Adipose tissue n-3/n-6 fatty acids ratios versus n-3 fatty acids fractions as predictors of myocardial infarction.

BACKGROUND: Tissue levels of n-3 polyunsaturated fatty acids (PUFAs) have been inversely related with risk of myocardial infarction (MI). Whether ratios of n-3 to n-6 PUFAs, reflecting both dietary intake of n-3 PUFAs and competing n-6 PUFAs, are better predictors of future MI than n-3 PUFA fractions is unclear. We aimed at investigating whether such ratios in adipose tissue better predict MI than n-3 PUFA fractions. METHODS: Subcutaneous adipose tissue biopsies were obtained in a random sample (n = 3,500) of the Diet, Cancer and Health cohort (n = 57,053). Adipose tissue content of eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), alpha-linolenic acid (ALA), arachidonic acid (AA) and linoleic acid was determined using gas chromatography. Fractions of selected n-3 PUFAs and n-3/n-6 PUFA ratios were correlated to the 15-year occurrence of MI in a case-cohort design. RESULTS: A total of 2,406 participants experienced an MI during follow-up. Adipose tissue total marine n-3 PUFAs, EPA+DHA, EPA, EPA/AA, DHA/AA and (EPA + DPA + DHA)/AA were all inversely associated with risk of incident MI. Evaluating the predictive power (Harrel's C-index) of the selected metrics, fractions of marine n-3 PUFAs and ratios of EPA/AA, DHA/AA, (EPA + DHA)/AA and (EPA + DPA + DHA)/AA all refined risk prediction over age and sex alone. At multivariable analyses, however, the above ratios were the only metrics providing additional risk prediction. Differences in ratios were related to differences in food intake. CONCLUSIONS: Both adipose tissue n-3 PUFAs fractions and ratios of n-3 PUFAs/AA were associated with a lower occurrence of MI, but ratios provided superior risk prediction. Dietary strategies affecting n-3/n-6 PUFA ratios should be further investigated for prediction of MI with dietary interventions at the population level and in intervention studies.

Intake of marine and plant-derived n-3 fatty acids and development of atherosclerotic cardiovascular disease in the Danish Diet, Cancer and Health cohort.

PURPOSE: The objective of this study was to investigate the association between intake of seafood and plant-derived n-3 polyunsaturated fatty acids (PUFA) and development of total atherosclerotic cardiovascular disease (ASCVD) and acute major ischemic events. METHODS: A total of 53,909 men and women were enrolled between 1993 and 1997 into the Danish Diet, Cancer and Health cohort and followed through nationwide Danish registries for development of total ASCVD defined as a first registration of myocardial infarction, peripheral artery disease, or ischemic stroke due to large artery atherosclerosis or small-vessel occlusion. At recruitment, the intake of the major marine n-3 PUFA, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and the plant-derived n-3 PUFA, alpha-linolenic acid (ALA), was assessed using a validated food frequency questionnaire. Statistical analyses were conducted using sex-stratified multivariable Cox proportional hazard regression models. RESULTS: During a median of 13.5 years of follow-up, 3958 participants developed ASCVD including 3270 patients with an acute major ischemic event. In multivariable analyses including adjustment for established risk factors, we found no associations for intake of ALA, but indications of inverse associations between intake of EPA, DHA and EPA + DHA and the rate of total ASCVD and acute major ischemic events. CONCLUSIONS: A high intake of marine n-3 PUFA was associated with a lower risk of total ASCVD and acute major ischemic events, whereas no association could be demonstrated for the plant-derived ALA.

Plant n-3 PUFA intake may lower the risk of atherosclerotic cardiovascular disease only among subjects with a low intake of marine n-3 PUFAs.

