Publications by authors named "Tomi-Pekka Tuomainen"

160 Publications

Lipid levels, apolipoproteins, and risk of incident atrial fibrillation in men: A report from the Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD).

J Clin Lipidol 2022 Apr 26. Epub 2022 Apr 26.

Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L7 8TX, United Kingdom; Liverpool Centre for Cardiovascular Sciences, University of Liverpool, Liverpool, Merseyside L7 8TX, United Kingdom.

Background: Apolipoproteins are associated with risk of coronary heart disease but the association with risk of incident atrial fibrillation (AF) has been inconsistent.

Objectives: This study investigated the association of apolipoproteins A-1 (apoA-1) and B (apoB), and lipid levels including triglyceride (TG), total cholesterol (TC), very low-density lipoprotein cholesterol (VLDL-C), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), with the risk of new-onset AF.

Methods: A total of 2533 men from the prospective, population-based Kuopio Ischaemic Heart Disease Risk Factor Study, aged 42-60 years, were studied. Cox proportional hazards adjusted for potential confounders was used to estimate hazard ratio (HR) of incident events across serum lipid, lipoprotein, and apoA-1 and apoB concentrations.

Results: During the mean follow-up of 22.4 years, 594 AF cases occurred. Cox proportional hazards regression indicated that higher serum HDL-C and apoA-1 concentrations were associated with lower risk of AF [the extreme-quartile multivariable-adjusted HR 0.72 (95% CI 0.57-0.92, P = 0.02) for HDL-C, and 0.72 (95% CI 0.52-1.00, P = 0.05)] for apoA-1]. No significant associations were observed for apoB and other lipids (TC, VLDL-C, LDL-C, non-HDL-C, and TG) with risk of incident AF.

Conclusion: Over the time of follow-up in this study lower new-onset incident AF was in association with higher HDL-C and apo-A1 levels. Future studies should investigate mechanisms underlying the association of low HDL-C and low apoA1 with higher risk of incident AF.
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http://dx.doi.org/10.1016/j.jacl.2022.04.003DOI Listing
April 2022

Epidemiological predictive modeling: lessons learned from the Kuopio ischemic heart disease risk factor study.

Ann Epidemiol 2022 Mar 27;70:1-8. Epub 2022 Mar 27.

Department of Environmental and Biological Sciences, University of Eastern Finland, Kuopio, Finland.

Purpose: The use of predictive models in epidemiology is relatively narrow as most of the studies report results of traditional statistical models such as Linear, Logistic, or Cox regressions. In this study, a high-dimensional epidemiological cohort, collected within the Kuopio Ischemic Heart Disease Risk Factor Study in 1984-1989, was used to investigate the predictive ability of models with embedded variable selection.

Methods: Simple Logistic Regression with seven preselected risk factors was compared to k-Nearest Neighbors, Logistic Lasso Regression, Decision Tree, Random Forest, and Multilayer Perceptron in predicting cardiovascular death for the aged men from Kuopio Ischemic Heart Disease Risk Factor for the long horizon of 30 ± 3 years: 746 predictor variables were available for 2682 men (705 cardiovascular deaths were registered). We considered two scenarios of handling competing risks (removing subjects and treating them as non-cases).

Results: The best average AUC on the test sample was 0.8075 (95%CI, 0.8051-0.8099) in scenario 1 and 0.7155 (95%CI, 0.7128-0.7183) in scenario 2 achieved with Logistic Lasso Regression, which was 6.04% and 5.50% higher than the baseline AUC provided by Logistic Regression with manually preselected predictors.

Conclusions: In both scenarios Logistic Lasso Regression, Random Forest, and Multilayer Perceptron outperformed Simple Logistic Regression.
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http://dx.doi.org/10.1016/j.annepidem.2022.03.010DOI Listing
March 2022

Associations of fermented and non-fermented dairy consumption with serum C-reactive protein concentrations - A cross-sectional analysis.

Clin Nutr ESPEN 2022 04 15;48:401-407. Epub 2022 Jan 15.

University of Eastern Finland, Institute of Public Health and Clinical Nutrition, P.O. Box 1627, 70211 Kuopio, Finland. Electronic address:

Background And Aims: The results of epidemiological studies on dairy products and low-grade inflammation are scarce and inconsistent. Some studies have suggested that the associations may vary depending on the type of dairy product consumed. The aim of this cross-sectional study was to investigate the associations between intake of fermented and non-fermented dairy products and separately butter and serum high-sensitivity C-reactive protein (hs-CRP), a common inflammation marker, among a population with high dairy intake.

Methods: The study included 1338 generally healthy men aged 42-60 years and serum hs-CRP ≤10 mg/L from the Kuopio Ischaemic Heart Disease Risk Factory Study, examined in 1984-1989. Dietary intakes were assessed using 4-day food records. ANCOVA and linear and logistic regression were used for analyses.

Results: The reported mean intakes of fermented and non-fermented dairy products and butter were 189 (SD 217), 522 (SD 330) and 33 (SD 27) g/d, respectively. In the model adjusted for age, year of examination and energy intake (Model 1), higher intake of total dairy, total non-fermented dairy, total milk and butter were associated with higher concentration of serum hs-CRP, whereas fermented dairy intake was not associated with serum hs-CRP. After further adjustment for potential confounders, only higher butter intake remained statistically significantly associated with increased serum hs-CRP (P-trend = 0.049). The odds ratio for elevated hs-CRP (>3 mg/L) in the highest vs. the lowest quartile was 2.50 (95% confidence interval 1.19-5.26, P-trend = 0.02).

Conclusions: These results suggest that high intake of butter, but not other dairy products may be associated with increased low-grade inflammation.
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http://dx.doi.org/10.1016/j.clnesp.2022.01.011DOI Listing
April 2022

Economic Recession and the Long Term Risk of Psychiatric Disorders and Alcohol Related Diseases-A Cohort Study From Eastern Finland.

Front Psychiatry 2022 17;13:794888. Epub 2022 Feb 17.

Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.

Background: Long-term development of psychiatric disorders and alcohol-related diseases after economic recessions is insufficiently studied. We investigated the overall impact of the economic recession between 1991 and 1994 in Finland on the long-term incidence of psychiatric and alcohol-related diseases.

Methods: A population-based sample of 1,774 women and men aged 53-73 years were examined between 1998 and 2001 from the Kuopio Ischemic Heart Disease Risk Factor Study (KIHD). Participants completed comprehensive questionnaires on the possible impact of the 1990s recession in Finland on their lives. They were followed-up until 2018. Cox proportional hazards regression was used to estimate hazard ratios (HR) of new incident psychiatric and alcohol-related disorders during the 20-years follow-up after linkage to the National Hospital Registry. Logistic regression was used to estimate odds ratios (OR) of psychiatric disorders at baseline.

