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We examined the longitudinal associations of fat mass, lean mass, and blood pressure (BP) from childhood through young adulthood with changes in carotid-femoral pulse wave velocity (cfPWV), a measure of arterial stiffness, and carotid intima-media thickness (cIMT). We included 3863 participants from the Avon Longitudinal Study of Parents and Children birth cohort. Fat mass and lean mass, measured by dual-energy X-ray absorptiometry, and BP were measured at ages 9, 17 and 24 years and classified into low, moderate, and high tertiles. cfPWV and cIMT were measured at 17 and 24 years of age. Associations were examined via linear mixed effect models and adjusted for cardiometabolic and lifestyle factors. Among 1720 [44.5%] male and 2143 [55.5%] female participants, cumulative high exposures to lean mass (effect estimate 0.006 m/s [95% CI 0.001 to 0.010; p = 0.022]), systolic BP (0.013 m/s [0.009 to 0.017; p p p p = 0.001]), and systolic BP (0.010 mm; [0.006 to 0.014; p

Purpose Evidence on the association between dairy intake and depression is conflicting. Given numerous dietary guidelines recommend the consumption of low-fat dairy products, this study examined associations between total dairy, high-fat dairy, and low-fat dairy intake and the prevalence of elevated depressive symptoms. Associations between dairy products, which differed in both fat content and fermentation status, and depressive symptoms were also explored. Methods This cross-sectional study included 1600 Finnish adults (mean age 63 ± 6 years; 51% female) recruited as part of the Kuopio Ischaemic Heart Disease Risk Factor Study. Dairy intake was assessed using 4-day food records. Elevated depressive symptoms were defined as having a score ≥ 5 on the Diagnostic and Statistical Manual of Mental Disorders-III Depression Scale, and/or regularly using one or more prescription drugs for depressive symptoms. Results In total, 166 participants (10.4%) reported having elevated depressive symptoms. Using multivariate logistic regression models, intake in the highest tertile of high-fat dairy products (OR 0.64, 95% CI 0.41–0.998, p trend = 0.04) and high-fat non-fermented dairy products (OR 0.60, 95% CI 0.39–0.92, p trend = 0.02) were associated with reduced odds for having elevated depressive symptoms. Whereas no significant association was observed between intake of total dairy, low-fat dairy, or other dairy products, and depressive symptoms. Conclusion Higher intake of high-fat dairy and high-fat non-fermented dairy products were associated with reduced odds for having elevated depressive symptoms in middle-aged and older Finnish adults. Given the high global consumption of dairy products, and widespread burden of depression, longitudinal studies that seek to corroborate these findings are required.

Background Renal hyperfiltration (RHF), recently established as a risk factor for mortality, is linked to current and subsequent diabetes mellitus (DM). DM could be seen as a mediator in the pathway between RHF and mortality. However, the mediating role of DM in the relationship between RHF and mortality is unclear. Methods and results Based on a cohort of 2682 Finnish men from the Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) followed-up for 35 years, we evaluated the association between RHF and mortality, with DM as a mediator, following two methods: a classic mediation analysis approach, using Cox regression, and a counterfactual framework for mediation analysis, using g-computation, Cox regression, and logistic regression. RHF is associated with an increased risk of mortality. This association was not mediated by DM. Under a counterfactual framework and on a hazard ratio scale, RHF association with mortality had a total effect of 1.54 (95% confidence interval, 1.26–1.98) and a controlled direct effect of 1.66 (1.34–2.16). Conclusion An association between RHF and mortality risk, independent of DM, was established. RHF should be considered, managed, and followed-up as a mortality-associated condition, regardless of the status of DM. We suggest clinicians to consider including RHF screening in routine clinical care, especially diabetic care.

Background/objectives 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). Subjects/methods 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. Results 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). Conclusions 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.

Purpose Recent studies have suggested that higher postmenopausal follicle stimulating hormone (FSH) may be associated with lower risk of diabetes. However, relatively little is known about postmenopausal FSH levels, including the level of variation between women and whether reproductive factors are associated with this variation. Methods We assessed the relationship of multiple reproductive factors with FSH levels among 588 postmenopausal women in the Kuopio Ischaemic Heart Disease Risk Factor Study. Participants were aged 53 to 73 years and not using hormone therapy at study enrollment (1998–2001) when reproductive factors were assessed and FSH was measured. Results After adjustment for age, menopause timing, sex steroid levels, adiposity and behavioral factors, we observed numbers of pregnancies and age at first birth were each inversely associated with FSH levels. For example, women with ≥ 3 births and an age at first birth ≥ 25 years had mean FSH levels that were 7.8 IU/L lower than those of women with 1–2 births and an age at first birth ≤ 24 years (P = 0.003). Number of miscarriages was inversely associated with FSH levels (-2.7 IU/L per miscarriage; P = 0.02). Women reporting 4 or more years of past hormone therapy use had significantly higher mean FSH levels than women who had never used hormone therapy (P for trend = 0.006). Conclusion Multiple reproductive factors were associated with postmenopausal FSH, independent of estradiol, adiposity and other confounders. These findings warrant replication and further exploration of potential underlying mechanism.

