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Higher arterial stiffness but not carotid-intima media thickness in adolescence preceded higher resting heart rate in young adulthood, however, elevated high sensitivity C-reactive protein in adolescence preceded higher arterial stiffness and carotid intima-thickness in young adulthood in the temporal causal path. Low-grade inflammation during adolescence may be causally associated with the development of subclinical arteriosclerosis and atherosclerosis in young adulthood.

Fasting plasma glucose, insulin, and insulin resistance had a J- or U-shaped increase from 15 to 24 yr with the base of the curve at age 17 yr. Cumulative high insulin and high insulin resistance from 15 to 24 yr were negatively associated with arterial stiffness progression from ages 17 to 24 yr. Age 17 yr may be an optimal timing for intervention targeted at sustaining the protective effect of the decline of insulin and insulin resistance on arterial stiffness progression.

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.

Despite the putative health benefits of fermented dairy products, evidence on the association between fermented dairy and nonfermented dairy intake, and depression incidence is limited.This study examined cross-sectional and prospective associations between total dairy, fermented dairy, and nonfermented dairy intake with 1) the presence of elevated depressive symptoms and 2) the risk of a future hospital discharge or outpatient diagnosis of depression.Data from 2603 Finnish men (aged 42-60 y), recruited as part of the Kuopio Ischaemic Heart Disease Risk Factor Study, were included. Multivariable logistic regression models were used to examine ORs and 95% CIs for elevated depressive symptoms (Human Population Laboratory scale ≥5 points) at baseline. Cox proportional hazards regression models were used to estimate HRs and 95% CIs between dairy categories and risk of depression diagnoses.In cross-sectional analyses, fermented dairy intake in the highest (compared with lowest) tertile was associated with lower odds of having elevated depressive symptoms (adjusted OR: 0.70; 95% CI: 0.52, 0.96). Each 100-g increase in nonfermented dairy intake was associated with higher odds of having elevated depressive symptoms (adjusted OR: 1.06; 95% CI: 1.01, 1.10). During a mean follow-up time of 24 y, 113 males received a diagnosis of depression. After excluding cheese intake, higher fermented dairy intake was associated with a lower risk of depression diagnosis (adjusted HR: 0.62; 95% CI: 0.38, 1.03), which was strengthened after excluding those with elevated depressive symptoms at baseline (adjusted HR: 0.55; 95% CI: 0.31, 0.99), whereas nonfermented dairy intake in the highest tertile was associated with a 2-fold higher risk of depression (adjusted HR: 2.02; 95% CI: 1.20, 3.42).Fermented dairy and nonfermented dairy intake were differentially associated with depression outcomes when examined cross-sectionally and over a mean period of 24 y. These findings suggest that dairy fermentation status may influence the association between dairy intake and depression in Finnish men. The KIHD study was registered at clinicaltrials.gov as NCT03221127.

The purpose of this study was to discover how considering multiplicative, additive, and interactive effects modifies results of a prospective cohort study on coronary heart disease (CHD) incidence and its main risk factors. The Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study provided the study material, 2682 Eastern Finnish middle-aged men, followed since the 1980s. We applied multiplicative and additive survival models together with different statistical metrics and confidence intervals for risk ratios and risk differences to estimate the nature of associations. The mean (SD) follow-up time among men who were free of CHD at baseline (n = 1958) was 21.4 (10.4) years, and 717 (37%) of them had the disease and 301 (15%) died for CHD before the end of follow-up. All tested non-modifiable and modifiable risk factors statistically significantly predicted CHD incidence. We detected three interactions: circulating low-density lipoprotein cholesterol (LDL-C) × age, obesity × age, and obesity × smoking of which LDL-C × age was the most evident one. High LDL-C increased the risk of CHD more among men younger than 50 [risk ratio (RR) 2.10] than those older than 50 (RR 1.22). LDL-C status was the only additive covariate. The additive effect of high LDL-C increased almost linearly up to 18 years and then reached a plateau. The simple multiplicative survival model stressed glycemic status as the strongest modifiable risk factor for developing CHD [hazard ratio (HR) for diabetes vs. normoglycemia was 2.69], whereas the model considering interactions and time dependence emphasised the role of LDL-C status (HR for high LDL-C vs. lower than borderline was 4.43). Age was the strongest non-modifiable predictor. Including covariate interactions and time dependence in survival models potentially refine results of epidemiological analyses and ease to define the order of importance across CHD risk factors. KEY MESSAGESIncluding covariate interactions and time dependence in survival models potentially refine results of epidemiological analyses on coronary heart disease.Including covariate interactions and time dependence in survival models potentially ease to define the order of importance across coronary heart disease risk factors. Including covariate interactions and time dependence in survival models potentially refine results of epidemiological analyses on coronary heart disease. Including covariate interactions and time dependence in survival models potentially ease to define the order of importance across coronary heart disease risk factors.