Results: At baseline, 93 participants had psychiatric disorders. During 20-years follow-up, 138 new psychiatric disorders and 45 alcohol-related diseases were developed. The covariate-adjusted risk of psychiatric disorders was over twice higher among men who experienced recession-induced hardships compared to those who did not (HR = 2.20, 95%CI = 1.04-4.70, = 0.04). The risk of alcohol-related diseases was more than four times higher among men with hardships (HR = 4.44, 95%CI = 1.04-18.90, = 0.04). No such associations were observed among women. No association was observed between recession-induced hardships and having psychiatric disorders at baseline in both genders (multivariate-adjusted = 0.63 for women, multivariate-adjusted = 0.36 for men).

Conclusion: Long-term risk of psychiatric disorders and alcohol-related diseases was increased after the 1990s economic recession in Finland, but only among middle-age and older men.
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http://dx.doi.org/10.3389/fpsyt.2022.794888DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8891480PMC
February 2022

How competing risks affect the epidemiological relationship between vitamin D and prostate cancer incidence? A population-based study.

Andrologia 2022 Feb 28:e14410. Epub 2022 Feb 28.

Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.

We hypothesized that controversial results regarding the epidemiological relationship between circulating 25-hydroxyvitamin D, 25(OH)D, and risk of prostate cancer (PCA) incidence are partly due to competing risks. To test the hypothesis, we studied associations across 25(OH)D, PCA and death in 2578 middle-aged men belonging to the Kuopio Ischaemic Heart Disease Risk Factor Study. The men were free of cancer at baseline, and the mean (SD) follow-up time was 23.3 (9.1) years. During this period, 296 men had a PCA diagnosis, and 1448 men died without the PCA diagnosis. The absolute risk of developing PCA was highest in the highest 25(OH)D tertile (15%), whereas that of death was highest in the lowest 25(OH)D tertile (67%). A competing risk analysis showed that belonging to the highest 25(OH)D tertile increased the risk of PCA incidence and improved survival with the respective hazard ratios (HR) of 1.35 (95% CI = 1.07-1.70) and 0.79 (95% CI = 0.71-0.89). Adjusting for 10 covariates together with 25(OH)D did not significantly change the results, but the respective adjusted HRs for PCA and death were 1.20 and 0.87. To conclude, the competing risk analysis did not eliminate the direct relationship between 25(OH)D and PCA but rather strengthened it.
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http://dx.doi.org/10.1111/and.14410DOI Listing
February 2022

Associations of dairy, meat, and fish intakes with risk of incident dementia and with cognitive performance: the Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD).

Eur J Nutr 2022 Feb 25. Epub 2022 Feb 25.

Institute of Public Health and Clinical Nutrition, University of Eastern Finland, P.O. Box 1627, 70211, Kuopio, Finland.

Purpose: To investigate if dairy, meat, and fish intakes associate with dementia and cognitive performance.

Methods: We included 2497 dementia-free men from Eastern Finland, aged 42-60 years in 1984-1989 at the baseline examinations. Data on cognitive tests [Mini Mental State Exam (MMSE), trail making test (TMT), verbal fluency test (VFL), selective reminding test (SRT), and Russell's adaptation of the visual reproduction test (VRT)] at the 4-year re-examinations were available for 482 men and on the ApoE phenotype for 1259 men. Data on dementia events were obtained by linkage to national health registers. Diet was assessed with baseline 4-day food records. Cox regression and analysis of covariance were used for analyses.

Results: During a mean 22-year follow-up, 337 men had a dementia diagnosis. Among the foods, only cheese intake associated with dementia risk (hazard ratio in the highest vs. the lowest quartile = 0.72, 95% confidence interval = 0.52-0.99, P-trend = 0.05). In the cognitive tests, higher non-fermented dairy and milk intakes associated with worse verbal fluency (VFT). Higher processed red meat intake associated with worse verbal (SRT) and visual memory (VRT), whereas higher unprocessed red meat intake associated with better general cognitive functioning (MMSE) and processing speed and executive functioning (TMT). Higher fish intake associated with better verbal memory (SRT). Among APOE-ε4 carriers, especially non-fermented dairy intake associated with higher risk of dementia outcomes, and higher fish intake indicated better cognitive performance.

Conclusion: Although higher intake of some food groups associated with cognitive performance, we found little evidence for associations with dementia risk.
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http://dx.doi.org/10.1007/s00394-022-02834-xDOI Listing
February 2022

Serum ferritin and incident cardiometabolic diseases in Scottish adults.

Cardiovasc Diabetol 2022 02 16;21(1):26. Epub 2022 Feb 16.

Usher Institute, University of Edinburgh, Edinburgh, UK.

Background: Iron stores, estimated as ferritin levels, and type 2 diabetes (T2D) have been associated previously, while findings regarding coronary heart disease (CHD) and cerebrovascular disease (CEVD) are still inconclusive. No study has focused on simultaneous evaluation of associations between iron stores and the above cardiometabolic diseases (CMD) in the same population. We aim to evaluate the association between serum ferritin and risk of T2D, CHD and CEVD in Scottish population over a wide range of ferritin levels.

Methods: Longitudinal study in 6,497 participants of the 1995 and 1998 Scottish health surveys, who were followed-up until 2011. Cox regression models were conducted adjusting for age, sex/menopausal status, fibrinogen, GGT levels, smoking, alcohol consumption, total cholesterol, HDL-cholesterol, blood pressure, and BMI. Ferritin was used as continuous (sex/menopausal status-specific Z score) and categorical variable (sex/menopausal status-specific quartiles, quintiles and sextiles).

Results: During follow-up, 4.9% of the participants developed T2D, 5.3% CHD, and 2.3% CEVD. By using ferritin quartiles, serum ferritin was positively associated with T2D, CHD and CEVD but only the association with T2D remained after adjustment for covariates [Quartile 4 v. 1: adjusted HR 95% CI 1.59 (1.10-2.34); P = 0.006]. When ferritin sextiles were used (6 v. 1), the ferritin-CEVD association became slightly stronger and significant [adjusted HR 95% CI 2.08 (1.09-3.94); P = 0.024].

