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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.

To evaluate the effect of vitamin D(3) supplementation on cancer mortality in the general population and on prognosis in cancer patients, a systematic review and meta-analysis of randomised, placebo-controlled trials (RCTs) and individual patient data (IPD) was conducted. Overall, 14 RCTs with a total of 104,727 participants (2015 cancer deaths) were identified and 7 RCTs, including 90 % of all study participants (n = 94,068), could be included in the IPD meta-analyses. The main meta-analysis of the 14 RCTs yielded a statistically non-significant reduction in cancer mortality by 6 % (risk ratio (RR) [95%-confidence interval (95%CI)]: 0.94 [0.86–1.02]). Subgroup analyses revealed a 12 % lower cancer mortality in the vitamin D(3) group compared with the placebo group in 10 trials with a daily dosing regimen (RR [95%CI]: 0.88 [0.78–0.98]), whereas no mortality reduction was seen in 4 trials using a bolus regimen (RR [95%CI]: 1.07 [0.91–1.24]; p-value for interaction: 0.042). The IPD meta-analysis (RR [95%CI]: 0.93 [0.84; 1.02]) confirmed the finding of all trials. The IPD were used to test effect modification by age, sex, body mass index, ethnicity, baseline serum 25-hydroxyvitamin D concentration, adherence and cancer-related factors but no statistically significant findings were obtained in meta-analyses of all trials. When restricted to trials with daily dosing in a post-hoc analysis, adults aged ≥ 70 years (RR [95%CI]: 0.83 [0.77; 0.98]) and subjects with vitamin D(3) therapy initiation before cancer diagnosis (RR [95%CI]: 0.87 [0.69; 0.99]) appeared to benefit most from daily vitamin D(3) supplementation. Measurements of baseline 25-hydroxyvitamin D levels and inclusion of other than non-Hispanic White adults were too sparse in the trials to draw conclusions. Results for all-cause and cancer-specific survival of participants with cancer were comparable to those obtained in the general population for cancer mortality. In conclusion, vitamin D(3) did not reduce cancer mortality in the main meta-analysis of all RCTs because the observed risk reduction by 6 % was not statistically significant. However, a subgroup analysis revealed that vitamin D(3) administered daily, in contrast to bolus supplementation, reduced cancer mortality by 12 %.

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: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke. Methods: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition–Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank. Results: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values 105 mL·min –1 ·1.73 m –2 , compared with those with eGFR between 60 and 105 mL·min –1 ·1.73 m –2 . Mendelian randomization analyses for CHD showed an association among participants with eGFR –1 ·1.73 m –2 , with a 14% (95% CI, 3%–27%) higher CHD risk per 5 mL·min –1 ·1.73 m –2 lower genetically predicted eGFR, but not for those with eGFR >105 mL·min –1 ·1.73 m –2 . Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD. Conclusions: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function.

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.

Low intake or tissue concentrations of the

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.

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.

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: Vitamin D insufficiency is associated with risk 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 incidence. DESIGN: 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 three arms: placebo, 1600 IU/day or 3200 IU/day vitamin D3. Follow-up was by annual study questionnaires and national registry data. A representative sub-cohort 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 (vs. placebo: hazard ratio (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 sub-cohort, the mean (standard deviation) baseline serum 25-hydroxyvitamin D concentration was 75 (18) nmol/L. After 12 months, the concentrations were 73 (18) nmol/L, 100 (21) nmol/L and 120 (22) nmol/L in the placebo, 1600 IU/d and 3200 IU/d arms, respectively. CONCLUSIONS: Vitamin D3 supplementation did not lower the incidence of major CVD events or invasive cancer among older adults, possibly due to sufficient vitamin D status in most participants at baseline. Clinical Trial Registry number: ClinicalTrials.gov: NCT01463813, https://clinicaltrials.gov/ct2/show/NCT01463813. CC BY 4.0Virtanen, Jyrki K.(corresponding author)Published: 04 January 2022This study was supported by funding from the Academy of Finland (#137826), University of Eastern Finland, Juho Vainio Foundation, Medicinska Understödsföreningen Liv och Hälsa, Finnish Foundation for Cardiovascular Research, Finnish Diabetes Research Foundation, and Finnish Cultural Foundation.

Sense of coherence (SOC) scale measures one’s orientation to life. SOC is the core construct in Antonovsky’ssalutogenic model of health. It has been shown that weak SOC correlates with poor perceived health, low qualityof life, and increased mortality. Some studies have indicated that SOC is not stable across life, but there are noprevious studies on how a change of SOC is reflected in mortality. However, there is some evidence that a changein perceived quality of life is associated with mortality. The study explores the association between the change inSOC and mortality using longitudinal data from a cohort of middle-aged Finnish men recruited between 1986and 1989. Approximately 11 years after the baseline examinations, between 1998 and 2001, 854 men returnedthe SOC questionnaire a second time. The baseline SOC was adjusted for the regression to the mean phenomenonbetween the two measurements. The hazard ratios of the SOC difference scores were adjusted for initial SOC ageand 12 somatic risk factors of mortality (alcohol consumption, blood pressure, body mass index, cholesterolconcentration, physical activity, education, smoking, marital status, employment status, history of cancer, his-tory of cardiovascular disease and diabetes). SOC was not stable among middle-aged Finnish men and a declinein SOC was associated with an increased hazard of all-cause mortality. In the fully adjusted model, a decrease ofone standard deviation (SD) of the SOC mean difference increased the mortality hazard by about 35 %, two SDsdecrease about 70 %, and 2.5 SDs about 100 %. Strengthening SOC showed a limited association with decreasingmortality hazards in the age-adjusted model. Policies, strategies, or plans, supporting SOC in the middle-age mayhelp to decrease mortality and increase quality of life in later years. CC BY 4.0Corresponding author: E-mail address: ilkkapi@uef.fi (I. Piiroinen)

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.

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