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Objectives To investigate the 5-year all-cause mortality in patients with RA compared with the general population. Methods This was a nationwide population-based matched cohort study. RA patients diagnosed between 1996 and the end of 2015 were identified using administrative heath registries and followed until the end of 2020 allowing 5 years of follow-up. Patients with incident RA were matched 1:5 on year of birth and sex with non-RA individuals from the Danish general population. Time-to-event analyses were performed using the pseudo-observation approach. Results Compared with matched controls in 1996–2000, the risk difference for RA patients ranged from 3.5% (95% CI 2.7%, 4.4%) in 1996–2000 to –1.6% (95% CI –2.3%, –1.0%) in 2011–15, and the relative risk from 1.3 (95% CI 1.2, 1.4) in 1996–2000 to 0.9 (95% CI 0.8, 0.9) in 2011–15. The age-adjusted 5-year cumulative incidence proportion of death for a 60-year-old RA patient decreased from 8.1% (95% CI 7.3%, 8.9%) when diagnosed in 1996–2000 to 2.9% (95% CI 2.3%, 3.5%) in 2011–15, and for matched controls from 4.6% (95% CI 4.2%, 4.9%) to 2.1% (95% CI 1.9%, 2.4%). Excess mortality persisted in women with RA throughout the study period, while the mortality risk for men with RA in 2011–15 was similar to their matched controls. Conclusions Enhanced improvement in mortality was found in RA patients compared with matched controls, but for sex-specific differences excess mortality was only persistent in women with RA. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The cardiovascular benefit from n‐3 polyunsaturated fatty acids (PUFAs) after acute myocardial infarction (AMI) is controversial, and the importance of serum eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) concentrations for clinical events is unclear. Objectives: To assess changes in EPA and DHA serum concentrations during n‐3 PUFA supplementation and their association with incident cardiovascular events. Methods: In the OMEMI trial, elderly patients with a recent AMI were randomized to 1.8 g/day of EPA/DHA or control (corn oil) for 2 years. The primary outcome was a composite of AMI, coronary revascularization, stroke, heart failure hospitalization, or all‐cause death (major adverse cardiovascular event [MACE]) and the secondary outcome was new‐onset atrial fibrillation (AF). Results: EPA and DHA measurements were available in 881 (92% of survivors) participants at randomization and study completion. EPA and DHA increased in the active treatment arm (n = 438) by a median of 87% and 16%, respectively. Greater on‐treatment increases in EPA and DHA were associated with decreasing triglycerides, increasing high‐density lipoprotein cholesterol, and lower baseline EPA and DHA concentrations. Greater on‐treatment increases in EPA were associated with lower risk of MACE (adjusted hazard ratio 0.86 [95% confidence interval, CI, 0.75–0.99], p = 0.034), and higher risk of AF (adjusted hazard ratio (HR) 1.36 [95% CI 1.07–1.72], p = 0.011). Although there were similar tendencies for DHA changes and outcomes, these associations were not statistically significant (HR 0.84 [0.66–1.06] for MACE and 1.39 [0.90–2.13] for AF). Conclusion: Greater on‐treatment increases in EPA were associated with lower risk of MACE and higher risk of new‐onset AF. These data suggest that the cardiovascular effects of increasing n‐3 PUFA levels through supplements are complex, involving both potential benefits and harm. [ABSTRACT FROM AUTHOR]

Intake of vegetables is recommended for the prevention of myocardial infarction (MI). However, vegetables make up a heterogeneous group, and subgroups of vegetables may be differentially associated with MI. The aim of this study was to examine replacement of potatoes with other vegetables or subgroups of other vegetables and the risk of MI. Substitutions between subgroups of other vegetables and risk of MI were also investigated. We followed 29 142 women and 26 029 men aged 50–64 years in the Danish Diet, Cancer and Health cohort. Diet was assessed at baseline by using a detailed validated FFQ. Hazard ratios (HR) with 95 % CI for the incidence of MI were calculated using Cox proportional hazards regression. During 13·6 years of follow-up, 656 female and 1694 male cases were identified. Among women, the adjusted HR for MI was 1·02 (95 % CI 0·93, 1·13) per 500 g/week replacement of potatoes with other vegetables. For vegetable subgroups, the HR was 0·93 (95 % CI 0·77, 1·13) for replacement of potatoes with fruiting vegetables and 0·91 (95 % CI 0·77, 1·07) for replacement of potatoes with other root vegetables. A higher intake of cabbage replacing other vegetable subgroups was associated with a statistically non-significant higher risk of MI. A similar pattern of associations was found when intake was expressed in kcal/week. Among men, the pattern of associations was overall found to be similar to that for women. This study supports food-based dietary guidelines recommending to consume a variety of vegetables from all subgroups. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Greater consumption of red meat has been associated with a higher risk of type 2 diabetes mellitus (T2DM). A decreased intake of red meat and simultaneous increased intake of other high-protein foods may be associated with a lower risk of T2DM. These analyses of specific food replacements for red meat may provide more accurate dietary advice. Objective We examined the association between a decrease in intake of red meat accompanied by an increase in other major dietary protein sources and risk of T2DM. Methods We prospectively followed 27,634 males in the Health Professionals Follow-up Study, 46,023 females in the Nurses' Health Study, and 75,196 females in the Nurses' Health Study II. Diet was assessed by a validated FFQ and updated every 4 y. Cox proportional hazards models adjusted for T2DM risk factors were used to model the food replacements. We calculated HRs and 95% CIs for the T2DM risk associated with replacements of 1 daily serving of red meat with another protein source. Results During 2,113,245 person-years of follow-up, we identified 8763 incident T2DM cases from 1990 to 2013. In the pooled analyses, a decrease in total red meat intake during a 4-y period replaced with another common protein food was associated with a lower risk of T2DM in the subsequent 4-y period. The HR (95% CI) per 1 serving/d was 0.82 (0.75, 0.90) for poultry, 0.87 (0.77, 0.98) for seafood, 0.82 (0.78, 0.86) for low-fat dairy, 0.82 (0.77, 0.86) for high-fat dairy, 0.90 (0.81, 0.99) for eggs, 0.89 (0.82, 0.98) for legumes, and 0.83 (0.78, 0.89) for nuts. The associations were present for both unprocessed and processed red meat, although stronger for the replacement of processed red meat. Conclusions Replacing red meat consumption with other protein sources was associated with a lower risk of T2DM. [ABSTRACT FROM AUTHOR]

