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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: 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]

Abstract: Obesity is associated with an increased risk of cardiovascular disease, whereas long-chain n-3 polyunsaturated fatty acids (PUFAs) from fish may have cardioprotective and anti-inflammatory effects. This study aimed to investigate the hypothesis that acute and short-term supplementation with a low dose of marine n-3 PUFA exerts an anti-inflammatory effect in overweight subjects. In a double-blind, placebo-controlled trial with 2 parallel groups, 50 overweight subjects were randomized to receive daily supplementation with 2 capsules containing either 2 g of fish oil (1.1 g marine n-3 PUFA) or 2 g of olive oil. Blood samples and adipose tissue biopsies were collected at baseline, after 1 day (acute effect), and after 6 weeks (short-term effect) of supplementation. No significant effects were seen after supplementation for 1 day, but after 6 weeks, subjects receiving fish oil had a significant increase in the n-3 PUFA content of granulocytes and adipose tissue (P < .01). Serum adiponectin levels were increased by 0.55 μg/mL (95% confidence interval, 0.02-1.08) in the fish oil group compared with the control group (P = .04) after 6 weeks of supplementation. Levels of interleukin 6 were inversely correlated to the marine n-3 PUFA content of granulocytes and adipose tissue at baseline (excluding α-linolenic acid). In conclusion, daily supplementation with 1.1 g of marine n-3 PUFA significantly increased serum adiponectin, but the effect was small, and no overall anti-inflammatory effect of the supplement could be demonstrated. [Copyright &y& Elsevier]

Background Road traffic is a source of both air pollution and noise; two environmental hazards both found to increase the risk of ischemic heart disease. Given the high correlation between these pollutants, it is important to investigate combined effects, in relation to myocardial infarction (MI). Methods Among 50,744 middle-aged Danes enrolled into the Diet, Cancer and Health cohort from 1993 to 97, we identified 2403 cases of incident MI during a median follow-up of 14.5 years. Present and historical residential addresses from 1987 to 2011 were found in national registries, and traffic noise (L den ) and air pollution (NO 2 ) were modelled for all addresses. Analyses were performed using Cox proportional hazard models. Results Road traffic noise and NO 2 were both individually associated with a higher risk of MI, with hazard ratios of 1.14 (1.07–1.21) and 1.08 (1.03–1.12) per inter-quartile range higher 10-year mean of road traffic noise and NO 2 , respectively. Mutual exposure adjustment reduced the association with 10-year NO 2 exposure (1.02 (0.96–1.08)), whereas the association with road traffic noise remained: 1.12 (1.03–1.21). For fatal incident MI, the pattern was similar, but the associations for both pollutants were stronger. In analyses of tertiles across both pollutants, the strongest effects were seen for combined medium/high exposure, especially for fatal MI's. Conclusion Both road traffic noise and NO 2 were associated with a higher risk of MI in single-pollutant models. In two-pollutant models, mainly noise was associated with MI. Combined exposure to both pollutants was associated with the highest risk. [ABSTRACT FROM AUTHOR]

Background Epidemiological studies have shown that intake of drinking water with high levels of arsenic (>100 μg/L) is associated with risk for cardiovascular diseases, but studies on lower levels of arsenic show inconsistent results. Objective The aim of this study was to investigate the relationship between exposure to low level arsenic in drinking water and risk of myocardial infarction in Denmark. Methods From the Danish Diet, Cancer and Health cohort of 57,053 people aged 50–64 years at enrolment in 1993–1997, we identified 2707 cases of incident myocardial infarction from enrolment to end of follow-up in February 2012. Cohort participants were enrolled in the Copenhagen and Aarhus areas. We geocoded residential addresses of the cohort members and used a geographic information system to link addresses with water supply areas. Arsenic in tap water at each cohort members address from 1973 to 2012 was estimated for all cohort members. Poisson regression was used to estimate incidence rate ratios (IRRs) for myocardial infarction after adjustment for lifestyle factors and educational level. Results Arsenic levels in drinking water at baseline addresses ranged from 0.03 to 25.34 μg/L, with the highest concentrations in the Aarhus area. We found no overall association between 20-years average concentration of arsenic and risk of myocardial infarction. However, in the Aarhus area, fourth arsenic quartile (2.21–25.34 μg/L) was associated with an IRR of 1.48 (95% confidence interval (CI): 1.19–1.83) when compared with first quartile (0.05–1.83 μg/L). An IRR of 1.26 (95% CI: 0.89–1.79) was found for ever (versus never) having lived at an address with 10 μg/L or more arsenic in the drinking water. Conclusions This study provides some support for an association between low levels of arsenic in drinking water and the risk of myocardial infarction. [ABSTRACT FROM AUTHOR]