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.

Physical activity and risk of atrial fibrillation in the general population: meta-analysis of 23 cohort studies involving about 2 million participants.

Regular physical activity is well established to be associated with reduced risk of cardiovascular disease outcomes. Whether physical activity is associated with the future risk of atrial fibrillation (AF) remains a controversy. Using a systematic review and meta-analysis of published observational cohort studies in general populations with at least one-year of follow-up, we aimed to evaluate the association between regular physical activity and the risk of AF. Relevant studies were sought from inception until October 2020 in MEDLINE, Embase, Web of Science, and manual search of relevant articles. Extracted relative risks (RRs) with 95% confidence intervals (CIs) for the maximum versus the minimal amount of physical activity groups were pooled using random-effects meta-analysis. Quality of the evidence was assessed by GRADE. A total of 23 unique observational cohort studies comprising of 1,930,725 participants and 45,839 AF cases were eligible. The pooled multivariable-adjusted RR (95% CI) for AF comparing the most physically active versus the least physically active groups was 0.99 (0.93-1.05). This association was modified by sex: an increased risk was observed in men: 1.20 (1.02-1.42), with a decreased risk in women: 0.91 (0.84-0.99). The quality of the evidence ranged from low to moderate. Pooled observational cohort studies suggest that the absence of associations reported between regular physical activity and AF risk in previous general population studies and their aggregate analyses could be driven by a sex-specific difference in the associations - an increased risk in men and a decreased risk in women.Systematic review registration: PROSPERO 2020: CRD42020172814.

Normalized handgrip strength and future risk of hypertension: findings from a prospective cohort study.

Previous reports of an association between handgrip strength (HGS) and the risk of hypertension have utilized cross-sectional designs. We aimed to assess the prospective association between HGS and hypertension risk in a general population. Handgrip strength was assessed at baseline in 463 Finnish men and women aged 61-73 years. Handgrip strength was normalized (HGS/body weight2/3). After 16 years median follow-up, 110 hypertension cases occurred. Comparing the extreme tertiles of normalized HGS, the multivariable adjusted hazard ratio (95% CI) for hypertension was 0.63 (0.38-1.04). Previous evidence of associations may have been driven by study design limitations such as lack of temporality.

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.

Physical activity and risk of venous thromboembolism: systematic review and meta-analysis of prospective cohort studies.

The inverse association between physical activity and arterial thrombotic disease is well established. Evidence on the association between physical activity and venous thromboembolism (VTE) is divergent. We conducted a systematic review and meta-analysis of published observational prospective cohort studies evaluating the associations of physical activity with VTE risk. MEDLINE, Embase, Web of Science, and manual search of relevant bibliographies were systematically searched until 26 February 2019. Extracted relative risks (RRs) with 95% confidence intervals (CIs) for the maximum versus minimal amount of physical activity groups were pooled using random effects meta-analysis. Twelve articles based on 14 unique prospective cohort studies comprising of 1,286,295 participants and 23,753 VTE events were eligible. The pooled fully-adjusted RR (95% CI) of VTE comparing the most physically active versus the least physically active groups was 0.87 (0.79-0.95). In pooled analysis of 10 studies (288,043 participants and 7069 VTE events) that reported risk estimates not adjusted for body mass index (BMI), the RR (95% CI) of VTE was 0.81 (0.70-0.93). The associations did not vary by geographical location, age, sex, BMI, and methodological quality of studies. There was no evidence of publication bias among contributing studies. Pooled observational prospective cohort studies support an association between regular physical activity and low incidence of VTE. The relationship does not appear to be mediated or confounded by BMI.

Handgrip strength is not associated with risk of venous thromboembolism: a prospective cohort study.

