Diabetes and mortality risk in patients undergoing coronary angiography: The KARDIO study.

BACKGROUND: Diabetes is an established risk factor for adverse cardiovascular outcomes including mortality, but the relationship between diabetes and mortality risk in the presence of the extensive or diffuse form of coronary artery disease (CAD) is controversial. AIMS: We evaluated the association between diabetes and mortality risk in patients who underwent coronary angiography using a real-life clinical database. METHODS: We utilized the KARDIO registry, which comprised data on demographics, prevalent diseases, including diabetes status, cardiovascular risk factors, coronary angiographies, and other interventions in 79,738 patients. Hazard ratios (HRs) (95% confidence intervals [CIs]) for the association between prevalent diabetes and all-cause mortality were estimated. RESULTS: During a median follow-up of 5.5 years, 11,896 all-cause deaths occurred. In analyses adjusted for age, smoking status, hypertension, family history of CAD, dyslipidaemia, urgency of intervention, body mass index, sex, and sex-age interaction, the HR (95% CI) for mortality comparing diabetes with no diabetes was 1.44 (1.38, 1.50). Following additional adjustment for the degree of CAD (1-3 vessels disease) as confirmed by angiography, the HR (95% CI) for mortality remained similar 1.43 (1.36, 1.49). The association did not vary significantly across several relevant clinical characteristics except for a stronger association in those with a family history of CAD than those without (p = 0.034) and former smokers than nonsmokers (p = 0.046). CONCLUSION: In patients undergoing coronary angiography, diabetes is associated with an increased mortality risk, independent of several risk factors including the degree of CAD. The association may be modified by family history of CAD and smoking status.

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.

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.

Screening Sportsmen and Sportswomen Over Age 35: The Relevance of an Exercise Electrocardiogram. Data From the SEEPRED Study.

INTRODUCTION: The importance of exercise electrocardiogram (ECG) is still controversial in the prevention of cardiovascular events among sportsmen and sportswomen. The aim of this study was to assess the relevance of exercise ECG as a screening tool to prevent cardiovascular events when any cardiovascular disease (CVD) risk factors are present. METHODS: The study included leisure time asymptomatic sportsmen and sportswomen over age 35 evaluated from 2011 to 2016 at the University Hospital of Saint-Etienne (France). Major adverse cardiovascular events (MACE) and atrial fibrillation were collected at 3 years. RESULTS: Of the cohort of 2457 sportsmen and sportswomen (mean age 50.2 ± 9.4 years), 50 (2%) had a high-risk SCORE2. A total of 256 exercise ECGs (10%) were defined as positive, most of them due to silent myocardial ischemia (SMI) (n = 196; 8%). These 196 SMI cases led to 33 coronary angiograms (1%), which revealed 23 significant coronary stenoses requiring revascularization. In multivariate logistic regression analysis, having at least two CVD risk factors was independently associated with (1) positive exercise ECG (OR = 1.80 [95% CI: 1.29-2.52], p = 0.0006), with (2) suspected SMI (OR = 2.57 [95% CI: 1.10-6.02], p = 0.0304), with (3) confirmed SMI (OR = 8.20 [95% CI: 3.46-19.46], p < 0.0001) and with (4) cardiovascular events (MACE or atrial fibrillation) (OR = 6.95 [95% CI: 3.49-13.81], p < 0.0001) at 3 years (median). CONCLUSIONS: The study supports the European recommendations for the use of exercise ECG in evaluation of asymptomatic leisure time sportsmen over age 35. Having at least two CVD risk factors was the best predictor for presence of coronary artery stenosis that may increase the risk for adverse events. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06024863.

Reduced Body Flexibility Is Associated With Poor Survival in Middle-Aged Men and Women: A Prospective Cohort Study.