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.

Abstract. Results regarding the epidemiological association of vitamin D with lung (LCA) and prostate cancer (PCA) are controversial. This study tested whether serum 25-hydroxyvitamin D [25(OH)D] concentrations have interactive epidemiological associations with smoking, the number-one risk factor for LCA, and age, the number-one risk factor for PCA. Also, this study investigated whether the associations of 25(OH)D, smoking, age, alcohol consumption, body mass index, diet (the healthy Nordic diet score), and physical activity with incident LCA and PCA are multiplicative or additive. The study of association types makes it easier to select appropriate statistical methods. The Kuopio Ischaemic Heart Disease Risk Factor Study provided the data of 2578 men with 112 LCA and 300 PCA cases over 35 years by the end of 2019. Serum 25(OH)D did not associate with LCA and PCA or interact with smoking and age. The association of smoking with LCA was additive; 13 extra cases per 1000 men every 10 years. Age and alcohol consumption multiplicatively increased the hazard of LCA (hazard ratio, 95% confidence interval for age >50: 3.56, 1.82–6.17; drink per week: 1.01, 1.00–1.03), whereas adherence to healthy Nordic diet decreased it (per score point: 0.95, 0.89–1.00). The association of age >50 with PCA was additive; 2.5 extra cases per 1000 men every 10 years. To conclude, there was no epidemiological relationship of pre-diagnostic 25(OH)D concentrations with the incidence of LCA and PCA. The respective associations of smoking and age >50 with LCA and PCA were additive rather than multiplicative.

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.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.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).These results suggest that high intake of butter, but not other dairy products may be associated with increased low-grade inflammation.

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]; P =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]; P =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 ( β =0.06, SE, 0.12, P =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.

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.

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.

Supplemental digital content is available in the text., 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 (

We aimed to examine the longitudinal associations of total cholesterol (TC), non-high-density lipoprotein cholesterol (non-HDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride, and low-density lipoprotein cholesterol (LDL-C) with carotid-femoral pulse wave velocity (cfPWV) and carotid intima-media thickness (cIMT) progression.We studied 1779, 15-year-old participants from the Avon Longitudinal Study of Parents and Children, UK birth cohort, followed up for 9 years. Fasting TC, non-HDL-C, HDL-C, triglyceride, and LDL-C were measured at 15, 17, and 24 years and age-categorized as normal, elevated, and dyslipidemia based on National Heart, Lung, and Blood Institute lipid guidelines. cfPWV and cIMT were measured at 17 and 24 years. Associations were examined using linear mixed-effect models. To simulate the treatment of dyslipidemia we conducted temporal inverse allocation model analyses.Among 1779 [49.9% female] participants, mean lipid levels and proportions at elevated or dyslipidemia categories increased from ages 15 through 24 years. Persistently elevated TC: effect estimate 0.026 mm; [95% CI 0.004 to 0.049; p = 0.024], elevated non-HDL-C, and elevated LDL-C were cumulatively associated with cIMT progression. Persistent borderline-low HDL-C: -0.027 mm; [-0.050 to -0.005; p = 0.019] and very-low HDL-C -0.035 mm; [-0.057 to -0.013; p = 0.002] levels were associated with cIMT progression. A temporal inverse allocation of elevated and dyslipidemic levels with normal lipid levels at age 17 years attenuated the associations of cumulative elevated TC, non-HDL-C, LDL-C, and low HDL-C with cIMT progression. Cumulative elevated lipids or dyslipidemia were not associated with cfPWV progression.Late adolescence is key to preventing, halting, and reversing dyslipidemic-related preclinical atherosclerosis progression, warranting universal lipid screening in the general pediatric population.

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.

Low intake or tissue concentrations of the

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 0.0001]) and diastolic BP (0.023 m/s [0.019 to 0.027; p 0.0001]) from 9-24 years of age were positively associated with the 7-year increase in cfPWV. Persistent high exposures to lean mass (0.012 mm; [0.008 to 0.016; p 0.0001]), body mass index (0.007 mm [0.003 to 0.011; p = 0.001]), and systolic BP (0.010 mm; [0.006 to 0.014; p 0.0001]) from ages 9-24 years were positively associated with thicker cIMT at 17-24 years of age. Total fat and trunk fat mass from childhood had no association with cfPWV or cIMT progression. In conclusion, increased lean mass and BP but not fat mass from childhood drives arterial remodeling in young adulthood.

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, P=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, P=0.029). Conclusions: The early 1990s economic recession was associated with a subsequently increased risk of cardiovascular disease among Finnish women.

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 (1H) 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.

