Incidence of seropositive and seronegative rheumatoid arthritis in Denmark: a nationwide population-based study.

OBJECTIVE: To investigate and compare trends in incidence rates (IRs) of seropositive and seronegative rheumatoid arthritis (RA) in Denmark using various data sources for serostatus definition. METHOD: This nationwide population-based cohort study was based on data from Danish healthcare and clinical quality registries between 2000 and 2018. Information on anti-cyclic citrullinated peptide and immunoglobulin M rheumatoid factor was obtained, and definitions of seropositivity according to the number of applied data sources were prespecified. Annual age- and sex-standardized IRs were calculated as the number of incident seropositive and seronegative cases, divided by the number of person-years (PY) in the general population in that given year. RESULTS: An increasing temporal trend in IR of seropositive RA and a decreasing trend in seronegative RA were observed. The IRs were higher for seropositive RA than for seronegative RA from 2009 onwards, with a widening of the IR gap between 2009 and 2016 regardless of the definition of seropositivity. When combining laboratory- and physician-reported autoantibody information and ICD-10 codes, the IR of seropositive RA in 2018 was approximately twice that of seronegative RA, at 19.0 and 9.0 per 100 000 PY, respectively. The level of antibody testing increased significantly during the study period. CONCLUSIONS: The IR of seropositive RA increased over time, whereas the IR of seronegative RA decreased. Temporal IR changes may be caused by a real change in the RA serology subtypes, an increase in autoantibody testing and availability, changes in registration practice over time, or a combination of these factors.

Incidence and prevalence of rheumatoid arthritis in Denmark from 1998 to 2018: a nationwide register-based study.

OBJECTIVE: To investigate the incidence and prevalence of rheumatoid arthritis (RA) in the adult Danish population. METHOD: In this nationwide register-based cohort study, patients with incident RA between 1998 and the end of 2018 were identified using Danish administrative registries. The age- and sex-standardized incidence rate (IR), incidence proportion (IP), lifetime risk (LR), and point prevalence (PP) of RA were calculated. RA was defined as a first-time RA diagnosis registered in the Danish National Patient Registry combined with a redeemed prescription of a conventional synthetic disease-modifying anti-rheumatic drug in the following year. In addition, three different case definitions of RA were explored. RESULTS: The overall age- and sex-standardized IR of RA from 1998 to 2018 was 35.5 [95% confidence interval (CI) 35.1-35.9] per 100 000 person-years while the IP was 35.2 (95% CI 34.8-35.5) per 100 000 individuals. The IR was two-fold higher for women than for men. The LR of RA ranged from 2.3% to 3.4% for women and from 1.1% to 1.5% for men, depending on the RA case definition used. The overall PP of RA was 0.6% (95% CI 0.5-0.6%) in 2018: 0.8% (95% CI 0.7-0.8%) for women and 0.3% (95% CI 0.3-0.4%) for men. The prevalence increased about 1.5-fold from 2000 to 2018. CONCLUSION: The IR and PP were approximately two-fold higher for women than for men. The prevalence of RA in Denmark increased significantly from 2000 to 2018. The RA case definition had more impact on the results than the choice of denominator.

Beneficial effect of n-3 polyunsaturated fatty acids on inflammation and analgesic use in psoriatic arthritis: a randomized, double blind, placebo-controlled trial.

OBJECTIVE: This study aimed to investigate the effects of marine n-3 polyunsaturated fatty acids (PUFAs) on disease activity, use of analgesics, and inflammatory biomarkers in patients with psoriatic arthritis (PsA). METHOD: Patients with established PsA (n = 145) were investigated in a randomized, double-blind, placebo-controlled study. The participants received a supplement of 3 g n-3 PUFA/day or 3 g olive oil/day (control) for 24 weeks. Outcome measures for disease activity, use of analgesics, and leukotriene formation from activated granulocytes were assessed at baseline and at study end. RESULTS: In total, 145 patients were included and 133 completed the study. After 24 weeks, the n-3 PUFA group showed a decrease in Disease Activity Score (DAS28-CRP), 68 tender joint count, enthesitis score, and psoriasis area and severity index, although not significantly different from the controls. There was a significant reduction in non-steroidal anti-inflammatory drug (NSAID) and paracetamol use compared with controls (p = 0.04). In addition, the participants in the n-3 PUFA group had significantly lower formation of leukotriene B4 (p = 0.004) from stimulated granulocytes and significantly higher formation of leukotriene B5 (p < 0.001) compared with controls. CONCLUSION: The n-3 PUFA-supplemented group showed improvement in outcome measures for disease activity, although the difference between the groups was not statistically significant. However, use of NSAIDs and paracetamol was significantly reduced in the n-3 PUFA group compared to the control group. Finally, there was a significant decrease in leukotriene B4 formation in the n-3 PUFA group compared with controls.