Conclusions: Iron stores relate differently to each CMD. Serum ferritin levels were positively and independently associated with incident T2D, and with incident CEVD if higher cut-off points for high ferritin levels were considered.
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http://dx.doi.org/10.1186/s12933-022-01450-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8851777PMC
February 2022

Synergic Interaction of Vitamin D Deficiency and Renal Hyperfiltration on Mortality in Middle-Aged Men.

J Ren Nutr 2022 Feb 2. Epub 2022 Feb 2.

Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.

Objective: Vitamin D deficiency and renal hyperfiltration (RHF) are prevalent conditions both recently linked with mortality. The two conditions are interrelated, but their combined effect and interaction on mortality have not been studied. The objective of this study was to assess the combined effect and interaction of vitamin D deficiency and RHF on all-cause, cardiovascular (CV), and non-CV mortality in nondiabetic middle-aged men.

Methods: Middle-aged nondiabetic men (n = 1,959) were followed up for a median of 28 years. With adjustment for age, body mass index (BMI), smoking, BMI-smoking interaction, healthy Nordic diet (HND), alcohol consumption, and hypertension, we fitted Cox proportional hazard models to estimate the hazard ratios (HRs) of all-cause-, CV-, and non-CV mortality with respect to vitamin D deficiency and RHF. We evaluated the effect of interaction between RHF and vitamin D on the outcomes on the additive and multiplicative scales.

Results: Vitamin D deficiency and RHF, both individually and combined, are associated with a high hazard of mortality. The HRs for all-cause- and non-CV mortality were highest among men with coexisting vitamin D deficiency and RHF (HR, 3.02; 95% CI, 1.90 to 4.79; and HR, 3.63; 95% CI, 2.07 to 6.36; respectively). We found a synergic interaction between vitamin D deficiency and RHF in respect to all-cause (RERI, 1.47; 95% CI, 0.03 to 2.9) and non-CV mortality (RERI, 2.09; 95% CI, 0.02 to 4.16) of type positive multiplicative, positive additive.

Conclusion: The synergic interaction of vitamin D deficiency and RHF on mortality might have importance in the global burden of the two conditions. Further studies investigating cause-specific mortality are needed to highlight underlying mechanisms by which vitamin D deficiency and RHF interact.
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http://dx.doi.org/10.1053/j.jrn.2022.01.009DOI Listing
February 2022

Lipid profile, lipid ratios, apolipoproteins, and risk of cardiometabolic multimorbidity in men: The Kuopio Ischaemic Heart Disease Risk Factor Study.

Lipids 2022 03 20;57(2):141-149. Epub 2022 Jan 20.

Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK.

The blood level of lipids, apolipoproteins, and lipid ratios are important predictors of some chronic diseases. However, their association with cardiometabolic multimorbidity (CMM) is less known. We evaluated a wide range of lipid profiles and lipid ratios, including low-density lipoprotein-cholesterol (LDL-C), very-low-density lipoprotein-cholesterol (VLDL-C), high-density lipoprotein-cholesterol (HDL-C), and apoA1 and B, as well triglyceride and total cholesterol with risk of incident CMM. In 1728 men aged 52.5 ± 5.2 years from the Kuopio Ischaemic Heart Disease were included in this study. We defined CMM as coexisting of two or more of stroke, type 2 diabetes mellitus (T2D), coronary heart disease (CHD). A Cox proportional hazard regression method was applied to evaluate the risk of CMM against the exposures. During the mean follow-up of 22.4 years, 335 men suffered from CMM conditions. Higher serum triglyceride and VLDL concentrations were associated with a higher risk of coexisting T2D-CHD (HRs 1.99 (95% CI, 1.12-3.53) and HRs 1.79 (95% CI, 1.04-3.11), respectively. Whereas higher HDL was associated with lower incident [HRs 0.49 (95% CI, 0.40-1.00)]. The HRs for coexisting T2D-CHD was 2.02 (95% CI, 1.01-3.07) for total cholesterol/HDL-C, 1.85 (95% CI, 1.04-3.29) for triglyceride/HDL-C, 1.69 (95% CI, 1.01-2.31) for Non-HDL-C/HDL-C, and 1.89 (95% CI, 1.03-2.46) for apoB/apoA1. In contrast, serum LDL-C/apoB ratios were inversely associated with the risk of coexisting T2D-CHD [HRs 0.50 (95% CI, 0.28-0.90)]. No associations were observed between our exposures and other CMM conditions. In conclusion, elevated triglyceride, VLDL-C, total cholesterol/HDL-C, TG/HDL-C, apoB/apoA1 as well as lower LDL-C/apoB were independently associated with the higher risk of T2D-CHD coexistence.
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http://dx.doi.org/10.1002/lipd.12337DOI Listing
March 2022

Effect of Arterial Stiffness and Carotid Intima-Media Thickness Progression on the Risk of Dysglycemia, Insulin Resistance, and Dyslipidemia: a Temporal Causal Longitudinal Study.

Hypertension 2022 03 18;79(3):667-678. Epub 2022 Jan 18.

Institute of Public Health and Clinical Nutrition, School of Medicine, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland (A.O.A., T.-P.T).

Background: We investigated the temporal causal longitudinal associations of carotid-femoral pulse wave velocity (cfPWV), a measure of arterial stiffness, and carotid intima-media thickness (cIMT) progression with the risk of dysglycemia, insulin resistance, and dyslipidemia.

Methods: We included 3862, 17.7-year-old, participants from the Avon Longitudinal Study of Parents and Children, followed up for 7 years. cfPWV, cIMT, and fasting plasma samples were repeatedly measured. We computed homeostatic model assessment (HOMA) of insulin resistance and percent pancreatic beta-cell function. Data were analyzed using logistic regression, linear mixed-effect, and cross-lagged structural equation models.

Results: A higher cfPWV at 17.7 years was associated with higher insulin at age 24.5 years (odds ratio, 1.25 [CI, 1.08-1.44]; =0.003), which slightly attenuated after covariates adjustment. Higher cIMT at 17.7 years was associated with lower insulin (odds ratio, 0.06 [0.01-0.95]; =0.046) at 24.5 years, after covariate adjustments. In mixed-effect models, the 7-year progression in cfPWV (predictor) was directly associated with the increase in triglyceride (outcome). cIMT progression was associated with the 7-year increase in LDL (low-density lipoprotein), triglyceride, and glucose. In cross-lagged models, higher cfPWV at 17.7 years was associated with higher insulin (=0.06, SE, 0.12, =0.014), HOMA of insulin resistance, and HOMA-percent pancreatic beta-cell function at 24.5 years. However, insulin, HOMA of insulin resistance, and HOMA-percent pancreatic beta-cell function at 17.7 years were not associated with cfPWV at 24.5 years. Higher cIMT at 17.7 years was associated with reduced insulin, HOMA of insulin resistance, and HOMA-percent pancreatic beta-cell function at 24.5 years, but not vice versa. Higher glucose at 17.7 years was associated with higher cfPWV and cIMT at 24.5 years only.

