Low intake or tissue concentrations of the n-6 PUFA, especially to the major n-6 PUFA linoleic acid (LA), and low exercise cardiac power (ECP) are both associated with CVD risk. However, associations ...of the n-6 PUFA with ECP are unknown. The aim of the present study was to explore cross-sectional associations of the serum total n-6 PUFA, LA, arachidonic acid (AA), γ-linolenic acid (GLA) and dihomo-γ-linolenic acid (DGLA) concentrations with ECP and its components. In total, 1685 men aged 42–60 years from the Kuopio Ischaemic Heart Disease Risk Factor Study and free of CVD were included. ANCOVA was used to examine the mean values of ECP (maximal oxygen uptake (VO2max)/maximal systolic blood pressure (SBP)) and its components in quartiles of the serum total and individual n-6 PUFA concentrations. After multivariable adjustments, higher serum total n-6 PUFA concentration was associated with higher ECP and VO2max (for ECP, the extreme-quartile difference was 0·77 ml/mmHg (95 % CI 0·38, 1·16, P
for trend across quartiles < 0·001) and for VO2max 157 ml/min (95 % CI 85, 230, P
for trend < 0·001), but not with maximal SBP. Similar associations were observed with serum LA concentration. Higher serum AA concentration was associated with higher ECP but not with VO2max or maximal SBP. The minor serum n-6 PUFA GLA and DGLA were associated with higher maximal SBP during exercise test and DGLA also with higher VO2max but neither with ECP. In conclusion, especially LA concentration was associated with higher ECP. This may provide one mechanism for the cardioprotective properties of, especially, LA.
The metabolic effects of omega-6 polyunsaturated fatty acids (PUFAs) remain contentious, and little evidence is available regarding their potential role in primary prevention of type 2 diabetes. We ...aimed to assess the associations of linoleic acid and arachidonic acid biomarkers with incident type 2 diabetes.
We did a pooled analysis of new, harmonised, individual-level analyses for the biomarkers linoleic acid and its metabolite arachidonic acid and incident type 2 diabetes. We analysed data from 20 prospective cohort studies from ten countries (Iceland, the Netherlands, the USA, Taiwan, the UK, Germany, Finland, Australia, Sweden, and France), with biomarkers sampled between 1970 and 2010. Participants included in the analyses were aged 18 years or older and had data available for linoleic acid and arachidonic acid biomarkers at baseline. We excluded participants with type 2 diabetes at baseline. The main outcome was the association between omega-6 PUFA biomarkers and incident type 2 diabetes. We assessed the relative risk of type 2 diabetes prospectively for each cohort and lipid compartment separately using a prespecified analytic plan for exposures, covariates, effect modifiers, and analysis, and the findings were then pooled using inverse-variance weighted meta-analysis.
Participants were 39 740 adults, aged (range of cohort means) 49-76 years with a BMI (range of cohort means) of 23·3-28·4 kg/m
, who did not have type 2 diabetes at baseline. During a follow-up of 366 073 person-years, we identified 4347 cases of incident type 2 diabetes. In multivariable-adjusted pooled analyses, higher proportions of linoleic acid biomarkers as percentages of total fatty acid were associated with a lower risk of type 2 diabetes overall (risk ratio RR per interquintile range 0·65, 95% CI 0·60-0·72, p<0·0001; I
=53·9%, p
=0·002). The associations between linoleic acid biomarkers and type 2 diabetes were generally similar in different lipid compartments, including phospholipids, plasma, cholesterol esters, and adipose tissue. Levels of arachidonic acid biomarker were not significantly associated with type 2 diabetes risk overall (RR per interquintile range 0·96, 95% CI 0·88-1·05; p=0·38; I
=63·0%, p
<0·0001). The associations between linoleic acid and arachidonic acid biomarkers and the risk of type 2 diabetes were not significantly modified by any prespecified potential sources of heterogeneity (ie, age, BMI, sex, race, aspirin use, omega-3 PUFA levels, or variants of the FADS gene; all p
≥0·13).
Findings suggest that linoleic acid has long-term benefits for the prevention of type 2 diabetes and that arachidonic acid is not harmful.
Funders are shown in the appendix.
Epidemiological studies suggest that whole grain intake has inverse associations with low-grade inflammation, but findings regarding refined grains are inconclusive. Our objective was to investigate ...whether consumption of whole or refined grains is associated with serum high sensitivity CRP (hs-CRP).
The study included 756 generally healthy men and women aged 53-73 years from the Kuopio Ischaemic Heart Disease Risk Factory Study, examined in 1999-2001. Dietary intakes were assessed using 4-day food records. ANCOVA and linear regression were used for analyses.