Background: High levels of plasma marine n-3 fatty acids (n-3FAs) are associated with improved patient and graft survival in renal transplant recipients (RTRs). The aim of this study was to evaluate the utility of a new food frequency questionnaire (FFQ) to estimate marine n-3FA consumption in future epidemiological research. Methods: We developed an FFQ with a simple design of 10 questions to assess intake of marine sources of n-3FAs. RTRs included in the recent ORENTRA trial (n = 132) completed the study FFQ at the baseline visit eight weeks after engraftment and at the end of study visit one year post-transplant. We measured the reference biomarker plasma phospholipid (PL) marine n-3FA levels by gas chromatography at the same time points to evaluate association and degree of agreement between FFQ based marine n-3FA consumption estimates and the biomarker. Results: The median plasma PL marine n-3FA level was 6.0 weight percentage (wt)% (interquartile range [IQR] 4.7 to 7.3) at baseline and 6.3 wt% (IQR 4.8 to 7.4) at end of study. Median FFQ based marine n-3FA consumption estimates were 22.8 g/month (IQR 13.0 to 34.0) at baseline and 20.3 g/month (IQR 14.5 to 32.3) at end of study. FFQ based marine n-3FA consumption estimates showed a moderate correlation with plasma PL marine n-3FA levels at baseline (Spearman's correlation coefficient rs = 0.43, p<0.001) and a stronger correlation at end of study (rs = 0.62, p<0.001). Bland Altman plots showed a reasonable degree of agreement between the two methods at both time points. Conclusions: Marine n-3FA consumption estimates based on the FFQ showed a moderate correlation with the reference biomarker plasma PL marine n-3FA levels. The FFQ might be useful in epidemiological studies where resources are limited. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Marine n-3 PUFA exert beneficial effects that might inhibit atherosclerosis and reduce vascular disease. Previous studies have, however, reported conflicting results and here we have summarised the early history and the most recent findings from follow-up studies and randomised clinical trials investigating marine n-3 PUFA in relation to the risk of atherosclerotic CVD. Most follow-up studies have suggested that the intake of marine n-3 PUFA may be associated with a lower risk of CVD. Recent studies have also shown that it is important to focus on substitution issues and dietary patterns. Further, the use of gold standard biomarkers of fatty acid exposure such as adipose tissue should be encouraged. Findings from clinical supplemental trials have shown conflicting results and findings from previous meta-analyses and guidelines have generally not supported the use of fish oil supplements for the prevention of CVD. However, a recent meta-analysis including three recent large clinical trials with fish oil supplements reported a moderate beneficial effect on cardiovascular endpoints. Interestingly, results from a large clinical trial (REDUCE-IT) have suggested that supplementation with a high dose of purified EPA ethyl ester for 4⋅9 years significantly and markedly reduced the risk of cardiovascular events in patients with CVD and mild hypertriglyceridaemia; findings that need to be confirmed. While it seems appropriate to recommend consumption of fish, particular fatty fish for prevention of CVD, an effect of fish oil supplements is probably at best marginal perhaps apart from patients with hypertriglyceridaemia. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to investigate the association between adipose tissue content of the plant-derived n-3 fatty acid, alpha-linolenic acid, and the rate of incident peripheral artery disease (PAD). Methods: We conducted a case-cohort study nested within the Danish Diet, Cancer and Health cohort (n = 57,053), which was established between 1993 and 1997. Potential PAD cases were identified using linkage with The Danish National Patient Register and all potential cases were validated. Adipose tissue samples from the buttock were collected at baseline and fatty acid composition was determined in cases and in a random sample (n = 3500) from the cohort by gas chromatography. Statistical analyses were performed using weighted Cox regression allowing for different baseline hazards among sexes. Results: During a median of 13.5 years of follow-up, we identified 863 PAD cases with complete information. The median adipose tissue content of ALA in the sub-cohort (n = 3197) was 0.84% (interquartile range 0.73–0.94%) of total fatty acids. In multivariate analyses including adjustment for established risk factors, we observed a U-shaped association between ALA in adipose tissue and rate of PAD, but the association was not statistically significant (P = 0.131). Similar pattern of associations were observed between ALA content in adipose tissue and the rate of PAD among men and women. Conclusions: We found indications of a U-shaped association between adipose tissue content of ALA and the rate of PAD, but the association was not statistically significant. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Telomeres are non-coding sequences at the end of eukaryote chromosomes, which in complex with associated proteins serve to protect subtelomeric DNA. Telomeres shorten with each cell division, are regarded as a biomarker for aging and have also been suggested to play a role in atherosclerosis and cardiovascular disease (CVD). The aim of the present study was to explore the associations between leukocyte telomere length and serum polyunsaturated fatty acids, diet, cardiovascular risk factors and features of myocardial infarction (MI) in elderly patients.Methods: The material is based upon the first 299 included patients in the OMEMI trial, where patients aged 70-82 years of age are randomized to receive omega-3 supplements or corn oil (placebo) after MI. Patients were included 2-8 weeks after the index MI. DNA was extracted from whole blood, and leukocyte telomere length (LTL) was analyzed by qPCR and reported as a number relative to a reference gene. Serum long chain polyunsaturated fatty acid (LCPUFA) content was analyzed by gas chromatography. Diet was evaluated with the validated SmartDiet food frequency questionnaire. Medical records, patient interviews and clinical examination provided previous medical history and anthropometric data. Non-parametric statistical tests were used.Results: Median (25, 75 percentile) LTL was 0.55 (0.42, 0.72). Patients had a median age of 75 years, 70.2% were male and 45.2% used omega-3 supplements. There was a weak, but significant correlation between LTL and linoleic acid (r = 0.139, p = 0.017), but not with other LCPUFAs. There was a trend towards longer telomeres with a healthier diet, but this did not reach statistical significance (p = 0.073). No associations were found between LTL and CVD risk factors or features of MI.Conclusions: In our population of elderly with a recent myocardial infarction LTL was associated with linoleic acid concentrations, but not with other LCPUFAs. Patients with a healthy diet tended to have longer telomeres. The limited associations may be due to age and the narrow age-span in our population. Further studies, designed to detect longitudinal changes should be performed to explore the role of telomeres in cardiovascular aging.Trial Registration: Clinical trials no. NCT01841944, registration date April 29, 2013. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The risk of coronary heart disease associated with intake of individual trans fatty acids (TFAs) is not clear. Adipose tissue content of TFAs is a biomarker of TFA intake and metabolism. Objective: We investigated the rate of myocardial infarction (MI) associated with the adipose tissue content of total 18:1t, isomers of 18:1t (18:1 Δ6-10t and 18:1 Δ11t) and 18:2 Δ9c, 11t. Methods: A case-cohort study, nested within the Danish Diet, Cancer and Health cohort (n = 57,053), was conducted, which included a random sample (n = 3156) of the total cohort and all incident MI cases (n = 2148) during follow-up (14 years). Information on MI cases was obtained by linkage with nationwide registers and validated. Adipose tissue was taken from the participants buttocks and the fatty acid composition was determined by gas chromatography. Results: Women with higher adipose tissue content of total 18:1t had a 57% higher MI rate (quintiles 5 versus 1, hazard ratio, 1.57; 95% confidence interval, 1.12–2.20; P-trend = 0.011) and women with higher content of 18:1 Δ6-10t had a 76% higher MI rate (quintiles 5 versus 1, hazard ratio, 1.76; 95% confidence interval, 1.23–2.51; P-trend = 0.002). No association between 18:1 Δ11t content and MI rate was observed. In men, no associations between adipose tissue content of total 18:1t and 18:1 Δ6-10t and MI rate were observed. However, men with higher content of 18:1 Δ11t had a 48% higher MI rate (quintiles 5 versus 1, hazard ratio, 1.48; 95% confidence interval, 1.17–1.86; P-trend = 0.003). Adipose tissue content of 18:2 Δ9c, 11t was not associated with MI rate in women or men. Conclusions: Adipose tissue content of 18:2 Δ9c, 11t was not associated with MI rate in women or men, whereas higher contents of isomers of 18:1t were associated with higher MI rates but the associations for individual 18:1t isomers differed, however, in women and men. [ABSTRACT FROM AUTHOR]