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.

Purpose To investigate the association between healthy Nordic diet and risk of disease death in middle-aged and older men from eastern Finland. Methods A total of 1547 men aged 42–60 years and free of cardiovascular disease (CVD), cancer and type 2 diabetes at baseline in 1984–1989 were included. Diet was assessed with 4-day food records at baseline and the healthy Nordic diet score was calculated based on the Baltic Sea Diet Score. The incidence of death was assessed by a computer linkage to the national cause of death register. Cox proportional hazards regression analyses were used to estimate the associations between the healthy Nordic diet score and mortality. Results During the mean follow-up of 23.6 years (SD 7.0), 576 men died due to disease: 250 due to CVD, 194 due to cancer and 132 due to other diseases. The multivariable-adjusted hazard ratios (95% confidence interval) in the lowest vs. the highest quartile of the healthy Nordic diet score were 1.27 (1.01–1.59) for any disease death (P-trend across quartiles P-trend = 0.049) for CVD death, 1.26 (0.84–1.89, P-trend = 0.316) for cancer death and 1.04 (0.65–1.68, P-trend = 0.563) for other disease deaths. Conclusions In this prospective population-based cohort study among middle-aged and older men, low adherence to a healthy Nordic diet was associated with a higher risk of any disease death, possibly largely attributable to higher CVD mortality.

Purpose Long-chain omega-3 polyunsaturated fatty acids (PUFA) from fish have been associated with risk of cardiovascular diseases (CVD), especially sudden cardiac death (SCD). Mercury exposure, mainly due fish consumption, has been associated with higher risk. However, the impact of PUFAs or mercury on the ventricular cardiac arrhythmias, which often precede SCD, is not completely known. We investigated the associations of the serum long-chain omega-3 PUFAs and hair mercury with ventricular repolarization, measured by heart rate-corrected QT and JT intervals (QTc and JTc, respectively). Methods A total of 1411 men from the prospective, population-based Kuopio Ischaemic Heart Disease Risk Factor Study, aged 42–60 years and free of CVD in 1984–1989, were studied. Results Serum long-chain omega-3 PUFA concentrations were inversely associated with QTc and JTc (multivariate-adjusted P trend across quartiles = 0.02 and 0.002, respectively) and, during the mean 22.9-year follow-up, with lower SCD risk. However, further adjustments for QTc, JTc or hair mercury did not attenuate the associations with SCD. Hair mercury was not associated with QTc, JTc or SCD risk, but it slightly attenuated the associations of the serum long-chain omega-3 PUFA with QTc and JTc. Conclusions Higher serum long-chain omega-3 PUFA concentrations, mainly a marker for fish consumption, were inversely associated with QTc and JTc in middle-aged and older men from Eastern Finland, but QTc or JTc did not attenuate the inverse associations of the long-chain omega-3 PUFA with SCD risk. This suggests that prevention of prolonged ventricular repolarization may not explain the inverse association of the long-chain omega-3 PUFA with SCD risk., final draft, peerReviewed

Fish intake and the long-chain omega-3 polyunsaturated fatty acids (PUFAs) in fish have been suggested to lower the risk of cognitive decline. We assessed whether serum long-chain omega-3 PUFAs eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) are associated with performance on neuropsychological tests in an older population and whether exposure to methylmercury, mainly from fish, or apolipoprotein-E4 (Apo-E4) phenotype can modify the associations.A total of 768 participants from the population-based Kuopio Ischaemic Heart Disease Risk Factor Study were included. Cognitive function was measured using five neuropsychological tests: the Trail Making Test, the Verbal Fluency Test, the Selective Reminding Test, the Visual Reproduction Test and the Mini Mental State Exam. Multivariate-adjusted analysis of covariance and linear regression were used to analyze the cross-sectional associations.We found statistically significant associations between serum EPA+DPA+DHA and better performance in the Trail Making Test and the Verbal Fluency Test. The individual associations with EPA and DHA were similar with the findings with EPA+DPA+DHA, although the associations with DHA were stronger. No associations were observed with serum DPA. Pubic hair mercury content was associated only with a worse performance in the Trail Making Test, and mercury had only little impact on the associations between the serum PUFAs and cognitive performance. Apo-E4 phenotype did not modify the associations with PUFAs or mercury.Higher serum long-chain omega-3 PUFA concentrations were associated with better performance on neuropsychological tests of frontal lobe functioning in older men and women. Mercury exposure or Apo-E4 phenotype had little impact on cognitive performance.

