Serum n-6 polyunsaturated fatty acids and risk of atrial fibrillation: the Kuopio Ischaemic Heart Disease Risk Factor Study

Purpose N-6 polyunsaturated fatty acids (PUFA), particularly linoleic acid (LA), have been associated with lower risk of coronary heart disease (CHD), but little is known about their antiarrhythmic properties. We investigated the association of the serum n-6 PUFAs with the risk of atrial fibrillation (AF), the most common type of cardiac arrhythmia. Methods The study included 2450 men from the Kuopio Ischaemic Heart Disease Risk Factor Study, aged 42–60 years at baseline. The total n-6 PUFA includes linoleic acid (LA), arachidonic acid (AA), γ-linolenic acid (GLA) and dihomo-γ-linolenic acid (DGLA). Cox proportional hazards regression was used to estimate hazard ratio (HR) of incident events. Results During the mean follow-up of 22.4 years, 486 AF cases occurred. The multivariable-adjusted HR in the highest versus the lowest quartile of total serum n-6 PUFA concentration was 0.79 (95% CI 0.58–1.08, P trend = 0.04). When evaluated individually, only serum LA concentration was inversely associated with AF risk (multivariable-adjusted extreme-quartile HR 0.69, 95% CI 0.51–0.94, P trend = 0.02). These associations were stronger among the men without history of CHD or congestive heart failure at baseline, compared to men with such disease history (P for interaction = 0.05 for total n-6 PUFA and LA). Similar associations were observed with dietary LA and AA intakes. No significant associations were observed with serum AA, GLA or DGLA concentrations. Conclusions Higher circulating concentration and dietary intake of n-6 PUFA, mainly LA, are associated with lower risk of AF, especially among men without history of CHD or congestive heart failure.

Post-Analysis of Predictive Modeling with an Epidemiological Example

Post-analysis of predictive models fosters their application in practice, as domain experts want to understand the logic behind them. In epidemiology, methods explaining sophisticated models facilitate the usage of up-to-date tools, especially in the high-dimensional predictor space. Investigating how model performance varies for subjects with different conditions is one of the important parts of post-analysis. This paper presents a model-independent approach for post-analysis, aiming to reveal those subjects’ conditions that lead to low or high model performance, compared to the average level on the whole sample. Conditions of interest are presented in the form of rules generated by a multi-objective evolutionary algorithm (MOGA). In this study, Lasso logistic regression (LLR) was trained to predict cardiovascular death by 2016 using the data from the 1984–1989 examination within the Kuopio Ischemic Heart Disease Risk Factor Study (KIHD), which contained 2682 subjects and 950 preselected predictors. After 50 independent runs of five-fold cross-validation, the model performance collected for each subject was used to generate rules describing “easy” and “difficult” cases. LLR with 61 selected predictors, on average, achieved 72.53% accuracy on the whole sample. However, during post-analysis, three categories of subjects were discovered: “Easy” cases with an LLR accuracy of 95.84%, “difficult” cases with an LLR accuracy of 48.11%, and the remaining cases with an LLR accuracy of 71.00%. Moreover, the rule analysis showed that medication was one of the main confusing factors that led to lower model performance. The proposed approach provides insightful information about subjects’ conditions that complicate predictive modeling.

Serum copper-to-zinc-ratio and risk of incident infection in men: the Kuopio Ischaemic Heart Disease Risk Factor Study

Infections are one of the main causes of mortality in elderly due to the decrease of immune response, for which copper (Cu) and zinc (Zn) are claimed to be crucial. High serum copper-to-zinc-ratio (Cu/Zn-ratio) has been reported with infections, but little is known whether it could also predict the incidence of infections. The study cohort consisted of 1975 men aged 42–60 years and free of severe infectious disease at baseline in 1984–1989 from the prospective population-based Kuopio Ischaemic Heart Disease Risk Factor Study. The main outcome was an incident infection leading to hospitalization. Cox proportional hazards regression models were used for statistical analysis. During the average follow-up of 19.2 years, 636 incident first cases of infections were diagnosed. The hazard ratio (HR) of developing an incident infectious disease in the highest compared to the lowest Cu/Zn-ratio quartile after adjustment for age and baseline examination year was 1.35 [95% confidence interval (CI) = 1.07–1.69, P-trend across quartiles = 0.005]. The association was slightly attenuated after additional adjustment for potential confounders (HR = 1.21, 95% CI = 0.96–1.53, P-trend = 0.054). Furthermore, higher serum Cu concentration was associated with higher risk of an incident infection. The multivariable-adjusted HR was 1.39 (95% CI = 1.10–1.75, P-trend = 0.005) in the highest versus the lowest serum Cu quartile. Serum Zn concentration was not associated with the risk (multivariable-adjusted extreme-quartile HR = 0.83, 95% CI = 0.67–1.04, P-trend = 0.218). In conclusion, our data suggest that an increased Cu/Zn-ratio and especially serum Cu concentration are associated with increased risk of incident infections in middle-aged and older men in Eastern Finland.

