Heart Disease Risk Factor Study Research Articles

Egg consumption, cholesterol intake, and risk of incident stroke in men: the Kuopio Ischaemic Heart Disease Risk Factor Study

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

Dietary proteins and protein sources and risk of death: the Kuopio Ischaemic Heart Disease Risk Factor Study

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

Association of fatty liver disease with mortality outcomes in an Eastern Finland male cohort

ObjectiveFatty liver disease (FLD) has been associated with extrahepatic morbidity outcomes. However, reports on the association of FLD, assessed using fatty liver index (FLI), with mortality outcomes have been inconsistent....

Follicle-stimulating hormone is associated with lipids in postmenopausal women.

The purpose of this study was to evaluate the relation between FSH and lipid levels in postmenopausal women from the Kuopio Ischaemic Heart Disease Risk Factor Study. Postmenopausal women (n = 588) aged 53 to 73 years and not using hormone therapy were included. The relation between FSH and total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TGs) was evaluated using linear regression, adjusting for estradiol, body mass, smoking, and other hormonal and lifestyle factors. The relation between FSH, dyslipidemia, and abnormal lipid levels were also evaluated. FSH was positively and linearly associated with TC (P = 0.001) and LDL-C (P = 0.01) in all participants, with stronger relations seen in younger compared with older postmenopausal women. FSH was less strongly associated with HDL-C and TG. FSH was not associated with dyslipidemia; however, higher FSH was associated with increased risk of high TC (P = 0.02) and high LDL-C (P = 0.03). These data suggest that higher FSH in postmenopausal women is related to higher levels of both TC and LDL-C.

Metabolic Profiling of High Egg Consumption and the Associated Lower Risk of Type 2 Diabetes in Middle-Aged Finnish Men.

Higher egg intake was previously associated with a lower risk of developing type 2 diabetes (T2D) in the prospective, population-based Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) in eastern Finland. Potential compounds that can explain this association are explored using nontargeted LC-MS-based metabolic profiling. Two hundred and thirty-nine baseline serum samples from the KIHD are analyzed in four groups: subjects with higher (mean intake one egg per day) or lower (mean intake two eggs per week) egg intake who developed T2D (cases) or remained heatlhy (controls) during the mean follow-up of 19.3 years. Different serum profiles of subjects who had either higher or lower egg intakes, and of those who developed type 2 diabetes or remained healthy, are observed. The higher baseline tyrosine level predicts higher odds of T2D (OR 1.94; 95% CI 1.45, 2.60; p < 0.001; FDR 0.023) along with an unknown hexose-containing compound (OR 2.13; 95% CI 1.57, 2.88; p < 0.001; FDR 0.005). Certain predominant metabolites in T2D cases are correlated positively with ones in the lower-egg-intake group and negatively with ones in the higher-egg-intake group. Our current findings may underline some potential metabolites that can explain how egg intake is associated with a lower risk of T2D.

Intake of fermented and non-fermented dairy products and risk of incident CHD: the Kuopio Ischaemic Heart Disease Risk Factor Study.

Recent dairy product studies have suggested that fermented rather than non-fermented dairy products might provide benefits on cardiovascular health, but the evidence is inconclusive. Therefore, we investigated whether fermented and non-fermented dairy products have distinct associations with the risk of incident CHD in a population with high dairy product intake. The present study included a total of 1981 men, aged 42-60 years, from the Kuopio Ischaemic Heart Disease Risk Factor Study, with no CHD at baseline. Dietary intakes were assessed with instructed 4-d food records. We used Cox's proportional hazards regression model to estimate the associations with the risk of CHD. Fatal and non-fatal CHD events were ascertained from national registries. During a mean follow-up of 20·1 years, 472 CHD events were recorded. Median intakes were 105 g/d for fermented (87 % low-fat products) and 466 g/d for non-fermented dairy products (60 % low-fat products). After adjusting for potential confounders, those in the highest (v. lowest) intake quartile of fermented dairy products had 27 % (95 % CI 5, 44; P-trend=0·02) lower risk of CHD. In contrast, those in the highest intake quartile of non-fermented dairy products had 52 % (95 % CI 13, 104; P-trend=0·003) higher risk of CHD. When analysed based on fat content, low-fat (<3·5 % fat) fermented dairy product intake was associated with lower risk (hazard ratio in the highest quartile=0·74; 95 % CI 0·57, 0·97; P-trend=0·03), but high-fat fermented dairy and low-fat or high-fat non-fermented dairy products had no association. These results suggest that fermented and non-fermented dairy products can have opposite associations with the risk of CHD.

