Sauna bathing and mortality risk: unraveling the interaction with systolic blood pressure in a cohort of Finnish men.

Objectives: This cohort study aimed to investigate the potential interplay between systolic blood pressure (SBP), frequency of sauna bathing (FSB), and all-cause mortality risk among Caucasian men. Design: A prospective study was conducted, involving 2575 men aged 42 to 61 years. Baseline assessments included resting blood pressure measurements and self-reported sauna bathing habits. SBP levels were categorized as normal (<140 mmHg) or high (≥140 mmHg), while FSB was classified as low (≤2 sessions/week) or high (3-7 sessions/week). Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox regression analysis, while adjusting for lifestyle factors, lipids, inflammation, and comorbidities. Results: Over a median follow-up of 27.8 years, 1,618 deaths were recorded. In the adjusted analysis, individuals with high SBP versus low SBP showed a 29% increased all-cause mortality risk (HR 1.29, 95% CI 1.16-1.43). Similarly, those with low FSB versus high FSB exhibited a 16% elevated mortality risk (HR 1.16, 95% CI 1.02-1.31). When considering combined effects, participants with high SBP-low FSB had a 47% higher mortality risk (HR 1.47, 95% CI 1.24-1.74) compared to those with normal SBP-high FSB. However, no significant association was observed between individuals with high SBP-high FSB and mortality risk (HR 1.24, 95% CI 0.98-1.57). There were potential additive and multiplicative interactions between SBP and sauna bathing concerning mortality risk. Conclusions: This study reveals a potential interplay between SBP, sauna bathing, and mortality risk in Finnish men. Frequent sauna bathing may mitigate the increased mortality risk associated with elevated SBP.

Hemodynamic gain index and risk of ventricular arrhythmias: a prospective cohort study.

Objectives: Hemodynamic gain index (HGI), a novel hemodynamic index obtained from cardiopulmonary exercise testing (CPX), is associated with adverse cardiovascular outcomes. However, its specific relationship with ventricular arrhythmias (VAs) is unknown. We aimed to assess the association of HGI with risk of VAs in a prospective study. Design: Hemodynamic gain index was estimated using heart rate and systolic blood pressure (SBP) responses ascertained in 1945 men aged 42-61 years during CPX from rest to maximum exercise, using the formula: [(Heart ratemax x SBPmax) - (Heart raterest x SBPrest)]/(Heart raterest x SBPrest). Cardiorespiratory fitness (CRF) was measured using respiratory gas exchange analysis. Hazard ratios (HRs) (95% confidence intervals, CIs) were estimated for VAs. Results: Over a median follow-up duration of 28.2 years, 75 cases of VA were recorded. In analysis adjusted for established risk factors, a unit (bpm/mmHg) higher HGI was associated with a decreased risk of VA (HR 0.72, 95% CI: 0.55-0.95). The results remained consistent on adjustment for lifestyle factors and comorbidities (HR 0.72, 95% CI: 0.55-0.93). Comparing the top versus bottom tertiles of HGI, the corresponding adjusted HRs (95% CIs) were 0.51 (0.27-0.96) and 0.52 (0.28-0.94), respectively. The associations were attenuated on addition of CRF to the model. HGI improved risk discrimination beyond established risk factors but not CRF. Conclusions: Higher HGI is associated with a reduced risk of VAs in middle-aged and older Caucasian men, but dependent on CRF levels. Furthermore, HGI improves the prediction of the long-term risk for VAs beyond established risk factors but not CRF.

Serum C-reactive protein-to-albumin ratio may be a potential risk indicator for venous thromboembolism: Findings from a prospective cohort study.

BACKGROUND AND AIMS: Circulating C-reactive protein (CRP) and albumin are commonly used inflammatory biomarkers. C-reactive protein-to-albumin ratio (CAR), a novel inflammatory biomarker, has been suggested to be a more reliable risk indicator compared to CRP or albumin alone. An inflammatory hypothesis has been postulated in VTE aetiology, but the association between CAR and VTE has not been investigated. We aimed to assess the prospective association of CAR with VTE risk. METHODS AND RESULTS: C-reactive protein and albumin were measured in serum samples at baseline from 2479 men aged 42-61 years. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated. During a median follow-up of 27.0 years, 168 VTE cases were recorded. In analysis adjusted for potential confounders, the HR (95% CI) for VTE comparing extreme tertiles of CAR was 1.49 (1.01-2.21), which was minimally attenuated on further adjustment for prevalent cancer, a potential mediator 1.48 (1.00-2.19). Serum CRP and albumin were each modestly associated with VTE risk in the same set of participants. CONCLUSION: In middle-aged and older men, elevated serum CAR may be associated with an increased risk of VTE. Further research is needed to replicate or refute these findings in other populations and assess if CAR may be of potential value in VTE management.