OBJECTIVES: Flexibility is recognized as one of the components of physical fitness and commonly included as part of exercise prescriptions for all ages. However, limited data exist regarding the relationship between flexibility and survival. We evaluated the sex-specific nature and magnitude of the associations between body flexibility and natural and non-COVID-19 mortality in a middle-aged cohort of men and women. DESIGN: Prospective cohort study. METHODS: Anthropometric, health and vital data from 3139 (66% men) individuals aged 46-65 years spanning from March 1994 to October 2022 were available. A body flexibility score, termed Flexindex, was derived from a combination of 20 movements (scored 0-4) involving seven different joints, resulting in a score range of 0-80. Kaplan-Meier survival curves were obtained, and unadjusted and adjusted hazard ratios (HRs) for mortality estimated. RESULTS: During a mean follow-up of 12.9 years, 302 individuals (9.6%) comprising 224 men/78 women died. Flexindex was 35% higher in women compared to men (mean ± SD: 41.1 ± 9.4 vs. 30.5 ± 8.7; p < 0.001) and exhibited an inverse relationship with mortality risk in both sexes (p < 0.001). Following adjustment for age, body mass index, and health status, the HR (95% CI) for mortality comparing upper and bottom of distributions of Flexindex were 1.87 (1.50-2.33; p < 0.001) for men and 4.78 (1.23-31.71; p = 0.047) for women. CONCLUSIONS: A component of physical fitness-body flexibility-as assessed by the Flexindex is strongly and inversely associated with natural and non-COVID-19 mortality risk in middle-aged men and women. Future studies should assess whether training-induced flexibility gains are related to longer survival.

Two-week step-reduction has limited negative effects on physical function and metabolic health in older adults.

PURPOSE: This study determined the effects of a 2-week step-reduction period followed by 4-week exercise rehabilitation on physical function, body composition, and metabolic health in 70-80-year-olds asymptomatic for injury/illness. METHODS: A parallel-group randomized controlled trial (ENDURE-study, NCT04997447) was used, where 66 older adults (79% female) were randomized to either intervention or control group. The intervention group reduced daily steps to < 2000, monitored by accelerometer, for two weeks (Period I) and then step-reduction requirement was removed with an additional exercise rehabilitation 4 times per week for 4 weeks (Period II). The control group continued their habitual physical activity throughout with no additional exercise intervention. Laboratory tests were performed at baseline, after Period I and Period II. The primary outcome measure was leg lean mass (LLM). Secondary outcomes included total lean and fat mass, blood glucose and insulin concentration, LDL cholesterol and HDL cholesterol concentration, maximal isometric leg press force (MVC), and chair rise and stair climb performance. RESULTS: LLM remained unchanged in both groups and no changes occurred in physical function nor body composition in the intervention group in Period I. HDL cholesterol concentration reduced after Period I (from 1.62 ± 0.37 to 1.55 ± 0.36 mmol·L-1, P = 0.017) and returned to baseline after Period II (1.66 ± 0.38 mmol·L-1) in the intervention group (Time × Group interaction: P = 0.065). MVC improved after Period II only (Time × Group interaction: P = 0.009, Δ% = 15%, P < 0.001). CONCLUSION: Short-term step-reduction in healthy older adults may not be as detrimental to health or physical function as currently thought.

The Impact of Multimorbidity Patterns on Changes in Physical Activity and Physical Capacity Among Older Adults Participating in a Year-Long Exercise Intervention.

This study investigated the impact of multimorbidity patterns on physical activity and capacity outcomes over the course of a year-long exercise intervention, and on physical activity 1 year later. Participants were 314 physically inactive community-dwelling men and women aged 70-85 years, with no contraindications for exercise at baseline. Physical activity was self-reported. Physical capacity measurements included five-time chair-stand time, 6-minute walking distance, and maximal isometric knee-extension strength. The intervention included supervised and home-based strength, balance, and walking exercises. Multimorbidity patterns comprised physician-diagnosed chronic disease conditions as a predictor cluster and body mass index as a measure of obesity. Multimorbidity patterns explained 0%-12% of baseline variance and 0%-3% of the change in outcomes. The magnitude and direction of the impact of unique conditions varied by outcome, time point, and sex. Multimorbid older adults with no contraindications for exercise may benefit from multimodal physical training.

Sauna bathing, renal function and chronic kidney disease: Cross-sectional and longitudinal findings from the KIHD study.

