3 PUFA in plasma free fatty acids (FFA), plasma phospholipids, and platelet phospholipids was measured by gas chromatography. Eight patients were included, and six of these completed the study. The content of n-3 PUFA as FFA and in platelet phospholipids increased more after n-3 PUFA infusion than after placebo (P<0.001). Of the five patients who were inducible after placebo, two were no longer inducible after n-3 PUFA infusion and another two required stronger stimulation to induce VT. The difference in the stimulation required after placebo and after n-3 PUFA was borderline significant (P=0.063, Wilcoxon signed-rank test). CONCLUSION: Intravenous n-3 PUFA tended to decrease VT inducibility, but a larger study is warranted.

Adhesion molecules and C-reactive protein are associated to adverse events in angina pectoris.

OBJECTIVES: To examine the prognostic value of soluble cellular adhesion molecules (CAMs) and highly sensitive C reactive protein (hsCRP) on long-term outcome for patients with stable angina pectoris (SAP). DESIGN: In a prospective study, 291 patients referred for coronary angiography due to clinically suspected SAP had serum level of soluble intercellular adhesion molecule-1 (sICAM-1), vascular adhesion molecule-1 (sVCAM-1), sP-selectin and hsCRP determined at baseline. The primary outcome was predefined as death from any cause, myocardial infarction or stroke during a mean follow-up of 7.1 years. RESULTS: Thirty four patients experienced the primary outcome. Hazard ratios and 95% confidence intervals for the primary outcome were: sVCAM-1: 2.4 [1.1-4.9], sICAM-1: 3.3 [1.5-7.2], sP-selectin: 1.2 [0.6-2.6] and hs-CRP: 3.1 [1.5-6.3], when comparing patients in the 4th quartile with those in lower quartiles in a multivariable model. Higher risk of adverse outcome was observed in patients having levels of both hsCRP and sICAM-1 (HR 4.7 [1.7-9.9]) or hsCRP and sVCAM-1 (HR 4.2 [1.7-9.9]) in the 4th quartile. CONCLUSIONS: sVCAM-1, sICAM-1 and hsCRP were significantly associated with long term outcomes of patients with SAP beyond the risk associated with traditional risk factors. Risk predictions were improved when combining information about sCAMs and hsCRP.

The effect of marine n-3 fatty acids in different doses on plasma concentrations of Lp-PLA2 in healthy adults.

BACKGROUND: Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is an emerging independent risk factor for cardiovascular disease (CVD). Lp-PLA(2) can be modified by lipid lowering drugs, but it is unknown whether diet can reduce plasma levels of Lp-PLA(2). AIM OF THE STUDY: The aim of the trial was to study the effect of marine n-3 polyunsaturated fatty acids (PUFA) on plasma Lp-PLA(2) levels in healthy subjects. METHODS: Sixty healthy subjects were randomized to a moderate dose (2 g) of n-3 PUFA, a high dose (6.6 g) of n-3 PUFA or olive oil (control) daily for 12 weeks. Plasma Lp-PLA(2) was measured at baseline and after the interventions. RESULTS: Plasma Lp-PLA(2) levels were unchanged in all three groups before and after the supplements. Neither did the results differ between groups. There was no correlation between the content of n-3 PUFA in platelets or granulocytes or plasma Lp-PLA(2). CONCLUSION: Marine n-3 PUFA had no effect on plasma levels of Lp-PLA(2) in healthy adults and relatively young people.

The Effect of Marine n-3 Polyunsaturated Fatty Acids on Heart Rate Variability in Renal Transplant Recipients: A Randomized Controlled Trial.