Conclusions: Arterial stiffness in adolescence may be a causal risk factor for hyperinsulinemia and insulin resistance in young adulthood.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.121.18754DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8823909PMC
March 2022

Vitamin D supplementation and prevention of cardiovascular disease and cancer in the Finnish Vitamin D Trial: a randomized controlled trial.

Am J Clin Nutr 2022 May;115(5):1300-1310

Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.

Background: 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.

Objectives: To investigate the effects of vitamin D3 supplementation on CVD and cancer incidences.

Methods: 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.

Results: 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.

Conclusions: 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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http://dx.doi.org/10.1093/ajcn/nqab419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9071497PMC
May 2022

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

Eur J Nutr 2022 Jun 27;61(4):1981-1989. Epub 2021 Dec 27.

Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio Campus, PO Box 1627, 70211, Kuopio, Finland.

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.
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http://dx.doi.org/10.1007/s00394-021-02780-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9106603PMC
June 2022

Effects of Arterial Stiffness and Carotid Intima-Media Thickness Progression on the Risk of Overweight/Obesity and Elevated Blood Pressure/Hypertension: a Cross-Lagged Cohort Study.

Hypertension 2022 01 17;79(1):159-169. Epub 2021 Nov 17.

Institute of Public Health and Clinical Nutrition, School of Medicine, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland (A.O.A., T.-P.T.).

We examined the temporal longitudinal associations of carotid-femoral pulse wave velocity (cfPWV), a measure of arterial stiffness, and carotid intima-media thickness (cIMT) with the risk of overweight/obesity and elevated blood pressure (BP)/hypertension. We studied 3862 adolescents aged 17.7 years from the Avon Longitudinal Study of Parents and Children, followed-up for 7 years. cfPWV and cIMT were measured by ultrasound. Total and trunk fat mass and lean mass were assessed by dual-energy X-ray absorptiometry. Body mass index and BP were measured. Data were analyzed using logistic regression, linear mixed-effect, and cross-lagged structural equation models, with covariate adjustments. Among 1719 male and 2143 female participants, higher cfPWV at 17.7 years was associated with the risk of elevated systolic BP/hypertension (odds ratio, 1.20 [1.02-1.41]; =0.026), elevated diastolic BP/hypertension (1.77 [1.32-2.38]; <0.0001), body mass index-overweight/obesity (1.19 [1.01-1.41]; =0.041), and trunk fat mass overweight/obesity (1.24 [1.03-1.49]; =0.023) at 24.5 years. Higher cIMT at 17.7 years had no associations with obesity and elevated BP at follow-up. cfPWV progression was directly associated with 7-year increase in systolic BP (effect estimate 16 mm Hg [9-24]; <0.0001) and diastolic BP (28 mm Hg [23-34]; <0.0001). cIMT progression was directly associated with the 7-year increase of all adiposity measures and diastolic BP. In the temporal analysis, baseline cfPWV was directly associated with follow-up systolic and diastolic BP, however, baseline BP was unassociated with follow-up cfPWV. cfPWV but not cIMT was bidirectionally associated with adiposity. Obesity and hypertension prevention from adolescence may require developing novel approaches to mitigate arterial stiffness.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.121.18449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8654123PMC
January 2022

Mortality-based definition of renal hyperfiltration in middle-aged men: a 35-year cohort from Finland.

Int Urol Nephrol 2021 Nov 3. Epub 2021 Nov 3.

Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.

Background: While the impact of low glomerular filtration rate (eGFR) on various outcomes has been extensively studied, the other adverse occurrence, renal hyperfiltration (RHF), remains understudied, poorly defined, and, therefore, its impact on mortality unestablished.

Methods: Using a population-based subcohort from the Kuopio Ischaemic Disease Risk Factor Study restricted to non-diabetic Finnish men aged 54 or 55 years, we followed up n = 1179 study participants for up to 35 years. We evaluated the hazard of all-cause mortality associated to RHF at different cutoff points defining eGFR. Based on models' accuracy we suggested an optimal eGFR cutoff point for the definition of RHF. We divided the RHF category to three subgroups and evaluated them in terms of baseline characteristics and mortality hazard.

Results: The eGFR value of 97 mL/min/1.73 m corresponded to the models with the highest accuracy. Overall RHF associated with an increased risk of mortality (hazard ratio [HR] 1.42; 95% confidence interval [CI] 1.21 to 1.67). Moderate RHF associated with a decreased HR of mortality when compared to mild (0.64; 95% CI 0.46 to 0.9) or to extreme RHF (0.61; 95% CI 0.43 to 0.85), suggesting a rather U-shaped relationship between RHF's eGFR values and mortality hazard.

Conclusion: The burden of increased eGFR within what is still considered normal eGFR category was highly underestimated. RHF's eGFR values had a U-shaped association with the risk of overall mortality. A more uniform consensual definition of RHF is needed, as higher to normal eGFR values that are not without consequences.
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http://dx.doi.org/10.1007/s11255-021-03048-6DOI Listing
November 2021

The associations between whole grain and refined grain intakes and serum C-reactive protein.

Eur J Clin Nutr 2022 04 17;76(4):544-550. Epub 2021 Aug 17.

University of Eastern Finland, Institute of Public Health and Clinical Nutrition, Kuopio, Finland.

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.
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http://dx.doi.org/10.1038/s41430-021-00996-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8993682PMC
April 2022

Negative interaction of fatty liver and hypertension on cardiovascular mortality in non-diabetic men: 34 years of follow-up.

Scand J Gastroenterol 2021 09 6;56(9):1096-1102. Epub 2021 Aug 6.

Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.

Background And Objectives: Fatty liver disease (FLD) and hypertension are separately associated with cardiovascular (CV) mortality. The two conditions are related in multiple ways. This work aimed to study the joint effect and interaction of FLD and hypertension in respect to overall and CV mortality.

Methods: The population-based cohort, Kuopio Ischaemic Disease Risk Factor Study, followed 1569 middle-aged non-diabetic Finnish men for 34 years. Considering adjustment for age, body mass index, smoking and alcohol consumption, separate and combined effects of FLD and hypertension and their interaction at the multiplicative and additive scales regarding all-cause and CV death were assessed using Cox proportional hazards models.