Introduction: Elevated resting heart rate in adults is an established risk factor in the lifelong process of atherogenesis and its intermediate process such as arterial stiffness. Arterial stiffness is an independent predictor of cardiovascular events. However, it is unclear whether resting heart rate temporally and bi-directionally associates with arterial stiffness especially among healthy adolescents and young adults. Hence, plausible biologic pathways through which elevated resting heart rate associate with arterial stiffness in the young population remains unknown. Hypothesis: To examine the temporal longitudinal associations of carotid-femoral pulse wave velocity (cfPWV), a measure of arterial stiffness, with resting heart rate among adolescents aged 17.7 years. Methods: We studied 3862 (55.5% female) British adolescents followed up for 7 years until 24.5 years of age, using data from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort, England, UK. At baseline and follow-up, fat mass and lean mass were measured by dual-energy Xray absorptiometry, systolic blood pressure and heart rate by Omron BP/pulse monitor, and cfPWV by Vicorder ultrasound scan. We conducted logistic regression and cross-lagged autoregressive structural equation model analyses and adjusted for age at baseline, sex, moderate to vigorous physical activity, smoking status, family history of cardiometabolic diseases, time in years between measurement at 17.7 and 24.5 years, systolic blood pressure, fat mass, lean mass, and fasting plasma samples viz. low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, high-sensitivity C-reactive protein, glucose, and insulin. Results: Participants' mean (SD) age in years was 17.72 (0.33) and 24.54 (0.73) at baseline and follow-up, respectively. Among 3862 adolescents, 10% were at moderate to high risk of elevated resting heart rate at 24.5 years. Higher cfPWV at 17.7 years was associated with the risk of elevated resting heart rate at follow-up [ Odds ratio = 1.32 (95% confidence interval 1.06 - 1.65); p=0.014]. In the cross-lagged temporal analysis, higher cfPWV at 17.7 years was associated with higher resting heart rate [ Standardized regression coefficient (β) = 0.06 standard error (SE) = 3.85, p Conclusion: We observed, for the first time, in a large healthy cohort of adolescents that arterial stiffness temporally preceded elevated resting heart rate in young adulthood, after controlling for cardiometabolic and lifestyle factors. This evidence informs that public health and clinical effort may be targeted at early detection and prevention of arterial stiffness from adolescence.

Introduction: Elevated resting heart rate in adults is an established risk factor in the lifelong process of atherogenesis and its intermediate process such as arterial stiffness. Arterial stiffness is an independent predictor of cardiovascular events. However, it is unclear whether resting heart rate temporally and bi-directionally associates with arterial stiffness especially among healthy adolescents and young adults. Hence, plausible biologic pathways through which elevated resting heart rate associate with arterial stiffness in the young population remains unknown. Hypothesis: To examine the temporal longitudinal associations of carotid-femoral pulse wave velocity (cfPWV), a measure of arterial stiffness, with resting heart rate among adolescents aged 17.7 years. Methods: We studied 3862 (55.5% female) British adolescents followed up for 7 years until 24.5 years of age, using data from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort, England, UK. At baseline and follow-up, fat mass and lean mass were measured by dual-energy Xray absorptiometry, systolic blood pressure and heart rate by Omron BP/pulse monitor, and cfPWV by Vicorder ultrasound scan. We conducted logistic regression and cross-lagged autoregressive structural equation model analyses and adjusted for age at baseline, sex, moderate to vigorous physical activity, smoking status, family history of cardiometabolic diseases, time in years between measurement at 17.7 and 24.5 years, systolic blood pressure, fat mass, lean mass, and fasting plasma samples viz. low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, high-sensitivity C-reactive protein, glucose, and insulin. Results: Participants' mean (SD) age in years was 17.72 (0.33) and 24.54 (0.73) at baseline and follow-up, respectively. Among 3862 adolescents, 10% were at moderate to high risk of elevated resting heart rate at 24.5 years. Higher cfPWV at 17.7 years was associated with the risk of elevated resting heart rate at follow-up [ Odds ratio = 1.32 (95% confidence interval 1.06 - 1.65); p=0.014]. In the cross-lagged temporal analysis, higher cfPWV at 17.7 years was associated with higher resting heart rate [ Standardized regression coefficient (β) = 0.06 standard error (SE) = 3.85, p Conclusion: We observed, for the first time, in a large healthy cohort of adolescents that arterial stiffness temporally preceded elevated resting heart rate in young adulthood, after controlling for cardiometabolic and lifestyle factors. This evidence informs that public health and clinical effort may be targeted at early detection and prevention of arterial stiffness from adolescence.

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.

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.

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.