Galectin-3, a marker of cardiac remodeling, is inversely related to serum levels of marine omega-3 fatty acids. A cross-sectional study.

OBJECTIVE: Marine polyunsaturated n-3 fatty acids (n-3 PUFA) may have cardioprotective effects and beneficial influence on the fibrotic process. We evaluated the associations between serum marine n-3 PUFA and selected biomarkers of fibrosis and cardiac remodeling in elderly patients with acute myocardial infarction. SETTING: From the ongoing OMega-3 fatty acids in Elderly patients with Myocardial Infarction (OMEMI) trial, 299 patients were investigated. Soluble ST2 (sST2), Galectin-3 (Gal-3) and the serum content of major marine n-3 and n-6 PUFA were analyzed 2-8 weeks after the index acute myocardial infarction. RESULTS: Gal-3 was inversely correlated to eicosapentaenoic acid (r = -.120, p = .039) and docosahexaenoic acid (r = -.125, p = .031) and positively correlated to the n-6/n-3 ratio (r = .131, p = .023). Gal-3 levels were significantly higher in diabetics vs non-diabetics (12.00 vs 9.61 ng/mL, p = .007) and in patients with NYHA class ≥III for dyspnea at inclusion (11.33 vs 9.75 ng/mL, p = .006). CONCLUSIONS: The associations between the marine n-3 PUFA and levels of Gal-3 indicate beneficial effects of n-3 PUFA on cardiac remodeling in an elderly population with acute myocardial infarction.

Validity of Peripheral Arterial Disease Diagnoses in the Danish National Patient Registry.

OBJECTIVES/BACKGROUND: The objective was to validate the diagnoses of peripheral arterial disease (PAD) in the legs, obtained from national registers in Denmark. METHODS: In total, 1435 registered cases of PAD were identified in the Danish National Patient Registry among 57,053 middle aged participants from the Danish Diet, Cancer and Health cohort study. Validation was performed by reviewing all medical records using pre-specified criteria for a diagnosis of PAD. RESULTS: The overall positive predictive value (PPV) of PAD diagnoses was 69.4% [95% confidence interval (CI) 67.0-71.7]. The PPV of diagnoses given in departments of vascular surgery was significantly higher than diagnoses given in other departments: 71.9% (95% CI 69.2-74.4) versus 58.3% (95% CI 52.2-64.2), respectively. In a sub-study, 141 potential cases of PAD also registered in the Danish National Vascular Registry were evaluated, and a PPV of 87.9% (95% CI 81.4-92.4) was found for these diagnoses. CONCLUSION: More than 30% of the diagnoses of PAD notified in the Danish National Patient Registry were not valid, stressing the importance of validation when using register information for research purposes. In contrast, diagnoses obtained from the Danish National Vascular Registry had a high validity ready for use without further validation.

Plasma levels of marine n-3 fatty acids and cardiovascular risk markers in renal transplant recipients.