BACKGROUND: It is uncertain if passive heat therapies are associated with adverse renal outcomes. We sought to evaluate the cross-sectional and longitudinal associations of the frequency of sauna bathing with renal function measures and chronic kidney disease (CKD). MATERIALS AND METHODS: Baseline self-reported sauna bathing habits were assessed in 2071 men aged 42-61 years with normal kidney function. Baseline estimated glomerular filtration rate (GFR) and serum levels of creatinine, potassium (K) and sodium (Na) were measured, with only 11-year measurements of K and Na 11 years in a random subset of participants due to logistical reasons. Study participants were followed up for CKD diagnosed using KDOQI guidelines, which were collected from the National Hospital Discharge Registry. The associations of frequency of sauna bathing with renal function measures were evaluated using regression analyses. Hazard ratios (HRs; 95% CIs) were estimated for CKD. RESULTS: There were no significant changes in baseline levels of estimated GFR, creatinine and Na comparing 4-7 sauna sessions/week versus 1 sauna session/week; there was a slight increase in K .05 mmoL/L (95% CI, .00, .10; p = .033). There were no significant changes in levels of serum K and Na at 11 years. After 25.7 years overall median follow-up, 188 CKD cases were recorded. Comparing 4-7 sauna sessions/week with 1 sauna session/week, there was no evidence of an association with CKD .84 (95% CI, .46-1.53; p = .56). CONCLUSIONS: Cross-sectional and longitudinal observational evidence suggests that frequent sauna bathing is not associated with impaired renal function or the future risk of CKD.

Haemodynamic Gain Index Is Associated with Risk of Sudden Cardiac Death and Improves Risk Prediction: A Cohort Study.

INTRODUCTION: Haemodynamic gain index (HGI) is a novel haemodynamic parameter which can be obtained from cardiopulmonary exercise testing (CPX), but its association with sudden cardiac death (SCD) is not known. We aimed to assess the association of HGI with SCD risk in a long-term prospective cohort study. METHODS: HGI was calculated using heart rate and systolic blood pressure (SBP) responses measured in 1897 men aged 42­61 years during CPX from rest to peak exercise. Cardiorespiratory fitness (CRF) was measured using respiratory gas exchange analysis. Multivariable adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) were estimated for SCD. RESULTS: During a median follow-up of 28.7 years, 205 SCDs occurred. The risk of SCD decreased gradually with increasing HGI (p value for non-linearity = 0.63). A unit (bpm/mm Hg) higher HGI was associated with a decreased risk of SCD (HR: 0.84; 95% CI: 0.71-0.99), which was attenuated following adjustment for CRF. CRF was inversely associated with SCD, which remained after further adjustment for HGI (HR: 0.85; 95% CI: 0.77-0.94) per each unit higher CRF. Addition of HGI to a SCD risk prediction model containing established risk factors improved risk discrimination (C-index change = 0.0096; p = 0.017) and reclassification (net reclassification improvement [NRI] = 39.40%, p = 0.001). The corresponding values for CRF were (C-index change = 0.0178; p = 0.007) and (NRI = 43.79%, p = 0.001). CONCLUSION: Higher HGI during CPX is associated with a lower SCD risk, consistent with a dose-response relationship but dependent on CRF levels. Though HGI significantly improves the prediction and classification of SCD beyond common cardiovascular risk factors, CRF remains a stronger risk indicator and predictor of SCD compared to HGI.

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.

Serum copper and the risk of cardiovascular disease death in Finnish men.

BACKGROUND AND AIMS: Copper (Cu) is a component of enzymes catalyzing oxidation-reduction reactions. With the persisting burden of cardiovascular disease (CVD), there is evident need to identify biomarkers and potential risk factors for CVD. We therefore examined the association between serum Cu levels and the risk of CVD death in Finnish men and across different body mass index (BMI) categories. METHODS AND RESULTS: This Finnish prospective study is based on 1911 men aged 42-60 years who were free of coronary heart disease at baseline. Cu concentrations (mg/l) were determined using atomic absorption spectrometer and categorized into quartiles (<1.0; 1 to <1.1; 1.1 to <1.21; ≥1.21). Participants were categorized into normal weight <25 kg/m2, pre-obesity 25-29.9 kg/m2, and obesity >30 kg/m2. The association between Cu and CVD death was analyzed using multivariable Cox regression models. During a median follow-up of 25.8 years, 358 CVD deaths occurred. The risk of CVD death increased continuously with increasing Cu levels (for non-linearity, p = 0.64). Using the first quartile as reference after adjustment for covariates, the hazard ratios (HR) (95% confidence interval (CI)) for CVD death for Cu concentrations in second, third and fourth quartiles were 1.45(1.05-2.01), 1.69(1.25-2.27), and 1.68(1.23-2.29), respectively. Obese men in the third quartile of serum Cu concentrations had highest risk of CVD death (HR (95%CI) 2.71(1.27-5.78)). CONCLUSION: Elevated serum Cu level was associated with increased risk of CVD death across all BMI categories in middle-aged and older Finnish men. Serum Cu may have prognostic implication for CVD mortality risk; however, further studies are needed.

