Kuopio Ischaemic Heart Disease Risk Research Articles

Dietary fat quality and serum androgen concentrations in middle-aged men

Background/ObjectivesAverage testosterone concentrations in men have declined over the last few decades. The reasons for this are not fully known, but changes in dietary fat quality have been suggested to have a role. This study aimed to investigate the associations of different dietary fatty acids with serum androgen concentrations.Subjects/MethodsA total of 2546 men with a mean age of 53 from the Kuopio Ischaemic Heart Disease Risk Factor Study were included in this cross-sectional study. Associations between dietary saturated (SFA), monounsaturated (MUFA), polyunsaturated (PUFA) and trans (TFA) fatty acids and concentrations of serum total and free testosterone and steroid hormone binding globulin (SHBG) were analyzed with analysis of covariance and linear regression analysis. Associations of isocaloric replacement of nutrients and androgen concentrations were analyzed with multivariate nutrient-density models.ResultsAfter adjustment for age, examination year and energy intake, higher SFA intake was associated with higher serum total and free testosterone and SHBG concentrations, and higher PUFA intake with lower concentrations. However, the associations were attenuated and not statistically significant after further adjustments for potential confounders. MUFA and TFA intakes were not associated with androgen concentrations. In isocaloric substitution models, replacing dietary protein with SFA was associated with higher serum total testosterone and SHBG concentrations. After excluding men with history of CVD or diabetes (n = 1021), no statistically significant associations were found.ConclusionsDietary fat quality was not independently associated with serum androgen concentrations in middle-aged men. However, replacing protein with SFA may be associated with higher serum androgen concentrations.

O.2.3-11 Light standing work and high intensity occupational physical activities predict baseline and 8-year progression of carotid atherosclerosis among women

Abstract Purpose Recent reviews link higher levels of occupational physical activity (OPA) to cardiovascular disease (CVD). However, the evidence for women is inconsistent and studies of activity-limiting symptomatic CVD are prone to healthy worker selection effect. To address these limitations, this study investigated OPA effects on asymptomatic carotid artery intima-media thickness (IMT), a proxy for atherosclerosis, among women. Methods Participants include 905 women from the population-based Kuopio Ischemic Heart Disease Risk Factor Study with baseline (1998-2001) data on self-reported OPA and sonographic measurement of IMT. Linear mixed models with adjustment for 15 potential confounders estimated and compared mean baseline IMT and 8-year IMT progression for five levels of self-reported OPA. Analyses stratified by cardiovascular health and retirement status were planned because strong interactions between pre-existing CVD and OPA intensity have previously been reported. Results Light standing work, moderately heavy active work, and heavy or very heavy physical work were all consistently associated with greater baseline IMT and 8-year IMT progression than light sitting work, being hazardous for cardiovascular health. The greatest baseline IMT was observed for heavy or very heavy physical work (1.21 mm), and the greatest 8-year IMT progression for light standing work and moderately heavy active work (both 0.13 mm), 30% above sitting work (0.10 mm). Stratified analyses showed that these differences were driven by much stronger OPA effects among women with baseline carotid artery stenosis. Retired women experienced slower IMT progression than those still working at baseline. Conclusions Light standing work and higher levels of OPA intensity predict higher baseline IMT and 8-year IMT progression, especially among women with baseline stenosis. This study suggests that inconsistent findings regarding the effects of OPA on cardiovascular diseaes and mortality outcomes may be due to healthy worker selection and exposure misclassification biases including the failure to distinguish between standing and sitting work postures in many cohort studies. Funding Source This project is funded by the Danish taxpayers, via the Danish Work Environment Research Foundation, grant number 20195100247.

