The epidemiological evidence of the role of dietary saturated fatty acids (SFA) in the development of coronary heart disease (CHD) is inconsistent. We investigated the associations of dietary fatty ...acids with the risk of CHD and carotid atherosclerosis in men with high SFA intake and high rates of CHD.
In total, 1981 men from the population-based Kuopio Ischemic Heart Disease Risk Factor Study (KIHD), aged 42 to 60 years and free of CHD at baseline in 1984 to 1989, were investigated. Food consumption was assessed with 4-day food recording. Multivariate nutrient-density models were used to analyze isocaloric replacement of nutrients. CHD events were ascertained from national registries. Carotid atherosclerosis was assessed by ultrasonography of the common carotid artery intima-media thickness in 1015 men. During the average follow-up of 21.4 years, 183 fatal and 382 nonfatal CHD events occurred. SFA or trans fat intakes were not associated with CHD risk. In contrast, monounsaturated fat intake was associated with increased risk and polyunsaturated fat intake with decreased risk of fatal CHD, whether replacing SFA, trans fat, or carbohydrates. The associations with carotid atherosclerosis were broadly similar, whereas the associations with nonfatal CHD were weaker.
Our results suggest that SFA intake is not an independent risk factor for CHD, even in a population with higher ranges of SFA intake. In contrast, polyunsaturated fat intake was associated with lower risk of fatal CHD, whether replacing SFA, trans fat, or carbohydrates. Further investigation on the effect of monounsaturated fat on the CHD risk is warranted.
Atrial fibrillation (AF) is a common cardiac arrhythmia. Regular fish consumption has been shown to reduce the risk of AF in some but not all studies. Long-chain n-3 polyunsaturated fatty acids ...(PUFAs) from fish have been suggested to account for these beneficial effects. We tested this hypothesis by studying the association between the serum long-chain n-3 PUFAs eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid and risk of AF in men.
A total of 2174 men from the prospective population-based Kuopio Ischemic Heart Disease Risk Factor Study, 42 to 60 years old and free of AF at baseline in 1984 to 1989, were studied. During the average follow-up time of 17.7 years, 240 AF events occurred. In the Cox proportional hazards model, the multivariable-adjusted hazard ratio in the highest (>5.33%) versus the lowest (<3.61%) quartile of eicosapentaenoic acid plus docosapentaenoic acid plus docosahexaenoic acid was 0.65 (95% confidence interval 0.44 to 0.96, P for trend=0.07). Evaluated individually, only serum docosahexaenoic acid was associated with the risk of AF (hazard ratio in the highest versus the lowest quartile 0.62, 95% confidence interval 0.42 to 0.92, P for trend=0.02). Exclusion of subjects (n=233) with myocardial infarction or congestive heart failure either at baseline or that preceded the AF event during follow-up slightly strengthened the associations. Serum intermediate chain-length n-3 PUFA, alpha-linolenic acid, or hair methylmercury concentration were not associated with the risk.
An increased concentration of long-chain n-3 PUFAs in serum, a marker of fish or fish oil consumption, may protect against AF. Serum docosahexaenoic acid concentration had the greatest impact.
Vitamin D modulates innate and adaptive immunity, the molecular mechanisms of which we aim to understand under human in vivo conditions. Therefore, we designed the study VitDHiD (NCT03537027) as a ...human investigation, in which 25 healthy individuals were supplemented with a single vitamin D3 bolus (80,000 IU). Transcriptome-wide differential gene expression analysis of peripheral blood mononuclear cells (PBMCs), which were isolated directly before and 24 h after supplementation, identified 452 genes significantly (FDR < 0.05) responding to vitamin D. In vitro studies using PBMCs from the same individuals confirmed 138 of these genes as targets of 1α,25-dihydroxyvitamin D3. A subset of the 91 most regulated in vivo vitamin D target genes indicated focal adhesion as the major pathway being upregulated by vitamin D3 supplementation of healthy individuals. Differences in the individual-specific responsiveness of in vivo vitamin D target genes in relation to the increase of the person’s vitamin D status allowed a segregation of the VitDHiD participants into 9 high, 12 mid and 4 low responders. The expression profile of nearly 600 genes elucidate the difference between high and low vitamin D responders, the most prominent of which is the HLA-C (major histocompatibility complex, class I, C) gene.
ABSTRACT
Background
Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver diseases worldwide, and lifestyle and diet are significant factors in its development. Recent studies have ...suggested that dietary fat quality is associated with the development of NAFLD.
Objectives
Our purpose was to investigate the cross-sectional and longitudinal associations of serum n–3 (ω-3) and n–6 (ω-6) PUFAs with NAFLD among middle-aged and older men and women from eastern Finland. We also investigated the associations of estimated Δ5-desaturase and Δ6-desaturase activities, enzymes involved in PUFA metabolism, with NAFLD.