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.

Inflammation, sauna bathing, and all-cause mortality in middle-aged and older Finnish men: a cohort study.

Inflammation and sauna bathing are each related to the risk of all-cause mortality. The interplay between inflammation, sauna bathing and all-cause mortality is not well understood. We aimed to evaluate the separate and joint associations of inflammation (high sensitivity C-reactive protein, hsCRP) and frequency of sauna bathing (FSB) with all-cause mortality in a cohort of Caucasian men. We used the Kuopio Ischaemic Heart Disease Study cohort comprising 2575 men aged 42-61 years at baseline. Serum hsCRP was measured using an immunometric assay and sauna bathing habits were assessed by a self-administered questionnaire. High sensitivity CRP was categorized as normal and high (≤ 3 and > 3 mg/L, respectively) and FSB as low and high (defined as ≤ 2 and 3-7 sessions/week respectively). A total of 1618 deaths occurred during a median follow-up of 27.8 years. Comparing high vs normal hsCRP levels, the multivariable-adjusted HR (95% CI) for all-cause mortality was 1.27 (1.13-1.44). Comparing high vs low FSB, the multivariable-adjusted HR (95% CI) for all-cause mortality was 0.86 (0.76-0.97). Compared with normal hsCRP-low FSB, high hsCRP-low FSB was associated with an increased risk of all-cause mortality 1.28 (1.12-1.47), with no evidence of an association for high hsCRP-high FSB and all-cause mortality risk 1.06 (0.81-1.40). Positive additive and multiplicative interactions were found between hsCRP and FSB in relation to mortality. In a general Finnish male population, both hsCRP and FSB are each independently associated with all-cause mortality. However, frequent sauna baths appear to offset the increased all-cause mortality risk related to high hsCRP levels.

Serum copper-to-zinc ratio is associated with heart failure and improves risk prediction in middle-aged and older Caucasian men: A prospective study.

BACKGROUND AND AIMS: Serum copper (Cu) and zinc (Zn) may play a role in the development of adverse cardiovascular outcomes including heart failure (HF). Serum Cu/Zn-ratio has been shown to be a risk indicator for cardiovascular disease, but its relationship with HF has not been previously investigated. We aimed to assess the association between Cu/Zn-ratio and incident HF risk using a prospective cohort study. METHODS AND RESULTS: Study participants were recruited in eastern Finland with baseline examinations carried out between March 1998 and December 2001. Serum levels of Cu and Zn were measured using atomic absorption spectrometry in 1866 men aged 42-61 years without a history of HF at baseline. Multivariable-adjusted hazard ratios (HRs) with confidence intervals (CIs) were calculated for incident HF. During 26.5 years median follow-up, 365 HF cases occurred. Restricted cubic splines suggested linear relationships of serum Cu/Zn-ratio, Cu and Zn with HF risk. A unit increase in Cu/Zn-ratio was associated with an increased HF risk in analysis adjusted for several potential confounders including nutritional factors such as total energy intake, intake of fruits, berries and vegetables, and red meat (HR 1.63; 95% CI 1.06-2.51). The corresponding multivariable-adjusted HRs (95% CIs) for serum Cu and Zn were 2.42 (1.32-4.44) and 1.34 (0.50-3.63), respectively. Addition of Cu/Zn-ratio to a HF risk prediction model was associated with improved risk prediction. CONCLUSION: In middle-aged and older Finnish men, increased serum Cu/Zn-ratio is associated with an increased risk of HF in a linear dose-response fashion and might improve HF risk assessment.

Combined effects of maximal oxygen uptake and glucose status on mortality: The Prospective KIHD cohort study.