Association of fatty liver index with the risk of incident cardiovascular disease and acute myocardial infarction.

Fatty liver disease (FLD) has been identified as constituting cardiometabolic risk. However, evidence on the association of fatty liver index (FLI) with cardiovascular disease (CVD) is largely cross-sectional, with limited evidence on the predictability of incident CVD, and specifically, acute myocardial infarction (AMI). Therefore, we aimed to investigate the prospective associations between fatty liver as estimated by FLI and incident CVD, and specifically AMI, in the Kuopio Ischaemic Heart Disease Risk Factor Study cohort. Our patients were 1205 middle-aged men free of CVD at baseline. The associations of baseline FLI with incident CVD and incident AMI were analyzed using multivariable-adjusted Cox regression models. During a median follow-up of 17 years, a total of 690 incident cases of CVD and 269 cases of AMI were recorded through Finnish registries. For incident CVD, for the high (FLI≥60) versus the low (≤30) FLI category, the hazard ratio (HR) was 1.77 [95% confidence interval (CI): 1.46-2.14] in the minimally adjusted model. With increasing adjustment, the association was attenuated progressively. In the most adjusted model, the HR was 1.41 (95% CI: 1.10-1.79). For incident AMI, for the high FLI category, the HR was 1.65 (95% CI: 1.22-2.23) in the minimally adjusted model, but in most comprehensive models when we included metabolic factors, the HR was not significant (HR=1.136, 95% CI: 0.777-1.662). FLI can predict incident CVD. However, the predictability of AMI using FLI is subject to interactions of metabolic factors. Individuals with FLI in the moderate to high category should be evaluated and monitored for subclinical or overt cardiovascular (including coronary) disease.

Associations of the serum long-chain omega-3 polyunsaturated fatty acids and hair mercury with exercise-induced myocardial ischemia in men: The kuopio ischaemic heart disease risk factor study

Rationale: Long-chain omega-3 polyunsaturated fatty acids (PUFA) from fish is associated with lower risk of coronary heart disease (CHD). Fish may also contain methylmercury, which is associated with higher CHD risk. However, mechanisms underlying these associations are not fully known. We investigated the association of serum long-chain omega-3 PUFA and hair mercury concentrations with the odds for myocardial ischemia during exercise, a predictor of future cardiac events.

Evolutionary methods for variable selection in the epidemiological modeling of cardiovascular diseases

BackgroundThe redundancy of information is becoming a critical issue for epidemiologists. High-dimensional datasets require new effective variable selection methods to be developed. This study implements an advanced evolutionary variable selection method which is applied for cardiovascular predictive modeling. The epidemiological follow-up study KIHD (Kuopio Ischemic Heart Disease Risk Factor Study) was used to compare the designed variable selection method based on an evolutionary search with conventional stepwise selection. The sample contains in total 433 predictor variables and a response variable indicating incidents of cardiovascular diseases for 1465 study subjects.ResultsThe effectiveness of variable selection methods was investigated in combination with two models: Generalized Linear Logistic Regression and Support Vector Machine. We managed to decrease the number of variables from 433 to 38 and save the predictive ability of the models used. Their performance was evaluated with an F-score metric. At most, we gained 65.6% and 67.4% of the F-score before and after variable selection respectively. All the results were averaged over 5-folds of a cross-validation procedure.ConclusionsThe presented evolutionary variable selection method allows a reduced set of variables to be chosen which are relevant to predicting cardiovascular diseases. A reference list of the most meaningful variables is introduced to be used as a basis for new epidemiological studies. In general, the multicollinearity of variables enables different combinations of predictors to be used and the same performance of models to be attained.

Highlights From the Circulation Family of Journals

Highlights From the <i>Circulation</i> Family of Journals

Are Metabolically Healthy Overweight/Obese Men at Increased Risk of Sudden Cardiac Death?