Marine n -3 PUFA may improve autonomic dysfunction by an increase in heart rate variability (HRV) and may reduce the risk of malignant ventricular arrhythmias. Only a few smaller studies have examined such effects in patients on chronic dialysis, who often have autonomic dysfunction and a high risk of sudden cardiac death, which accounts for almost 30 % of all deaths. This cross-sectional study investigated the association between the plasma phospholipid content of n -3 PUFA and 24-h HRV or ventricular arrhythmias in patients on chronic dialysis. A 48-h Holter monitoring was performed on 169 patients on in-centre dialysis (83 %), home haemodialysis (10 %) or peritoneal dialysis (7 %) obtaining data on arrhythmias (n 152) and 24-h HRV (n 135). The mean overall HRV (standard deviation of normal intervals (SDNN)) was low and 71 % had a reduced overall HRV (SDNN<100 ms) indicating autonomic dysfunction. No significant associations between plasma phospholipid content of total marine n -3 PUFA, EPA (22 : 5 n -3) or DHA (22 : 6 n -3) and time-domain or frequency-domain HRV were detected in crude or adjusted linear regression analysis. However, a higher plasma phospholipid content of DHA was associated with a significantly lower proportion of patients with ventricular tachycardia (higher DHA-tertile: 9 % v. lower DHA-tertile: 28 %, P =0·02). In conclusion, the content of marine n -3 PUFA i n plasma phospholipids was not associated with 24-h HRV, but a higher plasma phospholipid content of DHA was associated with a lower occurrence of ventricular tachycardia suggesting an antiarrhythmic effect of marine n -3 PUFA in patients on chronic dialysis. [ABSTRACT FROM AUTHOR]

Background: Intake of the plant-derived omega-3 (n-3) fatty acid α-linolenic acid (ALA) may reduce the risk of ischemic stroke.Objective: We have investigated the associations between dietary intake of ALA and the risk of ischemic stroke and ischemic stroke subtypes.Methods: This was a follow-up study. A total of 57,053 participants aged 50-64 y were enrolled into the Danish Diet, Cancer and Health cohort between 1993 and 1997. Intake of ALA was assessed by a validated semiquantitative food frequency questionnaire. Potential incident cases of ischemic stroke were identified in the Danish National Patient Register, validated, and classified into subtypes based on assumed etiology. Statistical analyses were performed via Cox proportional hazard regression with adjustment for established ischemic stroke risk factors.Results: A total of 1859 ischemic stroke cases were identified during a median of 13.5 y of follow-up. In multivariable analyses using restricted cubic splines adjusting for traditional risk factors for ischemic stroke, we observed no clear associations between dietary intake of ALA and the risk of total ischemic stroke or any of its subtypes including ischemic stroke due to large artery atherosclerosis, ischemic stroke due to small-vessel occlusion, and ischemic stroke due to cardio-embolism.Conclusion: Dietary intake of ALA was neither consistently nor appreciably associated with the risk of ischemic stroke or ischemic stroke subtypes among middle-aged Danish men and women. This study was registered at clinicaltrials.gov as NCT03258983. [ABSTRACT FROM AUTHOR]

Objectives The aim of this study was to investigate the association between adipose tissue content of total saturated fatty acids including myristic (C14:0), palmitic (C16:0) and stearic (C18:0) acid, as a measure of exposure to saturated fatty acids and the risk of incident atrial fibrillation. Materials and methods A total of 57 053 Danish men and women aged 50-64 years participating in the Diet, Cancer and Health cohort had an adipose tissue biopsy taken at baseline, and this was analysed for saturated fatty acids content by gas chromatography. Follow-up was registry based and in this case-cohort study we used all cases and a randomly drawn subcohort of 3500 participants representative for the entire cohort. Results Data were analysed using weighted Cox proportional hazards regression. During a median follow-up of 14.6 years, a total of 4722 cases of incident atrial fibrillation were diagnosed. For both men and women, no association between adipose tissue content of total saturated fatty acids and the risk of atrial fibrillation could be demonstrated. Conclusion We did not find an association between adipose tissue content of total saturated fatty acids and the risk of incident atrial fibrillation. [ABSTRACT FROM AUTHOR]

Aims: To determine the positive predictive values for stroke discharge diagnoses, including subarachnoidal haemorrhage, intracerebral haemorrhage and cerebral infarction in the Danish National Patient Register. Methods: Participants in the Danish cohort study Diet, Cancer and Health with a stroke discharge diagnosis in the National Patient Register between 1993 and 2009 were identified and their medical records were retrieved for validation of the diagnoses. Results: A total of 3326 records of possible cases of stroke were reviewed. The overall positive predictive value for stroke was 69.3% (95% confidence interval (CI) 67.8–70.9%). The predictive values differed according to hospital characteristics, with the highest predictive value of 87.8% (95% CI 85.5–90.1%) found in departments of neurology and the lowest predictive value of 43.0% (95% CI 37.6–48.5%) found in outpatient clinics. Conclusions: The overall stroke diagnosis in the Danish National Patient Register had a limited predictive value. We therefore recommend the critical use of non-validated register data for research on stroke. The possibility of optimising the predictive values based on more advanced algorithms should be considered. [ABSTRACT FROM AUTHOR]