BACKGROUND/OBJECTIVES: Cardiovascular (CV) disease is the leading cause of death after renal transplantation. Marine n-3 polyunsaturated fatty acids (PUFAs) exert potential cardio-protective metabolic effects and might reduce CV morbidity and mortality in renal transplant recipients (RTRs). SUBJECTS/METHODS: In this cross-sectional study of 1990 Norwegian RTRs, transplanted between 1999 and 2011, associations between plasma phospholipid marine n-3 PUFA levels and various CV risk markers at 10 weeks after transplant were evaluated. RESULTS: Higher plasma marine n-3 PUFA levels were associated with lower resting heart rate (rHR), lower fasting plasma glucose (fPG) levels, lower plasma triglyceride levels and higher plasma high-density lipoprotein (HDL) cholesterol levels. Plasma levels of eicosapentaenoic acid, but not docosahexaenoic acid, showed a positive association with plasma HDL cholesterol levels. Plasma marine n-3 PUFA levels were not associated with plasma low-density lipoprotein cholesterol levels, pulse wave velocity or systolic and diastolic blood pressure. A negative association between plasma marine n-3 PUFA levels and CV mortality was weakened by additional adjustment for plasma triglyceride levels and rHR. The ratio of n-6 to n-3 PUFAs showed similar associations with CV risk markers as absolute plasma marine n-3 PUFA levels. CONCLUSIONS: This is the first study in RTRs showing that marine n-3 PUFAs are negatively associated with rHR and fPG in addition to beneficial effects on plasma HDL cholesterol and triglyceride levels. Especially, effects on autonomic nervous function and triglyceride metabolism might contribute to explain the lower CV mortality risk with higher plasma marine n-3 PUFA levels previously shown in this cohort.

Baseline patterns of adipose tissue fatty acids and long-term risk of breast cancer: a case-cohort study in the Danish cohort Diet, Cancer and Health.

BACKGROUND/OBJECTIVES: The evidence regarding fatty acids and breast cancer risk is inconclusive. Adipose tissue fatty acids can be used as biomarkers of fatty acid intake and of endogenous fatty acid exposure. Fatty acids in adipose tissue are correlated owing to common dietary sources and shared metabolic pathways, which group fatty acids into naturally occurring patterns. We aimed to prospectively investigate associations between adipose tissue fatty acid patterns and long-term risk of total breast cancer and breast cancer subtypes characterised by oestrogen and progesterone receptor status (ER and PR). SUBJECTS/METHODS: This case-cohort study was based on data from the Danish cohort Diet, Cancer and Health. At baseline, a fat biopsy and information on lifestyle and reproductive factors were collected. From the 31 original fatty acids measured, patterns of fatty acids were identified using the treelet transform. During a median follow-up of 5.3 years, 474 breast cancer cases were identified. Hazard ratios and 95% confidence intervals of risk of total breast cancer and of subtypes according to quintiles of factor score were determined by weighted Cox proportional hazards regression. RESULTS: After adjustment for potential confounders, factor scores for the seven patterns identified by the treelet transform were not associated with risk of total breast cancer, nor with risk of ER+, ER-, PR+ or PR- tumours. CONCLUSIONS: No clear associations between the patterns of fatty acids at baseline and long-term risk of total breast cancer or ER+, ER-, PR+ or PR- tumours were observed.

Randomized clinical trial of perioperative omega-3 fatty acid supplements in elective colorectal cancer surgery.

BACKGROUND: Omega-3 fatty acids (n-3 FAs) may have beneficial clinical effects, and n-3 FA supplements may improve outcome after surgery. METHODS: In a randomized double-blind placebo-controlled trial in single centre, patients referred for elective colorectal cancer surgery received either an n-3 FA-enriched oral nutritional supplement (ONS) (Supportan, 200 ml twice daily) providing 2.0 g eicosapentaenoic acid (EPA) and 1.0 g docosahexaenoic acid (DHA) per day, or a standard isocaloric and isonitrogenous ONS, for 7 days before and 7 days after surgery. The primary endpoint was infectious and non-infectious complications within 30 days of surgery. Secondary endpoints were length of hospital stay, intensive care unit admission, readmissions, and concentrations of marine n-3 FAs and arachidonic acid in granulocyte membranes. RESULTS: Some 148 consecutive patients (68 women, 80 men; mean age 71 (range 41-89) years) were randomized. There was no significant difference between groups in infectious or non-infectious postoperative complications (P = 1.000). Granulocyte levels of EPA, DHA and docosapentaenoic acid (DPA) were significantly higher in the n-3 FA-enriched supplement group compared with the control group (P < 0.001). The arachidonic acid level in granulocytes was significantly lower in the enriched group than in the control group (P < 0.001). CONCLUSION: EPA, DHA and DPA were incorporated into granulocytes in patients receiving n-3 FAs, but this was not associated with improved postoperative outcomes. REGISTRATION NUMBER: NCT00488904 (http://www.clinicaltrials.gov).