The role of the major plant-derived n-3 PUFA, alpha-linolenic acid (ALA), on the risk of atherosclerotic cardiovascular (ASCVD) remains unclear, but most studies have reported no association. However, the association between intake of ALA and the risk of ASCVD may depend on the intake of marine n-3 PUFAs. We investigated this hypothesis among more than 53,909 middle-aged, Danish men and women followed for a median of 13.4 years. We found a statistically significant inverse association between ALA intake modelled as a restricted cubic spline and the rate of ASCVD in subjects with a low intake of marine n-3 PUFAs, while no association was observed among subjects with a higher intake of marine n-3 PUFAs. Our findings suggest that the intake of ALA may be associated with a lower risk of total ASCVD, but only among subjects with a low intake of marine n-3 PUFAs.

Subclinical atherosclerosis determined by coronary artery calcium deposition in patients with clinical familial hypercholesterolemia.

Background and aims: Limited knowledge exists regarding the association between coronary artery calcium (CAC) deposition in patients with clinical familial hypercholesterolemia (FH) and FH subtypes such as polygenic causes. We studied CAC score in patients with clinical FH and subtypes including polygenic causes of FH compared to healthy controls. Methods: In a case-control study, we identified potential clinical FH cases registered with an LDL-C >6.7 mmol/l within a nationwide clinical laboratory database on the Faroe Islands and invited them for diagnostic evaluation according to clinical FH scoring systems. Controls were identified in the background population. All subjects were aged 18-75 years and without a history of cardiovascular disease. FH mutation testing and genotypes of twelve LDL-C associated single nucleotide polymorphisms were determined using conventional methods in selected individuals. CAC scores were assessed by cardiac CT. Odds ratios obtained using multivariate logistic regression were used as measures of association. Results: A total of 120 clinical FH patients and 117 age- and sex-matched controls were recruited. We found a very low frequency of monogenic FH (3%), but a high level of polygenic FH (60%) in those genetically tested (54%). There was a statistically significant association between the CAC score and a diagnosis of clinical FH with the highest observed odds ratio of 5.59 (95% CI 1.65; 18.94, p = 0.006) in those with a CAC score ≥300 compared to those with a CAC of zero. In supplemental analyses, there was a strong association between CAC scores and clinical FH of a polygenic cause. Conclusion: We found a statistically significant association between CAC levels and clinical FH with the highest observed risk estimates among clinical FH cases of a presumed polygenic cause.

Omega-3 fatty acids in adipose tissue and risk of atrial fibrillation.

BACKGROUND: The aim of the present study was to examine the relation between adipose tissue content of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and the risk of incident atrial fibrillation (AF). METHODS: In this case-cohort study based on data from the Danish Diet, Cancer and Health cohort, a total of 5255 incident cases of AF was identified during 16.9 years of follow-up. Adipose tissue biopsies collected at baseline from all cases and from a randomly drawn subcohort of 3440 participants were determined by gas chromatography. Data were analysed using weighted Cox regression. RESULTS: Data were available for 4741 incident cases of AF (2920 men and 1821 women). Participants in the highest vs. the lowest quintile of EPA experienced a 45% lower risk of AF (men HR 0.55 (95% CI 0.41-0.69); women HR 0.55 (0.41-0.72)). For DHA, no clear association was found in men, whereas in women, participants in the highest quintile of DHA in adipose tissue had a 30% lower risk of incident AF (HR 0.70 (0.54-0.91)) compared to participants in the lowest quintile. CONCLUSIONS: A monotonous inverse association was found for the content of EPA in adipose tissue and risk of AF in both men and women. The content of DHA was inversely associated with the risk of AF in women, whereas no clear association was found for men.

Intake of marine n-3 polyunsaturated fatty acids and the risk of incident peripheral artery disease.

BACKGROUND: A high intake of marine n-3 polyunsaturated fatty acids (PUFAs) may lower the risk of coronary heart disease and ischemic stroke. The association between intake of marine n-3 PUFAs and development of peripheral artery disease (PAD), however, remains unexplored. We hypothesised that intake of marine n-3 PUFAs, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and the sum of EPA + DHA was associated with a lower risk of incident PAD. METHODS: We used data from the Danish Diet, Cancer and Health cohort and investigated the associations between intake of EPA, DHA and EPA + DHA and development of PAD. Information on intake of n-3 PUFAs was obtained through a validated food frequency questionnaire. Potential PAD cases were identified through linkage to the Danish National Patient Register and subsequently, all cases were validated. RESULTS: Data were available from 55,248 participants and during a median of 13.6 years of follow-up, 950 cases of PAD were identified. Multivariate Cox regression analyses with adjustments for established risk factors showed no statistically significant associations between intake of EPA (p = 0.255), DHA (p = 0.071) or EPA + DHA (p = 0.168) and the rate of incident PAD. CONCLUSIONS: We did not confirm our hypothesis that intake of EPA, DHA or EPA + DHA was associated with a lower risk of incident PAD.