The mean intake of whole and refined grains was 136 g/day (SD 80) and 84 g/day (SD 46), respectively. Higher whole grain intake was associated with lower hs-CRP concentration and higher refined grain intake with higher concentration after adjustment for lifestyle and dietary factors. Each 50 g/d higher whole grain intake was associated with 0.12 mg/L (95% Cl 0.02-0.21 mg/L) lower hs-CRP concentration and each 50 g/d higher refined grain intake with 0.23 mg/L (95% Cl 0.08-0.38) higher concentration. Adjustment for fibre from grains attenuated the associations especially with whole grains. There were no statistically significant interactions according to gender or BMI (P for interactions >0.065).
The results of this study suggest that higher intake of whole grains is associated with lower concentrations of hs-CRP and higher intake of refined grains is associated with higher concentrations. However, especially the association with whole grain intake was attenuated after adjusting for fibre intake from grains, suggesting that cereal fibre may partly explain the association.
Fatty liver disease (FLD) has been identified as constituting cardiometabolic risk. However, evidence on the association of fatty liver index (FLI) with cardiovascular disease (CVD) is largely ...cross-sectional, with limited evidence on the predictability of incident CVD, and specifically, acute myocardial infarction (AMI). Therefore, we aimed to investigate the prospective associations between fatty liver as estimated by FLI and incident CVD, and specifically AMI, in the Kuopio Ischaemic Heart Disease Risk Factor Study cohort.
Our patients were 1205 middle-aged men free of CVD at baseline. The associations of baseline FLI with incident CVD and incident AMI were analyzed using multivariable-adjusted Cox regression models.
During a median follow-up of 17 years, a total of 690 incident cases of CVD and 269 cases of AMI were recorded through Finnish registries. For incident CVD, for the high (FLI≥60) versus the low (≤30) FLI category, the hazard ratio (HR) was 1.77 95% confidence interval (CI): 1.46-2.14 in the minimally adjusted model. With increasing adjustment, the association was attenuated progressively. In the most adjusted model, the HR was 1.41 (95% CI: 1.10-1.79). For incident AMI, for the high FLI category, the HR was 1.65 (95% CI: 1.22-2.23) in the minimally adjusted model, but in most comprehensive models when we included metabolic factors, the HR was not significant (HR=1.136, 95% CI: 0.777-1.662).
FLI can predict incident CVD. However, the predictability of AMI using FLI is subject to interactions of metabolic factors. Individuals with FLI in the moderate to high category should be evaluated and monitored for subclinical or overt cardiovascular (including coronary) disease.
There are concerns that high intake of n-6 polyunsaturated fatty acids (PUFA) may promote inflammation, because the end-product of n-6 PUFA metabolism, arachidonic acid, is a precursor for ...pro-inflammatory eicosanoids. Our aim was to investigate cross-sectional associations of the serum n-6 PUFAs, objective biomarkers for exposure, with serum high-sensitivity C-reactive protein (CRP), a key inflammation marker.
The study included 1287 generally healthy men aged 42-60 years from the population-based Kuopio Ischaemic Heart Disease Risk Factor Study, examined in 1984-1989. ANCOVA and logistic regression were used for analyses.
In the multivariable-adjusted analyses, both serum total n-6 PUFA and linoleic acid, the predominant n-6 PUFA, were associated with lower CRP. The mean CRP concentrations in quartiles of linoleic acid were 1.86, 1.51, 1.53, and 1.37 mg/L (P-trend = 0.001). The odds ratio for elevated CRP (>3 mg/L) in the highest vs. the lowest quartile was 0.47 (95% confidence interval (CI) 0.25-0.87, P-trend = 0.01). Arachidonic acid or the mainly endogenously produced n-6 PUFAs, gamma-linolenic acid and dihomo-gamma-linolenic acid, were not associated with higher CRP, either. Age, body mass index, or serum long-chain n-3 PUFA concentration did not modify the associations (P-interactions > 0.14).
Serum n-6 PUFAs were not associated with increased inflammation in men. In contrast, the main n-6 PUFA linoleic acid had a strong inverse association with the key inflammation marker, CRP.
The cardioprotective properties of linoleic acid (LA), a major n–6 (ω-6) polyunsaturated fatty acid (PUFA), have been recognized, but less is known about its associations with other causes of death. ...Relatively little is also known about how the minor n–6 PUFAs—γ-linolenic acid (GLA), dihomo-γ-linolenic acid (DGLA), and arachidonic acid (AA)—relate to mortality risk.
We investigated the associations of serum n–6 PUFAs, an objective biomarker of exposure, with risk of death in middle-aged and older men and whether disease history modifies the associations.
We included 2480 men from the prospective Kuopio Ischaemic Heart Disease Risk Factor Study, aged 42–60 y at baseline in 1984–1989. The stratified analyses by baseline disease status included 1019 men with a history of cardiovascular disease (CVD), cancer, or diabetes and 1461 men without a history of disease.