No effect of high-dose atorvastatin on leukotriene B4 formation from neutrophils in patients treated with coronary bypass surgery: a randomized placebo-controlled double-blinded trial with a crossover design.

Inflammation plays a pivotal role in the pathophysiology of cardiovascular disease, (CVD) and leukotrienes may play a role in atherogenesis. Statins reduce mortality from CVD by reducing LDL cholesterol and potentially by other (pleiotropic) mechanisms. The aim of this study was to investigate if atorvastatin exerts an anti-inflammatory effect by reducing leukotriene B4 (LTB4) formation from stimulated neutrophils in patients treated with coronary artery bypass grafting. The study was a randomized, placebo-controlled, double-blinded crossover study. Patients (n=80) were allocated to 80 mg atorvastatin or placebo for 6 weeks before crossing over to the opposite treatment for another 6 weeks. There was no significant correlation between baseline LDL cholesterol levels on formation of LTB4, and atorvastatin had no effect on LTB4 formation. Hence, this study does not support any effect of atorvastatin on LTB4 formation as part of the explanation for its beneficial effect on CVD.

The effect of low-dose marine n-3 fatty acids on the biosynthesis of pro-inflammatory 5-lipoxygenase pathway metabolites in overweight subjects: a randomized controlled trial.

INTRODUCTION: Marine n-3 polyunsaturated fatty acids (PUFA) have a variety of anti-inflammatory properties. This study evaluated the effect of n-3 PUFA in a low, but recommended cardioprotective dosage on the formation of 5-lipoxygenase pathway metabolites in overweight subjects. MATERIALS AND METHODS: Fifty subjects were randomized to 1.1g of n-3 PUFA or olive oil for 6 weeks. RESULTS: Leukotriene B(4) formation decreased by 14% in the n-3 PUFA group which proved to be significant within the group (p=0.005) but not between groups (p=0.25). The formation of 5-hydroxyeicosatetraenoic acid (5-HETE) did not differ significantly between the groups. In the n-3 PUFA group, both 5-hydroxyeicosapentaenoic (5-HEPE) acid and leukotriene B(5) increased significantly compared to the control group (p<0.001). CONCLUSION: In conclusion, we did not observe any significant net anti-inflammatory effect on the 5-lipoxygenase pathway from a daily supplement of 1.1g marine n-3 PUFA for 6 weeks.

A difficult conversation? The views and experiences of parents and professionals on the consent process for perinatal postmortem after stillbirth.

OBJECTIVE: To describe the experiences, knowledge and views of both parents and professionals regarding the consent process for perinatal postmortem. DESIGN: Internet-based survey. SETTING: Obstetricians, midwives and perinatal pathologists currently working in the UK. Parents who have experienced a stillbirth in the UK in the previous 10 years. SAMPLE: Obstetricians, midwives and perinatal pathologists registered with their professional bodies. Parents who accessed the Sands website or online forum. METHODS: Online self-completion questionnaire with both fixed-choice and open-ended questions. RESULTS: Responses were analysed from 2256 midwives, 354 obstetricians, 21 perinatal pathologists and 460 parents. The most common reason for parents to request postmortem examination was to find a cause for their baby's death; the prevention of stillbirths in others also ranked highly. Perinatal pathologists possessed greatest knowledge of the procedure and efficacy of postmortem, but were unlikely to meet bereaved parents. The majority of professionals and parents ranked emotional distress and a lengthy wait for results as barriers to consent. The majority of staff ranked workload, negative publicity, religion and cultural issues as important barriers, whereas most parents did not. Almost twice as many parents who declined postmortem examination later regretted their decision compared with those who accepted the offer (34.4 versus 17.4%). CONCLUSION: Emotional, practical and psychosocial issues can act as real or perceived barriers for staff and bereaved parents. Education is required for midwives and obstetricians, to increase their knowledge to ensure accurate counselling, with due regard for the highly individual responses of bereaved parents. The contribution of perinatal pathologists to staff education and parental decision-making would be invaluable.