ObjectiveTo the association between metabolically healthy overweight/obesity and the risk of sudden cardiac death in middle-aged men. Participants and MethodsThis prospective study was based on a population sample of 2185 men aged 42 to 60 years from the Kuopio Ischaemic Heart Disease Risk Factor Study. Participants were divided into 4 groups on the basis of body mass index and metabolic health status. Metabolically healthy overweight/obesity was defined as body mass index 25 kg/m2 or greater without metabolic abnormalities, and metabolically unhealthy normal weight was defined as body mass index less than 25 kg/m2 with 1 or more metabolic abnormalities. ResultsDuring a median follow-up of 26 years (interquartile range, 18.7-28.1 years), 240 sudden cardiac deaths (11%) occurred. Compared with metabolically healthy normal weight men, metabolically unhealthy overweight/obese men had a higher risk of sudden cardiac death (hazard ratio, 1.99; 95% CI, 1.03-3.85) after adjusting for potential confounders. However, metabolically healthy overweight/obese men were not at increased risk of sudden cardiac death (hazard ratio, 0.95; 95% CI, 0.40-2.24) as compared with their metabolically healthy normal weight counterparts after adjusting for age, smoking, low-density lipoprotein cholesterol level, high-sensitivity C-reactive protein level, insulin level, history of myocardial infarction, and directly measured peak oxygen uptake. ConclusionOur findings indicate that metabolically healthy normal weight men and metabolically healthy overweight/obese men were at comparable risk of sudden cardiac death over a 26-year follow-up period, suggesting that a baseline body mass index of 25 kg/m2 or greater per se does not adversely affect the risk of sudden cardiac death.

Association of childhood stress with late-life dementia and Alzheimer’s disease: the KIHD study

There remains a dearth of life-course studies analyzing childhood environment and late-life chronic illness. In particular, few have addressed possible early-life predictors of dementia. This study examines relationships between childhood stress and later-age dementia, specifically Alzheimer's disease (AD). We used data from 2682 men in the population-based Kuopio Ischemic Heart Disease Risk Factor Study who participated in extensive baseline health examinations and interviews between 1984 and 1989, when they were between 42 and 61 years of age. Childhood events were documented in these structured interviews. We created a composite childhood stress variable that included living in custody or an orphanage, experience of crisis in childhood, having problems with teachers and emigrating because of war. Data on incident cases of dementia, including AD, were obtained through 2014 via national health register linkages. Risk of developing dementia was estimated using Cox regression adjusting for age, education, income and prior/existing diseases at baseline. Childhood stress was associated with increased risk of dementia (HR = 1.86, 95% CI: 1.12-3.10). Associations remained statistically significant after adjustment for age, education, income and other covariates (HR = 1.93, 95% CI: 1.14-3.25). Associations were marginally significant with AD, with HRs of similar magnitude. Childhood stress plays an important role in late-life dementia risk among men. Support systems should be developed for children suffering from stressful conditions. Further research examining childhood social and environmental effects on later morbidity, in diverse populations, is necessary to develop a holistic understanding of life-course disease burden.

Dietary intake of magnesium and the risk of epilepsy in middle-aged and older Finnish men: A 22-year follow-up study in a general population.

Magnesium may play an important role in the prevention or treatment of epilepsy. We aimed to examine the association between dietary intake of magnesium and the incidence of epilepsy in middle-aged Finnish men in a prospective setting. As a secondary analysis, we also considered a possible association between dietary intake of magnesium and inflammation in subjects with epilepsy. The study included 2442 men, ages 42 to 60 y, from the prospective Kuopio Ischaemic Heart Disease Risk Factor Study who were free of epilepsy at baseline between 1984 and 1989. Dietary intake of magnesium was assessed with a 4-d food record. The hospital discharge diagnosis of epilepsy was used as an outcome variable. During the average follow-up period of 22.4 y, 74 men (3%) developed epilepsy. Those who followed the recommended dietary intake (>350 mg/d) of magnesium had a lower risk of epilepsy (hazard ratio [HR]: 0.52; confidence interval [CI], 0.28-0.99; P = 0.045) after multivariate adjustments. However, the risk was not significant after adjustment for C-reactive protein (CRP). We also found that CRP concentration was directly associated with the risk of epilepsy (HR: 1.24; CI, 1.00-1.54; P = 0.048). This association was attenuated after adjustment for dietary intake of magnesium and no longer significantly associated with the risk of epilepsy (HR: 1.22; CI, 0.99-1.52; P = 0.07). A higher dietary intake of magnesium was associated with lower incident epilepsy, and this association was slightly mediated by CRP. Further studies are required to identify the potential mechanisms.