Background The major risk factors for atherosclerotic cardiovascular disease differ by race or ethnicity but have largely been defined using populations of European ancestry. Despite the rising prevalence of cardiovascular disease in Africa there are few related data from African populations. Therefore, we compared the association of established cardiovascular risk factors with carotid‐intima media thickness (CIMT), a subclinical marker of atherosclerosis, between African, African American, Asian, European, and Hispanic populations. Methods and Results Cross‐sectional analyses of 34 025 men and women drawn from 15 cohorts in Africa, Asia, Europe, and North America were undertaken. Classical cardiovascular risk factors were assessed and CIMT measured using B‐mode ultrasound. Ethnic differences in the association of established cardiovascular risk factors with CIMT were determined using a 1‐stage individual participant data meta‐analysis with beta coefficients expressed as a percentage using the White population as the reference group. CIMT adjusted for risk factors was the greatest among African American populations followed by Asian, European, and Hispanic populations with African populations having the lowest mean CIMT. In all racial or ethnic groups, men had higher CIMT levels compared with women. Age, sex, body mass index, and systolic blood pressure had a significant positive association with CIMT in all races and ethnicities at varying magnitudes. When compared with European populations, the association of age, sex, and systolic blood pressure with CIMT was weaker in all races and ethnicities. Smoking (beta coefficient, 0.39; 95% CI, 0.09–0.70), body mass index (beta coefficient, 0.05; 95% CI, 0.01–0.08) and glucose (beta coefficient, 0.13; 95% CI, 0.06–0.19) had the strongest positive association with CIMT in the Asian population when compared with all other racial and ethnic groups. High‐density lipoprotein‐cholesterol had significant protective effects in African American (beta coefficient, −0.31; 95% CI, −0.42 to −0.21) and African (beta coefficient, −0.26; 95% CI, −0.31 to −0.19) populations only. Conclusions The strength of association between established cardiovascular risk factors and CIMT differed across the racial or ethnic groups and may be due to lifestyle risk factors and genetics. These differences have implications for race‐ ethnicity‐specific primary prevention strategies and also give insights into the differential contribution of risk factors to the pathogenesis of cardiovascular disease. The greatest burden of subclinical atherosclerosis in African American individuals warrants further investigations.

Background Moderate 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. Objectives We 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. Methods A 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-e4 compared with other phenotypes). These data were available for 1259 men. Results The 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. Conclusion Higher 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.

Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver diseases worldwide, and lifestyle and diet are significant factors in its development. Recent studies have suggested that dietary fat quality is associated with the development of NAFLD.Our purpose was to investigate the cross-sectional and longitudinal associations of serum n-3 (ω-3) and n-6 (ω-6) PUFAs with NAFLD among middle-aged and older men and women from eastern Finland. We also investigated the associations of estimated Δ5-desaturase and Δ6-desaturase activities, enzymes involved in PUFA metabolism, with NAFLD.After exclusions, the cross-sectional analyses included 1533 men examined in 1984-1989 and 674 men and 870 women examined in 1998-2001 in the Kuopio Ischaemic Heart Disease Risk Factor Study. The longitudinal analyses included 520 men examined in 1991-1993 and 301 men and 466 women examined in 2005-2008. Fatty liver index (FLI) was used as a surrogate for NAFLD. Hepatic steatosis was defined as FLI 60. ANCOVA and logistic regression were used for analyses.In the longitudinal analyses, participants with higher serum concentrations of total n-6 PUFA and linoleic acid, the major n-6 PUFA, had markedly lower FLI and lower odds for hepatic steatosis (e.g., odds ratios for incident hepatic steatosis in the highest compared with lowest quartiles were ≤0.41), whereas serum γ-linolenic acid concentration was associated with a higher FLI and higher odds for hepatic steatosis. The associations with the other PUFAs were generally weaker and nonsignificant. In the cross-sectional analyses, also the long-chain n-3 PUFAs had inverse associations. In most analyses, high estimated Δ5-desaturase activity was associated with lower risk and high estimated Δ6-desaturase activity with higher risk for NAFLD.In middle-aged and older Finnish adults, higher serum concentrations of total n-6 PUFAs and linoleic acid were associated with lower odds for future NAFLD.

Supplemental Digital Content is available in the text., 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]; P=0.026), elevated diastolic BP/hypertension (1.77 [1.32–2.38]; P