Methods
After exclusions, the cross-sectional analyses included 1533 men examined in 1984–1989 and 674 men and 870 women examined in 1998–2001 in the Kuopio Ischaemic Heart Disease Risk Factor Study. The longitudinal analyses included 520 men examined in 1991–1993 and 301 men and 466 women examined in 2005–2008. Fatty liver index (FLI) was used as a surrogate for NAFLD. Hepatic steatosis was defined as FLI >60. ANCOVA and logistic regression were used for analyses.
Results
In the longitudinal analyses, participants with higher serum concentrations of total n–6 PUFA and linoleic acid, the major n–6 PUFA, had markedly lower FLI and lower odds for hepatic steatosis (e.g., odds ratios for incident hepatic steatosis in the highest compared with lowest quartiles were ≤0.41), whereas serum γ-linolenic acid concentration was associated with a higher FLI and higher odds for hepatic steatosis. The associations with the other PUFAs were generally weaker and nonsignificant. In the cross-sectional analyses, also the long-chain n–3 PUFAs had inverse associations. In most analyses, high estimated Δ5-desaturase activity was associated with lower risk and high estimated Δ6-desaturase activity with higher risk for NAFLD.
Conclusions
In middle-aged and older Finnish adults, higher serum concentrations of total n–6 PUFAs and linoleic acid were associated with lower odds for future NAFLD.
Epidemiologic studies suggest inverse associations between consumption of egg, a major source of dietary cholesterol, and stroke. However, the evidence of the relation remains limited, especially ...among carriers of apolipoprotein E4 (apoE4), which influences cholesterol metabolism.
The aim of this study was to investigate associations of egg and cholesterol intakes with risk of stroke and with the major stroke risk factor, blood pressure, in middle-aged and older men from eastern Finland and whether apoE phenotype could modify these associations.
A total of 1950 men aged 42–60 y in 1984–1989 were included at the baseline examinations of the prospective population-based Kuopio Ischaemic Heart Disease Risk Factor Study. Data on apoE phenotype were available for 1015 men. Dietary intakes were assessed with 4-d food records at baseline and incident stroke events were assessed by record linkage to hospital discharge registries. Cox proportional hazards regression analyses were used to estimate associations with stroke risk. Associations with baseline blood pressure were evaluated with ANCOVA.
During the mean ± SD follow-up of 21.2 ± 7.2 y, there were 217 incidences of any stroke: 166 of ischemic stroke and 55 of hemorrhagic stroke. Comparing the highest egg intake quartile with the lowest, the multivariable-adjusted HRs were 0.81 for total stroke (95% CI: 0.54, 1.23; P-trend = 0.32), 0.84 for ischemic stroke (95% CI: 0.53, 1.34; P-trend = 0.44), and 0.75 for hemorrhagic stroke (95% CI: 0.32, 1.77; P-trend = 0.40). The respective HRs for the highest cholesterol intake quartile compared with the lowest were 0.86 (95% CI: 0.57, 1.32; P-trend = 0.42), 0.74 (95% CI: 0.46, 1.20; P-trend = 0.32), and 1.10 (95% CI: 0.45, 2.66; P-trend = 0.75). Diastolic blood pressure was 1.6 mm Hg (P-trend = 0.04) lower in the highest egg intake quartile compared with the lowest, but there were no associations with systolic blood pressure or with cholesterol intake. ApoE phenotype (32% had apoE4 phenotype) did not modify the associations.
Neither egg nor cholesterol intakes were associated with stroke risk in this cohort, regardless of apoE phenotype. This trial was registered at www.clinicaltrials.gov as NCT03221127.
Background: The prevalence of type 2 diabetes (T2D) is increasing around the world. Eggs are a major source of cholesterol, which has been associated with elevated blood glucose and an increased risk ...of T2D. However, there are limited and conflicting data from prospective population studies on the association between egg consumption and risk of T2D. Objective: We investigated the association between egg consumption and risk of incident T2D in middle-aged and older men from eastern Finland. Design: The study included 2332 men aged 42–60 y in 1984–1989 at the baseline examinations of the prospective, population-based Kuopio Ischaemic Heart Disease Risk Factor Study. Dietary intakes were assessed with 4-d food records at baseline. Incident T2D was assessed by self-administered questionnaires; by fasting and 2-h oral-glucose-tolerance-test blood glucose measurement at re-examination rounds 4, 11, and 20 y after baseline; and by record linkage to a hospital discharge registry and reimbursement register of diabetes medication expenses. Cox proportional hazards regression analyses were used to estimate associations with the risk of incident T2D. Associations with the metabolic risk markers at baseline and at the 4-y examinations were analyzed by ANCOVA. Results: During an average follow-up of 19.3 y, 432 men developed T2D. After adjustment for potential confounders, those in the highest compared with the lowest egg intake quartile had a 38% (95% CI: 18%, 53%; P -trend across quartiles <0.001) lower risk of incident T2D. Analyses with metabolic risk markers also suggested an inverse association with fasting plasma glucose and serum C-reactive protein but not with serum insulin. The associations between cholesterol intake and risk of T2D, plasma glucose, serum insulin, and C-reactive protein were mainly nonsignificant, especially after accounting for egg consumption. Conclusion: Higher egg intake was associated with a lower risk of T2D in this cohort of middle-aged and older men.