Frailty Predicts Incident Atrial Fibrillation in Women but Not in Men: The Kuopio Ischaemic Heart Disease Risk Factor Study

Introduction: Frailty and atrial fibrillation (AF) are common aging problems and increasing globally. The association(s) between frailty and AF has been inconclusive. The purpose of this prospective population-based cohort was to investigate the associations between frailty and incident AF in older men and women. Methods: In total 839 participants, women (n = 458) and men (n = 381), aged 61–74 years from the Kuopio Ischaemic Heart Disease Risk Factor Study were included (March 1, 1998, to December 31, 2001). At the baseline, frailty prevalence was 49.3% (n = 414), and non-frailty 50.7% (n = 425) of the total population. Frailty was ascertained with the presence of 3–5 and prefrailty 1–2 of the following criteria: weight loss (highest 20% over 7 years), self-reported tiredness, weakness (measured by handgrip strength), slow walking speed (walking pace), and low physical activity (lowest 20%). AF events were obtained by record linkages from the national computerized hospitalization registry in Finland up to December 31, 2019. Multivariate Cox proportional hazard regression estimated the hazard ratio (HR) of incident events, adjusted for potential confounders. Results: During the mean follow-up of 14.2 years, 288 AF cases (169 women; 119 men) occurred. After adjustment for possible confounders, the HRs (95% confidence intervals [CIs]) for AF was 1.46 (1.48–1.85) in the frail population, compared to the non-frail group. The association was observed only among older frail women (multivariable-adjusted HR 1.78, 95% CI [1.28–2.48]) (p for interaction = 0.04). No statistically significant associations were observed between frailty and future AF incident among men (multivariable-adjusted HRs 1.12, 95% CI (0.77–1.63)). Conclusions: In this population-based epidemiological cohort, the risk of developing AF was increased in women affected by frailty at baseline but not in men.

Occupational physical activity predicts baseline and 8-year progression of carotid atherosclerosis among women.

Recent reviews link higher levels of occupational physical activity (OPA) to cardiovascular disease (CVD). However, the evidence for women is inconsistent and studies of activity-limiting symptomatic CVD are prone to healthy worker survivor effect. To address these limitations, this study investigated OPA effects on asymptomatic carotid artery intima-media thickness (IMT) among women. Participants include 905 women from the population-based Kuopio Ischemic Heart Disease Risk Factor Study with baseline (1998-2001) data on self-reported OPA and sonographic measurement of IMT. Linear mixed models with adjustment for 15 potential confounders estimated and compared mean baseline IMT and 8-year IMT progression for five levels of self-reported OPA. Analyses stratified by cardiovascular health and retirement status were planned because strong interactions between preexisting CVD and OPA intensity have previously been reported. Light standing work, moderately heavy active work, and heavy or very heavy physical work were all consistently associated with greater baseline IMT and 8-year IMT progression than light sitting work. The greatest baseline IMT was observed for heavy or very heavy physical work (1.21 mm), and the greatest 8-year IMT progression for light standing work and moderately heavy active work (both 0.13 mm), 30% above sitting work (0.10 mm). Stratified analyses showed that these differences were driven by much stronger OPA effects among women with baseline carotid artery stenosis. Retired women experienced slower IMT progression than those working at baseline. Higher levels of OPA predict higher baseline IMT and 8-year IMT progression, especially among women with baseline stenosis.

Frailty alone and interactively with obesity predicts heart failure: Kuopio Ischaemic Heart Disease Risk Factor Study.