Results: FLD and hypertension coexisted in 8.54% of the men ( = 134). FLD and hypertension associated, independently and combined, with an increased hazard of all-cause and CV deaths. Non-CV mortality associated with FLD, but not with hypertension. We found a negative interaction between FLD and hypertension regarding the hazard of all-cause (relative excess risk due to interaction (RERI), -0.97; 95% confidence interval (CI), -1.65 to -0.28) and CV mortality (RERI, -1.74; 95% CI, -2.98 to -0.5). The interaction was also found on a multiplicative scale.

Conclusions: We found evidence of a negative interaction between FLD and hypertension in respect to CV mortality. We thus recommend adjusting for FLD or hypertension when studying the effect of the other condition on mortality or CV diseases in middle-aged men.
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http://dx.doi.org/10.1080/00365521.2021.1951836DOI Listing
September 2021

Cardiorespiratory Fitness, Fat Mass, and Cardiometabolic Health with Endothelial Function, Arterial Elasticity, and Stiffness.

Med Sci Sports Exerc 2022 01;54(1):141-152

Institute of Public Health and Clinical Nutrition, School of Medicine, University of Eastern Finland, Kuopio, FINLAND.

Purpose: This study aimed to determine whether estimated cardiorespiratory fitness (CRF), fat mass (FM), lean mass (LM), and adiponectin bidirectionally associate with arterial function and structure and if CRF mediates the relationship between cardiometabolic health and arterial outcomes in 9- to 11-yr-old children drawn from the Avon Longitudinal Study of Parents and Children birth cohort, United Kingdom.

Methods: Brachial artery flow-mediated dilation (FMD), distensibility coefficient (DC), and carotid-radial pulse wave velocity (PWV) were measured by ultrasonography; CRF was measured during the submaximal ergometer test; total FM, trunk FM, and LM were measured by dual-energy x-ray absorptiometry; plasma adiponectin was measured by enzyme assay; and cardiometabolic health was computed based on the International Diabetes Federation criteria for diagnosing metabolic syndrome. We tested bidirectionality by including CRF, FM, LM, and adiponectin as exposures and FMD, DC, and PWV as outcomes, alternatively.

Results: Among 5566 participants (2816 (51%) girls; median age, 9.75 yr), CRF per body mass0.21 was directly related to DC (β (95% confidence interval) = 0.004 (<0.0001 to 0.008); P = 0.046), whereas CRF per LM0.54 was inversely associated with PWV (-0.034 (-0.063 to -0.003); 0.032) after adjusting for covariates. These associations remained in bidirectional analyses. Total FM, trunk FM, and LM were bidirectionally and positively associated with FMD and DC. Total FM and trunk FM but not LM had bidirectional and inverse associations with PWV. Adiponectin was not related to FMD, DC, or PWV. CRF partially mediated the associations of cardiometabolic health with FMD (1.5% mediation), DC (12.1% mediation), and PWV (3.5% mediation).

Conclusions: Associations of poor cardiometabolic health with adverse arterial structure and function in childhood may be mitigated by increasing CRF. Higher CRF was associated with better arterial structure whereas higher total FM and trunk FM were associated with better arterial function and structure. In the reverse analysis, healthy arterial structure and function were independently associated with increased total FM and trunk FM, suggesting an "arterial paradox."
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http://dx.doi.org/10.1249/MSS.0000000000002757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8677603PMC
January 2022

Post-Analysis of Predictive Modeling with an Epidemiological Example.

Healthcare (Basel) 2021 Jun 24;9(7). Epub 2021 Jun 24.

Department of Environmental and Biological Sciences, University of Eastern Finland, Yliopistonranta 1 E, P.O. Box 1627, FI-70211 Kuopio, Finland.

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.
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http://dx.doi.org/10.3390/healthcare9070792DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8304882PMC
June 2021

Effects of data preprocessing on results of the epidemiological analysis of coronary heart disease and behaviour-related risk factors.

Ann Med 2021 12;53(1):890-899

Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.

Background: We carried out this study to demonstrate the effects of outcome sensitivity, participant exclusions, and covariate manipulations on results of the epidemiological analysis of coronary heart disease (CHD) and its behaviour-related risk factors.

Material And Methods: Our study population consisted of 1592 54-year-old men, who participated in the Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study. We used the Cox proportional-hazards model to predict the hazard of CHD and applied different sets of outcomes concerning outcome sensitivity and data preprocessing procedures regarding participant exclusions and covariate manipulations.

Results: The mean follow-up time was 23 years, and 730 men received the CHD diagnosis. Cox regressions based on data with no participant exclusions most often discovered statistically significant associations. Loose inclusion criteria for study participants with any CVD during the follow-up and strict exclusion criteria for participants with no CVD were best in discovering the associations between risk factors and CHD. Outcome sensitivity affected the associations, whereas the covariate type, continuous or categorical, did not.

Conclusions: This study suggests that excluding study participants who are not disease-free at baseline is probably unnecessary for epidemiological analyses. Epidemiological research reports should present results based on no data exclusions together with results based on reasoned exclusions.
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http://dx.doi.org/10.1080/07853890.2021.1921838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8231358PMC
December 2021

Adherence to a healthy Nordic diet and risk of type 2 diabetes among men: the Kuopio Ischaemic Heart Disease Risk Factor Study.

Eur J Nutr 2021 Oct 27;60(7):3927-3934. Epub 2021 Apr 27.

Institute of Public Health and Clinical Nutrition, University of Eastern Finland, P.O. Box 1627, 70211, Kuopio, Finland.

Purpose: To investigate the association between healthy Nordic diet and risk of type 2 diabetes (T2D) in middle-aged and older men from eastern Finland.

Methods: A total of 2332 men aged 42-60 years and free of T2D 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 a modified Baltic Sea Diet Score. T2D 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. Cox proportional hazards regression and analysis of covariance were used for analyses.

Results: During the mean follow-up of 19.3 years, 432 men (18.5%) were diagnosed with T2D. The multivariable-adjusted hazard ratio for T2D in the lowest vs. the highest quartile of the healthy Nordic diet score was 1.35 (95% CI 1.03-1.76) (P trend across quartiles 0.028). Lower adherence to healthy Nordic diet was also associated with higher plasma glucose and insulin concentrations.

Conclusions: In this prospective population-based cohort study among middle-aged and older men from eastern Finland, lower adherence to healthy Nordic diet was associated with higher risk of T2D and higher plasma glucose and serum insulin concentrations.
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http://dx.doi.org/10.1007/s00394-021-02569-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8437904PMC
October 2021

A healthy Nordic diet score and risk of incident CHD among men: the Kuopio Ischaemic Heart Disease Risk Factor Study.