OBJECTIVE: To examine the combined effects of cardiorespiratory fitness (CRF) and prediabetes or diabetes on cardiovascular and noncardiovascular mortality. PATIENTS AND METHODS: This prospective study evaluated a population-based cohort of 1562 men aged 42-60 years at baseline (1984-1989). We utilized maximal oxygen uptake (VO2max ) for assessing aerobic capacity and CRF in the cohort and stratified participants into six groups according to both their glucose status (diabetes, prediabetes, or no diabetes) and whether they were below- or above-median VO2max . Deaths in the cohort were recorded till December 31 2016. Cox regression was used to calculate hazard ratios (HR) with 95% confidence intervals (CI) for cardiovascular and noncardiovascular mortality. Smoking, alcohol consumption, BMI, blood pressure, cholesterol, diagnosis of ischemic heart disease, and socioeconomic status served as covariates in the mortality analyses. RESULTS: During the follow-up (mean 24.2 years), 341 men died from cardiovascular and 468 men from noncardiovascular causes. When compared to men with no diabetes and above-median VO2max , the presence of either diabetes (HR = 4.10, 95% CI: 2.27-7.40) or prediabetes (HR = 2.10, 95% CI: 1.18-3.73) combined with below-median VO2max increased the risk of cardiovascular death. Noncardiovascular mortality was increased by low oxygen uptake in men with prediabetes (HR = 2.24, 95% CI: 1.30-3.84), and among men with diabetes, the increase was not statistically significant (HR = 1.99, 95% CI: 0.91-4.32). CONCLUSIONS: Cardiorespiratory fitness modifies the risk of death related to prediabetes and diabetes. This highlights the importance of CRF assessment and interventions to support the uptake of regular physical activity among aging men with disturbed glucose metabolism.

Percentage of Age-Predicted Cardiorespiratory Fitness Is Inversely Associated with Cardiovascular Disease Mortality: A Prospective Cohort Study.

INTRODUCTION: Percentage of age-predicted cardiorespiratory fitness (% age-predicted CRF) is a potentially useful cardiopulmonary exercise testing (CPX) parameter, but there are limited data on its prognostic relevance for adverse cardiovascular disease (CVD) outcomes. We aimed to assess the association of % age-predicted CRF with CVD mortality and the extent to which % age-predicted CRF measurements could improve the prediction of CVD mortality. METHODS: Peak oxygen uptake, used as the measure of CRF, was directly assessed in 2,276 men who underwent CPX. The age-predicted CRF estimated from a regression equation for age was transformed to % age-predicted CRF with the following formula: (achieved CRF/age-predicted CRF) × 100. Hazard ratios (HRs) (95% confidence intervals [CIs]) and measures of risk discrimination for CVD mortality were calculated. RESULTS: During a median follow-up of 28.5 years, 643 fatal CVDs were recorded. The relationship between % age-predicted CRF and CVD mortality was dose response in nature. In analysis adjusted for conventional risk factors, one standard deviation increase in % age-predicted CRF was associated with a reduced risk of CVD mortality (HR 0.61; 95% CI: 0.56-0.67), which was minimally attenuated on further adjustment for several other confounders (HR 0.71; 95% CI: 0.64-0.78). Addition of % age-predicted CRF to a CVD mortality risk prediction model containing established risk factors significantly improved risk discrimination and reclassification. CONCLUSION: Percentage of age-predicted CRF is inversely and independently associated with CVD mortality in a graded fashion and significantly improves the prediction and classification of the long-term risk for CVD mortality beyond established risk factors.

The combined effect of blood pressure and C-reactive protein with the risk of mortality from coronary heart and cardiovascular diseases.