We aim to evaluate the association of frailty and high body mass index with risk of incident heart failure. From the Kuopio Ischaemic Heart Disease Risk Factor Study, 408 women and 369 men, aged 61-74years were included in this study. Frailty was ascertained with the presence of 3-5 and prefrailty 1-2 of the following criteria: weight loss (highest 20% over 7years), self-reported tiredness, weakness (measured by handgrip strength), slow walking speed (walking pace), and low physical activity (lowest 20%). At the baseline, participants were allocated to frail (n=36), prefrail (n=340), and robust (n=441). HF incidents were obtained by record linkages from the national hospitalization registry in Finland up to 31 December 2019. Multivariate Cox proportional hazards regression estimated the hazard ratio (HR) of incident events, adjusted for potential confounders. Two hundred one HF events were recorded (111 in women and 90 in men) during the 14.2years follow-up. After adjustment for the age and sex, the risk of HF events was higher among prefrail (HR 1.42, 95% CI 1.08 to 1.79, P=0.02) and frail (HR 3.39, 95% CI 1.89 to 4.79, P≤0.001) compared with the robust group. After adjusting for multiple confounders result remained significant for HF indecent in prefrail [1.46 (HR 1.46, 95% CI 1.09 to 1.95, P=0.01] and frail (HR 3.33, 95% CI 1.86 to 5.70, P≤0.001). In the sensitivity analysis, significant interaction between high BMI (≥25kg/m2 ) and frailty was observed (P for interaction=0.02). The association of frailty [multivariate-adjusted HR: 2.88 (1.56 to 5.33), P≤0.001)] and prefrailty [multivariate-adjusted HR: 1.40 (1.08 to 1.91), P=0.03)] with risk of HF indecent was more pronounced in those with high BMI. Frailty is highly common in older age, and our results indicated the high risk of HF incident in frail and prefrail groups. While frailty is clinically recognized by weight loss phenotype, our finding showed that frailly and high BMI can coexist and worsen the risk of HF incidence. Further research is warranted to substantiate these results in large studies and clinical settings.

What is the most appropriate follow-up time for detecting the epidemiological relationship between coronary artery disease and its main risk factors: novel findings from a 35-year follow-up study.

The aim was to investigate the most appropriate follow-up time to detect the associations of coronary artery disease (CAD) with its traditional risk factors in a long-term prospective cohort study. The Kuopio Ischaemic Heart Disease Risk Factors Study provided the study material of 1958 middle-aged men free from CAD at baseline and followed up for 35 years. We performed Cox models adjusted for age, family history, diabetes, obesity, hypercholesterolemia, hypertension, smoking, and physical activity, investigated covariate interactions, and tested Schoenfeld residuals to detect time-dependent covariates. Moreover, we applied a sliding window procedure with a subarray of 5 years to better differentiate between risk factors manifested within years and those manifested within decades. The investigated manifestations were CAD and fatal acute myocardial infarction (AMI). Seven hundred seventeen (36.6%) men had CAD, and 109 (5.6%) men died from AMI. After 10 years of follow-up, diabetes became the strongest predictor of CAD with a fully adjusted hazard ratio (HR) of 2.5-2.8. During the first 5 years, smoking was the strongest predictor (HR 3.0-3.8). When the follow-up time was 8-19 years, hypercholesterolemia predicted CAD with a HR of >2. The associations of CAD with age and diabetes depended on time. Age hypertension was the only statistically significant covariate interaction. The sliding window procedure highlighted the significance of diabetes over the first 20 years and hypertension after that. Regarding AMI, smoking was associated with the highest fully adjusted HR (2.9-10.1) during the first 13 years. The associations of extreme and low physical activity with AMI peaked when the follow-up time was 3-8 years. Diabetes showed its highest HR (2.7-3.7) when the follow-up time was 10-20 years. During the last 16 years, hypertension was the strongest predictor of AMI (HR 3.1-6.4). The most appropriate follow-up time for most CAD risk factors was 10-20 years. Concerning smoking and hypertension shorter and longer follow-up times could be considered, respectively, particularly when studying fatal AMI. In general, prospective cohort studies of CAD would provide more comprehensive results by reporting point estimates in relation to more than one timepoint and concerning sliding windows.

The association between renal hyperfiltration and mortality is not mediated by diabetes mellitus

BackgroundRenal 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 resultsBased 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).ConclusionAn 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 45: Life's Essential 8 and the Risk of Stroke in Finnish Men: The Kuopio Ischaemic Heart Disease Risk Factor Study

