Renal Hyperfiltration as a New Mechanism of Smoking-Related Mortality.

INTRODUCTION: Renal hyperfiltration (RHF), an established risk factor for mortality, is prevalent among tobacco smokers. The aim of this study was to assess the mediating role of RHF in the association between smoking and mortality. AIMS AND METHODS: Data of this study were retrieved from the cohort of the Kuopio Ischemic Heart Disease Risk Factor Study (KIHD), including 2064 males from Finland. Study participants were followed over a 35-year period. Using classic and counterfactual mediation analysis approaches, we estimated the mediative effect of RHF in the association between smoking and each of the following outcomes: All-cause mortality, cardiovascular disease (CVD) mortality, and non-CVD mortality. RESULTS: The risk of all-cause mortality in smokers was twice that in nonsmokers (hazard ratio [HR], 2.06; 95% confidence interval [CI]: 1.84 to 2.31). Under the counterfactual framework the direct effect of smoking on all-cause mortality, controlled for RHF, corresponded to an HR of 2.00 (95% CI: 1.78 to 2.30). Of the effect of smoking on mortality, 5% (p-value = .016) was mediated by RHF. This finding concerned particularly non-CVD mortality. CONCLUSIONS: RHF mediated the effect of smoking on non-CVD and all-cause mortality, but not on CVD mortality. The generalizability of our study results is however limited by its focus on a Finnish male cohort, underscoring the need for further investigation into RHF's broader implications across diverse populations. IMPLICATIONS: This study elucidates the complex interplay between smoking, renal hyperfiltration (RHF), and mortality, offering novel insights into the mediating role of RHF. Our findings demonstrate that RHF significantly mediates the relationship between smoking and non-cardiovascular disease (non-CVD), but not CVD mortality. This distinction underscores the multifaceted role of RHF beyond its established association with cardiovascular events. By highlighting the specific pathways through which RHF mediates some of the smoking-attributed mortality, this research contributes to our understanding of the mechanisms linking smoking to mortality.

Meaningfulness and mortality: exploring the sense of coherence in Eastern Finnish men.

AIMS: The sense of coherence scale has been shown to have an epidemiological relationship with mortality. This study aimed to investigate how the three components of sense of coherence (meaningfulness, comprehensibility and manageability) and the individual items of these components relate to mortality. METHODS: Eastern Finnish men (n=2315) aged 42-60 years at baseline in the 1980s completed a 12-item sense of coherence scale and were followed for 25 years, on average, until death or until the end of 2019. Hazard ratios for mortality were calculated using two models: one adjusted for age and the second for an additional 12 mortality risk factors. RESULTS: Of the three sense of coherence components, only meaningfulness was associated with all-cause mortality, and in the fully adjusted model, those in the weakest tertile had a 1.14 (95% confidence interval 1.01-1.29, P=0.042) times higher hazard ratio for mortality than those in the strongest tertile. Of the individual sense of coherence items, only the first question, 'How often do you have the feeling that you really don't care about what is going on around you?', was associated with all-cause mortality, and in the fully adjusted Cox model, the hazard ratio of weak versus strong was 1.18 (95% confidence interval 1.03-1.36, P=0.020). CONCLUSIONS: The sense of coherence component related to meaningfulness, including its first item, 'Caring about what goes on around you', plays a significant role in the association with mortality among middle-aged men in Eastern Finland. This item should be considered a noteworthy patient-reported variable when predicting mortality in public health settings.

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.

Cumulative insulin resistance and hyperglycemia with arterial stiffness and carotid IMT progression in 1,779 adolescents: a 9-yr longitudinal cohort study.

In pediatric population with diabetes and obesity, insulin resistance (HOMA-IR) has been associated with worsening vascular outcomes, however, the cumulative role of HOMA-IR, hyperglycemia, and hyperinsulinemia on repeatedly measured vascular outcomes in asymptomatic youth is unknown. We examined the longitudinal associations of fasting glucose, insulin, and HOMA-IR with carotid-femoral pulse wave velocity (cfPWV) and carotid intima-media thickness (cIMT). From the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort, UK 1,779, 15-yr-old participants were followed up for 9 yr. Glucose, insulin, and HOMA-IR assessed at 15, 17, and 24 yr and sex-specifically dichotomized as ≥75th percentile, indicating high category and <75th percentile as reference. cfPWV and cIMT were measured at ages 17 and 24 yr. Associations were examined using linear mixed-effect models adjusted for cardiometabolic and lifestyle covariates. Among 1,779 participants [49.9% female], glucose, insulin, and HOMA-IR had a J- or U-shaped increase from ages 15 through 24 yr. The cumulative exposures to hyperinsulinemia effect estimate -0.019 mU/L; [95% CI -0.019 to -0.002; P = 0.033] and high HOMA-IR: -0.021; [-0.039 to -0.004; P = 0.019] from 15 to 24 yr of age were negatively associated with the 7-yr cfPWV progression. Only cumulative hyperinsulinemia and high HOMA-IR from ages 15 to 17 yr but not from ages 17 to 24 yr was associated with decreased cfPWV progression. There were no associations between cumulative hyperglycemia and cfPWV or cIMT progression. Hyperinsulinemia and HOMA-IR were not associated with cIMT progression. In conclusion, late adolescence 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.NEW & NOTEWORTHY 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.

The effect of vitamin D3 supplementation on atrial fibrillation in generally healthy men and women: The Finnish Vitamin D Trial.