Serum Copper-to-Zinc Ratio and Risk of Chronic Obstructive Pulmonary Disease: A Cohort Study.

PURPOSE: Serum copper (Cu), zinc (Zn), and Cu/Zn-ratio have emerged as ageing-related biomarkers. We sought to assess the association between Cu/Zn-ratio and chronic obstructive pulmonary disease (COPD) risk. METHODS: Serum Cu and Zn were measured using atomic absorption spectrometry in 2,503 men aged 42-61 years. RESULTS: During a median follow-up of 27.1 years, 210 COPD cases occurred. Serum Cu/Zn-ratio and Cu concentrations were linearly associated with COPD risk, whereas the relationship was curvilinear for Zn and COPD risk. A unit increase in Cu/Zn-ratio was associated with an increased COPD risk in multivariable analysis (hazard ratio, HR 1.81; 95% CI 1.08-3.05). The corresponding adjusted HR (95% CI) was 3.17 (1.40-7.15) for Cu. Compared to the bottom tertile of Zn, the HRs (95% CIs) were 0.68 (0.48-0.97) and 1.01 (0.73-1.41) for the middle and top tertiles of Zn, respectively. CONCLUSIONS: Increased serum Cu/Zn-ratio and Cu concentrations were linearly associated with an increased COPD risk in men.

Effects of regular sauna bathing in conjunction with exercise on cardiovascular function: a multi-arm, randomized controlled trial.

Regular exercise and sauna bathing have each been shown to improve cardiovascular function in clinical populations. However, experimental data on the cardiovascular adaptations to regular exercise in conjunction with sauna bathing in the general population are lacking. Therefore, we compared the effects of exercise and sauna bathing to regular exercise using a multi-arm randomized controlled trial. Participants (n = 47) aged 49 ± 9 with low physical activity levels and at least one traditional cardiovascular disease (CVD) risk factor were randomly assigned (1:1:1) to guideline-based regular exercise and 15-min postexercise sauna (EXS), guideline-based regular exercise (EXE), or control (CON) for 8 wk. The primary outcomes were blood pressure (BP) and cardiorespiratory fitness (CRF). Secondary outcomes included fat mass, total cholesterol levels, and arterial stiffness. EXE had a greater change in CRF (+6.2 mL/kg/min; 95% CI, +4.2 to +8.3 mL/kg/min) and fat mass but no differences in BP when compared with CON. EXS displayed greater change in CRF (+2.7 mL/kg/min; 95% CI, +0.2 to +5.3 mL/kg/min), lower systolic BP (-8.0 mmHg; 95% CI, -14.6 to -1.4 mmHg), and lower total cholesterol levels compared with EXE. Regular exercise improved CRF and body composition in sedentary adults with CVD risk factors. However, when combined with exercise, sauna bathing demonstrated a substantially supplementary effect on CRF, systolic BP, and total cholesterol levels. Sauna bathing is a valuable lifestyle tool that complements exercise for improving CRF and decreasing systolic BP. Future research should focus on the duration and frequency of exposure to ascertain the dose-response relationship.

Underweight and obesity are related to higher mortality in patients undergoing coronary angiography: The KARDIO invasive cardiology register study.