Marine and plant-based n-3 PUFA and atherosclerotic cardiovascular disease.

n-3 PUFA may exert favourable effects on several processes that may inhibit the atherosclerotic process. However, the role of n-3 PUFA in lowering the risk of atherosclerotic CVD (ASCVD) has been fiercely debated. In the present paper, we summarise the main findings from previous follow-up studies of intake and studies using adipose tissue as an objective biomarker to investigate exposure to n-3 PUFA in relation to ASCVD risk and discuss some perspectives for further research. The majority of previous studies investigating intake of marine- and plant-based n-3 PUFA have focused on CHD while other ASCVD such as ischaemic stroke and peripheral artery disease have been less studied. However, recent data from Danish Diet, Cancer and Health cohort suggest that marine n-3 PUFA may be inversely associated with risk of myocardial infarction, ischaemic stroke and peripheral arterial disease caused by atherosclerosis. The effect of the plant-derived n-3 PUFA α-linolenic acid on ASCVD is less clear and several gaps in the literature remain to be explored.

Intake of α-linolenic acid is not consistently associated with a lower risk of peripheral artery disease: results from a Danish cohort study.

Intake of the plant-derived n-3 fatty acid α-linolenic acid (ALA) has been associated with anti-atherosclerotic properties. However, information on the association between ALA intake and development of peripheral artery disease (PAD) is lacking. In this follow-up study, we investigated the association between dietary intake of ALA and the rate of PAD among middle-aged Danish men and women enrolled into the Danish Diet, Cancer and Health cohort between 1993 and 1997. Incident PAD cases were identified through the Danish National Patient Register. Intake of ALA was assessed using a validated FFQ. Statistical analyses were performed using Cox proportional hazard regression allowing for separate baseline hazards among sexes and adjusted for established risk factors for PAD. During a median of 13·6 years of follow-up, we identified 950 valid cases of PAD with complete information on covariates. The median energy-adjusted ALA intake within the cohort was 1·76 g/d (95 % central range: 0·94-3·28). In multivariable analyses, we found no statistically significant association between intake of ALA and the rate of PAD (P = 0·339). Also, no statistically significant associations were observed in analyses including additional adjustment for co-morbidities and in sex-specific analyses. In supplemental analyses with additional adjustment for potential dietary risk factors, we found a weak inverse association of PAD with ALA intake above the median, but the association was not statistically significant (P = 0·314). In conclusion, dietary intake of ALA was not consistently associated with decreased risk of PAD.

Marine n-3 Polyunsaturated Fatty Acids and the Risk of Ischemic Stroke.