Introduction: An American Heart Association’s statement recommended investigating the natural history of arterial stiffness and blood pressure (BP) vis-à-vis the rate at which arterial stiffness and BP increase with age. Hypothesis: To test whether carotid-femoral pulse wave velocity (cfPWV), a measure of arterial stiffness, and carotid intima-media thickness (cIMT) progression independently predict increased fat mass and BP. Methods: We studied 3862 participants from the Avon Longitudinal Study of Parents and Children birth cohort. cfPWV and cIMT were measured by ultrasound scan, total and trunk fat mass, and lean mass by dual-energy Xray absorptiometry scan, body mass index (BMI), BP, heart rate, fasting insulin, glucose, high sensitivity C-reactive protein, and lipid profile were measured at ages 17.7 and 24.5 years. Participants at >75th percentile of total and trunk fat mass or having >24.9 kg/m 2 BMI were classified as overweight and obese, >75th percentile as high lean mass, and >120/80 mm Hg as elevated BP and hypertension. Data were analysed with logistic regression and linear mixed models, adjusting for cardiometabolic and lifestyle factors. Results: Among 1719 [44.5%] male and 2143 [55.5%] female participants, cfPWV at 17.7 years independently predicted systolic hypertension [Odds ratio (OR) 1.19 (1.01 - 1.40); p=0.043], diastolic hypertension [OR 1.77 (1.32 - 2.38); p2 (-0.06 - -0.01); p=0.039]. cIMT progression from age 17.7 - 24.5 years was directly associated with the 7-year increase in total fat mass, trunk fat mass, lean mass, BMI, and diastolic BP. Conclusions: Arterial stiffness and cIMT progression independently predicted obesity, high lean mass, and incident hypertension among young adults.

Introduction: Carotid-femoral pulse wave velocity (cfPWV), a measure of arterial stiffness, and carotid intima-media thickness (cIMT) are strong predictors of cardiovascular and all-cause mortality in adults. However, due to the unavailability of hard outcomes among adolescents and young adults, it remains unclear how cfPWV and cIMT predict metabolic outcomes in these age groups. Hypothesis: We tested whether cfPWV and cIMT during adolescence similarly or differently predict higher insulin, glucose, plasma lipid, and increased inflammation in young adulthood. Methods: Altogether 3862 British (56% females) participants from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort, England, UK were studied. cfPWV was measured by Vicorder device, cIMT by CardioHealth ultrasound scan, systolic blood pressure (BP) and heart rate by Omron BP/pulse monitor, total fat mass and lean mass by dual-energy Xray absorptiometry, moderate to vigorous physical activity by accelerometer, and smoking status by questionnaire. Insulin, plasma glucose, lipid profiles, and high sensitivity C-reactive protein were measured during a fasting state. Insulin resistance (HOMA-IR) was estimated from (insulin x glucose)/22.5. We conducted linear regression analyses and adjusted for cardiometabolic and lifestyle factors at 17.7 years. Results: Participants' mean (SD) age in years at different time points were [17.72 (0.33) and 24.54 (0.73)]. cfPWV at age 17.7 years was inversely associated with high-density lipoprotein cholesterol [β = -0.32 (CI: -0.60 to -0.04); p=0.028] and directly associated with insulin [0.28 (0.05 to 0.50); p=0.019] and HOMA-IR [0.28 (0.04 to 0.53); p=0.026] at 24.5 years. cIMT at age 17.7 years was inversely associated with insulin [-0.33 (-0.59 to -0.07); p=0.024] and HOMA-IR [-0.32 (-0.59 to -0.04); p=0.026] at 24.5 years. cfPWV and cIMT at 17.7 years were unrelated to other metabolic and inflammatory markers at 24.5 years. Conclusions: Arterial stiffness during adolescence may be a novel risk factor for predicting reduced high-density lipoprotein cholesterol and increased insulin resistance in young adults. However, carotid wall thickening in adolescence predicted higher insulin sensitivity 7 years later.

Background The American Heart Association's scientific statement on the importance of arterial stiffness recommended that future studies investigate whether increasing arterial stiffness with advancing age results from the age-associated increase in systolic blood pressure (BP). The statement also recommended investigating the natural history of arterial stiffness and BP vis-à-vis the rate at which arterial stiffness and BP increase with age. These questions remain largely unanswered in a population sample of apparently healthy adolescence and young adults. Purpose To investigate whether carotid-femoral pulse wave velocity (cfPWV), a measure of arterial stiffness, during adolescence predicts increased systolic and diastolic blood pressure in young adulthood. Methods We studied 3862 British (56% females) participants from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort, Bristol, UK. cfPWV was measured by Vicorder device ultrasound scan, total fat mass and lean mass were measured by dual-energy Xray absorptiometry, and systolic and diastolic BP by Omron BP/pulse monitor. We conducted multivariable linear regression analyses and adjusted for baseline covariates such as age, sex, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, high sensitivity C-reactive protein, fasting blood glucose, fasting insulin concentration, heart rate, moderate to vigorous physical activity, smoking status, family history of cardiometabolic diseases, total fat mass, lean mass and systolic or diastolic BP depending on the outcome. All variables were measured both at age 17.7 and 24.5 years. Results Participants mean (SD) age in years at different time points were [17.72 (0.33) and 24.54 (0.73)]. Over a 7-year follow-up period, cfPWV was directly and independently associated with systolic BP [β = 10.762 (CI: 3.107 to 18.417); p=0.006] and diastolic BP [19.535 (12.879 to 26.191); p Conclusion Our findings showed that increasing arterial stiffness independently predicts higher systolic and diastolic BP with advancing age. Besides, a 0.1 m/s increase in arterial stiffness at age 17.7 years may result in a 1 mmHg increase in systolic BP and a 2 mmHg increase in diastolic BP seven years later. Therefore, public health effort should be targeted at preventing or reducing arterial stiffness during adolescence in order to decrease the risk of elevated BP in later life. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Jenny and Antti Wihuri Foundation and the Finnish Cultural Foundation