Dietary fibre intake and ischaemic heart disease mortality: the European Prospective Investigation into Cancer and Nutrition-Heart study.

BACKGROUND/OBJECTIVES: Evidence from prospective studies is consistent in showing an inverse association between dietary fibre intake and risk of ischaemic heart disease (IHD), but whether dietary fibre from various food sources differ in their effect on IHD risk is less clear. The objective of this study was to assess the associations of total and food sources of dietary fibre with IHD mortality in the European Prospective Investigation into Cancer and Nutrition-Heart study. SUBJECTS/METHODS: Participants were 306,331 men and women from eight European countries. Dietary fibre intake was assessed using centre or country-specific diet questionnaires and calibrated using a 24-h diet recall. RESULTS: After an average follow-up of 11.5 years, there were 2381 IHD deaths among participants without cardiovascular disease at baseline. The calibrated intake of dietary fibre was inversely related with IHD mortality; each 10 g/day was associated with a 15% lower risk (relative risk (RR) 0.85; 95% confidence interval (CI): 0.73-0.99, P=0.031). There was no difference in the associations of the individual food sources of dietary fibre with the risk of IHD mortality; RR for each 5 g/day higher cereal fibre intake was 0.91 (CI: 0.82-1.01), RR for each 2.5 g/day fruit fibre intake was 0.94 (CI: 0.88-1.01) and RR for each 2.5 g/day vegetable fibre intake was 0.90 (95% CI: 0.76-1.07). CONCLUSION: A higher consumption of dietary fibre is associated with a lower risk of fatal IHD with no clear difference in the association with IHD for fibre from cereals, fruits or vegetables.

The effect of n-3 polyunsaturated fatty acids on leukotriene B4 and leukotriene B5 production from stimulated neutrophil granulocytes in patients with chronic kidney disease.

The proinflammatory leukotriene B4 (LTB4) may be of importance in the progression of chronic kidney disease (CKD). We investigated whether n-3 polyunsaturated fatty acids (PUFA) decrease LTB4 and increase the formation of the less inflammatory leukotriene B5 (LTB5) in patients with CKD. Fifty-six patients with CKD stage 2-5 were randomised to 2.4 g n-3 PUFA or olive oil for 8 weeks. Compared to controls, n-3 PUFA significantly decreased release of LTB4 (p<0.001) and 5-hydroxyeicosatetraenoic acid (5-HETE) (p<0.01) and significantly increased release of LTB5 (p<0.001) and 5-hydroxyeicosapentaenoic acid (5-HEPE) (p<0.001) from stimulated neutrophil granulocytes. Kidney function evaluated by creatinine clearance and proteinuria did not improve. In conclusion, n-3 PUFA supplementation for 8 weeks in patients with CKD stage 2-5 significantly decreased LTB4 and 5-HETE and significantly increased LTB5 and 5-HEPE. No effect was seen on kidney function.

Body composition and body fat distribution in relation to later risk of acute myocardial infarction: a Danish follow-up study.

INTRODUCTION: Obesity is a modifiable risk factor for acute myocardial infarction (MI), but lean body mass (LBM) may also be an important factor. Low LBM may increase the risk of MI and LBM may modify the effect of obesity on MI. Thus, the inability of the classical anthropometric measures to evaluate LBM may lead to misclassification of MI risk in both lean and obese persons. We investigated the associations between incident MI and bioelectrical impedance analyses (BIA) derived measures of body composition in combination with body mass index (BMI) and anthropometric measures of body fat distribution. METHODS AND RESULTS: From 1993 to 1997, 27 148 men and 29 863 women, aged 50 to 64 year, were recruited into the Danish prospective study Diet, Cancer and Health. During 11.9 years of follow-up we identified 2028 cases of incident MI (1487 men and 541 women). BMI, waist circumference (WC), hip circumference and BIA of body composition including body fat mass (BFM), body fat percentage and LBM were measured at baseline. We used Cox proportional hazard models with age as time axis and performed extensive control for confounding. Weight, BMI, classical estimates of abdominal obesity and BIA estimates of obesity showed significant positive associations with incident MI. However, BFM adjusted for WC showed no association. Low LBM was associated with a higher risk of incident MI in both genders, and high LBM was associated with a higher risk in men. CONCLUSION: Obesity was positively associated with MI. Estimates of obesity achieved by BIA seemed not to add additional information to classical anthropometric measures regarding MI risk. Both high and low LBM may be positively associated with MI.