Atrial fibrillation is a common cardiac arrhythmia with high morbidity risk. Observational studies suggest that vitamin D deficiency is associated with higher atrial fibrillation risk but there is limited evidence whether vitamin D supplementation could affect the risk. In these post hoc analyses from the Finnish Vitamin D Trial, we compared the incidence of atrial fibrillation with 5-year supplementation of vitamin D3 (1600 IU/d or 3200 IU/d) vs placebo. CLINICAL TRIAL REGISTRY NUMBER: ClinicalTrials.gov: NCT01463813, https://clinicaltrials.gov/ct2/show/NCT01463813.

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.

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

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.

Serum ferritin and incident cardiometabolic diseases in Scottish adults.

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.

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

BACKGROUND: 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. OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

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

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.

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.

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

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.

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

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.

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.

BACKGROUND: Lower 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. METHODS: One 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. RESULTS: Overall, 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). CONCLUSION: UNa 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.

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

BACKGROUND: Little 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. METHODS: From 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. RESULTS: A 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. CONCLUSION: The 1990s economic recession was associated with increased risk of all cancers, especially prostate-genital cancer among Finnish middle-age and older men, but no association with cancer was observed in women.

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

AIMS: Little is known about the effect of economic recessions on cardiovascular disease. Therefore, we investigated the association of the economic recession in Finland in the 1990s with the incidence of cardiovascular disease among middle-aged and older women. METHODS: A total of 918 women aged 53-73 years were examined for health and socioeconomic position in 1998-2001, as part of the population-based prospective Kuopio Ischaemic Heart Disease Risk Factor Study. The participants were asked whether Finland's economic recession in the early 1990s had affected their lives socially or economically. The cohort was followed for 18 years, and incident physician-diagnosed cases of cardiovascular disease were obtained through record linkage with the national hospital discharge registry that covers every hospitalisation in Finland. Cox proportional hazards regression models were used to estimate the risk of cardiovascular disease among those with and without exposure to socioeconomic hardships during the recession, after adjusting for possible confounders. RESULTS: At the baseline, 587 women reported having experienced socioeconomic hardships due to the recession. During the 20 years' follow-up, 501 women developed cardiovascular disease. After adjustment for age, the risk of cardiovascular disease was 27% higher among women exposed to socioeconomic hardships compared to those who were not (hazard ratio 1.27, 95% confidence interval 1.06-1.53, 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.

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

OBJECTIVE: Vitamin D deficiency and renal hyperfiltration (RHF) are prevalent conditions both recently linked with mortality. The two conditions are interrelated, but their combined effect and interaction on mortality have not been studied. The objective of this study was to assess the combined effect and interaction of vitamin D deficiency and RHF on all-cause, cardiovascular (CV), and non-CV mortality in nondiabetic middle-aged men. METHODS: Middle-aged nondiabetic men (n = 1,959) were followed up for a median of 28 years. With adjustment for age, body mass index (BMI), smoking, BMI-smoking interaction, healthy Nordic diet (HND), alcohol consumption, and hypertension, we fitted Cox proportional hazard models to estimate the hazard ratios (HRs) of all-cause-, CV-, and non-CV mortality with respect to vitamin D deficiency and RHF. We evaluated the effect of interaction between RHF and vitamin D on the outcomes on the additive and multiplicative scales. RESULTS: Vitamin D deficiency and RHF, both individually and combined, are associated with a high hazard of mortality. The HRs for all-cause- and non-CV mortality were highest among men with coexisting vitamin D deficiency and RHF (HR, 3.02; 95% CI, 1.90 to 4.79; and HR, 3.63; 95% CI, 2.07 to 6.36; respectively). We found a synergic interaction between vitamin D deficiency and RHF in respect to all-cause (RERI, 1.47; 95% CI, 0.03 to 2.9) and non-CV mortality (RERI, 2.09; 95% CI, 0.02 to 4.16) of type positive multiplicative, positive additive. CONCLUSION: The synergic interaction of vitamin D deficiency and RHF on mortality might have importance in the global burden of the two conditions. Further studies investigating cause-specific mortality are needed to highlight underlying mechanisms by which vitamin D deficiency and RHF interact.

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

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.

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

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.

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

PURPOSE: To investigate the association between healthy Nordic diet and risk of type 2 diabetes (T2D) in middle-aged and older men from eastern Finland. METHODS: A total of 2332 men aged 42-60 years and free of T2D at baseline in 1984-1989 were included. Diet was assessed with 4-day food records at baseline and the healthy Nordic diet score was calculated based on a modified Baltic Sea Diet Score. T2D diagnosis was based on self-administered questionnaires, fasting and 2-h oral glucose tolerance test blood glucose measurements, or by record linkage to national health registries. Cox proportional hazards regression and analysis of covariance were used for analyses. RESULTS: During the mean follow-up of 19.3 years, 432 men (18.5%) were diagnosed with T2D. The multivariable-adjusted hazard ratio for T2D in the lowest vs. the highest quartile of the healthy Nordic diet score was 1.35 (95% CI 1.03-1.76) (P trend across quartiles 0.028). Lower adherence to healthy Nordic diet was also associated with higher plasma glucose and insulin concentrations. CONCLUSIONS: In this prospective population-based cohort study among middle-aged and older men from eastern Finland, lower adherence to healthy Nordic diet was associated with higher risk of T2D and higher plasma glucose and serum insulin concentrations.