Fatty liver disease (FLD) and hypertension are separately associated with cardiovascular (CV) mortality. While the two conditions are established as separate predictors of CV outcomes, FLD and hypertension are interrelated in multiple ways. A biological interaction in respect to CV disease outcomes could exist between FLD and hypertension. In this study, we investigated the joint effect and interaction of FLD and hypertension regarding CV mortality using an interaction framework. Using a population-based cohort, we followed 1,569 middle-aged non-diabetic Finnish men for 34 years. We computed the fatty liver index and considered values ≥60 as indicative of FLD. We defined hypertension as either i) self-reported hypertension and a confirmed use of antihypertension medication, or ii) a mean systolic ≥160 or diastolic ≥105 blood pressure on baseline examination. The choice of the blood pressure measurement threshold to define hypertension was based on a sensitivity analysis. With 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. Among the men, 372 had FLD and 342 had hypertension. FLD and hypertension coexisted in 134 men. FLD and hypertension associated, independently and combined, with an increased hazard of all-cause and CV deaths. Non-cardiovascular 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 -0.50). The interaction was also found on a multiplicative scale. We found evidence of a negative interaction between FLD and hypertension in respect to CV mortality. Our findings were robust to different definitions of hypertension but were more relevant at high blood pressure thresholds. 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 and call for further research on the topic.

Background A temporal association where better arterial function and structure predicts adiponectin level and skeletal muscle mass during childhood remains uninvestigated. Methods We studied 5566 children and adolescents (51% girls) aged 9-11 years from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort, Bristol, UK. Brachial artery endothelial function was determined using flow-mediated dilation (FMD), expressed as the percentage change in diameter from baseline after reactive hyperemia; arterial elasticity as distensibility coefficient (DC) expressed in mean percentage change in cross-sectional area relative to blood pressure (BP); and arterial stiffness by carotid to radial pulse wave velocity (crPWV). Skeletal muscle mass and total fat mass were assessed by dual-energy Xray absorptiometry. We conducted multivariable linear regressions with Sidak correction and adjusted for age, sex, total fat mass, cardiorespiratory fitness, pubertal status, brachial artery diameter, systolic BP, low-density lipoprotein cholesterol, mother’s social-economic class, and time (years) between the measurement of predictors and outcomes. Results FMD (β [95% CI]) = (0.027 [0.007 to 0.047]; P = 0.009) and DC (0.229 [0.088 to 0.369]; P = 0.001) were directly associated with skeletal muscle mass. FMD had a borderline inverse association with adiponectin (-0.004 [-0.008 to Conclusions Better endothelial function and arterial elasticity were associated with higher skeletal muscle mass while arterial stiffness was unrelated to adiponectin and lean mass. Key message Healthy arterial function and structure may enhance muscle growth in children.

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 (n = 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.

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.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.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.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.

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 m2 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.

Publisher Copyright: © 2022 Academy of Nutrition and Dietetics Background: Depression and diet quality appear to be associated in the general population. Nevertheless, little is known about their relationship among pregnant females. Objective: The aims of this study were first, to investigate longitudinally whether or not diet quality is associated with depressive symptoms during pregnancy; second, to examine whether or not variation in diet quality during pregnancy predicts variation in depressive symptoms; and third, to explore how individual dietary components are associated with depressive symptoms. Design: A longitudinal secondary analysis of the Kuopio Birth Cohort Study in eastern Finland was conducted. Data were collected from pregnant females during the first and third trimesters of pregnancy. Participants/setting: The participants were 1,362 pregnant females who entered the study between 2012 and 2017. Main outcome measures: Depressive symptoms, as measured with the Edinburgh Postnatal Depressive Scale during the first and third trimesters of pregnancy were used as continuous variables. Statistical analyses performed: The main analyses consisted of linear mixed model analyses adjusted for potential confounders to longitudinally assess the association between diet quality as measured by the Healthy Eating Index-2015, calculated using data from a food frequency questionnaire completed during the first trimester and third trimester, and depressive symptoms during the study period. An exploratory set of linear mixed models was also used to longitudinally assess the associations between selected individual food frequency questionnaire food groups and depressive symptoms. Results: Descriptive analyses revealed that 12.3% of the participants had clinically relevant levels of depressive symptoms (ie, Edinburgh Postnatal Depressive Scale score ≥10) during either the first or third trimester. Longitudinal modeling suggested that depressive symptoms in pregnant females tend to remain stable throughout pregnancy. Females with a poorer quality diet already displayed higher levels of depressive symptoms during the first trimester of pregnancy (β = –.038 ± .016; P = 0.022). Variation in diet quality did not predict variation in depressive symptoms over the course of pregnancy (β = –9.741 × 10–5 ± .001; P = 0.869). Conclusions: Females entering pregnancy with a poorer quality diet also displayed higher levels of depressive symptoms compared with females with a higher quality diet at the beginning of pregnancy, and this association remained constant throughout pregnancy. Further research is needed to assess the direction and the potential causality of the observed associations between diet quality and depressive symptoms.