Objectives. Consistent evidence suggests an inverse and independent association between handgrip strength and arterial thrombotic disease. However, whether handgrip strength is related to future risk of venous thromboembolism (VTE) is uncertain. We sought to assess the prospective association between handgrip strength and VTE risk. Design. Handgrip strength was assessed using a hand dynamometer in a population-based sample of 864 men and women aged 61-74 years without a history of VTE at baseline in the Kuopio Ischemic Heart Disease prospective cohort study. Handgrip strength was allometrically scaled to account for the effect of body weight (handgrip strength/body weight2/3) and to normalize the data. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated for VTE. Results. During a median (interquartile range) follow-up of 17.2 (12.1-18.3) years, 58 VTE events were recorded. The risk of VTE did not significantly decrease per 1 standard deviation increase in normalized handgrip strength in age- and sex-adjusted analysis (HR 0.89; 95% CI 0.65-1.22). The association remained similar in analyses adjusted for several established and emerging risk factors (HR 0.90; 95% CI 0.65-1.25). The corresponding adjusted HRs were 1.10 (95% CI: 0.56-2.18) and 1.15 (95% CI: 0.57-2.34), respectively, when comparing the extreme tertiles of normalized handgrip strength values. Conclusions. Normalized handgrip strength is not associated with future VTE risk in an older Caucasian population. Large-scale studies in other populations and age-groups are warranted to generalize these findings.

Sauna bathing reduces the risk of venous thromboembolism: a prospective cohort study.

Emerging evidence suggests there is an inverse and independent association between sauna bathing and arterial thrombotic disease. However, the potential association between sauna bathing and venous thromboembolism (VTE) has not yet been investigated. We aimed to assess the prospective association between frequency of sauna bathing and the risk of VTE. Baseline sauna bathing habits were assessed in 2242 men aged 42-61 years without a history of VTE in the Kuopio Ischemic Heart Disease prospective cohort. Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for VTE. During a median follow-up of 24.9 years, 146 (6.5%) incident VTE events were recorded. In age-adjusted analyses, the HRs 95% (CIs) of VTE were 0.67 (0.47-0.96) and 0.95 (0.53-1.70) for participants who had 2-3 and ≥ 4 sauna sessions per week respectively compared with participants who had ≤ 1 sauna session per week. After further adjustment for several established risk factors including lifestyle factors, the corresponding HRs (95% CIs) were 0.67 (0.46-0.96) and 0.92 (0.51-1.68) respectively. Having sauna baths was associated with a reduced risk of VTE in a middle-aged male Caucasian population. Further studies in other populations and age groups are required to confirm these findings.

Lipoprotein(a) is not associated with venous thromboembolism risk.

Objectives. Evidence from case-control studies as well as meta-analyses of these study designs suggest elevated lipoprotein(a) [Lp(a)] to be associated with an increased risk of venous thromboembolism (VTE). Prospective evidence on the association is limited, uncertain, and could be attributed to regression dilution bias. We aimed to assess the prospective association of Lp(a) with risk of VTE and correct for regression dilution. Design. We related plasma Lp(a) concentrations to the incidence of VTE in 2,180 men of the Kuopio Ischemic Heart Disease cohort study. Hazard ratios (HRs) (95% confidence intervals [CI]) were assessed and repeat measurements of Lp(a) at 4 and 11 years from baseline, were used to correct for within-person variability. Results. After a median follow-up of 24.9 years, 110 validated VTE cases were recorded. The regression dilution ratio of loge Lp(a) adjusted for age was 0.85 (95% CI: 0.82-0.89). In analyses adjusted for several established risk factors and potential confounders, the HR (95% CI) for VTE per 1 SD (equivalent to 3.56-fold) higher baseline loge Lp(a) was 1.06 (0.87-1.30). In pooled analysis of five population-based cohort studies (including the current study) comprising 66,583 participants and 1314 VTE cases, the fully-adjusted corresponding HR for VTE was 1.00 (95% CI: 0.94-1.07), with no evidence of heterogeneity between studies. Conclusions. Primary analysis as well as pooled evidence from previous studies suggest circulating Lp(a) is not prospectively associated with future VTE risk, indicating that evidence of associations demonstrated in case-control designs may be driven by biases such as selection bias.

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.

Duration of QRS complex in resting electrocardiogram is a predictor of sudden cardiac death in men.