Background and Purpose- We hypothesized that total marine n-3 polyunsaturated fatty acids (PUFA), in particular eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the diet and in adipose tissue (biomarkers of long-term intake and endogenous exposure) were inversely associated with the risk of ischemic stroke and its subtypes. Methods- The Diet, Cancer and Health cohort consisted of 57 053 participants aged 50 to 65 years at enrolment. All participants filled in a food frequency questionnaire and had an adipose tissue biopsy taken at baseline. Information on ischemic stroke during follow-up was obtained from The Danish National Patient Register, and all cases were validated. Cases and a random sample of 3203 subjects from the whole cohort had their fatty acid composition of adipose tissue determined by gas chromatography. Results- During 13.5 years of follow-up 1879 participants developed an ischemic stroke. Adipose tissue content of EPA was inversely associated with total ischemic stroke (hazard ratio [HR], 0.74; 95% CI, 0.62-0.88) when comparing the highest with the lowest quartile. Also, lower rates of large artery atherosclerosis were seen with higher intakes of total marine n-3 PUFA (HR, 0.69; 95% CI, 0.50-0.95), EPA (HR, 0.66; 95% CI, 0.48-0.91) and DHA (HR, 0.72; 95% CI, 0.53-0.99), and higher adipose tissue content of EPA (HR, 0.52; 95% CI, 0.36-0.76). Higher rates of cardioembolism were seen with higher intakes of total marine n-3 PUFA (HR, 2.50; 95% CI, 1.38-4.53) and DHA (HR, 2.12; 95% CI, 1.21-3.69) as well as with higher adipose tissue content of total marine n-3 PUFA (HR, 2.63; 95% CI, 1.33-5.19) and DHA (HR, 2.00; 95% CI, 1.04-3.84). The EPA content in adipose tissue was inversely associated with small-vessel occlusion (HR, 0.69; 95% CI, 0.55-0.88). Conclusions- EPA was associated with lower risks of most types of ischemic stroke, apart from cardioembolism, while inconsistent findings were observed for total marine n-3 PUFA and DHA.

Lowering the linoleic acid to alpha-linoleic acid ratio decreases the production of inflammatory mediators by cultured human endothelial cells.

Alpha-linolenic acid (ALA) and linoleic acid (LA) are precursors for longer-chain more unsaturated fatty acids and for lipid signalling molecules that may influence inflammatory processes through a variety of mechanisms. The actions of LA and ALA may be divergent and interdependent. The aim of this study was to investigate the incorporation and metabolism of ALA and LA in cultured in EA.hy926 endothelial cells and the production of inflammatory mediators (VEGF, RANTES, ICAM-1, MCP-1, IL-6 and IL-8) by these cells when exposed to different concentrations of ALA, LA and ratios of LA:ALA. Human endothelial cells were cultured with either culture medium or culture medium supplemented with ALA, LA or various ratios of LA:ALA (1:4, 1:1, 4:1, 9:1 or 19:1) followed by 24 h TNF-α stimulation; the total concentration of ALA plus LA was kept constant at 100 µM. The incorporation and metabolism of ALA and LA was measured using gas chromatography. The production of inflammatory mediators in the supernatant was assessed using a Luminex Multi-Analyte kit. Both ALA and LA were incorporated and metabolised by the endothelial cells. Cells incubated with ALA had a statistically significantly lower production of VEGF, RANTES, ICAM-1, MCP-1 and IL-6 compared to cells incubated without additional ALA. LA was not found to exert pro-inflammatory effects. Cells incubated with low LA:ALA ratios had lower production of VEGF, RANTES, MCP-1 and IL-6 when compared with a LA:ALA ratio of 19:1. These findings suggest that a low LA:ALA ratio exerts anti-inflammatory effects by lowering the production VEGF, RANTES, ICAM-1, MCP-1 and IL-6 in TNF-α stimulated endothelial cells compared to a high ratio. These effects were likely mediated by ALA, but LA may also possess some anti-inflammatory effects.

Marine n-3 Fatty Acids and the Risk of Peripheral Arterial Disease.

BACKGROUND: The content of marine n-3 polyunsaturated fatty acids (PUFAs) in adipose tissue is considered a long-term biomarker for the body's endogenous exposure to seafood. OBJECTIVES: This study sought to examine associations between the content of marine n-3 PUFAs in adipose tissue and the risk of incident peripheral arterial disease (PAD). METHODS: In this case-cohort study based on data from the Danish Diet, Cancer and Health cohort, adipose tissue biopsies were taken from the buttocks of all participants at baseline. After a median follow-up of 13.5 years, 870 validated cases of PAD were identified and included together with a randomly drawn subcohort of 3,204 participants using weighted Cox regression. Adipose tissue samples were analyzed by gas chromatography. RESULTS: In multivariable analyses using the lowest quintile as the reference and adjusting for established risk factors for PAD, we found a statistically significant lower rate of PAD in the highest quintile of eicosapentaenoic acid (EPA) (hazard ratio [HR]: 0.55; 95% confidence interval [CI]: 0.41 to 0.74) and a nonsignificant lower rate for docosahexaenoic acid (HR: 0.79; 95% CI: 0.59 to 1.06). We observed a lower rate of PAD, when comparing the highest quintile of the combined EPA and docosahexaenoic acid with the reference (HR: 0.71; 95% CI: 0.53 to 0.96). In contrast, docosapentaenoic acid had an HR of 1.31 (95% CI: 0.97 to 1.77) in the highest quintile. CONCLUSIONS: A high content of marine n-3 PUFAs in adipose tissue, in particular EPA, was associated with a lower risk of incident PAD.