BACKGROUND AND AIMS: Both blood pressure and C-reactive protein (CRP) are individually associated with cardiovascular mortality risk. However, the combined effect of systolic blood pressure (SBP) and CRP on coronary heart disease (CHD) and cardiovascular disease (CVD) mortality risk, has not been studied. METHODS AND RESULTS: We evaluated the joint impact of SBP and CRP and the risk of mortality in the Kuopio Ischemic Heart Disease prospective cohort study of 1622 men aged 42-61 years at recruitment with no history of CVD. SBP and CRP were measured. SBP was categorized as low and high (cut-off 135 mmHg) and CRP as low and high (cut-off 1.54 mg/L) based on ROC curves. Multivariable adjusted hazard ratios (HRs) with confidence intervals (CI) were calculated. During a median follow-up of 28 years, 196 cases of CHD and 320 cases of CVD deaths occurred. Elevated SBP (>135 mmHg) combined with elevated (CRP >1.54 mg/L) were associated with CHD and CVD mortality (HR 3.41, 95% CI, 2.20-5.28, p < 0.001) and (HR 2.93, 95% CI, 2.11-4.06, p < 0.001) respectively after adjustment for age, examination year, smoking, alcohol consumption, BMI, Type 2 diabetes, energy expenditure, total cholesterol, serum HDL cholesterol, antihypertensive medication and use of aspirin. CONCLUSION: The combined effect of both high systolic blood pressure and high CRP is associated with increased risk of future CHD and CVD mortality as compared with both low SBP and low CRP levels in general male Caucasian population.

Sense of Coherence and Mortality: A Systematic Review and Meta-Analysis.

OBJECTIVE: The aim of the study was to investigate the association between sense of coherence (SOC) and all-cause mortality in the general adult population. METHODS: We conducted a systematic review and meta-analysis of prospective cohort studies. We searched eight electronic bibliographic databases for eligible studies. A random effects model and the restricted maximum likelihood method were used to calculate the pooled effect size. RESULTS: Eight studies were eligible for the meta-analysis. The studies included 48,138 participants, of whom 5307 died during a median follow-up of 14.1 years (range, 8-29.5 years). Their age ranged from 20 to 80 years, and 53% of them were men. In the meta-analysis model of crude values, the risk of all-cause mortality for individuals with a weak SOC (lowest tertile) was 1.30 (95% confidence interval [CI] = 1.09-1.55, p = .003, I = 78.84%) compared with individuals with a strong SOC (highest tertile). In the model adjusted for age, the risk remained almost the same (risk ratio = 1.26, 95% CI = 1.15-1.38, p < .001, I = 69.59%). In the model adjusted for several other risk factors for mortality, the risk was still 1.17 (95% CI = 1.07-1.27, p < .001, I = 57.85%). CONCLUSIONS: This meta-analysis shows that a weak SOC is associated with an increased risk of all-cause mortality in the general adult population. Future studies are needed to further develop assessment tools for SOC with good psychometric properties and to determine the disease processes that mediate the association of SOC with mortality.

Leisure-time cross-country skiing is associated with lower incidence of type 2 diabetes: A prospective cohort study.

BACKGROUND: Cross-country skiing is associated with reduction in risk of adverse vascular outcomes, but its association with type 2 diabetes is uncertain. We aimed to assess the associations between leisure-time cross-country skiing habits and incident type 2 diabetes. METHODS: We analysed the data of 2483 middle-aged men with no history of diabetes at baseline in the Kuopio Ischemic Heart Disease prospective study. The frequency, average duration, and intensity of leisure cross-country skiing were assessed at baseline using a 12-month physical activity questionnaire. Hazard ratios (HRs) (95% CIs) for type 2 diabetes were estimated. RESULTS: During a median follow-up of 21.6 years, 539 men developed type 2 diabetes. Type 2 diabetes risk decreased with increasing total volume of cross-country skiing up to 1,215 metabolic equivalent task (MET) hours/year. In analyses adjusted for several established risk factors, when compared with men with no cross-country skiing activity, the HRs (95% CIs) for type 2 diabetes were 0.75 (0.62-0.92) and 0.59 (0.46-0.76) for men who did 1-200 and >200 MET hours/year of cross-country skiing, respectively. Compared with men with no cross-country skiing activity, the corresponding adjusted HRs (95% CIs) for type 2 diabetes were 0.73 (0.60-0.89) and 0.64 (0.50-0.82) for men who did 1-60 and >60 minutes/week of cross-country skiing, respectively. The associations remained consistent following further adjustment for prevalent comorbidities. CONCLUSION: Total volume and duration of leisure-time cross-country skiing are each inversely and independently associated with future type 2 diabetes risk in a male population. Cross-country skiing undertaken as a leisure activity has the potential to promote public health.

Mapping of 79 loci for 83 plasma protein biomarkers in cardiovascular disease.