BACKGROUND: Previous studies indicate that increased QRS duration in ECG is related to the risk of all-cause death. However, the association of QRS duration with the risk of sudden cardiac death (SCD) is not well documented in large population-based studies. Our aim was to examine the relation of QRS duration with SCD in a population-based sample of men. METHODS AND RESULTS: This prospective study was based on a cohort of 2049 men aged 42 to 60 years at baseline with a 19-year follow-up, during which a total of 156 SCDs occurred. As a continuous variable, each 10-ms increase in QRS duration was associated with a 27% higher risk for SCD (relative risk, 1.27; 95% confidence interval, 1.14-1.40; P<0.001). Subjects with QRS duration of >110 ms (highest quintile) had a 2.50-fold risk for SCD (relative risk, 2.50; 95% confidence interval, 1.38-4.55; P=0.002) compared with those with QRS duration of <96 ms (lowest quintile), after adjustment for established key demographic and clinical risk factors (age, alcohol consumption, previous myocardial infarction, smoking, serum low- and high-density lipoprotein cholesterol, C-reactive protein, type 2 diabetes mellitus, body mass index, systolic blood pressure, and cardiorespiratory fitness). In addition to QRS duration, smoking, previous myocardial infarction, type 2 diabetes mellitus, cardiorespiratory fitness, body mass index, systolic blood pressure, and C-reactive protein were independently associated with the risk of SCD. CONCLUSIONS: QRS duration is an independent predictor of the risk of SCD and may have utility in estimating SCD risk in the general population.

The effect of bone marrow microenvironment on the functional properties of the therapeutic bone marrow-derived cells in patients with acute myocardial infarction.

BACKGROUND: Treatment of acute myocardial infarction with stem cell transplantation has achieved beneficial effects in many clinical trials. The bone marrow microenvironment of ST-elevation myocardial infarction (STEMI) patients has never been studied even though myocardial infarction is known to cause an imbalance in the acid-base status of these patients. The aim of this study was to assess if the blood gas levels in the bone marrow of STEMI patients affect the characteristics of the bone marrow cells (BMCs) and, furthermore, do they influence the change in cardiac function after autologous BMC transplantation. The arterial, venous and bone marrow blood gas concentrations were also compared. METHODS: Blood gas analysis of the bone marrow aspirate and peripheral blood was performed for 27 STEMI patients receiving autologous stem cell therapy after percutaneous coronary intervention. Cells from the bone marrow aspirate were further cultured and the bone marrow mesenchymal stem cell (MSC) proliferation rate was determined by MTT assay and the MSC osteogenic differentiation capacity by alkaline phosphatase (ALP) activity assay. All the patients underwent a 2D-echocardiography at baseline and 4 months after STEMI. RESULTS: As expected, the levels of pO(2), pCO(2), base excess and HCO(3) were similar in venous blood and bone marrow. Surprisingly, bone marrow showed significantly lower pH and Na(+) and elevated K(+) levels compared to arterial and venous blood. There was a positive correlation between the bone marrow pCO(2) and HCO(3) levels and MSC osteogenic differentiation capacity. In contrast, bone marrow pCO(2) and HCO(3) levels displayed a negative correlation with the proliferation rate of MSCs. Patients with the HCO(3) level below the median value exhibited a more marked change in LVEF after BMC treatment than patients with HCO(3) level above the median (11.13 ± 8.07% vs. 2.67 ± 11.89%, P = 0.014). CONCLUSIONS: Low bone marrow pCO(2) and HCO(3) levels may represent the optimal environment for BMCs in terms of their efficacy in autologous stem cell therapy in STEMI patients.

Low serum lycopene and ß-carotene increase risk of acute myocardial infarction in men.