Intake of Different Dietary Proteins and Risk of Heart Failure in Men: The Kuopio Ischaemic Heart Disease Risk Factor Study.

Animal and plant protein intakes have indicated opposite associations with cardiovascular mortality risk. Whether dietary proteins are associated with risk of heart failure (HF) is unclear. Thus, we examined the associations of proteins from different food sources with risk of HF. The study included 2441 men aged 42 to 60 years at the baseline examinations in 1984 to 1989 in the Kuopio Ischaemic Heart Disease Risk Factor Study. Protein intakes at baseline were assessed with 4-day dietary records. Data on incident HF cases were obtained from national registers. HF risk according to protein intake was estimated by Cox proportional hazard ratios. During the mean follow-up of 22.2 years, 334 incident HF cases occurred. Higher intake of total protein indicated a trend toward increased risk of HF (multivariable-adjusted hazard ratio in the highest versus lowest quartile=1.33; 95% confidence interval: 0.95-1.85; P-trend=0.05). The associations between specific types and sources of protein with incident HF were consistent with this overall finding although not all associations reached statistical significance. For example, the hazard ratio in the highest versus lowest quartile was 1.43 (95% confidence interval: 1.00-2.03; P-trend=0.07) for total animal protein and 1.17 (95% confidence interval: 0.72-1.91; P-trend=0.35) for total plant protein. In middle-aged men, higher protein intake was marginally associated with increased risk of HF. URL: https://www.clinicaltrials.gov. Unique identifier: NCT03221127.

Youth Participation in Competitive Sports Associates with Midlife Lean Body Mass and Physical Activity

Benefits of life-long physical activity (PA) are widely recognized. Fewer studies have investigated how being young competing athlete reflects to later life body composition and PA. PURPOSE: To investigate the impact of participation in competitive sports in youth on the body composition and subjectively and objectively measured PA at middle- age. METHODS: The study participants are 47-to-55-year old Finnish women (n=985) attending to the Estrogenic Regulation of Muscle Apoptosis study (ERMA). Their participation in competitive sports at the age of 13-to-16 was assessed with retrospective self-report. Midlife lean body mass (LBM), skeletal muscle mass (SMM) and fat mass (FM) were measured with bioimpedance (Inbody 720) after overnight fast (n=866). Midlife PA included 7-scaled self-estimate that was reclassified to form sedentary, light, moderate and vigorous PA categories (n=985), a detailed assessment of leisure-time PA volume, duration and intensity (a modified Kuopio Ischemic Heart Disease Risk Factor Study Questionnaire, n=982) enabling calculation of mean daily metabolic equivalent (MET-h/day) index as a proxy of the previous 12 months PA and objectively measured total PA over seven-days by hip-worn accelerometer (Actigraph GT3X+ or wGT3X+, n=734). Statistical differences were tested using chi-squared test, independent samples t-test or Mann-Whitney U test. RESULTS: Participants were assigned into youth athlete (n=136) or non-athlete (n=849) groups based on their participation in competitive sports at the age of 13-to-16. Youth athlete group had 1.5 kg higher LBM (p=0.002) and 1.0 kg higher SMM (p=0.001) at middle-age, but no statistically significant difference in FM. Youth athletes reported more vigorous PA (32.4% vs. 20.3%, p=0.007) and higher leisure-time MET index (4.3 vs. 3.4 h/day, p<0.001) than non-athletes. No difference was observed in accelerometer-measured sedentary time, light PA, moderate-to-vigorous PA or total PA (counts) between groups. CONCLUSION: Participation in sport competitions as a teenager has long lasting health benefits that associates with healthier body composition and higher leisure-time PA later in life. However, the discrepancy between self-reports and objective measures needs further studies to delineate the benefits of different components of PA.