Recent advances in highly multiplexed immunoassays have allowed systematic large-scale measurement of hundreds of plasma proteins in large cohort studies. In combination with genotyping, such studies offer the prospect to 1) identify mechanisms involved with regulation of protein expression in plasma, and 2) determine whether the plasma proteins are likely to be causally implicated in disease. We report here the results of genome-wide association (GWA) studies of 83 proteins considered relevant to cardiovascular disease (CVD), measured in 3,394 individuals with multiple CVD risk factors. We identified 79 genome-wide significant (p<5e-8) association signals, 55 of which replicated at P<0.0007 in separate validation studies (n = 2,639 individuals). Using automated text mining, manual curation, and network-based methods incorporating information on expression quantitative trait loci (eQTL), we propose plausible causal mechanisms for 25 trans-acting loci, including a potential post-translational regulation of stem cell factor by matrix metalloproteinase 9 and receptor-ligand pairs such as RANK-RANK ligand. Using public GWA study data, we further evaluate all 79 loci for their causal effect on coronary artery disease, and highlight several potentially causal associations. Overall, a majority of the plasma proteins studied showed evidence of regulation at the genetic level. Our results enable future studies of the causal architecture of human disease, which in turn should aid discovery of new drug targets.

Cardiorespiratory fitness is not associated with risk of venous thromboembolism: a cohort study.

Objectives. The inverse and independent association between cardiorespiratory fitness (CRF) and arterial thrombotic disease is well established. However, the potential association between CRF and venous thromboembolism (VTE) is not well known. We aimed to assess the prospective association of CRF with the risk of VTE. Design. Cardiorespiratory fitness, as measured by maximal oxygen uptake (VO2max), was assessed using a respiratory gas exchange analyser in 2,249 men aged 42-61 years without a history of VTE at baseline in the Kuopio Ischemic Heart Disease prospective cohort. Cox-regression models were used to calculate hazard ratios (HR) with 95% confidence interval (CI) for VTE. We corrected for within-person variability in CRF levels using data from repeat measurements taken several years apart. Results. There were 144 (6.4%) incident VTE events recorded during a median follow-up of 25.2 years. The age-adjusted regression dilution ratio of CRF was 0.58 (95% CI: 0.53-0.64). The risk of VTE did not significantly decrease per 1 standard deviation increase in CRF in age-adjusted analysis (HR 0.90; 95% CI 0.75-1.08). The association remained consistent in analyses adjusted for several established and emerging risk factors (HR 0.90; 95% CI 0.73-1.12). The corresponding adjusted HRs were 0.80 (95% CI: 0.52-1.23) and 0.82 (95% CI: 0.51-1.32) respectively, when comparing the extreme tertiles of CRF levels. Conclusions. In a middle-aged Caucasian male population, CRF was not associated with future risk of VTE. Further studies are required to confirm and to generalize these findings, particulary in women and other age groups.

Increased Levels of Circulating Fatty Acids Are Associated with Protective Effects against Future Cardiovascular Events in Nondiabetics.

Cardiovascular disease (CVD) is a major cause of morbidity and mortality worldwide, particularly in individuals with diabetes. The current study objective was to determine the circulating metabolite profiles associated with the risk of future cardiovascular events, with emphasis on diabetes status. Nontargeted metabolomics analysis was performed by LC-HRMS in combination with targeted quantification of eicosanoids and endocannabinoids. Plasma from 375 individuals from the IMPROVE pan-European cohort was included in a case-control study design. Following data processing, the three metabolite data sets were concatenated to produce a single data set of 267 identified metabolites. Factor analysis identified six factors that described 26.6% of the variability in the given set of predictors. An association with cardiovascular events was only observed for one factor following adjustment (p = 0.026). From this factor, we identified a free fatty acid signature (n = 10 lipids, including saturated, monounsaturated, and polyunsaturated fatty acids) that was associated with lower risk of future cardiovascular events in nondiabetics only (OR = 0.65, 0.27-0.80 95% CI, p = 0.030), whereas no association was observed among diabetic individuals. These observations support the hypothesis that increased levels of circulating omega-6 and omega-3 fatty acids are associated with protective effects against future cardiovascular events. However, these effects were only observed in the nondiabetic population, further highlighting the need for patient stratification in clinical investigations.

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.

Global electrical heterogeneity as a predictor of cardiovascular mortality in men and women.