Background: The 5-lipoxygenase pathway has been linked to atherothrombotic disease, and a functional tandem repeat polymorphism in the arachidonate lipoxygenase-5 (ALOX-5) gene has been associated with the risk of myocardial infarction (MI). Interestingly, 2 studies have reported an interaction between dietary intakes of the ALOX-5 substrates, arachidonic acid (AA) and eicosapentaenoic acid (EPA), and genotype.Objective: We investigated whether the interactions between the ALOX-5 tandem repeat polymorphism (rs59439148) and adipose tissue AA and EPA were associated with incident MI.Methods: In the Danish Diet, Cancer and Health study, we conducted a case-cohort study including 3089 participants with incident MI identified from national registries and a randomly selected subcohort of 3000 participants. Participants were men and women with a median age of 56 y at baseline and no previous history of cancer. Adipose tissue and blood samples were collected at baseline along with comprehensive questionnaires on lifestyle and demographic data. The ALOX-5 tandem repeat polymorphism was genotyped by multititer plate sequencing. Associations were analyzed by using Cox proportional hazards models.Results: We observed a higher risk of MI for homozygous carriers of the variant alleles in the fifth quintile of AA content than for the reference group with the lowest quintile of AA and carrying the wild-type allele (HR: 3.02; 95% CI: 1.41, 6.44). In contrast, homozygotes for the variant alleles tended to have a higher risk of MI when comparing the lowest quintile of EPA content with the reference group with the highest quintile of EPA and carrying the wild-type allele (HR: 2.15; 95% CI: 0.91, 5.09; P = 0.08). Although our results suggested interactions between the polymorphism and adipose tissue AA and EPA, a quantitative evaluation of interaction by calculating the relative excess risk due to interactions was not significant.Conclusions: Adipose tissue EPA and AA and the ALOX-5 tandem repeat polymorphism did not significantly interact to affect the risk of MI. However, the results should be replicated in larger, heterogeneous populations. [ABSTRACT FROM AUTHOR]

Background: Adding long-chain n-3 (ω-3) polyunsaturated fatty acids (PUFAs) to a rodent diet reduces fat mass and prevents the development of obesity, but evidence of a similar effect in humans is rather limited.Objectives: We investigated the associations between dietary intake and adipose tissue content of long-chain n-3 PUFAs and subsequent 5-y change in body weight and waist circumference in humans. Effect modification by the carbohydrate:protein ratio and glycemic index was also investigated.Design: A total of 29,152 participants included in the Diet, Cancer, and Health cohort were followed. Dietary intake was assessed with the use of a validated 192-item semiquantitative food-frequency questionnaire. Adipose tissue content of fatty acids was determined by gas chromatography in a random sample of the cohort (n = 1660). Anthropometric measurements were taken at baseline and 5 y later. Associations were investigated with the use of a linear regression model.Results: For high (1.22 g/d) compared with low (0.28 g/d) total n-3 PUFA intake, the difference in 5-y weight change was 147.6 g (95% CI: -42.3, 337.5 g); P-trend = 0.088. No associations between the individual n-3 PUFAs eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid were observed. Intake of n-3 PUFAs was not associated with a 5-y change in waist circumference. For high (0.16%) compared with low (0.06%) adipose tissue content of EPA, the difference in 5-y weight change was -649.6 g (95% CI: -1254.2, -44.9 g); P-trend = 0.027. No associations between total n-3 PUFA, docosapentaenoic acid, and docosahexaenoic acid and 5-y weight change were observed. Adipose tissue content of n-3 PUFAs was not associated with 5-y change in waist circumference. No effect modification by carbohydrate:protein ratio or glycemic index was found.Conclusion: Dietary intake and adipose tissue content of long-chain n-3 PUFAs were neither consistently nor appreciably associated with change in body weight or waist circumference. [ABSTRACT FROM AUTHOR]

Background: The 5-lipoxygenase pathway (5-LOX) has been implicated in the development of cardiovascular disease and studies have suggested that genetic polymorphisms related to key enzymes in this pathway may confer risk of myocardial infarction (MI). This study investigated the association of pre-selected genetic polymorphisms in four candidate genes of 5-LOX (arachidonate 5-lipoxygenase and its activating protein (ALOX-5 and FLAP), leukotriene A4 hydroxylase (LTA4-H) and leukotriene C4 synthase (LTC4-S)) with incident MI. Methods: In a Danish cohort including 57,053 participants, aged 50–64 at enrolment and recruited from 1993–97, we conducted a case-cohort study including cases with incident MI and a randomly selected sub cohort of 3,000 participants. Cases were identified from national registries through July 2013. A total of 22 SNPs were selected and genotyped using the commercially available KASP™ assay. A tandem-repeat polymorphism, located in the ALOX-5 gene, was genotyped by multi-titre plate sequencing. Haplotypes were inferred using PHASE 2.1. Results: During a median follow-up of 17.0 years we identified 3,089 cases of incident MI. In FLAP, two SNPs were negatively associated with incident MI (rs9551963 & rs17222842) while one SNP (rs2247570) located in LTA4-H, was associated with higher risk of MI when comparing subjects with two copies of the variant allele to homozygotes for the wild type. However, only rs17222842 remained significantly associated with MI after correcting for multiple testing. Furthermore, the promoter polymorphism rs59439148 was associated with risk of MI in men. For male carriers of two variant alleles we found a hazard ratio of 1.63 (95% CI: 1.06;2.52) compared to homozygotes for the wild type. Previously described haplotypes (Hap-A -B, -E and -K) were not associated with MI in our population. Conclusion: In conclusion, some common polymorphisms in the 5-lipoxygenase pathway were modestly associated with incident MI, suggesting a potential role for this pathway in the development of cardiovascular disease. [ABSTRACT FROM AUTHOR]