During the mean follow-up of 22.4 y, 1143 deaths due to disease occurred. Of these, 575 were CVD deaths, 317 were cancer deaths, and 251 were other-cause deaths. A higher serum LA concentration was associated with a lower risk of death from any cause (multivariable-adjusted HR for the highest compared with the lowest quintile: 0.57; 95% CI: 0.46, 0.71; P-trend < 0.001) and with deaths due to CVD (extreme-quintile HR: 0.54; 95% CI: 0.40, 0.74; P-trend < 0.001) and non-CVD or noncancer causes (HR: 0.48; 95% CI: 0.30, 0.76; P-trend = 0.001). Serum AA had similar, although weaker, inverse associations. Serum GLA and DGLA were not associated with risk of death, and none of the fatty acids were associated with cancer mortality. The results were generally similar among those with or without a history of major chronic disease (P-interaction > 0.13).
Our findings showed an inverse association of a higher biomarker of LA intake with total and CVD mortality and little concern for risk, thus supporting the current dietary recommendations to increase LA intake for CVD prevention. The finding of an inverse association of serum AA with the risk of death needs replication in other populations.
Vitamin D3 has via its metabolites 25-hydroxyvitamin D3 (25(OH)D3) and 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) direct effects on the transcriptome and the epigenome of most human cells. In the ...VitDbol study we exposed 35 healthy young adults to an oral vitamin D3 dose (2000μg) or placebo and took blood samples directly before the supplementation as well as at days 1, 2 and 30. Within 24h the vitamin D3 intake raised the average serum levels of both 25(OH)D3 and 1,25(OH)2D3 by approximately 20%. However, we observed large inter-individual differences in these serum levels, reflected by the average ratios between 25(OH)D3 and 1,25(OH)2D3 concentrations ranging from 277 to 1365. Interestingly, average serum parathyroid hormone (PTH) levels increased at day 1 by some 10% but then decreased within the following four weeks to levels 5% below baseline. In peripheral blood mononuclear cells (PBMCs) that were isolated at the same time points we determined vitamin D-modulated chromatin accessibility by FAIRE-qPCR at selected genomic loci. This method is well suited to evaluate both short-term and long-term in vivo effects of vitamin D on the epigenome of human subjects. The differential vitamin D responsiveness of the VitDbol study participants was determined via individual changes in their PTH levels or chromatin accessibility in relation to alterations in 25(OH)D3 concentrations. This led to the segregation of the subjects into 14 high, 11 mid and 10 low responders. In summary, the vitamin D responsiveness classification provides additional information compared to a vitamin D status assessment based on single 25(OH)D3 serum measurements. The study was registered at Clinicaltrials.gov (NCT02063334).
Atrial fibrillation is a common cardiac arrhythmia with high morbidity risk. Observational studies suggest that vitamin D deficiency is associated with higher atrial fibrillation risk but there is ...limited evidence whether vitamin D supplementation could affect the risk. In these post hoc analyses from the Finnish Vitamin D Trial, we compared the incidence of atrial fibrillation with 5-year supplementation of vitamin D3 (1600 IU/d or 3200 IU/d) vs placebo.
ClinicalTrials.gov: NCT01463813, https://clinicaltrials.gov/ct2/show/NCT01463813
Atrial fibrillation is a common cardiac arrhythmia with high morbidity risk. Observational studies suggest that vitamin D deficiency is associated with higher atrial fibrillation risk but there is ...limited evidence whether vitamin D supplementation could affect the risk. In these post hoc analyses from the Finnish Vitamin D Trial, we compared the incidence of atrial fibrillation with 5-year supplementation of vitamin D
(1600 IU/d or 3200 IU/d) vs placebo. CLINICAL TRIAL REGISTRY NUMBER: ClinicalTrials.gov: NCT01463813, https://clinicaltrials.gov/ct2/show/NCT01463813.
Mercury is a heavy metal that exists naturally in the environment. Major sources include the burning of fossil fuels (especially coal) and municipal waste incineration. Mercury can exist in several ...forms, with the most hazardous being organic methylmercury. In waterways (lakes, rivers, reservoirs, etc.), mercury is converted to methylmercury, which then accumulates in fish, especially in large predatory fish. Fish and fish products are the major—if not the only—source of methylmercury in humans. Mercury has long been recognized as a neurotoxin for humans, but in the last 10 years, its potentially harmful effects on cardiovascular diseases (CVD) have raised a cause for concern, mostly due to the proposed role of mercury in oxidative stress propagation. Some epidemiological studies have indeed found an association between increased levels of mercury in the body and risk of CVD. There are several plausible mechanisms to explain the association; these are discussed in this review. We also review the epidemiological studies that have investigated the association between mercury and CVD.
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