Resting heart rate (rHR) and heart rate variability (HRV) are non-invasive measurements that predict the risk of sudden cardiac death (SCD). Marine n-3 polyunsaturated fatty acid (PUFA) supplementation may decrease rHR, increase HRV, and reduce the risk of SCD. To date, no studies have investigated the effect of marine n-3 PUFA on HRV in renal transplant recipients. In a randomized controlled trial, 132 renal transplant recipients were randomized to receive either three 1 g capsules of marine n-3 PUFA, each containing 460 mg/g EPA and 380 mg/g DHA, or control (olive oil) for 44 weeks. HRV was calculated in the time and frequency domains during a conventional cardiovascular reflex test (response to standing, deep breathing, and Valsalva maneuver) and during 2 min of resting in the supine position. There was no significant effect of marine n-3 PUFA supplementation on time-domain HRV compared with controls. rHR decreased 3.1 bpm (± 13.1) for patients receiving marine n-3 PUFA compared to 0.8 (± 11.0) in controls (p = 0.28). In the frequency domain HRV analyses, there was a significant change in response to standing in both high and low frequency measures, 2.9 (p = 0.04, 95% CI (1.1;8)) and 2.7 (p = 0.04, 95% CI (1.1;6.5)), respectively. In conclusion, 44 weeks of supplemental marine n-3 PUFAs in renal transplant recipients significantly improved the cardiac autonomic function, assessed by measuring HRV during conventional cardiovascular reflex tests.

Pancreas-specific plasma amylase for assessment and diagnosis of chronic pancreatitis: New insights on an old topic.

Background: Pancreatic function testing and imaging are used to inform the diagnosis of chronic pancreatitis, but most of these methods are time- and cost-consuming or lack diagnostic accuracy. Objective: We investigated the utility of pancreas-specific plasma amylase for assessment and diagnosis of chronic pancreatitis. Design: This was a prospective study of 121 consecutive patients with chronic pancreatitis and a reference population of 94 healthy controls. Pancreas-specific plasma amylase level was determined and analysed for its association with exocrine pancreatic insufficiency, diabetes and other clinical variables. Receiver operating characteristic curve analyses were performed to determine the diagnostic utility of plasma amylase for diagnosing chronic pancreatitis and to study associations with disease severity. The findings were validated in a further cohort of 57 patients with chronic pancreatitis. Results: Significant and independent associations between plasma amylase level and duration of chronic pancreatitis as well as the presence of exocrine pancreatic insufficiency and diabetes were observed (all p < 0.001). An amylase level below 17.3 U/l had a high specificity (94%) and moderate sensitivity (59%) for the diagnosis of chronic pancreatitis. Diagnostic performance was influenced by disease stage with the best performance observed for advanced disease. The findings were replicated in the validation cohort. Conclusion: Pancreas-specific plasma amylase may provide a clinically useful mean for assessment and diagnosis of chronic pancreatitis.

Effect of the administration of n-3 polyunsaturated fatty acids on circulating levels of microparticles in patients with a previous myocardial infarction.

BACKGROUND: Increased levels of microparticles exposing tissue factor circulate in the blood of patients with coronary heart disease, possibly disseminating their pro-thrombotic and pro-inflammatory potential. Because diets rich in n-3 (polyunsaturated) fatty acids have been associated with reduced incidence of coronary heart disease-related events, we investigated the in vivo effects of treatments with n-3 fatty acids on levels of circulating microparticles and their tissue factor- dependent procoagulant activity in patients with a previous myocardial infarction. DESIGN AND METHODS: Forty-six post-myocardial infarction patients were assigned to receive either 5.2 g of n-3 fatty acids daily (n=23) or an olive oil placebo (n = 23) for 12 weeks. Circulating microparticles were isolated from peripheral blood. The number of microparticles, their cellular source and tissue factor antigen were determined by flow cytometry, and their procoagulant potential assayed by a fibrin generation test. RESULTS: The total number of microparticles, endothelium-derived microparticles and microparticle tissue factor antigen were not significantly different between the two groups. However, the number of platelet-derived microparticles [from a median of 431 (126-1796, range) x 10(6)/L to a median of 226 (87-677, range)] x 10(6)/L and monocyte-derived microparticles [from a median of 388 (9-1681, range) x 10(6)/L to a median of 265 (7-984, range) x 10(6)/L] in plasma were significantly (p < 0.05) decreased by n-3 fatty acids, while they were unchanged in the placebo group. Total microparticle tissue factor-procoagulant activity was also reduced in the n-3 fatty acid group compared to that in the placebo group. CONCLUSIONS: Treatment with n-3 fatty acids after myocardial infarction exerts favorable effects on levels of platelet- and monocyte-derived microparticles, thus possibly explaining some of the anti-inflammatory and anti-thrombotic properties of these natural compounds.