OBJECTIVE: Previous studies have shown that high intake or concentrations of serum carotenoids may protect against acute myocardial infarction (AMI). The role of carotenoids on the risk of AMI remains inconsistent. The aim of the present study was to examine if serum concentrations of major carotenoids are related to AMI in men. METHODS: The study population consisted of 1031 Finnish men aged 46-65 years in the Kuopio Ischaemic Heart Disease Risk Factor (KIHD) cohort. Serum concentrations of carotenoids, retinol and α-tocopherol were measured by high-performance liquid chromatography. The association between the serum concentrations of lycopene α-carotene and ß-carotene and the risk of AMI was studied by using the Cox proportional hazard models. RESULTS: A total of 194 incident AMI cases occurred during an average of 11.5 follow-up years. After adjusting for potential confounders, the risk of AMI for men in the lowest tertile of serum concentrations compared with men in the highest tertile was 1.55 (95% CI 1.05- 2.30; P = 0.028) for lycopene and 1.60 (95% CI 1.09-2.35; P = 0.017) for ß-carotene. CONCLUSIONS: This cross-sectional study shows that low serum lycopene and ß-carotene concentrations may increase the risk of AMI in men.

Cardiorespiratory Fitness, Inflammation, and Risk of Chronic Obstructive Pulmonary Disease in Middle-Aged Men: A COHORT STUDY.

PURPOSE: Chronic obstructive pulmonary disease (COPD) is characterized by chronic lung inflammation. The relationship between cardiorespiratory fitness (CRF) and COPD has not been well characterized. We aimed to evaluate the independent and joint associations of inflammation (high-sensitivity C-reactive protein [hsCRP]) and CRF with COPD risk in a cohort of White men. METHODS: Among 2274 men aged 42-61 yr at baseline, serum hsCRP level was measured using an immunometric assay and CRF was assessed using a respiratory gas exchange analyzer. The level of hsCRP was categorized as normal and high (≤3 and >3 mg/L, respectively) and CRF as low and high. We corrected for within-person variability in exposures using repeat measurements taken several years apart. RESULTS: A total of 116 COPD cases occurred during a median follow-up of 26.0 yr. The age-adjusted regression dilution ratio of hsCRP and CRF was 0.57 (95% CI, 0.50-0.64) and 0.58 (95% CI, 0.53-0.64), respectively. Comparing high versus normal hsCRP levels, the multivariable-adjusted HR for COPD was 1.79 (95% CI, 1.20-2.68). The COPD risk decreased linearly with increasing CRF. The multivariable-adjusted HR for COPD per 1-SD increase in CRF was 0.75 (95% CI, 0.60-0.95). Compared with men with normal hsCRP-low CRF, high hsCRP-low CRF was associated with an increased COPD risk, 1.80 (95% CI, 1.12-2.89), with no evidence of an association for high hsCRP-high CRF and COPD risk, 1.35 (95% CI, 0.68-2.69). CONCLUSIONS: Both hsCRP and CRF are associated with COPD risk in middle-aged men. However, high CRF levels attenuate the increased COPD risk related to high hsCRP levels.

Exercise cardiac power and the risk of heart failure in men: A population-based follow-up study.

BACKGROUND: Little is known about exercise cardiac power (ECP), defined as the ratio of directly measured maximal oxygen uptake with peak systolic blood pressure during exercise, on heart failure (HF) risk. We examined the association of ECP and the risk of HF. METHODS: This was a population-based cohort study of 2351 men from eastern Finland. The average time to follow-up was 25 years. Participants participated at baseline in an exercise stress test. A total of 313 cases of HF occurred. RESULTS: Men with low ECP (<9.84 mL/mmHg, the lowest quartile) had a 2.37-fold (95% confidence interval (95%CI): 1.68-3.35, p < 0.0001) hazards ratio of HF as compared with men with high ECP (>13.92 mL/mmHg, the highest quartile), after adjusting for age. Low ECP was associated with a 1.96-fold risk (95%CI: 1.38-2.78, p < 0.001) of HF after additional adjustment for conventional risk factors. After further adjustment for left ventricular hypertrophy, the results hardly changed (hazards ratio = 1.87, 95%CI: 1.31-2.66, p < 0.001). One SD increase in ECP (3.16 mL/mmHg) was associated with a decreased risk of HF by 28% (95%CI: 17%-37%). CONCLUSION: ECP provides a noninvasive and easily available measure from cardiopulmonary exercise tests in predicting HF. However, ECP did not provide additional value over maximal oxygen uptake.

High fitness levels offset the increased risk of chronic obstructive pulmonary disease due to low socioeconomic status: A cohort study.