Dietary intake of choline and phosphatidylcholine and risk of type 2 diabetes in men: The Kuopio Ischaemic Heart Disease Risk Factor Study

Purpose To investigate associations of total dietary choline intake and its major dietary form, phosphatidylcholine, with type 2 diabetes risk. Methods We included 2332 men aged 42–60 years at baseline in 1984–1989 from the Kuopio Ischaemic Heart Disease Risk Factor Study in eastern Finland. Dietary intakes were assessed with 4-d food recording at baseline. Type 2 diabetes diagnosis was based on self-administered questionnaires, fasting and 2-h oral glucose tolerance test blood glucose measurements, or by record linkage to national health registries. Multivariable-adjusted Cox proportional hazards regression models were used for statistical analysis. Results During the mean 19.3-year follow-up, 432 men had type 2 diabetes diagnosis. After multivariable adjustments, those in the highest vs. lowest choline intake quartile had 25% (95% CI 2–43%) lower relative risk (P trend across quartiles = 0.02) and those in the highest vs. lowest phosphatidylcholine quartile had 41% (95% CI 22–55%) lower relative risk (P trend < 0.001) of type 2 diabetes. Conclusions Higher choline intake, especially phosphatidylcholine, was associated with lower type 2 diabetes risk among men.

Fatty liver index as a predictor of increased risk of cardiometabolic disease: finding from the Kuopio Ischaemic Heart Disease Risk Factor Study Cohort

ObjectiveFatty liver disease (FLD), a global epidemic, is also a predictor of cardiometabolic disease (CMD) (type 2 diabetes or cardiovascular disease). Our objective was to examine whether progressive FLD, as assessed by fatty liver index (FLI), predicts increasing future CMD risk compared with relatively stable FLD, among middle-aged men.DesignProspective epidemiological study.SettingUniversity affiliated research centre in Kuopio, Eastern Finland.ParticipantsOur subjects were 501 men without CMD during the initial 4-year follow-up in the Kuopio Ischaemic Heart Disease Risk Factor Study cohort.Outcome measureOver the initial 4-year follow-up, 135 men (26.9%) had a significant (≥10) FLI increase. The association of 4-year FLI increase with incident CMD was analysed in multivariable-adjusted Cox regression models, adjusting for baseline constitutional and lifestyle factors (model 1) and, in addition, metabolic and inflammation biomarker factors (model 2).ResultsDuring a mean follow-up of 15 years, 301 new CMD cases occurred. We used subjects with low baseline FLI and no significant 4-year FLI increase as the reference. For subjects with intermediate baseline FLI and significant 4-year FLI increase, the HRs and 95% CIs for incident CMD in model 1 (2.13 (1.45 to 3.13)) and model 2 (1.73 (1.13 to 2.66)) exceeded values for subjects with similar baseline FLI without a significant 4-year change (HRs (95% CIs) were 1.36 (0.94 to 1.97) for model 1 and 1.18 (0.81 to 1.70) for model 2). They approached HRs (95% CI) for subjects who maintained high FLI over the 4 years (HRs (95% CIs) were 2.18 (1.54 to 3.10) in model 1 and 1.85 (1.21 to 2.82) in model 2).ConclusionPersons with significant FLI increase are likely with increasing CMD risk. Such persons should be evaluated for progressive FLD and CMD and managed to reduce CMD risk.

Associations of dietary choline intake with risk of incident dementia and with cognitive performance: the Kuopio Ischaemic Heart Disease Risk Factor Study

ABSTRACTBackgroundModerate egg intake has been associated with better cognitive performance in observational studies. This association may be due to the rich content of choline, especially phosphatidylcholine, in eggs because choline has been suggested to have a role in the prevention of cognitive decline.ObjectivesWe investigated the associations of dietary choline intake with the risk of incident dementia and with cognitive performance in middle-aged and older men in the prospective, population-based Kuopio Ischaemic Heart Disease Risk Factor Study.MethodsA population-based sample of 2497 dementia-free men aged 42–60 y was examined in 1984–1989. A subset of 482 men completed 5 different cognitive performance tests 4 y later. Dementia and Alzheimer disease diagnoses were retrieved from Finnish health registers. Dietary intakes were assessed with the use of 4-d food records at baseline. Cox regression and ANCOVA were used for the analyses. All analyses were also stratified by the apolipoprotein E phenotype (APOE-ε4 compared with other phenotypes). These data were available for 1259 men.ResultsThe mean ± SD total choline intake was 431 ± 88 mg/d, of which 188 ± 63 mg/d was phosphatidylcholine. During a 21.9-y follow-up, 337 men were diagnosed with dementia. Those in the highest compared with the lowest phosphatidylcholine intake quartile had 28% (95% CI: 1%, 48%; P-trend = 0.02 across quartiles) lower multivariable-adjusted risk of incident dementia. Total choline intake had no association with the risk of incident dementia. However, both total choline and phosphatidylcholine intakes were associated with better performance in cognitive tests assessing frontal and temporal lobe functioning. For example, higher intakes were associated with better performance in verbal fluency and memory functions. The APOE phenotype had little or no impact on the associations.ConclusionHigher phosphatidylcholine intake was associated with lower risk of incident dementia and better cognitive performance in men in eastern Finland. This trial was registered at clinicaltrials.gov as NCT03221127.