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.

Introduction: Evidence on the associations of fat mass and lean mass with changes in carotid-femoral pulse wave velocity (cfPWV) and carotid intima-media thickness (cIMT), markers of pre-clinical atherosclerosis, from adolescence through young adulthood is lacking. Previous studies have reported strong associations of body mass index (BMI), a measure of adiposity, with these markers. However, it is unclear if increased BMI in relation to these markers represents a pathological process or physiological adaptation. A knowledge gap also exists on the independent associations of blood pressure (BP) measured from childhood through young adulthood with changes in cfPWV and cIMT between ages 17 and 24.5 years. Hypothesis: We assessed the hypothesis whether lean mass and systolic BP, independent of fat mass, cardiometabolic and lifestyle factors, measured at age 9, 17, and 24.5 years drive a 7-year change in cfPWV and cIMT. Methods: We studied 3863 British children from the Avon Longitudinal Study of Parents and Children's birth cohort (56% females). fat mass and lean mass were measured by dual-energy Xray absorptiometry, systolic and diastolic BP by Omron BP/pulse monitor, cfPWV by Vicorder device, and cIMT by CardioHealth ultrasound scan. All exposures were categorized in tertiles of low, normal, and high, with the low category as the reference group. We conducted linear mixed effect model analyses and adjusted for age, sex, low-density lipoprotein, C-reactive protein, fasting blood glucose, moderate to vigorous physical activity, smoking status, family history of cardiometabolic diseases, time in years between measure at 9 and 24.5 years, and systolic BP, fat mass, and/or lean mass depending on the predictor. Results: Participants mean (SD) age in years at different time points were [9.83 (0.30); 17.72 (0.33); 24.54 (0.73)]. Over a 15-year follow-up period, persistent exposure to high lean mass effect estimate =0.006 (CI 0.001 - 0.010, p=0.022), high systolic BP 0.013 (0.009 - 0.017, p Conclusion: For the first time, we showed in a healthy cohort that persistent exposure to higher lean mass and BP from childhood independently drives arterial wall adaptation in early adulthood. These arterial changes are likely normal responses to growth and maturation rather than subclinical signs of arterial diseases. Thus, cumulative exposure to high BMI in relation to higher cfPWV and cIMT may not indicate a deleterious effect of adiposity.

To investigate if dairy, meat, and fish intakes associate with dementia and cognitive performance.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.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.Although higher intake of some food groups associated with cognitive performance, we found little evidence for associations with dementia risk.

Background: Epidemiologic studies suggest inverse associations between consumption of egg, a major source of dietary cholesterol, and stroke. However, the evidence of the relation remains limited, especially among carriers of apolipoprotein E4 (apoE4), which influences cholesterol metabolism. Objective: The aim of this study was to investigate associations of egg and cholesterol intakes with risk of stroke and with the major stroke risk factor, blood pressure, inmiddle-aged and older men from eastern Finland and whether apoE phenotype could modify these associations. Methods: A total of 1950 men aged 42-60 y in 1984-1989 were included at the baseline examinations of the prospective population-based Kuopio Ischaemic Heart Disease Risk Factor Study. Data on apoE phenotype were available for 1015 men. Dietary intakes were assessed with 4-d food records at baseline and incident stroke events were assessed by record linkage to hospital discharge registries. Cox proportional hazards regression analyses were used to estimate associations with stroke risk. Associations with baseline blood pressure were evaluated with ANCOVA. Results: During the mean +/- SD follow-up of 21.2 +/- 7.2 y, there were 217 incidences of any stroke: 166 of ischemic stroke and 55 of hemorrhagic stroke. Comparing the highest egg intake quartile with the lowest, the multivariable-adjusted HRs were 0.81 for total stroke (95% CI: 0.54, 1.23; P-trend = 0.32), 0.84 for ischemic stroke (95% CI: 0.53, 1.34; P-trend = 0.44), and 0.75 for hemorrhagic stroke (95% CI: 0.32, 1.77; P-trend = 0.40). The respective HRs for the highest cholesterol intake quartile compared with the lowest were 0.86 (95% CI: 0.57, 1.32; P-trend = 0.42), 0.74 (95% CI: 0.46, 1.20; P-trend = 0.32), and 1.10 (95% CI: 0.45, 2.66; P-trend = 0.75). Diastolic blood pressure was 1.6 mm Hg (P-trend = 0.04) lower in the highest egg intake quartile compared with the lowest, but there were no associations with systolic blood pressure or with cholesterol intake. ApoE phenotype (32% had apoE4 phenotype) did not modify the associations. Conclusion: Neither egg nor cholesterol intakes were associated with stroke risk in this cohort, regardless of apoE phenotype. This trial was registered at www.clinicaltrials.gov as NCT03221127.