Bioavailability of marine n-3 fatty acid formulations.

The use of marine n-3 polyunsaturated fatty acids (n-3 PUFA) as supplements has prompted the development of concentrated formulations to overcome compliance problems. The present study compares three concentrated preparations - ethyl esters, free fatty acids and re-esterified triglycerides - with placebo oil in a double-blinded design, and with fish body oil and cod liver oil in single-blinded arms. Seventy-two volunteers were given approximately 3.3g of eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) daily for 2 weeks. Increases in absolute amounts of EPA and DHA in fasting serum triglycerides, cholesterol esters and phospholipids were examined. Bioavailability of EPA+DHA from re-esterified triglycerides was superior (124%) compared with natural fish oil, whereas the bioavailability from ethyl esters was inferior (73%). Free fatty acid bioavailability (91%) did not differ significantly from natural triglycerides. The stereochemistry of fatty acid in acylglycerols did not influence the bioavailability of EPA and DHA.

Fatty acid composition of the internal mammary artery in relation to dietary intake of marine n-3 polyunsaturated fatty acids and association with flow-mediated vasodilation.

Some evidence suggests that long-chain marine n-3 polyunsaturated fatty acids (n-3 PUFA) may increase production of vasodilatory nitric oxide from vascular endothelium. Fatty acids may therefore play a role for the left internal mammary artery (LIMA) graft function in coronary artery bypass grafting (CABG). However, little is known about the composition of fatty acids in the vessel wall of the LIMA. Using gas chromatography we investigated fatty acid composition in segments of the LIMA, in plasma nonesterified fatty acids (NEFA), in plasma phospholipid (PL) and in the pericardial adipose tissue (PAT) from 22 patients undergoing CABG. Furthermore, we investigated whether there was an association between the n-3 PUFA composition in LIMA and flow-mediated vasodilation (FMD). Self-reported fish consumption and supplementation of eicosapentaenoic acid and docosahexaenoic acids were reflected by the fatty acid composition in NEFA, PL and in PAT, but less so in the LIMA. There was no association between FMD and fatty acid composition of the LIMA.

The effect of N-3 fatty acids on plasma myeloperoxidase levels in healthy adults.

OBJECTIVE: To examine the effect of marine n-3 polyunsaturated fatty acids (PUFA) supplementation in a low to moderate and a high dose on plasma levels of myeloperoxidase (MPO) in healthy individuals. BACKGROUND: Atherosclerosis is a chronic inflammatory disease and MPO, which is secreted primarily from activated neutrophils and monocytes, has pro-inflammatory properties and has been linked with both initiation and propagation of atherosclerosis. Marine n-3 PUFA have anti-inflammatory properties, but whether n-3 PUFA affect plasma levels of MPO is largely unknown. METHODS: Sixty healthy adults were randomized to three groups receiving either 6.6 g PUFA/day, 2.0 g PUFA/day or a control oil (olive oil) for 12 weeks. Blood samples were drawn at baseline and after exposure. Plasma levels of MPO were measured using a MPO ELISA-kit (from Mercodia, Uppsala, Sweden) with specific mouse monoclonal antibodies. RESULTS: Plasma MPO concentrations (microg/L) at baseline were 36.9 +/- 9.4; 36.2 +/- 7.1 and 35.4 +/- 11.3 (for high dose-, low dose- and control-group, respectively). After 12 weeks of supplementation we found no significant changes in plasma MPO in any of the groups nor between groups, with values after intervention of 36.1 +/- 8.6; 37.0 +/- 8.2 and 34.4 +/- 11.1, respectively. CONCLUSION: Supplementation with n-3 PUFA has no effect on plasma levels of MPO in healthy adults with low baseline levels of MPO.