Background: Patients with chronic kidney disease have a markedly increased cardiovascular mortality compared with the general population. Long chain n-3 polyunsaturated fatty acids have been suggested to possess cardioprotective properties. This cross-sectional and comparative study evaluated correlations between hemodynamic measurements, resistance artery function and fish consumption to the content of long chain n-3 polyunsaturated fatty acids in adipose tissue, a long-term marker of seafood intake. Methods: Seventeen patients with chronic kidney disease stage 5 + 5d and 27 healthy kidney donors were evaluated with hemodynamic measurements before surgery; from these subjects, 11 patients and 11 healthy subjects had vasodilator properties of subcutaneous resistance arteries examined. The measurements were correlated to adipose tissue n-3 polyunsaturated fatty acids. Information on fish intake was obtained from a dietary questionnaire and compared with adipose tissue n-3 polyunsaturated fatty acids. Results: Fish intake and the content of n-3 polyunsaturated fatty acids in adipose tissue did not differ between patients and controls. n-3 polyunsaturated fatty acid levels in adipose tissue were positively correlated to systemic vascular resistance index; (r = 0.44; p = 0.07 and r = 0.62; p < 0.05, chronic kidney disease and healthy subjects respectively) and negatively correlated to cardiac output index (r = -0.69; p < 0.01 and r = -0.50; p < 0.05, chronic kidney disease and healthy subjects respectively). No correlation was observed between n-3 polyunsaturated fatty acid levels in adipose tissue and vasodilator properties in resistance arteries. n-3 PUFA content in adipose tissue increased with increasing self-reported fish intake. Conclusions: The correlations found, suggest a role for n-3 polyunsaturated fatty acids in hemodynamic properties. However, this is apparently not due to changes in intrinsic properties of the resistance arteries as no correlation was found to n-3 polyunsaturated fatty acids. [ABSTRACT FROM AUTHOR]

Red meat has been suggested to be adversely associated with risk of myocardial infarction (MI), whereas vegetable consumption has been found to be protective. The aim of this study was to investigate substitutions of red meat, poultry and fish with vegetables or potatoes for MI prevention. We followed up 29 142 women and 26 029 men in the Danish Diet, Cancer and Health study aged 50–64 years with no known history of MI at baseline. Diet was assessed by a validated 192-item FFQ at baseline. Adjusted Cox proportional hazard models were used to calculate hazard ratios (HR) and 95 % CI for MI associated with specified food substitutions of 150 g/week. During a median follow-up of 13·6 years, we identified 656 female and 1694 male cases. Among women, the HR for MI when replacing red meat with vegetables was 0·94 (95 % CI 0·90, 0·98). Replacing fatty fish with vegetables was associated with a higher risk of MI (HR 1·23; 95 % CI 1·05, 1·45), whereas an inverse, statistically non-significant association was found for lean fish (HR 0·93; 95 % CI 0·83, 1·05). Substituting poultry with vegetables was not associated with risk of MI (HR 1·00; 95 % CI 0·90, 1·11). Findings for substitution with potatoes were similar to findings for vegetables. Among men, a similar pattern was observed, but the associations were weak and mostly statistically non-significant. This study suggests that replacing red meat with vegetables or potatoes is associated with a lower risk of MI, whereas replacing fatty fish with vegetables or potatoes is associated with a higher risk of MI. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Intake of the plant-derived ω3 (n-3) fatty acid α-linolenic acid (ALA, 18:3; n-3) may reduce coronary heart disease (CHD) risk, but the results of previous studies have been inconsistent. Objective: We aimed to investigate the association between dietary intake of ALA, adipose tissue content of ALA, and risk of incident myocardial infarction (MI). Design: A total of 57,053 participants, aged 50-64 y, were enrolled in the prospective Danish cohort study Diet, Cancer and Health between 1993 and 1997. Dietary intake of ALA was assessed with the use of a validated semiquantitative food-frequency questionnaire in the full cohort, whereas the adipose tissue content of ALA was determined with the use of gas chromatography in all incident MI cases and in a random sex-stratified sample of the total cohort (n = 3500). Results: During a median of 17 y of follow-up, we identified 2177 male and 912 female cases of MI. After appropriate exclusions, we included 2124 men and 854 women for analyses of dietary intake of ALA, whereas 1994 men and 770 women were included in the analysis of the adipose tissue content of ALA. In multivariate analyses that were conducted with the use of restricted cubic splines and adjusted for established CHD risk factors, weak positive associations in men and weak U-shaped associations in women were shown between both dietary intake and the adipose tissue content of ALA and risk of MI, but these associations were not statistically significant. Additional adjustments for dietary factors did not influence the observed associations numerically. Conclusion: This study suggests that ALA has no appreciable association with risk of incident MI in either men or women. [ABSTRACT FROM AUTHOR]

Red meat has been suggested to be adversely associated with risk of myocardial infarction (MI), but previous studies have rarely taken replacement foods into consideration. We aimed to investigate optimal substitutions between and within the food groups of red meat, poultry and fish for MI prevention. We followed up 55 171 women and men aged 50-64 years with no known history of MI at recruitment. Diet was assessed by a validated 192-item FFQ at baseline. Adjusted Cox proportional hazard models were used to calculate hazard ratios (HR) and 95 % CI for specified food substitutions of 150 g/week. During a median follow-up time of 13⋅6 years, we identified 656 female and 1694 male cases. Among women, the HR for replacing red meat with fatty fish was 0⋅76 (95 % CI 0⋅64, 0⋅89), whereas the HR for replacing red meat with lean fish was 1⋅00 (95 % CI 0⋅89, 1⋅14). Similarly, replacing poultry with fatty but not lean fish was inversely associated with MI: the HR was 0⋅81 (95 % CI 0⋅67, 0⋅98) for fatty fish and was 1⋅08 (95 % CI 0⋅92, 1⋅27) for lean fish. The HR for replacing lean with fatty fish was 0⋅75 (95 % CI 0⋅60, 0⋅94). Replacing processed with unprocessed red meat was not associated with MI. Among men, a similar pattern was found, although the associations were not statistically significant. This study suggests that replacing red meat, poultry or lean fish with fatty fish is associated with a lower risk of MI. [ABSTRACT FROM AUTHOR]

Background. Epidemiological and randomized clinical trials indicate that marine polyunsaturated n-3 fatty acids (n-3 PUFAs) may have cardioprotective effects. Aim. Evaluate the associations between serum fatty acid profile, traditional risk factors, the presence of cardiovascular diseases (CVD), and peak Troponin T (TnT) levels in elderly patients with an acute myocardial infarction (AMI). Materials and Methods. Patients (n=299) consecutively included in the ongoing Omega-3 fatty acids in elderly patients with myocardial infarction (OMEMI) trial were investigated. Peak TnT was registered during the hospital stay. Serum fatty acid analysis was performed 2–8 weeks later. Results. No significant correlations between peak TnT levels and any of the n-3 PUFAs were observed. However, patients with a history of atrial fibrillation had significantly lower docosahexaenoic acid levels than patients without. Significantly lower peak TnT levels were observed in patients with a history of hyperlipidemia, angina, MI, atrial fibrillation, intermittent claudication, and previous revascularization (all p<0.02). Conclusions. In an elderly population with AMI, no association between individual serum fatty acids and estimated myocardial infarct size could be demonstrated. However, a history of hyperlipidemia and the presence of CVD were associated with lower peak TnT levels, possibly because of treatment with cardioprotective medications. [ABSTRACT FROM AUTHOR]