Background: Primordial prevention is an important way towards reducing risk of stroke with its associated health and economic burdens. So far, no study has shown how the recently updated American Heart Association’s cardiovascular health metrics, Life’s Essential 8 (LE8), relates to stroke events. Therefore, we sought to examine the association between LE8 and the risk of stroke among Finnish men. Methods: We employed the population-based Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) comprising men, aged 42 to 60 years, without pre-existing history of stroke at baseline. The LE8 was computed for 2614 men using AHA’s recently updated metrics. The LE8 includes four health behaviours (diet, physical activity, nicotine exposure, and sleep health) and four health factors (BMI, blood lipids, blood glucose and blood pressure). Each factor had points ranging from 0 to 100. Participants were classified into quartiles based on LE8 scores - Q1, ≤ 420; Q2, >420 to 485; Q3, >485 to 550; Q4, >550. Multivariable Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of LE8 scores for stroke event. Results: During a median follow-up of 26 years, 446 stroke events were recorded. The higher the LE8 scores, the more protection from future risk of stroke event. Thus, per quartile increase was associated with 26% lower risk of stroke (HR:0.74; 95%CI:0.68-0.82). Men within the 4 th quartile (Q4) of LE8 score had the highest protection (65%) from risk of stroke when compared with those within the 1 st quartile (Q1) (HR: 0.45; 95%CI:0.34-0.60). Conclusion: Life’s Essential 8 was strongly and inversely associated with the risk of stroke among middle-aged and ageing Finnish men. Measures that promote LE8 should be encouraged among the general population in Finland.

Multiplicative, additive, and interactive associations of 25-hydroxyvitamin D with lung and prostate cancer.

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.

Serum metabolites associated with wholegrain consumption using nontargeted metabolic profiling: a discovery and reproducibility study

PurposeTo identify fasting serum metabolites associated with WG intake in a free-living population adjusted for potential confounders.MethodsWe selected fasting serum samples at baseline from a subset (n = 364) of the prospective population-based Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) cohort. The samples were analyzed using nontargeted metabolomics with liquid chromatography coupled with mass spectrometry (LC–MS). Association with WG intake was investigated using both random forest followed by linear regression adjusted for age, BMI, smoking, physical activity, energy and alcohol consumption, and partial Spearman correlation adjusted for the same covariates. Features selected by any of these models were shortlisted for annotation. We then checked if we could replicate the findings in an independent subset from the same cohort (n = 200).ResultsDirect associations were observed between WG intake and pipecolic acid betaine, tetradecanedioic acid, four glucuronidated alkylresorcinols (ARs), and an unknown metabolite both in discovery and replication cohorts. The associations remained significant (FDR<0.05) even after adjustment for the confounders in both cohorts. Sinapyl alcohol was positively correlated with WG intake in both cohorts after adjustment for the confounders but not in linear models in the replication cohort. Some microbial metabolites, such as indolepropionic acid, were positively correlated with WG intake in the discovery cohort, but the correlations were not replicated in the replication cohort.ConclusionsThe identified associations between WG intake and the seven metabolites after adjusting for confounders in both discovery and replication cohorts suggest the potential of these metabolites as robust biomarkers of WG consumption.

Associations of reproductive factors with postmenopausal follicle stimulating hormone

PurposeRecent 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.MethodsWe 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.ResultsAfter 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).ConclusionMultiple 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.

Urinary sodium concentration predicts time to major adverse coronary events and all-cause mortality in men with heart failure over a 28–33-year period: a prospective cohort study