Aims: The aim of this study was to investigate the contribution of depolarization and repolarization abnormalities, specially abnormalities in global electrical heterogeneity of heart in cardiovascular disease (CVD) and all-cause mortality. Methods and results: Eight hundred and forty men and 911 women, average age of 63 years participated in this study with average follow-up was 14 years. Six electrocardiogram/vector electrocardiogram (ECG/VECG) markers QRS-duration, QTc-interval, QRST-angle, sum of absolute QRST integral (SAI QRST), T-wave roundness, and TV1-amplitude were estimated from VECG measurements. Hazard ratios (HRs) for CVD events (164 deaths) and all-cause mortality (383 deaths) for ECG parameters were calculated. Electrocardiogram or vector electrocardiogram parameter models adjusted for risk clinical factors showed that strongest predictors for CVD mortality were QRST-angle (HR 3.44, 95% confidence interval 2.12-5.36), QTc-interval (2.72, 1.73-4.29), and T-wave roundness (2.09, 1.26-3.46) among men. The strongest ECG/VECG parameters for CVD death were QRST-angle (2.47, 1.37-4.45), SAI QRST (2.37, 1.23-4.6), and QTc-interval (2.15, 1.16-4.01) among female participants. Multivariable adjusted models revealed that strongest independent ECG predictors for CVD death were QRST-angle, QTc-interval, resting heart rate, and T-roundness for men, QRST-angle and SAI QRST for women. QRST-angle, QTc-interval, resting heart rate, and T-roundness were associated with all-cause mortality in male population, although none of the ECG/VECG parameters predicted all-cause mortality among women. Conclusion: Characteristics of global electrical heterogeneity QRST-angle and QTc-interval in men and QRST-angle and SAI QRST among females were strong and independent risk markers for cardiovascular mortality. These parameters provide new additional ECG tools for cardiovascular risk stratification.

Cardiorespiratory fitness and nonfatalcardiovascular events: A population-based follow-up study.

BACKGROUND: To examine the prognostic value of cardiorespiratory fitness (CRF) with risk of first major nonfatal myocardial infarction (MI), stroke, and heart failure (HF) events. METHODS: Cardiorespiratory fitness, as measured by maximal oxygen uptake, was assessed at baseline in a prospective cohort of 2,089 men aged 42 to 61years. RESULTS: During a mean (SD) follow-up of 19.1(8.4) years, 522 nonfatal acute MI events, 198 acute all-cause nonfatal stroke events, and 221 nonfatal HF events were recorded. The hazard ratio per 1-metabolic-equivalent increase in CRF was 0.93 (95% CI 0.88-0.97) for nonfatal MI, 0.94 (95% CI0.87-1.01) for nonfatal stroke, and 0.84 (95% CI 0.78-0.91) for nonfatal HF events after adjustment for cardiovascular risk factors (age, systolic blood pressure, body mass index, history of cardiovascular disease, diabetes, smoking, alcohol use, serum creatinine, low-density lipoprotein levels, physical activity, and socioeconomic status). Further adjustment for left ventricular hypertrophy and resting heart rate did not attenuate these associations. Addition of CRF to conventional cardiovascular disease risk factors significantly improved both discrimination (C index) and category free net reclassification index (cf-NRI) for nonfatal MI (change in C index, 0.015 [95% CI 0.010-0.020] and change in cf-NRI 0.27, P<.01) and HF (change in C index 0.040 [95% CI 0.010-0.060] and change in cf-NRI 0.88, P<.01). CONCLUSION: In this Finnish population, there is a strong, inverse, and independent association between CRF and acute nonfatal MI and HF risk.

Associations of estimated Δ-5-desaturase and Δ-6-desaturase activities with stroke risk factors and risk of stroke: the Kuopio Ischaemic Heart Disease Risk Factor Study.