Br J Nutr 2022 02 7;127(4):599-606. Epub 2021 Apr 7.

University of Eastern Finland, Institute of Public Health and Clinical Nutrition, P.O. Box 1627, 70211 Kuopio, Finland.

Healthy Nordic diet has been beneficially associated with CHD risk factors, but few studies have investigated risk of developing CHD. We investigated the associations of healthy Nordic diet with major CHD risk factors, carotid atherosclerosis and incident CHD in middle-aged and older men from eastern Finland. A total of 1981 men aged 42-60 years and free of CHD at baseline in 1984-1989 were investigated. Diet was assessed with 4-d food recording and the healthy Nordic diet score was calculated based on the Baltic Sea Diet Score. Carotid atherosclerosis was assessed by ultrasonography of the common carotid artery intima-media thickness in 1053 men. ANCOVA and Cox proportional hazards regression analyses were used for analyses. Healthy Nordic diet score was associated with lower serum C-reactive protein (CRP) concentrations (multivariable-adjusted extreme-quartile difference 0·66 mg/l, 95 % CI 0·11, 1·21 mg/l) but not with serum lipid concentrations, blood pressure or carotid atherosclerosis. During the average follow-up of 21·6 years (sd 8·3 years), 407 men had a CHD event, of which 277 were fatal. The multivariable-adjusted hazard ratios in the lowest v. the highest quartile of the healthy Nordic diet score were 1·15 (95 % CI 0·87, 1·51) for any CHD event (Ptrend 0·361) and 1·44 (95 % CI 0·99, 2·08) (Ptrend 0·087) for fatal CHD event. We did not find evidence that adherence to a healthy Nordic diet would be associated with a lower risk of CHD or with carotid atherosclerosis or major CHD risk factors, except for an inverse association with serum CRP concentrations.
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http://dx.doi.org/10.1017/S0007114521001227DOI Listing
February 2022

ECONOMIC RECESSION AND THE RISK OF CANCER - A Cohort Study from Eastern Finland.

J Epidemiol 2021 Mar 13. Epub 2021 Mar 13.

University of Eastern Finland, Institute of Public Health and Clinical Nutrition.

BackgroundLittle is known about the role of economic recessions in the risk of cancer. Therefore, we evaluated the impact of the severe economic recession in Finland between 1991-1994 on the incidence of all cancers and cancer subtypes among middle-age and older population.MethodsFrom the Kuopio Ischemic Heart Disease Risk Factor Study (KIHD), a population-based sample of 1620 women and men aged 53-73 years were examined between 1998-2001. The cancer-free participants completed a questionnaire on the possible impact of the 1990s recession in Finland on their lives. Incident cases of cancer were obtained through record linkage with the Finnish Cancer Registry. Cox proportional hazards regression was used to estimate hazard ratios (HR) of incident cancer events after adjusting for possible confounders.ResultsA total of 1096 cancer-free participants had experienced socioeconomic hardships due to the recession at the baseline. During 20 years of follow-up, 473 participants developed cancer. After adjustment for age, baseline socioeconomic position and lifestyle factors, the risk of all cancers was 32% higher among men who experienced socioeconomic hardships compared to those who did not (HR 1.32, 95%CI, 0.99-1.75, p=0.05). Prostate-genital cancer was 71% higher among men with hardships (n=103, HR=1.71, 95%CI, 1.06-2.74, p=0.02). No association was observed between socioeconomic hardships and subsequent risk of total or any subtype of cancer among women.Conclusions:The 1990s economic recession was associated with increased risk of all cancers, especially prostate-genital cancer among Finnish middle-age and older men, but no association with cancer was observed in women.
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http://dx.doi.org/10.2188/jea.JE20200595DOI Listing
March 2021

The impact of postpartum depressive symptoms on self-reported infant health and analgesic consumption at the age of 12 months: A prospective cohort study.

J Psychiatr Res 2021 04 16;136:388-397. Epub 2021 Feb 16.

Institute of Clinical Medicine / Psychiatry, University of Eastern Finland, P.O. Box 1627, FI, 70211, Kuopio, Finland; Psychiatry, University of Helsinki and Helsinki University Hospital, P.O. Box 22, FI, 00014, Helsinki, Finland; Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, P.O. Box 21, FI, 00014, Helsinki, Finland.

The infants of mothers with elevated depressive symptoms (EDS) postpartum appear to be at increased risk of somatic health problems during their first 12 months of life in low- and lower-middle-income countries. However, in higher-income countries, knowledge of this association is scarce. We sought to examine whether maternal reports of infant health problems, adherence to vaccination schedules and analgesic supply to the infant during the first 12 months of life differ between mothers with and without postpartum EDS. Altogether, 969 women who were enrolled in the Kuopio Birth Cohort study (www.kubico.fi) during 2012-2017 were included in this investigation. Depressive symptoms were measured with the Edinburgh Postnatal Depression Scale during pregnancy (1st and/or 3rd trimester) and at eight weeks postpartum. Infant health data were collected as a part of a 12-month online follow-up questionnaire for mothers and were based on self-reports of either maternal observations or physician-determined diagnoses. Postpartum EDS were associated with a 2- to 5-fold increased likelihood of abnormal crying and paroxysmal wheezing (based on parental observations), as well as gastroesophageal reflux and food allergy (based on physician-determined diagnoses). Mothers with postpartum EDS also supplied their infants with analgesic medication for longer periods. Adherence to vaccination schedules was similar between the examined groups. In conclusion, infants of mothers with postpartum EDS may be more likely to experience health problems or to be perceived by their mother as having health problems, and thus receive more medications.
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http://dx.doi.org/10.1016/j.jpsychires.2021.02.036DOI Listing
April 2021

Economic recession and cardiovascular disease among women: a cohort study from Eastern Finland.

Scand J Public Health 2022 Mar 10;50(2):250-256. Epub 2021 Feb 10.

Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.

Aims: Little is known about the effect of economic recessions on cardiovascular disease. Therefore, we investigated the association of the economic recession in Finland in the 1990s with the incidence of cardiovascular disease among middle-aged and older women.

Methods: A total of 918 women aged 53-73 years were examined for health and socioeconomic position in 1998-2001, as part of the population-based prospective Kuopio Ischaemic Heart Disease Risk Factor Study. The participants were asked whether Finland's economic recession in the early 1990s had affected their lives socially or economically. The cohort was followed for 18 years, and incident physician-diagnosed cases of cardiovascular disease were obtained through record linkage with the national hospital discharge registry that covers every hospitalisation in Finland. Cox proportional hazards regression models were used to estimate the risk of cardiovascular disease among those with and without exposure to socioeconomic hardships during the recession, after adjusting for possible confounders.