Flow-mediated vasodilation and dietary intake of n-3 polyunsaturated acids in healthy subjects.

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the two major marine n-3 polyunsaturated fatty acids (PUFA), have been proposed to decrease the risk of atherosclerosis and coronary heart disease. An early event during atherogenesis is endothelial dysfunction. We studied the correlation between fish consumption, serum phospholipid (sPL) levels of DHA and EPA and flow-mediated vasodilation (FMD), a measure of endothelial function. Furthermore, subjects were classified according to whether they did (Fish+, n = 19) or did not (Fish-, n = 21) follow the Danish recommendations, consuming at least 300 g fish/week. Neither the fish intake, sPL EPA nor sPL DHA significantly correlated with FMD, -0.20 (p = 0.23), -0.23 (p = 0.15) and -0.06 (p = 0.72), respectively. Also, when comparing the Fish+ and the Fish- group we did not find any significant differences in FMD (p = 0.33). In conclusion, our results did not show any correlation between intake and sPL levels of marine n-3 PUFA and FMD in healthy subjects.

Effects of marine n-3 fatty acids on circulating levels of soluble adhesion molecules in patients with chronic heart failure.

Inflammatory markers as circulating soluble cellular adhesion molecules (sCAMs) and high sensitive C-reactive protein (hsCRP) are elevated in patients with chronic heart failure (CHF), and may constitute an increased risk of adverse outcome. Marine n-3 polyunsaturated fatty acids ( n-3 PUFA) may have anti-inflammatory effect and reduce levels of sCAMs (soluble intercellular adhesion molecule-1 (sICAM-1), vascular adhesion molecule-1 (sVCAM-1), P-selectin) and hsCRP. In a randomized, controlled trial, 138 patients with NYHA class II-III CHF were allocated to receive a daily supplement of 0.9 g of n-3 PUFA or olive oil for 24 weeks. After supplementation, no significant changes occurred in sCAMs or hsCRP after adjusting for possible confounders. However, a significant reduction was observed in sP-selectin in patients receiving n-3 PUFA, but this result was only of borderline significance in a between-group analysis. In conclusion, a daily supplement with 0.9 g of n-3 PUFA does not significantly affect plasma levels of sCAMs or hs-CRP in patients with CHF. n-3 PUFA may reduce sP-selectin, indicating a possible effect on platelet (and endothelial) activation. The results also indicate that the low dose of n-3 PUFA used in many intervention trials does not have deleterious effects on sCAMs or hsCRP.

Serum concentrations of matrix metalloproteinase-9, tissue inhibitor of matrix metalloproteinase-1 and alpha2-macroglobulin in healthy subjects after supplementation with different doses of marine n-3 fatty acids.

OBJECTIVE: Extracellular matrix modification by matrix metalloproteinase-9 (MMP-9), tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) and alpha2-macroglobulin may affect the stability of atherosclerotic plaques. Marine n-3 polyunsaturated fatty acids (n-3 PUFA) may protect against plaque rupture. The aim was to investigate the effect of marine n-3 PUFA supplementation on serum levels of MMP-9, TIMP-1, and alpha2-macroglobulin. METHODS: Healthy volunteers were randomized to receive capsules contributing either 6.6 g marine n-3 PUFA/day, 2.0 g marine n-3 PUFA/day or 6.6 g of olive oil (control). Serum MMP-9, TIMP-1 and alpha2-macroglobulin was measured at baseline and after 12 weeks of supplementation. One way ANOVA or Kruskal-Wallis test was used to compare groups. RESULTS: 60 healthy volunteers were enrolled and no subjects dropped out of the 12 week study. There were no statistically significant changes in serum levels of MMP-9, TIMP-1, and alpha2-macroglobulin in any of the three treatment groups (P=0.85, P=0.23 and P=0.87, respectively). CONCLUSION: Supplementation with marine n-3 PUFA had no effect on serum levels of MMP-9, TIMP-1 and alpha2-macroglobulin in healthy subjects. The possible protection offered by marine n-3 PUFA against plaque rupture is therefore unlikely to be mediated through a change in serum levels of MMP-9, TIMP-1 and alpha2-macroglobulin.