Serum n–6 polyunsaturated fatty acids and risk of death: the Kuopio Ischaemic Heart Disease Risk Factor Study

The cardioprotective properties of linoleic acid (LA), a major n-6 (ω-6) polyunsaturated fatty acid (PUFA), have been recognized, but less is known about its associations with other causes of death. Relatively little is also known about how the minor n-6 PUFAs-γ-linolenic acid (GLA), dihomo-γ-linolenic acid (DGLA), and arachidonic acid (AA)-relate to mortality risk. We investigated the associations of serum n-6 PUFAs, an objective biomarker of exposure, with risk of death in middle-aged and older men and whether disease history modifies the associations. We included 2480 men from the prospective Kuopio Ischaemic Heart Disease Risk Factor Study, aged 42-60 y at baseline in 1984-1989. The stratified analyses by baseline disease status included 1019 men with a history of cardiovascular disease (CVD), cancer, or diabetes and 1461 men without a history of disease. During the mean follow-up of 22.4 y, 1143 deaths due to disease occurred. Of these, 575 were CVD deaths, 317 were cancer deaths, and 251 were other-cause deaths. A higher serum LA concentration was associated with a lower risk of death from any cause (multivariable-adjusted HR for the highest compared with the lowest quintile: 0.57; 95% CI: 0.46, 0.71; P-trend<0.001) and with deaths due to CVD (extreme-quintile HR: 0.54; 95% CI: 0.40, 0.74; P-trend<0.001) and non-CVD or noncancer causes (HR: 0.48; 95% CI: 0.30, 0.76; P-trend=0.001). Serum AA had similar, although weaker, inverse associations. Serum GLA and DGLA were not associated with risk of death, and none of the fatty acids were associated with cancer mortality. The results were generally similar among those with or without a history of major chronic disease (P-interaction>0.13). Our findings showed an inverse association of a higher biomarker of LA intake with total and CVD mortality and little concern for risk, thus supporting the current dietary recommendations to increase LA intake for CVD prevention. The finding of an inverse association of serum AA with the risk of death needs replication in other populations.

Long-Term Change in Cardiorespiratory Fitness in Relation to Atrial Fibrillation and Heart Failure (from the Kuopio Ischemic Heart Disease Risk Factor Study)

The benefits of aerobic fitness in relation to all-cause and cardiovascular mortality is well established; however, the associations of long-term change in cardiorespiratory fitness (CRF) with incident heart failure (HF) and atrial fibrillation (AF) have not been studied before. The Kuopio Ischaemic Heart Disease Risk Factor Study is a prospective cohort comprising men aged 42 to 60 years from the city of Kuopio and its surroundings, with a baseline examination between 1984 and 1989 (V1), a re-examination at 11 years (V2), and up to 15 years of follow-up from V2. CRF, as assessed by VO2max, was measured at both visits using respiratory gas exchange during maximal exercise tolerance test. The difference (ΔVO2max) was estimated as VO2max (V2) - VO2max (V1). Participants with no missing data on both baseline and 11-year exercise test were included (n = 481). The mean ΔVO2max was -5.4 ml/min⋅kg (standard deviation 5.4). During a median follow-up of 14.3 years (interquartile range 13.3 to 15.1), 46 incident HF (9.6%) and 73 incident AF (15.2%) events were recorded. In a multivariate analysis adjusted for baseline age, baseline VO2max, systolic blood pressure, smoking, type 2 diabetes, and cardiovascular disease, per 1 ml/min⋅kg higher ΔVO2max was log linearly associated with incident HF with a 10% relative risk reduction of HF (hazard ratio 0.90, 95% confidence interval 0.83 to 0.97). No significant relation of ΔVO2max with incident AF was observed. In conclusion, overall long-term improvement in CRF is associated with reduced risk of HF, indicating the importance of maintaining good CRF over time.

Serum Concentrations of 25-Hydroxyvitamin D and Depression in a General Middle-Aged to Elderly Population in Finland.