Long-chain n-3 and n-6 polyunsaturated fatty acids and risk of atrial fibrillation: Results from a Danish cohort study.

BACKGROUND: Studies of the relation between polyunsaturated fatty acids and risk of atrial fibrillation have been inconclusive. The risk of atrial fibrillation may depend on the interaction between n-3 and n-6 polyunsaturated fatty acids as both types of fatty acids are involved in the regulation of systemic inflammation. OBJECTIVE: We investigated the association between dietary intake of long chain polyunsaturated fatty acids (individually and in combination) and the risk of atrial fibrillation with focus on potential interaction between the two types of polyunsaturated fatty acids. DESIGN: The risk of atrial fibrillation in the Diet, Cancer and Health Cohort was analyzed using the pseudo-observation method to explore cumulative risks on an additive scale providing risk differences. Dietary intake of long chain polyunsaturated fatty acids was assessed by food frequency questionnaires. The main analyses were adjusted for the dietary intake of n-3 α-linolenic acid and n-6 linoleic acid to account for endogenous synthesis of long chain polyunsaturated fatty acids. Interaction was assessed as deviation from additivity of absolute association measures (risk differences). RESULTS: Cumulative risks in 15-year age periods were estimated in three strata of the cohort (N = 54,737). No associations between intake of n-3 or n-6 long chain polyunsaturated fatty acids and atrial fibrillation were found, neither when analyzed separately as primary exposures nor when interaction between n-3 and n-6 long chain polyunsaturated fatty acids was explored. CONCLUSION: This study suggests no association between intake of long chain polyunsaturated fatty acids and risk of atrial fibrillation.

Marine n-3 fatty acids are incorporated into atrial tissue but do not correlate with postoperative atrial fibrillation in cardiac surgery.

OBJECTIVES: Postoperative new-onset atrial fibrillation (POAF) in cardiac surgery is associated with increased morbidity and mortality. Because n-3 polyunsaturated fatty acids (n-3 PUFA) have an antiarrhythmic effect, we hypothesized that a high content of marine n-3 PUFA in the atrial wall was associated with a reduced risk of POAF. DESIGN: Venous blood and tissue from the right atrial appendage were obtained from 50 patients undergoing elective cardiac surgery. We determined the content of marine n-3 PUFA in atrial tissue and in plasma phospholipids using gas chromatography. RESULTS: The mean age of the patients (results available from 49 patients) was 66.0±10.4years, and 22, 14, 10 and 3 patients underwent coronary artery bypass surgery, valve, combined or other cardiac surgery, respectively. Eighteen patients (36.7%) developed POAF. Concentrations of n-3 PUFA in the atrial wall and in plasma phospholipids did not predict the development of POAF, but there were significant correlations between marine n-3 PUFA in atrial tissue and plasma. CONCLUSION: Levels of marine n-3 PUFA in the atrial wall was not associated with the risk of POAF following cardiac surgery, despite significant correlations of marine n-3 PUFA in the atrium and in plasma phospholipids.

Association of fish consumption and dietary intake of marine n-3 PUFA with myocardial infarction in a prospective Danish cohort study.