OBJECTIVE: Evidence suggests that higher cardiorespiratory fitness (CRF) levels can offset the increased risk of adverse outcomes due to other risk factors. The impact of high CRF levels on the increased risk of chronic obstructive pulmonary disease (COPD) due to low socioeconomic status (SES) is unknown. We aimed to assess the combined effects of SES and CRF on the future risk of COPD. METHODS: We employed a prospective cohort of 2312 Finnish men aged 42-61 years at study entry. Socioeconomic status was self-reported and CRF was objectively assessed using respiratory gas exchange analyzers. Both exposures were categorized as low and high based on median cutoffs. Multivariable-adjusted hazard ratios (HRs) with confidence intervals (CIs) were estimated. RESULTS: During 26.0 years median follow-up, 120 COPD cases occurred. Low SES was associated with increased COPD risk and high CRF was associated with reduced COPD risk. Compared with high SES-low CRF, low SES-low CRF was associated with an increased COPD risk 2.36 (95% CI: 1.44-3.87), with no evidence of an association for low SES-high CRF and COPD risk 1.46 (95% CI:0.82-2.60). CONCLUSION: In middle-aged Finnish men, SES and CRF are each independently associated with COPD risk. However, high CRF levels offset the increased COPD risk related to low SES.

Physical activity and heart rate variability measured simultaneously during waking hours.

Heart rate (HR) variability (HRV) during ambulatory recordings may be affected by individual differences in daily physical activity (PA). However, the influence of various levels of PA on different measures of HRV is not exactly known. We examined the association between simultaneously measured HRV and objective PA data obtained with an accelerometer during waking hours among 45 healthy adults. Bouts of PA were identified from minute-by-minute accelerometer data as metabolic equivalent (METs) values and calculated as mean METs for 30 min. HRV was analyzed concurrently. Within-individual correlation analyses and sign tests were performed to study the relationships between various HRV indexes and PA. The mean PA time was 15:44 +/- 1:01 h, and the mean MET was 1.91 +/- 0.14. HR and sample entropy, but not the other measures of HRV, had a significant relationship with PA, as shown by both correlation analyses (r = 0.64, P = 0.021, and r = -0.55, P = 0.022, respectively) and sign tests (P < 0.0001 for both). Beat-to-beat R-R interval fluctuation expressed as SD1 also demonstrated a significant relation to PA according to the sign test (P = 0.037) and a trend of association according to the correlation analysis (r = -0.40, P = 0.129). The complexity measure of HRV, in addition to average HR and the short-term index of HRV (SD1), is significantly influenced by the level of PA during ambulatory conditions. Long-term HRV indexes remained relatively stable at various activity levels, making them the most robust indexes for the assessment of cardiac autonomic function during free-running ambulatory conditions.

Asymptomatic ST-segment depression during exercise testing and the risk of sudden cardiac death in middle-aged men: a population-based follow-up study.

AIMS: Silent electrocardiographic ST change predicts future coronary events in patients with coronary heart disease (CHD), but the prognostic significance of asymptomatic ST-segment depression with respect to sudden cardiac death in subjects without apparent CHD is not well known. METHODS AND RESULTS: We investigated the association between silent ST-segment depression during and after maximal symptom-limited exercise test and the risk of sudden cardiac death in a population-based sample of 1769 men without evident CHD. A total of 72 sudden cardiac death occurred during the median follow-up of 18 years. The risk of sudden cardiac death was increased among men with asymptomatic ST-segment depression during exercise [hazard ratio (HR) 2.1, 95% confidence interval (CI) 1.2-3.9] as well as among those with asymptomatic ST-segment depression during recovery period (HR 3.2, 95% CI 1.7-6.0). Asymptomatic ST-depression during exercise testing was a stronger predictor for the risk of sudden cardiac death especially among smokers as well as in hypercholesterolaemic and hypertensive men than in men without these risk factors. CONCLUSION: Asymptomatic ST-segment depression was a very strong predictor of sudden cardiac death in men with any conventional risk factor but no previously diagnosed CHD, emphasizing the value of exercise testing to identify asymptomatic high-risk men who could benefit from preventive measures.