Results: At the baseline, 587 women reported having experienced socioeconomic hardships due to the recession. During the 20 years' follow-up, 501 women developed cardiovascular disease. After adjustment for age, the risk of cardiovascular disease was 27% higher among women exposed to socioeconomic hardships compared to those who were not (hazard ratio 1.27, 95% confidence interval 1.06-1.53, =0.012). Further adjustments for overall socioeconomic position at baseline, prior cardiovascular health, and lifestyle factors did not attenuate the association (hazard ratio 1.23, 95% confidence interval 1.02-1.5, =0.029).

Conclusions: The early 1990s economic recession was associated with a subsequently increased risk of cardiovascular disease among Finnish women.
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http://dx.doi.org/10.1177/1403494821990259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8873296PMC
March 2022

Renal hyperfiltration, fatty liver index, and the hazards of all-cause and cardiovascular mortality in Finnish men.

Epidemiol Health 2021 24;43:e2021001. Epub 2020 Dec 24.

Department of Public Health, University of Eastern Finland, Kuopio, Finland.

Objectives: Renal hyperfiltration (RHF) and fatty liver are separately associated with adverse health outcomes. In this study, we investigated the mortality hazard of coexisting RHF and fatty liver.

Methods: Middle-aged men from the Kuopio Ischaemic Disease Risk Factor Study (n=1,552) were followed up for a median of 29 years. Associations among RHF, fatty liver index (FLI) score, age, body mass index, smoking status, alcohol consumption, and hypertension status were assessed using logistic regression. Cox proportional hazards models were used to determine the hazard ratios (HRs) for all-cause and cardiovascular disease (CVD) mortality with respect to RHF and fatty liver.

Results: Of the men, 5% had RHF (n=73), whereas a majority had fatty liver (n=848). RHF was associated specifically with smoking, and fatty liver was associated specifically with overweight. The all-cause mortality hazard was highest (HR, 1.96; 95% confidence interval [CI], 1.27 to 3.01) among men with RHF and fatty liver (n=33). Among men with RHF but normal FLI (n=40), the HR of all-cause mortality was 1.67 (95% CI, 1.15 to 2.42). Among men with fatty liver but a normal estimated glomerular filtration rate (n=527), the HR of all-cause mortality was 1.35 (95% CI, 1.09 to 1.66). CVD mortality hazard was associated with RHF, but not fatty liver. We detected no interaction effect between RHF and fatty liver for all-cause (synergy index, 0.74; 95% CI, 0.21 to 2.67) or CVD (synergy index, 0.94; 95% CI, 0.34 to 2.60) mortality.

Conclusions: RHF and fatty liver are independently associated with all-cause and CVD mortality.
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http://dx.doi.org/10.4178/epih.e2021001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952838PMC
February 2021

Metabolite Profiling of Osteoporosis and Atherosclerosis in Postmenopausal Women: A Cross-Sectional Study.

Vasc Health Risk Manag 2020 2;16:515-524. Epub 2020 Dec 2.

Kuopio Musculoskeletal Research Unit (KMRU), Surgery, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.

Purpose: Atherosclerosis (AS) and osteoporosis (OP) are common causes of morbidity and mortality in postmenopausal women and are connected via an unknown mechanistic link. Metabolite profiling of blood samples may allow the identification of new biomarkers and pathways for this enigmatic association.

Patients And Methods: We studied the difference in 148 metabolite levels from serum samples in postmenopausal women with AS and OP compared with those in healthy participants in this cross-sectional study. Quantitative AS was assessed by carotid artery intima-media thickness (cIMT) and carotid artery calcifications (CACs) by ultrasound, as well as OP by femoral neck (FN) bone mineral density (BMD) and 148 metabolic measures with high-throughput proton (H) nuclear magnetic resonance (NMR) in serum samples from 280 postmenopausal (PM) women. Subjects were a randomly selected subsample from the population-based Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) study. The final study population included the following groups: OP with CAC (n=16, group I), non-OP with no CAC (n=59, group II), high cIMT tertile with OP (n=11, group III) and low cIMT tertile without OP (n=48, group IV).

Results: There were differences in several metabolite levels between groups I and II. The acetate level was lower in group I compared to that in group II (group I mean ± SD: 0.033 ± 0.0070; group II: 0.041 ± 0.014, CI95%: 0.018‒0.15, p=0.014). The result was similar with diacylglycerol (p=0.002), leucine (p=0.031), valine (p=0.022) and several very low-density lipoprotein (VLDL) metabolite levels, which were lower in group I compared to those in group II. However, no associations were found in adjusted analyses with total body (TB) fat mass (FM), age and statin use (p>0.05).

Conclusion: Our novel study found differences in the metabolite profiling of altered amino acid and lipoprotein metabolism in participants with OP and AS compared with those in healthy women. The causative mechanisms remain unknown and further studies are needed.
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http://dx.doi.org/10.2147/VHRM.S279028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719314PMC
December 2020

Common and personal target genes of the micronutrient vitamin D in primary immune cells from human peripheral blood.

Sci Rep 2020 12 3;10(1):21051. Epub 2020 Dec 3.

School of Medicine, Institute of Biomedicine, University of Eastern Finland, POB 1627, 70211, Kuopio, Finland.

Vitamin D is essential for the function of the immune system. In this study, we treated peripheral blood mononuclear cells (PBMCs) of healthy adults with the biologically active form of vitamin D, 1α,25-dihydroxyvitamin D (1,25(OH)D) using two different approaches: single repeats with PBMCs obtained from a cohort of 12 individuals and personalized analysis based on triplicates of five study participants. This identified 877 (cohort approach) and 3951 (personalized approach) genes that significantly (p < 0.05) changed their expression 24 h after 1,25(OH)D stimulation. From these, 333 and 1232 were classified as supertargets, a third of which were identified as novel. Individuals differed largely in their vitamin D response not only by the magnitude of expression change but also by their personal selection of (super)target genes. Functional analysis of the target genes suggested the overarching role of vitamin D in the regulation of metabolism, proliferation and differentiation, but in particular in the control of functions mediated by the innate and adaptive immune system, such as responses to infectious diseases and chronic inflammatory disorders. In conclusion, immune cells are an important target of vitamin D and common genes may serve as biomarkers for personal responses to the micronutrient.
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http://dx.doi.org/10.1038/s41598-020-78288-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713372PMC
December 2020

Associations of the serum metabolite profile with a healthy Nordic diet and risk of coronary artery disease.