BackgroundLower urinary sodium concentrations (UNa) may be a biomarker for poor prognosis in chronic heart failure (HF). However, no data exist to determine its prognostic association over the long-term. We investigated whether UNa predicted major adverse coronary events (MACE) and all-cause mortality over 28–33 years.MethodsOne hundred and eighty men with chronic HF from the Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) were included. Baseline data was collected between 1984 and 1989. MACE and all-cause outcomes were obtained using hospital linkage data (1984–2017) with a follow-up of 28–33 years. Cox proportional hazards models were generated using 24-h UNa tertiles at baseline (1 ≤ 173 mmol/day; 2 = 173-229 mmol/day; 3 = 230-491 mmol/day) as a predictor of time-to-MACE outcomes, adjusted for relevant covariates.ResultsOverall, 63% and 83% of participants (n = 114 and n = 150) had a MACE event (median 10 years) and all-cause mortality event (median 19 years), respectively. On multivariable Cox Model, relative to the lowest UNa tertile, no significant difference was noted in MACE outcome for individuals in tertiles 2 and 3 with events rates of 28% (HR:0.72; 95% CI: 0.46–1.12) and 21% (HR 0.79; 95% CI: 0.5–1.25) respectively.. Relative to the lowest UNa tertile, those in tertile 2 and 3 were 39% (HR: 0.61; 95% CIs: 0.41, 0.91) and 10% (HR: 0.90; 95% CIs: 0.62, 1.33) less likely to experience to experience all-cause mortality. The multivariable Cox model had acceptable prediction precision (Harrell's C concordance measure 0.72).ConclusionUNa was a significant predictor of all-cause mortality but not MACE outcomes over 28–33 years with 173–229 mmol/day appearing to be the optimal level. UNa may represent an emerging long-term prognostic biomarker that warrants further investigation.

Associations of serum n–3 and n–6 polyunsaturated fatty acids with prevalence and incidence of nonalcoholic fatty liver disease

ABSTRACTBackgroundNonalcoholic 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.ObjectivesOur 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.MethodsAfter 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.ResultsIn 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.ConclusionsIn 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.

Associations between total dairy, high-fat dairy and low-fat dairy intake, and depressive symptoms: findings from a population-based cross-sectional study

PurposeEvidence 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.MethodsThis 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.ResultsIn 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.ConclusionHigher 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.

Associations of the serum n-6 PUFA with exercise cardiac power in men.

Low intake or tissue concentrations of the n-6 PUFA, especially to the major n-6 PUFA linoleic acid (LA), and low exercise cardiac power (ECP) are both associated with CVD risk. However, associations of the n-6 PUFA with ECP are unknown. The aim of the present study was to explore cross-sectional associations of the serum total n-6 PUFA, LA, arachidonic acid (AA), γ-linolenic acid (GLA) and dihomo-γ-linolenic acid (DGLA) concentrations with ECP and its components. In total, 1685 men aged 42-60 years from the Kuopio Ischaemic Heart Disease Risk Factor Study and free of CVD were included. ANCOVA was used to examine the mean values of ECP (maximal oxygen uptake (VO2max)/maximal systolic blood pressure (SBP)) and its components in quartiles of the serum total and individual n-6 PUFA concentrations. After multivariable adjustments, higher serum total n-6 PUFA concentration was associated with higher ECP and VO2max (for ECP, the extreme-quartile difference was 0·77 ml/mmHg (95 % CI 0·38, 1·16, Pfor trend across quartiles < 0·001) and for VO2max 157 ml/min (95 % CI 85, 230, Pfor trend < 0·001), but not with maximal SBP. Similar associations were observed with serum LA concentration. Higher serum AA concentration was associated with higher ECP but not with VO2max or maximal SBP. The minor serum n-6 PUFA GLA and DGLA were associated with higher maximal SBP during exercise test and DGLA also with higher VO2max but neither with ECP. In conclusion, especially LA concentration was associated with higher ECP. This may provide one mechanism for the cardioprotective properties of, especially, LA.

Economic Recession and the Risk of Cancer: A Cohort Study From Eastern Finland.