BACKGROUND: In patients with some cardiovascular disease conditions, slightly elevated body mass index (BMI) is associated with a lower mortality risk (termed "obesity paradox"). It is uncertain, however, if this obesity paradox exists in patients who have had invasive cardiology procedures. We evaluated the association between BMI and mortality in patients who underwent coronary angiography. METHODS: We utilised the KARDIO registry, which comprised data on demographics, prevalent diseases, risk factors, coronary angiographies, and interventions on 42,636 patients. BMI was categorised based on WHO cut-offs or transformed using P-splines. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated for all-cause mortality. RESULTS: During a median follow-up of 4.9 years, 4688 all-cause deaths occurred. BMI was nonlinearly associated with mortality risk: compared to normal weight category (18.5-25 kg/m2 ), the age-adjusted HRs (95% CIs) for all-cause mortality were 1.90 (1.49, 2.43), 0.96 (0.92, 1.01), 1.04 (0.99, 1.09), 1.08 (0.96, 1.20), and 1.45 (1.22, 1.72) for underweight (<18.5 kg/m2 ), preobesity (25 to <30 kg/m2 ), obesity class I (30 to <35 kg/m2 ), obesity class II (35 to <40 kg/m2 ), and obesity class III (>40 kg/m2 ), respectively. The corresponding multivariable adjusted HRs (95% CIs) were 2.00 (1.55, 2.58), 0.92 (0.88, 0.97) 1.01 (0.95, 1.06), 1.10 (0.98, 1.23), and 1.49 (1.26, 1,78), respectively. CONCLUSIONS: In patients undergoing coronary angiography, underweight and obesity class III are associated with increased mortality risk, and the lowest mortality was observed in the preobesity class. It appears the obesity paradox may be present in patients who undergo invasive coronary procedures.

Egg and cholesterol intake, apolipoprotein E4 phenotype and risk of venous thromboembolism: findings from a prospective cohort study.

The impact of egg consumption, a major source of dietary cholesterol, with the risk of atherosclerotic cardiovascular diseases (ASCVDs) is controversial. Venous thromboembolism (VTE) is a CVD which shares common risk factors and mechanistic pathways with ASCVD. However, there is no data on the relationship between egg or cholesterol intake and VTE risk. Therefore, we evaluated the prospective associations of egg and cholesterol intakes with VTE risk and whether the apolipoprotein E4 (apoE4) phenotype, which influences cholesterol metabolism, could modify the associations. Data involving 1,852 men aged 42-61 years at baseline without a history of VTE or coronary heart disease in the population-based Kuopio Ischaemic Heart Disease Risk Factor Study were analysed. Dietary intakes were assessed with 4-day food records. Incident VTE events were identified by record linkage to hospital discharge registries. Hazard ratios (95% confidence intervals [CIs]) for incident VTE were estimated using Cox regression. During a median follow-up of 28.8 years, 132 VTE events occurred. Comparing the top (>38 g/d) versus bottom (<20 g/d) tertiles of egg consumption, the HR (95% CI) for VTE was 0.99 (0.64-1.53) in analysis adjusted for several established risk factors and other dietary factors. There was also no evidence of an association between cholesterol intake and VTE risk. Imputed results were consistent with the observed results. The apoE4 phenotype did not modify the associations. In middle-aged and older Finnish men, egg or cholesterol intakes were not associated with future VTE risk. Other large-scale prospective studies are needed to confirm or refute these findings.

Cardiorespiratory fitness does not offset the increased risk of chronic obstructive pulmonary disease attributed to smoking: a cohort study.