Background. Marine n-3 polyunsaturated fatty acids (PUFAs) may exert beneficial effects on inflammation, fibrosis, endothelial function, lipid profile and blood pressure that may prevent graft loss. Methods. In this observational cohort study in Norwegian renal transplant recipients (n = 1990), transplanted between 1999 and 2011, associations between plasma marine n-3 PUFA levels and graft losswere assessed bymultivariable Cox proportional hazard regression analysis. Plasma phospholipid fatty acid composition was determined by gas chromatography and individual fatty acids recorded as weight percentage (wt%) of total fatty acids in a stable phase 10 weeks after transplantation. Results. During a median follow-up time of 6.8 years, 569 (28.6%) renal allografts were lost, either due to patient death (n = 340, 59.8% of graft loss) or graft loss in surviving patients (n = 229, 40.2%). Plasma marine n-3 PUFA levels ranged from 1.35 to 23.87 wt%, with a median level of 7.95 wt% (interquartile range 6.20-10.03 wt%). When adjusting for established graft loss risk factors, there was a 11% reduced risk of graft loss for every 1.0 wt% increase in marine n-3 PUFA level [adjusted hazard ratio (HR) 0.89; 95% confidence interval (CI) 0.84-0.93], and a 10% reduced risk of graft loss in surviving patients (adjusted HR 0.90; 95% CI 0.84-0.97). Conclusion. High levels of plasma marine n-3 PUFAs were associated with better renal allograft survival. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM PUBLISHER]

Previous studies have suggested that the intake of trans-fatty acids (TFA) plays a role in the development of obesity. The proportions of adipose tissue fatty acids not synthesised endogenously in humans, such as TFA, usually correlate well with the dietary intake. Hence, the use of these biomarkers may provide a more accurate measure of habitual TFA intake than that obtained with dietary questionnaires. The objective of the present study was to investigate the associations between the proportions of specific TFA in adipose tissue and subsequent changes in weight and waist circumference (WC). The relative content of fatty acids in adipose tissue biopsies from a random sample of 996 men and women aged 50–64 years drawn from a Danish cohort study was determined by GC. Baseline data on weight, WC and potential confounders were available together with information on weight and WC 5 years after enrolment. The exposure measures were total trans-octadecenoic acids (18 : 1t), 18 : 1 Δ6-10t, vaccenic acid (18 : 1 Δ11t) and rumenic acid (18 : 2 Δ9c, 11t). Data were analysed using multiple regression with cubic spline modelling. The median proportion of total adipose tissue 18 : 1t was 1·52 % (90 % central range 0·98, 2·19) in men and 1·47 % (1·01, 2·19) in women. No significant associations were observed between the proportions of total 18 : 1t, 18 : 1 Δ6-10t, vaccenic acid or rumenic acid and changes in weight or WC. The present study suggests that the proportions of specific TFA in adipose tissue are not associated with subsequent changes in weight or WC within the exposure range observed in this population. [ABSTRACT FROM PUBLISHER]

The intake of marine n-3 PUFA has been shown to decrease the risk of CVD in a number of studies. Since the development of CVD is often a lifelong process, marine n-3 PUFA intake early in life may also affect the development of later CVD. The aim of the present study was to investigate the association between maternal intake of marine n-3 PUFA during the second trimester of pregnancy and factors associated with cardiometabolic risk in the 20-year-old offspring. The study was based on the follow-up of the offspring of a Danish pregnancy cohort who participated in a study conducted from 1988 to 1989. A total of 965 pregnant women were originally included in the cohort and detailed information about the intake of marine n-3 PUFA during the second trimester was collected. In 2008–9, the offspring were invited to participate in a clinical examination including anthropometric, blood pressure (BP) and short-term heart rate variability measurements. Also, a fasting venous blood sample was drawn from them. Multiple linear regression modelling, using the lowest quintile of marine n-3 PUFA intake as the reference, was used to estimate the association with all outcomes. A total of 443 offspring participated in the clinical examination. No association between the intake of marine n-3 PUFA during the second trimester of pregnancy and offspring adiposity, glucose metabolism, BP or lipid profile was found. In conclusion, no association between the intake of marine n-3 PUFA during the second trimester of pregnancy and the factors associated with cardiometabolic risk in the 20-year-old offspring could be detected. [ABSTRACT FROM PUBLISHER]

Background: Epidemiologic studies have suggested that a higher intake of flavonoids may be associated with lower risk of ischemic heart disease. However, the traditional estimation of flavonoid intake by using dietary assessment methods is affected by subjective measures. Objective: We examined whether the objective measurement of dietary flavonoids excreted in urine is associated with lower risk of acute coronary syndrome (ACS). Design: A case-control study was nested in the Danish Diet, Cancer and Health cohort study. Cases were identified in participants who had received a first-time ACS diagnosis in the Danish National Patient Registry after the time of enrollment into the Diet, Cancer and Health study. The excretion of 10 flavonoids, which represent 5 subclasses, was measured in spot urine samples by using liquid chromatography-mass spectrometry. Results: A total of 393 eligible cases with ACS were identified and matched to 393 noncases by using incidence density sampling. For kaempferol, most of the individual ORs were statistically significant and from 42% to 61% lower when the higher 4 quintiles were compared with the lowest quintile. The P-trend was not significant. For daidzein, individual ORs were 5-38% lower. None of the individual ORs were significant, but the P-trend was 0.041. For the remaining flavonoids, there were no significant relations between urinary excretion and risk of ACS. Conclusions: Except for kaempferol and daidzein, there were no significant associations between the urinary excretion of flavonoids and risk of ACS. A lack of relations may be a result of the use of short-term exposure measures. [ABSTRACT FROM AUTHOR]