Stroke is a leading cause of morbidity and mortality. The role of PUFA in reducing the risk of stroke is uncertain. The concentrations of PUFA in the human body are determined both by dietary intake and by activities of desaturase enzymes. Desaturase enzymes have been associated with chronic diseases, but little is known about their association with stroke risk. We investigated the associations of Δ-6-desaturase (D6D) and Δ-5-desaturase (D5D) activities with stroke risk factors and risk of stroke among 1842 men from the prospective, population-based Kuopio Ischaemic Heart Disease Risk Factor Study, aged 42-60 years and free of CVD at baseline in 1984-1989. ANCOVA and Cox regression models were used for the analyses. Whole serum desaturase activities were estimated as product:precursor ratios - γ-linolenic acid:linoleic acid for D6D and arachidonic acid:dihomo-γ-linolenic acid for D5D. Higher D6D activity was associated with higher systolic and diastolic blood pressure, BMI, serum insulin and TAG concentrations and worse homoeostatic model assessment (HOMA) indices. In contrast, higher D5D activity was associated with lower systolic and diastolic blood pressure, BMI, serum insulin, LDL-cholesterol, TAG and C-reactive protein concentrations, higher HDL-cholesterol concentration, and better HOMA indices. During the mean follow-up of 21·2 years, 202 stroke cases occurred. Neither D6D activity (multivariable-adjusted extreme-quartile hazard ratios (HR) 1·18; 95 % CI 0·80, 1·74) nor D5D activity (HR 1·06; 95 % CI 0·70, 1·60) were associated with stroke risk. In conclusion, higher D5D activity was favourably associated and higher D6D activity unfavourably associated with several stroke risk factors, but not with the risk of incident stroke.

Associations of the serum long-chain omega-3 polyunsaturated fatty acids and hair mercury with heart rate-corrected QT and JT intervals in men: the Kuopio Ischaemic Heart Disease Risk Factor Study.

PURPOSE: Long-chain omega-3 polyunsaturated fatty acids (PUFA) from fish have been associated with risk of cardiovascular diseases (CVD), especially sudden cardiac death (SCD). Mercury exposure, mainly due fish consumption, has been associated with higher risk. However, the impact of PUFAs or mercury on the ventricular cardiac arrhythmias, which often precede SCD, is not completely known. We investigated the associations of the serum long-chain omega-3 PUFAs and hair mercury with ventricular repolarization, measured by heart rate-corrected QT and JT intervals (QTc and JTc, respectively). METHODS: A total of 1411 men from the prospective, population-based Kuopio Ischaemic Heart Disease Risk Factor Study, aged 42-60 years and free of CVD in 1984-1989, were studied. RESULTS: Serum long-chain omega-3 PUFA concentrations were inversely associated with QTc and JTc (multivariate-adjusted P trend across quartiles = 0.02 and 0.002, respectively) and, during the mean 22.9-year follow-up, with lower SCD risk. However, further adjustments for QTc, JTc or hair mercury did not attenuate the associations with SCD. Hair mercury was not associated with QTc, JTc or SCD risk, but it slightly attenuated the associations of the serum long-chain omega-3 PUFA with QTc and JTc. CONCLUSIONS: Higher serum long-chain omega-3 PUFA concentrations, mainly a marker for fish consumption, were inversely associated with QTc and JTc in middle-aged and older men from Eastern Finland, but QTc or JTc did not attenuate the inverse associations of the long-chain omega-3 PUFA with SCD risk. This suggests that prevention of prolonged ventricular repolarization may not explain the inverse association of the long-chain omega-3 PUFA with SCD risk.

Alcohol Consumption and Common Carotid Intima-Media Thickness: The USE-IMT Study.

AIMS: Epidemiological evidence indicates a protective effect of light to moderate alcohol consumption compared to non-drinking and heavy drinking. Although several mechanisms have been suggested, the effect of alcohol on atherosclerotic changes in vessel walls is unclear. Therefore, we explored the relationship between alcohol consumption and common carotid intima media thickness, a marker of early atherosclerosis in the general population. METHODS: Individual participant data from eight cohorts, involving 37,494 individuals from the USE-IMT collaboration were used. Multilevel age and sex adjusted linear regression models were applied to estimate mean differences in common carotid intima-media thickness (CIMT) with alcohol consumption. RESULTS: The mean age was 57.9 years (SD 8.6) and the mean CIMT was 0.75 mm (SD 0.177). About, 40.5% reported no alcohol consumed, and among those who drank, mean consumption was 13.3 g per day (SD 16.4). Those consuming no alcohol or a very small amount (<5 g per day) had significantly lower common CIMT values than those consuming >10 g per day, after adjusting for a range of confounding factors. CONCLUSION: In this large CIMT consortium, we did not find evidence to support a protective effect of alcohol on CIMT.