Low concentrations of serum 25-hydroxyvitamin D [25(OH)D] have been postulated to associate with an increased prevalence of depression. As there are a limited number of publications on this issue, we examined the association between serum 25(OH)D and depression in a general middle-aged or older population. A population-based cross-sectional study. A total of 1602 men and women from the population-based Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) in Eastern Finland, aged 53-73 y in 1998-2001, were analysed. Depressive symptoms were assessed with the DSM-III depression scale, and those individuals who had scores over 4 (range 0-12) or had reported undergoing current antidepressant therapy, were considered as suffering from depression. Associations were estimated in serum 25(OH)D tertiles using logistic regression. Among the participants, 183 subjects (11.4%) were considered to have depression. The mean age of the subjects was 62.6 years (SD 6.4, range 53.4-73.8 years). The mean serum 25(OH)D concentration was 43.8 nmol/L (SD 17.7, range 8.5-112.8 nmol/L), concentrations <50 nmol/L were observed in 65.0% of the subjects, and only 5.0% displayed concentrations ≥75 nmol/L. After multivariable adjustments, the odds ratios for having depression in the tertiles (from highest to the lowest) of serum 25(OH)D were 1, 1.35 (95 % CI: 0.87, 2.09) and 1.64 (95 % CI: 1.03, 2.59), P for trend=0.036. These findings indicate that a lower concentration of serum 25(OH)D is associated with a higher prevalence of depression in an elderly general population.

Associations of the serum long-chain n-3 PUFA and hair mercury with resting heart rate, peak heart rate during exercise and heart rate recovery after exercise in middle-aged men.

Long-chain n-3 PUFA from fish have been associated with lower risk of CVD. Fish may also contain methylmercury, which may attenuate the inverse associations of the long-chain n-3 PUFA. However, the mechanisms underlying these associations are not fully known. We evaluated the associations of the serum long-chain n-3 PUFA (EPA, DPA and DHA) and hair Hg with resting heart rate (HR), peak HR during cycle ergometer exercise and HR recovery after exercise. A total of 1008 men from the population-based Kuopio Ischaemic Heart Disease Risk Factor Study, aged 42-60 years and free of CVD, were studied. After multivariate-adjustments in ANCOVA, higher serum total long-chain n-3 PUFA concentration was associated with lower resting HR (extreme-quartile difference 2·2 beats/min; 95 % CI 0·2, 4·1, P trend across quartiles=0·02), but not with peak HR or HR recovery. Associations were generally similar when EPA, DPA and DHA were evaluated individually, except for DPA, which was also associated with better HR recovery after exercise (extreme-quartile difference 2·1 beats/min; 95 % CI 0·1, 4·2, P trend=0·06). Higher hair Hg content had a trend towards lower peak HR after adjusting for the long-chain n-3 PUFA (P trend=0·05), but it only slightly attenuated the associations of the serum long-chain n-3 PUFA with HR. These findings suggest that higher serum long-chain n-3 PUFA concentrations are associated with lower resting HR in middle-aged men from Eastern Finland, which may partially explain the potential cardioprotective effect of fish intake.

The associations of serum n-6 polyunsaturated fatty acids with serum C-reactive protein in men: the Kuopio Ischaemic Heart Disease Risk Factor Study.

There are concerns that high intake of n-6 polyunsaturated fatty acids (PUFA) may promote inflammation, because the end-product of n-6 PUFA metabolism, arachidonic acid, is a precursor for pro-inflammatory eicosanoids. Our aim was to investigate cross-sectional associations of the serum n-6 PUFAs, objective biomarkers for exposure, with serum high-sensitivity C-reactive protein (CRP), a key inflammation marker. The study included 1287 generally healthy men aged 42-60 years from the population-based Kuopio Ischaemic Heart Disease Risk Factor Study, examined in 1984-1989. ANCOVA and logistic regression were used for analyses. In the multivariable-adjusted analyses, both serum total n-6 PUFA and linoleic acid, the predominant n-6 PUFA, were associated with lower CRP. The mean CRP concentrations in quartiles of linoleic acid were 1.86, 1.51, 1.53, and 1.37 mg/L (P-trend = 0.001). The odds ratio for elevated CRP (>3 mg/L) in the highest vs. the lowest quartile was 0.47 (95% confidence interval (CI) 0.25-0.87, P-trend = 0.01). Arachidonic acid or the mainly endogenously produced n-6 PUFAs, gamma-linolenic acid and dihomo-gamma-linolenic acid, were not associated with higher CRP, either. Age, body mass index, or serum long-chain n-3 PUFA concentration did not modify the associations (P-interactions > 0.14). Serum n-6 PUFAs were not associated with increased inflammation in men. In contrast, the main n-6 PUFA linoleic acid had a strong inverse association with the key inflammation marker, CRP.