ObjectiveLong-chain omega-3 polyunsaturated fatty acids (PUFA) from fish have been inversely associated with coronary heart disease (CHD) risk. Fish may also contain methylmercury, which has been associated with higher CHD risk and may diminish the cardioprotective effect of long-chain omega-3 PUFA. We investigated the associations of serum long-chain omega-3 PUFA and hair mercury with the odds for myocardial ischaemia during exercise.MethodsA total of 2199 men from the Kuopio Ischaemic Heart Disease Risk Factor Study, aged 42–60 years were studied in 1984–89. Of the 2199 men, 342 had history of CHD. The men performed a maximal symptom-limited exercise stress test using an electrically braked bicycle ergometer. ORs for exercise-induced myocardial ischaemia were estimated with logistic regression.ResultsIn the multivariable analysis, those in the highest versus lowest serum long-chain omega-3 PUFA quartile had 33% lower odds of myocardial ischaemia (OR 0.67, 95% CI 0.51 to 0.87, p-trend=0.006). The association was stronger among those with CHD history (OR 0.10, 95% CI 0.03 to 0.39, p-trend ConclusionHigher circulating concentrations of the long-chain omega-3 PUFAs, a marker for fish consumption, were associated with lower occurrence of exercise-induced myocardial ischaemia, but only among men with CHD history. Hair mercury concentration was directly associated with the occurrence of exercise-induced myocardial ischaemia in the entire study population.

Background Previous studies investigating protein intake in relation to mortality have provided conflicting results. Objective We investigated the associations of dietary protein and protein sources with risk of disease death in the prospective, population-based Kuopio Ischaemic Heart Disease Risk Factor Study. Methods The study population consisted of 2641 Finnish men, aged 42-60 y at baseline in 1984-1989. We estimated protein intakes with 4-d dietary records at baseline and collected data on disease deaths from the national Causes of Death Register. Cox proportional hazards regression models were used to estimate HRs and 95% CIs. Results During the average follow-up of 22.3 y, we observed 1225 deaths due to disease. Higher intakes of total protein and animal protein had borderline statistically significant associations with increased mortality risk: multivariable-adjusted HR (95% CI) in the highest compared with the lowest quartile for total protein intake = 1.17 (0.99, 1.39; P-trend across quartiles = 0.07) and for animal protein intake = 1.13 (0.95, 1.35; P-trend = 0.04). Higher animal-to-plant protein ratio (extreme-quartile HR = 1.23; 95% CI: 1.02, 1.49; P-trend = 0.01) and higher meat intake (extreme-quartile HR = 1.23; 95% CI: 1.04, 1.47; P-trend = 0.01) were associated with increased mortality. When evaluated based on disease history at baseline, the association of total protein with mortality appeared more evident among those with a history of type 2 diabetes, cardiovascular disease, or cancer (n = 1094) compared with those without disease history (n = 1547) (P-interaction = 0.05 or 0.07, depending on the model). Intakes of fish, eggs, dairy, or plant protein sources were not associated with mortality. Conclusions Higher ratio of animal to plant protein in diet and higher meat intake were associated with increased mortality risk. Higher total protein intake appeared to be associated with mortality mainly among those with a predisposing disease. This trial was registered at clinicaltrials.gov as NCT03221127.

In the vitamin D intervention study VitDbol (NCT02063334) blood samples were drawn directly before an oral bolus (2000 μg vitamin D3) and 24 h later. The focus of phase II of VitDbol was the transcriptome-wide analysis of the effects of vitamin D gene expression in human peripheral blood mononuclear cells (PBMCs). All five participants responded in an individual fashion to the bolus by increases in serum levels of the vitamin D metabolites 25-hydroxyvitamin D3 (25(OH)D3) and 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3). RNA sequencing identified 15.040 commonly expressed genes in PBMCs, 702 (4,7%) of which were significantly (p

Background: Research has demonstrated that problem behavior has been associated with substance use, but knowledge is lacking on such associations in a low-income country like Nepal. Aims: This stud...

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.