Clin Nutr 2021 05 31;40(5):3250-3262. Epub 2020 Oct 31.

Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland; Department of Biology and Biological Engineering, Division of Food and Nutrition Science, Chalmers University of Technology, Gothenburg, Sweden; Department of Biochemistry, Food Chemistry and Food Development Unit, University of Turku, Turku, Finland. Electronic address:

Background & Aim: A healthy Nordic diet (HND) rich in wholegrain cereals, berries, vegetables, and fish, has been associated with a lower risk of cardiovascular disease, but the molecular links remain unclear. Here, we present the application of nontargeted metabolic profiling based on liquid chromatography with tandem mass spectrometry (LC-MS/MS) to identify metabolites that would potentially reflect the adherence to HND and their relationship with the risk of coronary artery disease (CAD).

Methods: From a Finnish population-based prospective cohort (Kuopio Ischaemic Heart Disease Risk Factor Study; KIHD), we collected 364 baseline serum samples in 4 groups: 1) 94 participants with high adherence to HND who developed CAD during the follow-up of 20.4 ± 7.6 years (cases), 2) 88 participants with high adherence who did not develop CAD during follow-up (controls), 3) 93 CAD cases with low adherence, and 4) 89 controls with low adherence.

Results: Indolepropionic acid, proline betaine, vitamin E derivatives, and medium-chain acylcarnitines were associated with adherence to HND after adjustments for age, waist-to-hip ratio (WHR), physical activity, and total cholesterol. These metabolites also correlated negatively with blood lipid profiles, BMI, insulin, inflammation marker high-sensitivity C reactive protein (hsCRP), smoking, and alcohol consumption, as well as positively with physical activity. Predictors of CAD risk included several lipid molecules, which also indicated lower adherence to HND. But, only the associations with the plasmalogens PC(O-16:0/18:2) and PC(O-16:1/18:2) remained significant after adjusting for age, smoking, systolic blood pressure, LDL cholesterol, and WHR. These plasmalogens did not correlate with any investigated risk factors of CAD at baseline, which may highlight their potential as novel predictors of CAD risk. Interestingly, the metabolic profile predicting CAD risk differed based on the adherence to HND. Also, HND adherence was more distinct within CAD cases than controls, which may emphasize the interaction between HND adherence and CAD risk.

Conclusions: The association between higher adherence to HND and a lower risk of CAD likely involves a complex interaction of various endogenous, plant-, and microbial-derived metabolites.
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http://dx.doi.org/10.1016/j.clnu.2020.10.051DOI Listing
May 2021

Cervical Cancer Screening Participation among Women of Russian, Somali, and Kurdish Origin Compared with the General Finnish Population: A Register-Based Study.

Int J Environ Res Public Health 2020 10 28;17(21). Epub 2020 Oct 28.

Department of Public Health Solutions, Finnish Institute for Health and Welfare (THL), P.O. Box 30, FI-00271 Helsinki, Finland.

Migrant-origin women are less prone to cervical screening uptake compared with host populations. This study examined cervical cancer screening participation and factors associated with it in the Finnish mass screening program during 2008-2012 in women of Russian, Somali and Kurdish origin compared with the general Finnish population (Finns) in Finland. The study population consists of samples from the Finnish Migrant Health and Well-being Study 2010-2012 and Health 2011 Survey; aged 30-64 ( = 2579). Data from the Finnish screening register linked with other population-based registry data were utilized. For statistical analysis we employed logistic regression. Age-adjusted screening participation rates were Russians 63% (95% CI: 59.9-66.6), Somalis 19% (16.4-21.6), Kurds 69% (66.6-71.1), and Finns 67% (63.3-69.8). In the multiple-adjusted model with Finns as the reference; odds ratios for screening were among Russians 0.92 (0.74-1.16), Somalis 0.16 (0.11-0.22), and Kurds 1.37 (1.02-1.83). Among all women, the substantial factor for increased screening likelihood was hospital care related to pregnancy/birth 1.73 (1.27-2.35), gynecological 2.47 (1.65-3.68), or other reasons 1.53 (1.12-2.08). Screening participation was lower among students and retirees. In conclusion, screening among the migrant-origin women varies, being significantly lowest among Somalis compared with Finns. Efforts using culturally tailored/population-specific approaches may be beneficial in increasing screening participation among women of migrant-origin.
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http://dx.doi.org/10.3390/ijerph17217899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7663516PMC
October 2020

Estimating Maximal Oxygen Uptake from the Ratio of Heart Rate at Maximal Exercise to Heart Rate at Rest in Middle-Aged Men.

World J Mens Health 2021 Oct 21;39(4):666-672. Epub 2020 Jul 21.

Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.

Purpose: To estimate the maximum mass-specific oxygen uptake (VO) from the ratio of the heart rate at maximal exercise (HR) to heart rate at rest (HR) in middle-aged men. VO is an essential measure of cardiorespiratory fitness, but it is difficult to utilize in clinical practice. The proportionality factor HR to HR is known to approximate 15 in young well-trained adults. Presumably, the same value is inaccurate for middle-aged men.

Materials And Methods: Six-hundred thirty-four men belonging to the Kuopio Ischaemic Heart Disease Risk Factor Study. Their mean age, body mass index (BMI), the daily total physical activity (TPA), VO, HR, and HR were: 49.4±6.4 years, 26.3±3.2 kg/m², 48.5±10.1 metabolic equivalent hours per day, 33.7±7.6 mL/min/kg, 170.1±15.4 beats/min, and 63.3±10.8 beats/min. They included never-smokers 38%, former smokers 29%, and current smokers 33%.

Results: The proportionality factor HR to HR in around 50-year-old men approximated 12. One year in age, one step change in BMI (normal weight, overweight, obese), smoking status (never, former, current), and TPA (moderately active, active, highly active) reduced the proportionality factor by 0.1, 0.6, 0.4, and 0.1, respectively. The proportionality factor in obese or current smoking middle-aged men was one point lower compared to normal weight or never-smoking peers. This corresponds to approximately 10 years in chronological age.

Conclusions: In around 50-year-old men with no cardiovascular diseases, bronchial asthma, or cancer, the HR to HR ratio should be multiplied by approximately 12 to estimate VO. BMI and smoking status can be considered in calculations to improve accuracy.
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http://dx.doi.org/10.5534/wjmh.200055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8443998PMC
October 2021
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