Background: The content of arachidonic acid in adipose tissue is positively associated with the risk of myocardial infarction, whereas the content of eicosapentaenoic acid in adipose tissue has been reported to be negatively associated with the risk of myocardial infarction. Both arachidonic acid and eicosapentaenoic acid are substrates for the synthesis of pro-inflammatory leukotrienes and leukotrienes derived from eicosapentaenoic acid are generally much less potent. In this study we hypothesized that a high content of arachidonic acid in adipose tissue would reflect a high formation of arachidonic acid derived leukotrienes and a high expression of 5-lipoxygenase in atherosclerotic plaques. Likewise, we hypothesized that a high content of eicosapentaenoic acid in adipose tissue would reflect a low formation of arachidonic acid derived leukotrienes and a low expression of 5-lipoxygenase in plaques. Methods: In a cross sectional study we included 45 consecutive subjects undergoing femoral thrombendarterectomy. The expression of 5-lipoxygenase in plaques was assessed by a semi-automated image analysis computer programme after immunohistochemical staining with mono-clonal 5-lipoxygenase antibodies. Leukotriene B4 and cysteinyl leukotriene formation from stimulated femoral artery plaques was quantified using ELISA methods. The fatty acid content of adipose tissue biopsies from the thigh was analyzed using gas chromatography. Associations between variables were assessed by Pearson correlations and were further explored in a multivariable linear regression model adjusting for potential confounders. Results: A high content of arachidonic acid in adipose tissue was associated with a higher expression of 5-lipoxygenase in plaques (r = 0.32, p = 0.03), but no significant associations with leukotriene B4 (r = 0.22, p = 0.14) and cysteinyl leukotriene (r = -0.11, p = 0.46) formation was seen. No significant associations were found between the content of eicosapentaenoic acid in adipose tissue and 5-lipoxygenase expression or leukotriene formation in plaque. Conclusions: Adipose tissue arachidonic acid contents correlated positively with the expression of 5-lipoxygenase in plaques. This association might represent a causal link between adipose tissue arachidonic acid and the risk of myocardial infarction but confirmatory studies are needed. [ABSTRACT FROM AUTHOR]

Studies in experimental animals and human subjects have suggested that intake of n-3 fatty acids in early life can affect cardiovascular risk factors in adult life. Therefore, the aim of the present study was to investigate the effect of fish oil (FO) supplementation during the third trimester of pregnancy on blood pressure (BP), heart rate (HR) and HR variability (HRV) in the 19-year-old offspring. The study was based on follow-up of a randomised, controlled trial from 1990, in which 533 pregnant women were randomised to FO, olive oil (OO) or no oil (NO) during the last trimester of pregnancy. The offspring was invited to a physical examination including BP, HR and HRV measurements. A subgroup consisting of the offspring of mothers with a low baseline fish intake also had 24 h HRV determined. The OO group was used as reference and multiple linear regression modelling was used to compare the FO and OO groups. A total of 180 of the offspring from the FO and OO groups agreed to participate in the study (45 %). The adjusted difference between the FO and OO groups was 2 (95 % CI − 1, 4) mmHg in systolic and 1 (95 % CI 0, 3) mmHg in diastolic BP. The difference in HR was 1 (95 % CI − 2, 4). Also, HRV indices did not differ significantly between groups. Hence, FO supplementation during late pregnancy was not associated with offspring BP, HR and HRV during adolescence. [ABSTRACT FROM PUBLISHER]

Background: Both road traffic noise and ambient air pollution have been associated with risk for ischemic heart disease, but only few inconsistent studies include both exposures. Methods: In a population-based cohort of 57 053 people aged 50 to 64 years at enrolment in 1993-1997, we identified 1600 cases of first-ever MI between enrolment and 2006. The mean follow-up time was 9.8 years. Exposure to road traffic noise and air pollution from 1988 to 2006 was estimated for all cohort members from residential address history. Associations between exposure to road traffic noise and incident MI were analysed in a Cox regression model with adjustment for air pollution (NOx) and other potential confounders: age, sex, education, lifestyle confounders, railway and airport noise. Results: We found that residential exposure to road traffic noise (Lden) was significantly associated with MI, with an incidence rate ratio IRR of 1.12 per 10 dB for both of the two exposure windows: yearly exposure at the time of diagnosis (95% confidence interval (CI): 1.02-1.22) and 5-years time-weighted mean (95% CI: 1.02-1.23) preceding the diagnosis. Visualizing of the results using restricted cubic splines showed a linear dose-response relationship. Conclusions: Exposure to long-term residential road traffic noise was associated with a higher risk for MI, in a dosedependent manner. [ABSTRACT FROM AUTHOR]

Background: It is well established that obesity tends to track from early childhood into adult life. Studies in experimental animals have suggested that changes in the peri- and early postnatal intake of n-3 (omega-3) polyunsaturated acids can affect the development of obesity in adult life. Objective: The aim of the current study was to investigate the effect of daily supplementation with 2.7 g long-chain n-3 fatty acids during the third trimester of pregnancy on adiposity in 19-y-old offspring. Design: The study was based on follow-up of a randomized controlled trial from 1990, in which 533 pregnant women were randomly assigned to receive fish oil, olive oil, or no oil. At ~19 y of age, the offspring of subjects from the randomized controlled trial were invited to undergo a physical examination, including anthropometric measurements and fasting blood sampling. The blood sample was analyzed for insulin, glucose, glycated hemoglobin, leptin, adiponectin, insulin-like growth factor I, and high-sensitivity C-reactive protein. Multiple linear regression modeling, adjusted for sex, smoking, and parental overweight, was used to estimate the effect of fish oil relative to that of olive oil on BMI (in kg/m2), waist circumference, and biochemical measures. Results: A total of 243 of the offspring were followed up. We found no difference between the fish-oil and olive oil groups in BMI (0.13; -0.92, 1.17) or waist circumference (0.7 cm; -2.1, 3.4 cm). Overall, results of the biochemical analyses supported the finding of no difference between the groups. Conclusion: We detected no effect of fish-oil supplementation during pregnancy on offspring adiposity in adolescence. [ABSTRACT FROM AUTHOR]

Background: Coronary angiography is the current standard method to evaluate coronary atherosclerosis in patients with suspected angina pectoris, but non-invasive CT scanning of the coronaries are increasingly used for the same purpose. Low-density lipoprotein (LDL) cholesterol and other lipid and lipoprotein variables are major risk factors for coronary artery disease. Small dense LDL particles may be of particular importance, but clinical studies evaluating their predictive value for coronary atherosclerosis are few. Methods: We performed a study of 194 consecutive patients with chest pain, a priori considered of low to intermediate risk for significant coronary stenosis (>50% lumen obstruction) who were referred for elective coronary angiography. Plasma lipids and lipoproteins were measured including the subtype pattern of LDL particles, and all patients were examined by coronary CT scanning before coronary angiography. Results: The proportion of small dense LDL was a strong univariate predictor of significant coronary artery stenosis evaluated by both methods. After adjustment for age, gender, smoking, and waist circumference only results obtained by traditional coronary angiography remained statistically significant. Conclusion: Small dense LDL particles may add to risk stratification of patients with suspected angina pectoris. [ABSTRACT FROM AUTHOR]