BackgroundLittle is known about the role of economic recessions in the risk of cancer. Therefore, we evaluated the impact of the severe economic recession in Finland from 1991–1994 on the incidence of all cancers and cancer subtypes among a middle-age and older population.MethodsFrom the Kuopio Ischemic Heart Disease Risk Factor Study (KIHD), a population-based sample of 1,620 women and men aged 53–73 years were examined from 1998–2001. The cancer-free participants completed a questionnaire on the possible impact of the 1990s recession in Finland on their lives. Incident cases of cancer were obtained through record linkage with the Finnish Cancer Registry. Cox proportional hazards regression was used to estimate hazard ratios (HR) of incident cancer events after adjusting for possible confounders.ResultsA total of 1,096 cancer-free participants had experienced socioeconomic hardships due to the recession at the baseline. During 20 years of follow-up, 473 participants developed cancer. After adjustment for age, baseline socioeconomic position, and lifestyle factors, the risk of all cancers was 32% higher among men who experienced socioeconomic hardships compared to those who did not (HR 1.32; 95% confidence interval [CI], 1.00–1.74, P = 0.05). Prostate-genital cancer was 71% higher among men with hardships (n = 103, HR 1.71; 95% CI, 1.06–2.74, P = 0.02). No association was observed between socioeconomic hardships and subsequent risk of total or any subtype of cancer among women.ConclusionThe 1990s economic recession was associated with increased risk of all cancers, especially prostate-genital cancer among Finnish middle-age and older men, but no association with cancer was observed in women.

Nonfermented Dairy Intake, but Not Fermented Dairy Intake, Associated with a Higher Risk of Depression in Middle-Age and Older Finnish Men

BackgroundDespite the putative health benefits of fermented dairy products, evidence on the association between fermented dairy and nonfermented dairy intake, and depression incidence is limited. ObjectivesThis 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. MethodsData 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. ResultsIn 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). ConclusionsFermented 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.

Predicting risk of cardiovascular death in the high-dimensional cohort follow-up data in the presence of competing events: a guide for building a modeling pipeline

Predictive models driven by time-to-event data are commonly used in survival analysis. Owing to the availability of high-dimensional epidemiological cohorts, there is a need for models and learning algorithms capable of utilizing hundreds or even thousands of predictors. Advanced machine learning tools with embedded variable selection are being modified for use with time-to-event data in the presence of competing risks and censoring. In this study, random survival forests were compared to the cause-specific and sub-distribution hazard models widely applied in survival analysis with competing risks. Using the extensive cohort data of 2,682 subjects and 950 predictors collected within the Kuopio Ischemic Heart Disease Risk Factor Study (1984–1989), we built models to predict cardiovascular and non-cardiovascular deaths for a 30-year prediction horizon in two scenarios: first, on a subset of manually selected risk factors and, second, on hundreds of more freely chosen available predictors. The experimental results show that without a manual pre-selection of predictors, the random forest reaches the highest area under the curve (AUC). In addition, this study presents a modeling pipeline, including a non-parametric analysis, missing data imputation, model validation, and result assessment.

Epidemiological analysis of coronary heart disease and its main risk factors: are their associations multiplicative, additive, or interactive?

Objective 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. Material and methods 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. Results 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. Conclusions 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 MESSAGES 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.

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

Apolipoproteins are associated with risk of coronary heart disease but the association with risk of incident atrial fibrillation (AF) has been inconsistent. This study investigated the association of apolipoproteins A-1 (apoA-1) and B (apoB), and lipid levels including triglyceride (TG), total cholesterol (TC), very low-density lipoprotein cholesterol (VLDL-C), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), with the risk of new-onset AF. A total of 2533 men from the prospective, population-based Kuopio Ischaemic Heart Disease Risk Factor Study, aged 42-60 years, were studied. Cox proportional hazards adjusted for potential confounders was used to estimate hazard ratio (HR) of incident events across serum lipid, lipoprotein, and apoA-1 and apoB concentrations. During the mean follow-up of 22.4 years, 594 AF cases occurred. Cox proportional hazards regression indicated that higher serum HDL-C and apoA-1 concentrations were associated with lower risk of AF [the extreme-quartile multivariable-adjusted HR 0.72 (95% CI 0.57-0.92, P=0.02) for HDL-C, and 0.72 (95% CI 0.52-1.00, P=0.05)] for apoA-1]. No significant associations were observed for apoB and other lipids (TC, VLDL-C, LDL-C, non-HDL-C, and TG) with risk of incident AF. Over the time of follow-up in this study lower new-onset incident AF was in association with higher HDL-C and apo-A1 levels. Future studies should investigate mechanisms underlying the association of low HDL-C and low apoA1 with higher risk of incident AF.