Though evidence suggests that higher cardiorespiratory fitness (CRF) levels can offset the adverse effects of other risk factors, it is unknown if CRF offsets the increased risk of chronic obstructive pulmonary disease (COPD) due to smoking. We aimed to evaluate the combined effects of smoking status and CRF on incident COPD risk using a prospective cohort of 2295 middle-aged and older Finnish men. Peak oxygen uptake, assessed with a respiratory gas exchange analyzer, was used as a measure of CRF. Smoking status was self-reported. CRF was categorised as low and high based on median cutoffs, whereas smoking status was classified into smokers and non-smokers. Multivariable-adjusted hazard ratios with confidence intervals (CIs) were calculated. During 26 years median follow-up, 119 COPD cases were recorded. Smoking increased COPD risk 10.59 (95% CI 6.64-16.88), and high CRF levels decreased COPD risk 0.43 (95% CI 0.25-0.73). Compared with non-smoker-low CRF, smoker-low CRF was associated with an increased COPD risk in multivariable analysis 9.79 (95% CI 5.61-17.08), with attenuated but persisting evidence of an association for smoker-high CRF and COPD risk 6.10 (95% CI 3.22-11.57). An additive interaction was found between smoking status and CRF (RERI = 6.99). Except for CRF and COPD risk, all associations persisted on accounting for mortality as a competing risk event. Despite a wealth of evidence on the ability of high CRF to offset the adverse effects of other risk factors, it appears high CRF levels have only modest attenuating effects on the very strong association between smoking and COPD risk.

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 and risk of incident pneumonia in caucasian men: a prospective cohort study.

Serum copper (Cu) and zinc (Zn), essential micronutrients that have important immunomodulatory and antimicrobial properties, are biomarkers of ageing. Serum Cu/Zn-ratio may be a more reliable marker for age-related degenerative conditions compared with serum Cu or Zn alone. We aimed to assess the association between Cu/Zn-ratio and the risk of incident pneumonia in a prospective cohort study. Serum levels of Cu and Zn were measured at baseline using atomic absorption spectrometry in 2503 men aged 42-61 years in the Kuopio Ischemic Heart Disease prospective cohort study. Hazard ratios (HRs) with confidence intervals (CIs) were calculated for incident pneumonia using Cox regression models. A total of 599 cases of pneumonia occurred during a median follow-up of 26.1 years. Serum Cu/Zn-ratio and Cu were each linearly associated with incident pneumonia. A unit increase in Cu/Zn-ratio was associated with an increased risk of pneumonia in analysis adjusted for potential confounders including C-reactive protein (HR 1.65; 95% CI 1.17-2.33). The corresponding adjusted HR (95% CI) was 2.04 (1.22-3.40) for serum Cu. The association between serum Zn and pneumonia was curvilinear. Compared to the bottom tertile of Zn, the multivariable adjusted HRs (95% CIs) for incident pneumonia were 0.68 (0.55-0.83) and 0.96 (0.79-1.16) for the middle and top tertiles of Zn, respectively. Further analysis in the same participants showed that Cu/Zn-ratio might be a stronger risk indicator for pneumonia than serum C-reactive protein. In middle-aged and older Finnish men, increased serum Cu/Zn-ratio and Cu concentrations are each linearly associated with an increased risk of incident pneumonia.

No evidence of a prospective relationship between serum zinc and venous thromboembolism in Caucasian men: a cohort study.

Serum zinc has been implicated as an important mediator of haemostasis and thrombosis. However, the nature and magnitude of any potential relationship between serum zinc and venous thromboembolism (VTE) is unknown. We aimed to evaluate the prospective association between serum zinc and VTE risk. We analyzed data involving 2472 men aged 42-61 years without a history of VTE in the Kuopio Ischemic Heart Disease population-based cohort study, with the assessment of serum zinc concentrations using atomic absorption spectrometry. Hazard ratios (95% confidence intervals [CIs]) for incident VTE were estimated. A total of 166 VTE cases occurred during a median follow-up of 27.1 years. The risk of VTE per 1 standard deviation increase in serum zinc in analysis adjusted for systolic blood pressure, body mass index, total cholesterol, triglycerides, smoking status, histories of type 2 diabetes and coronary heart disease, medication for dyslipidaemia, alcohol consumption, physical activity, and socioeconomic status was (HR 1.03; 95% CI 0.86-1.22), which remained similar (HR 1.04; 95% CI 0.87-1.23) following further adjustment for inflammation and history of cancer. Comparing the extreme tertiles of serum zinc, the corresponding adjusted HRs (95% CIs) were 0.92 (0.63-1.36) and 0.94 (0.64-1.39), respectively. Imputed results based on 2682 participants and 176 VTE events were consistent with the observed results. In middle-aged and older Finnish men, serum zinc is not associated with future VTE risk. Other large-scale prospective studies conducted in other populations are needed to confirm or refute these findings.

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.