Background: A Finnish joint research effort Kuopio Birth Cohort (KuBiCo) seeks to evaluate the effects of genetics, epigenetics and different risk factors (medication, nutrition, lifestyle factors and environmental aspects) during pregnancy on the somatic and psychological health status of the mother and the child. Methods: KuBiCo will ultimately include information on 10,000 mother-child pairs who have given their informed consent to participate in this cohort. Identification of foetal health risk factors that can potentially later manifest as disease requires a repository of relevant biological samples and a flexible open up-to-date data handling system to register, store and analyse biological, clinical and questionnaire-based data. KuBiCo includes coded questionnaire-based maternal background data gathered before, during and after the pregnancy and bio-banking of maternal and foetal samples that will be stored in deep freezers. Data from the questionnaires and biological samples will be collected into one electronic database. KuBiCo consists of several work packages which are complementary to each other: Maternal, foetal and placental metabolism and omits; Paediatrics; Mental wellbeing; Prenatal period and delivery; Analgesics and anaesthetics during peripartum period; Environmental effects; Nutrition; and Research ethics. Discussion: This report describes the set-up of the KuBiCo and descriptive analysis from 3532 parturients on response frequencies and feedback to KuBiCo questionnaires gathered from June 2012 to April 2016. Additionally, we describe basic demographic data of the participants (n = 1172). Based on the comparison of demographic data between official national statistics and our descriptive analysis, KuBiCo represents a cross-section of Finnish pregnant women.

Background The redundancy of information is becoming a critical issue for epidemiologists. High-dimensional datasets require new effective variable selection methods to be developed. This study implements an advanced evolutionary variable selection method which is applied for cardiovascular predictive modeling. The epidemiological follow-up study KIHD (Kuopio Ischemic Heart Disease Risk Factor Study) was used to compare the designed variable selection method based on an evolutionary search with conventional stepwise selection. The sample contains in total 433 predictor variables and a response variable indicating incidents of cardiovascular diseases for 1465 study subjects. Results The effectiveness of variable selection methods was investigated in combination with two models: Generalized Linear Logistic Regression and Support Vector Machine. We managed to decrease the number of variables from 433 to 38 and save the predictive ability of the models used. Their performance was evaluated with an F-score metric. At most, we gained 65.6% and 67.4% of the F-score before and after variable selection respectively. All the results were averaged over 5-folds of a cross-validation procedure. Conclusions The presented evolutionary variable selection method allows a reduced set of variables to be chosen which are relevant to predicting cardiovascular diseases. A reference list of the most meaningful variables is introduced to be used as a basis for new epidemiological studies. In general, the multicollinearity of variables enables different combinations of predictors to be used and the same performance of models to be attained. Electronic supplementary material The online version of this article (10.1186/s13040-018-0180-x) contains supplementary material, which is available to authorized users.

Fish or fish oil consumption has been associated with lower blood pressure. Fish may also contain methylmercury, which has been associated with cardiovascular diseases and higher blood pressure. Our aim was to study the associations of serum long-chain n-3 polyunsaturated fatty acids (PUFA) eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA), mainly reflecting fish or fish oil intake, and hair mercury concentration with blood pressure. Data were available for 848 men and 909 women from the Kuopio Ischaemic Heart Disease Risk Factor Study, aged 53-73 years. We excluded participants with ischemic heart disease, stroke, diabetes or hypertension treatment, leaving 396 men and 372 women. Log-transformed values were used to study the associations. The mean serum concentrations were 1.63% (s.d. 0.91) for EPA, 0.77% (s.d. 0.16) for DPA and 2.73% (s.d. 0.90) for DHA of all serum fatty acids. Multivariate-adjusted serum EPA+DPA+DHA was associated with lower systolic blood pressure (β = -4.50, 95% confidence interval (CI) -8.02 - -0.99) and pulse pressure (β = -4.41, 95% CI -6.95 - -1.87), but not with diastolic blood pressure (β = -0.45, 95% CI -2.31-1.52). The associations were similar with EPA, DPA and DHA evaluated individually. The mean hair mercury concentration was 1.42 μg g(-1) (s.d. 1.54). Hair mercury was not associated with blood pressure and it did not modify the association between PUFA and blood pressure. These results suggest that higher serum long-chain n-3 PUFA concentration has a modest inverse association with blood pressure in older men and women.

To investigate the association between serum 25-hydroxyvitamin D [25(OH)D] concentration, a marker of vitamin D status, and risk of all-cause and cardiovascular mortality in a general older population with relatively low average serum 25(OH)D concentrations.The study population included 552 men and 584 women aged 53-73 years who were free of CVD and cancer at baseline in 1998-2001 from the prospective, population-based Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study. Deaths were ascertained by a computer linkage to the national cause of death register. All deaths that occurred from the study entry to December 31, 2008, were included. Cox proportional hazards regression models were used to analyze the association between serum 25(OH)D and risk of death.The mean serum 25(OH)D concentration was 43.7 nmol/L (SD 17.8), with a strong seasonal variation. During the average follow-up of 9.1 years, 87 participants died, 35 from cardiovascular disease (CVD). After multivariable-adjustments, the hazard ratios (HR) for all cause death in the tertiles of serum 25(OH)D were 1, 1.68 (95% CI: 0.92, 3.07) and 2.06 (95% CI: 1.12, 3.80), p for trend = 0.02.Our study supports the accumulating evidence from epidemiological studies that vitamin D deficiency is associated with increased risk of death. Large-scale primary prevention trials with vitamin D supplementation are warranted.