Several studies have investigated the potential benefits of marine n-3 PUFA in CVD, generally suggesting a lower risk of CHD. However, recent trials have questioned these results. This study investigated the association of fish consumption with dietary intake of marine n-3 PUFA with incident myocardial infarction (MI). In a Danish cohort study, 57 053 subjects between 50 and 64 years of age were enrolled from 1993 to 1997. From national registries, we identified all cases of incident MI. Dietary fish consumption was assessed using a semi-quantitative food questionnaire, including twenty-six questions regarding fish intake. In addition, we calculated the intake of total and individual marine n-3 PUFA. During a median follow-up of 17·0 years, we identified 3089 cases of incident MI. For both men and women, a high intake of fatty fish was inversely related to incident MI. Thus, when comparing the highest and the lowest quintile of fatty fish intake, we found a 12 % lower relative risk of MI in men (hazard ratio (HR) 0·88; 95 % CI 0·77, 1·00) and a 22 % lower relative risk in women (HR 0·78; 95 % CI 0·63, 0·96) after adjustments. For women, similar associations were observed for individual and total marine n-3 PUFA. In contrast, intake of lean fish was not associated with MI. In conclusion, incident MI was inversely related to a high intake of fatty fish, but not lean fish. However, test for trends across quintiles was not statistically significant. In general, this study supports the view that consumption of fatty fish may protect against MI.

Marine n-3 polyunsaturated fatty acids lower plasma proprotein convertase subtilisin kexin type 9 levels in pre- and postmenopausal women: A randomised study.

OBJECTIVE: To investigate whether a supplement of 2.2g of marine n-3 polyunsaturated fatty acids (PUFA) influences plasma proprotein convertase subtilisin kexin type 9 (PCSK9) levels in pre- and postmenopausal women. METHODS: Ninety-two healthy women were randomly assigned to consume 2.2g marine n-3 PUFA or a control oil (thistle oil) daily for 12 weeks. Adipose tissue, a long-term marker of dietary intake of seafood was collected at baseline and blood samples were drawn at baseline and after 12 weeks of supplement intake. RESULTS: Plasma PCSK9 levels were significantly reduced by 11.4% for premenopausal women and 9.8% for postmenopausal women after the supplement of 2.2g of marine n-3 PUFA compared with control oil. The mean change of plasma PCSK9 levels between participants receiving marine n-3 PUFA and control oil was 16.1% for premenopausal women and 13.1% for postmenopausal women. There was, however, no correlation between baseline levels of plasma PCSK9 and the fatty acid content of marine n-3 PUFA in adipose tissue. CONCLUSION: This study showed that 2.2g marine n-3 PUFA reduce plasma PCSK9 levels in both pre- and postmenopausal women.

Risk of atrial fibrillation associated with coffee intake: Findings from the Danish Diet, Cancer, and Health study.

BACKGROUND: There have been discrepant findings on whether coffee consumption is associated with the rate of developing atrial fibrillation (AF). METHODS AND RESULTS: We used data on 57,053 participants (27,178 men and 29,875 women) aged 50-64 years in the Danish Diet, Cancer and Health study. All participants provided information on coffee intake via food-frequency questionnaires at baseline. Incident AF was identified using nationwide registries. During a median follow-up of 13.5 years, 3415 AF events occurred. Compared with no intake, coffee consumption was inversely associated with AF incidence, with multivariable-adjusted hazard ratios of 0.93 (95% confidence interval [CI] 0.74-1.15) for more than none to <1 cup/day, 0.88 (95% CI 0.71-1.10) for 1 cup/day, 0.86 (95% CI 0.71-1.04) for 2-3 cups/day, 0.84 (95% CI 0.69-1.02) for 4-5 cups/day, 0.79 (95% CI 0.64-0.98) for 6-7 cups/day and 0.79 (95% CI 0.63-1.00) for >7 cups/day (p-linear trend = 0.02). CONCLUSIONS: In this large population-based cohort study, higher levels of coffee consumption were associated with a lower rate of incident AF.

Effects of perioperative supplementation with omega-3 fatty acids on leukotriene B4 and leukotriene B5 production by stimulated neutrophils in patients with colorectal cancer: a randomized, placebo-controlled intervention trial.