The impact of egg consumption, a major source of dietary cholesterol, on the risk of atherosclerotic cardiovascular diseases (ASCVD) is controversial. Venous thromboembolism (VTE) is a CVD which ...shares common risk factors and mechanistic pathways with ASCVD. However, there is no data on the relationship between egg or cholesterol intake and VTE risk. Therefore, we evaluated the prospective associations of egg and cholesterol intakes with VTE risk and whether the apoE4 phenotype, which influences cholesterol metabolism, could modify the associations. Data involving 1852 men aged 42–61 years at baseline without a history of VTE or CHD in the population-based Kuopio Ischaemic Heart Disease Risk Factor Study were analysed. Dietary intakes were assessed with 4-d food records. Incident VTE events were identified by record linkage to hospital discharge registries. Hazard ratios (95 % CI) for incident VTE were estimated using Cox regression. During a median follow-up of 28·8 years, 132 VTE events occurred. Comparing the top (> 38 g/d) v. bottom (< 20 g/d) tertiles of egg consumption, the hazard ratio (95 % CI) for VTE was 0·99 (0·64, 1·53) in analysis adjusted for several established risk factors and other dietary factors. There was also no evidence of an association between cholesterol intake and VTE risk. Imputed results were consistent with the observed results. The apoE4 phenotype did not modify the associations. In middle-aged and older Finnish men, egg or cholesterol intakes were not associated with future VTE risk. Other large-scale prospective studies are needed to confirm or refute these findings.
Vitamin D insufficiency is associated with risks of cardiovascular diseases (CVD) and cancer in observational studies, but evidence for benefits with vitamin D supplementation is limited.
To ...investigate the effects of vitamin D3 supplementation on CVD and cancer incidences.
The study was a 5-year, randomized, placebo-controlled trial among 2495 male participants ≥60 years and post-menopausal female participants ≥65 years from a general Finnish population who were free of prior CVD or cancer. The study had 3 arms: placebo, 1600 IU/day, or 3200 IU/day vitamin D3. Follow-up was by annual study questionnaires and national registry data. A representative subcohort of 551 participants had more detailed in-person investigations. The primary endpoints were incident major CVD and invasive cancer. Secondary endpoints included the individual components of the primary CVD endpoint (myocardial infarction, stroke, and CVD mortality), site-specific cancers, and cancer death.
During the follow-up, there were 41 (4.9%), 42 (5.0%), and 36 (4.3%) major CVD events in the placebo, 1600 IU/d (compared with placebo: HR: 0.97; 95% CI: 0.63–1.49; P = 0.89), and 3200 IU/d (HR: 0.84; 95% CI: 0.54–1.31; P = 0.44) arms, respectively. Invasive cancer was diagnosed in 41 (4.9%), 48 (5.8%), and 40 (4.8%) participants in the placebo, 1600 IU/d (HR: 1.14; 95% CI: 0.75–1.72; P = 0.55), and 3200 IU/d (HR: 0.95; 95% CI: 0.61–1.47; P = 0.81) arms, respectively. There were no significant differences in the secondary endpoints or total mortality. In the subcohort, the mean baseline serum 25-hydroxyvitamin D concentration was 75 nmol/L (SD, 18 nmol/L). After 12 months, the concentrations were 73 nmol/L (SD, 18 nmol/L), 100 nmol/L (SD, 21 nmol/L), and 120 nmol/L (SD, 22 nmol/L) in the placebo, 1600 IU/d, and 3200 IU/d arms, respectively.
Vitamin D3 supplementation did not lower the incidences of major CVD events or invasive cancer among older adults, possibly due to sufficient vitamin D status in most participants at baseline.
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Background: The U.S. Environmental Protection Agency (U.S. EPA) has estimated the neurological benefits of reductions in prenatal methylmercury (MeHg) exposure in past assessments of rules ...controlling mercury (Hg) emissions. A growing body of evidence suggests that MeHg exposure can also lead to increased risks of adverse cardiovascular impacts in exposed populations. Data extraction: The U.S. EPA assembled the authors of this article to participate in a workshop, where we reviewed the current science concerning cardiovascular health effects of MeHg exposure via fish and seafood consumption and provided recommendations concerning whether cardiovascular health effects should be included in future Hg regulatory impact analyses. Data synthesis: We found the body of evidence exploring the link between MeHg and acute myocardial infarction (MI) to be sufficiently strong to support its inclusion in future benefits analyses, based both on direct epidemiological evidence of an MeHg—MI link and on MeHg's association with intermediary impacts that contribute to MI risk. Although additional research in this area would be beneficial to further clarify key characteristics of this relationship and the biological mechanisms that underlie it, we consider the current epidemiological literature sufficiently robust to support the development of a dose-response function. Conclusions: We recommend the development of a dose-response function relating MeHg exposures with MIs for use in regulatory benefits analyses of future rules targeting Hg air emissions.
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