Aims: To study the effect of fish consumption on the risk of acute coronary syndrome (ACS) in healthy subjects. [ABSTRACT FROM PUBLISHER]

Patients on antiretroviral therapy are reported to have an increased risk of cardiovascular disease. We aimed to investigate the effect of n-3 polyunsaturated fatty acids (n-3 PUFAs) on plasma lipids, lipoproteins and inflammatory markers in HIV-infected patients treated with antiretroviral therapy. We randomized 51 patients in a placebo-controlled, double-blind trial to receive either 2 capsules of Omacor® twice daily or 2 capsules of placebo. Compliance was measured by determining levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in neutrophils. Plasma triglycerides were reduced in the n-3 PUFA group by 0.14 mmol/l after 12 weeks of treatment (n=26), while plasma triglycerides increased by 0.36 mmol/l in the control group (n=25). The difference between groups was significant, p=0.03. No significant effect of treatment was found for total cholesterol, high-density lipoprotein (HDL) or low-density lipoprotein (LDL) cholesterol or apolipoproteins. There was a significant increase in leukotriene B5 (LTB5) and LTB5/LTB4 ratio in the n-3 PUFA group compared to the control group. Baseline values for intercellular adhesion molecule-1 (ICAM), vascular cell adhesion molecule-1 (VCAM) and highly sensitive C-reactive protein (hsCRP) were comparable at baseline, and the intervention did not change these parameters significantly. The present study showed that treatment with n-3 PUFA slightly decreased plasma triglycerides and induced anti-inflammatory effects by increasing formation of anti-inflammatory LTB5. [ABSTRACT FROM AUTHOR]

Background: Acute coronary syndrome (ACS) is a major cause of morbidity and mortality in the western world. Peroxisome proliferator-activated receptor γ (PPARγ) plays a key role in the regulation of the energy balance, adipocyte differentiation and lipid biosynthesis. The aim was to investigate if the polymorphism PPAR γ2 Pro12Ala, which encodes a less efficient transcription factor, was associated with risk of acute coronary disease and if there were interactions between this polymorphism and factors that modify PPARγ activity, such as alcohol intake, smoking, and use of non-steroidal anti-inflammatory medicine. Methods: A case-cohort study including 1031 ACS cases and a sub-cohort of 1703 persons was nested within the population-based prospective study Diet, Cancer and Health of 57,053 individuals. Results: Homozygous male variant allele carriers of PPAR γ2 Pro12Ala were at higher risk of ACS (HR = 2.12, 95% CI: 1.00-4.48) than homozygous carriers of the Pro-allele. Among men, there was a statistically significant interaction between genotypes and alcohol intake such that homozygous variant allele carriers with a low alcohol intake were at higher risk of ACS (HR = 25.3, CI: 16.5-38.7) compared to homozygous common allele carriers (p for interaction < 0.0001). Overall, the association was only observed among homozygous variant allele carriers. Thus, all the observed associations were obtained in subgroups including small numbers of cases. It is therefore possible that the observed associations were due to chance. Conclusion: In the present study, there were no consistent associations between PPARγ Pro12Ala and risk of ACS, and no consistent interaction with alcohol, BMI, NSAID or smoking in relation to ACS. [ABSTRACT FROM AUTHOR]

There are no generally accepted definitions for low-response (frequently called resistance) to the platelet inhibitors, aspirin and clopidogrel. Low-response may increase the risk of cardiovascular events in atherosclerotic patients. We aimed to define the normal drug responses in healthy men. Platelet function was measured in 20 healthy men during 11 days of aspirin or clopidogrel intake, using light transmission aggregometry (LTA) and the Platelet Function Analyzer 100 (PFA-100). The lower limits for LTA at baseline were 64% and 61%, using arachidonic acid and ADP as agonists, respectively. During aspirin intake the LTA results were stable from day to day, and an upper limit of 9% arachidonic acid stimulated aggregation was found. Clopidogrel intake was best shown by ADP induced aggregation. However, two out of 20 individuals exhibited low-response to clopidogrel. In the remaining 18 volunteers an upper limit of 48% aggregation was found. We found an upper limit for collagen-epinephrine stimulated PFA-100 results of 166 s at baseline. During aspirin intake, these results varied considerably from day to day in nine out of 20 men, resulting in an overlap between the reference ranges at baseline and during therapy. In conclusion, platelet inhibition by aspirin and clopidogrel assessed by aggregometry was stable during 11 days of treatment and reference ranges were established. The PFA-100 results varied greatly and low-response was not precisely defined by this method. [ABSTRACT FROM AUTHOR]

C-reactive protein (CRP) is a sensitive marker for low-grade inflammation. Long-chain n-3 polyunsaturated fatty acids (PUFA) have anti-inflammatory effects. The objective of the present study was to investigate the effect on serum levels of CRP of n-3 PUFA at two different doses. We also investigated correlations between CRP and the cellular contents of PUFA. Sixty healthy volunteers (twenty-five women and thirty-five men) were randomly assigned to three treatment groups in a double-blind design. The subjects received a supplement of either 6??6 g n-3 PUFA/d, 2??0 g n-3 PUFA/d or placebo (olive oil) for 12 weeks. CRP was measured using a highly sensitive assay. The median serum CRP concentration was 0??78 mg/l. No significant correlations were found between CRP and the content of n-3 PUFA in granulocytes or platelets. Subjects receiving n-3 PUFA had a significant (P<0??01) increase in the cellular contents of 20: 5n-3, 22: 5n-3 and 22: 6n-3, with the largest increase occurring in the group receiving 6??6 g PUFA/d. A significant (P<0??01) decrease in cellular content of 18: 2n-6 and 20: 4n-6 was observed simultaneously. Serum CRP concentrations, however, were unaffected by the PUFA-containing supplements. The present study shows that dietary supplementation with PUFA-containing supplements has no effect on serum concentrations of CRP, measured with a highly sensitive assay, in healthy subjects. [ABSTRACT FROM PUBLISHER]