Omega-3 fatty acids (n-3 FA) may have beneficial clinical and immune-modulating effects in surgical patients. In a randomized, double-blind, prospective, placebo-controlled trial, 148 patients referred for elective colorectal cancer surgery received an n-3 FA-enriched oral nutritional supplement (ONS) providing 2.0 g of eicosapentaenoic acid (EPA) and 1.0 g of docosahexaenoic acid (DHA) per day or a standard ONS for seven days before surgery. On the day of operation, there was a significant increase in the production of leukotriene B5 (LTB5) (p < 0.01) and 5-hydroxyeicosapentaenoic acid (5-HEPE) (p < 0.01), a significant decrease in the production of leukotriene B4 (LTB4) (p < 0.01) and a trend for a decrease in the production of 5-hydroxyeicosatetraenoic acid (5-HETE) (p < 0.1) from stimulated neutrophils in the active group compared with controls. There was no association between LTB4 values and postoperative complications. In conclusion, oral n-3 FA exerts anti-inflammatory effects in surgical patients, without reducing the risk of postoperative complications.

A U-shaped association between consumption of marine n-3 fatty acids and development of atrial fibrillation/atrial flutter-a Danish cohort study.

AIMS: Previous studies have suggested a lower risk of atrial fibrillation (AF) with higher intakes of fish and marine n-3 polyunsaturated fatty acids (PUFAs), but the results have been inconsistent. The aim was to investigate the association between consumption of marine n-3 PUFA and development of AF. METHODS AND RESULTS: A total of 57 053 Danish participants 50-64 years of age were enrolled in the Diet, Cancer, and Health Cohort Study between 1993 and 1997. Dietary intake of fish and marine n-3 PUFA was assessed by a semi-quantitative food frequency questionnaire. In total, 3345 incident cases of AF occurred over 13.6 years. Multivariate Cox regression analyses (3284 cases and 55 246 participants) using cubic splines showed a U-shaped association between consumption of marine n-3 PUFA and risk of incident AF, with the lowest risk of AF at a moderate intake of 0.63 g/day. For quintiles of marine n-3 PUFA intake, a 13% statistically significant lower risk of AF was seen in the middle vs. lowest quintile: Q1 reference, Q2 HR 0.92 (95% CI 0.82-1.03), Q3 HR 0.87 (95% CI 0.78-0.98), Q4 HR 0.96 (95% CI 0.86-1.08), and Q5 HR 1.05 (95% CI 0.93-1.18). Intake of total fish, fatty fish, and the individual n-3 PUFA eicosapentaenoic acid, docosahexaenoic acid, and docosapentaenoic acid also showed U-shaped associations with incident AF. CONCLUSION: We found a U-shaped association between consumption of marine n-3 PUFA and risk of incident AF, with the lowest risk close to the median intake of total marine n-3 PUFA (0.63 g/day).

The effect of low-dose marine n-3 fatty acids on plasma levels of sCD36 in overweight subjects: a randomized, double-blind, placebo-controlled trial.

CD36 is a scavenger receptor involved in lipid uptake and inflammation. Recently, non-cell-bound CD36 (sCD36) was identified in plasma and suggested to be a marker of lipid accumulation in the vessel wall. Marine n-3 polyunsaturated fatty acids (PUFA) may have cardioprotective effects. This study evaluated the effect of marine n-3 PUFA on sCD36 levels in overweight subjects. Fifty overweight subjects were randomized to 1.1 g of n-3 PUFA or 2 g of olive oil daily for six weeks. Neutrophils were isolated at baseline and after six weeks of treatment while an adipose tissue biopsy was obtained at baseline. The content of n-3 PUFA in adipose tissue and neutrophils was analyzed by gas chromatography, while plasma levels of sCD36 were determined using an enzyme-linked immunosorbent assay (ELISA). After six weeks of supplement plasma sCD36 did not differ between supplements (P = 0.18). There was no significant correlation between plasma sCD36 levels and n-3 PUFA in neutrophils at baseline (r = -0.02, P = 0.88), after six weeks supplement (r = -0.03, P = 0.85) or in adipose tissue (r = 0.14, P = 0.34). This study therefore does not provide evidence for a cardioprotective effect of n-3 PUFA acting through a CD36-dependent mechanism.