Search

The hemodynamic gain index (HGI), a novel non-invasive hemodynamic marker, represents a promising advancement in cardiovascular risk assessment. Cardiovascular disease and chronic kidney disease (CKD) are closely intertwined and share bidirectional relationships. We aimed to assess the association of HGI with CKD risk in a prospective study. Hemodynamic gain index was calculated using heart rate and systolic blood pressure (SBP) responses measured in 1765 men aged 42–61 years with normal kidney function during exercise testing using the formula: [(Heart ratemax x SBPmax)—(Heart raterest x SBPrest)]/(Heart raterest x SBPrest). Multivariable adjusted hazard ratios (HRs) (95% confidence intervals, CIs) were estimated for CKD. Over a median follow-up duration of 25.9 years, 175 CKD cases occurred. In analysis adjusted for established risk factors, a unit (bpm/mmHg) higher HGI was associated with a decreased risk of CKD (HR 0.78, 95% CI 0.65–0.95). Comparing extreme tertiles of HGI, the corresponding adjusted HR (95% CI) for CKD was 0.53 (0.33–0.85). Addition of HGI to a CKD risk prediction model containing established risk factors improved risk discrimination and reclassification (p-value for difference in -2 log likelihood =.011; net-reclassification-improvement = 59.37%, p =.018; integrated-discrimination-improvement = 0.0064, p =.008). Higher HGI is associated with a lower CKD risk and improves the prediction and classification of CKD beyond common established risk factors. [ABSTRACT FROM AUTHOR]

Cardiorespiratory fitness (CRF) not only reflects an individual's capacity to perform physical activities but also encapsulates broader effects on the basic biology of aging. This review aims to summarize the evidence on the influence of CRF on overall and site-specific cancer risks. It delves into the biological mechanisms through which CRF may exert its effects, explores the clinical implications of these findings, identifies gaps in the current evidence base, and suggests directions for future research. The synthesis of findings reveals that higher CRF levels (general threshold of > 7 METs) are consistently associated with a reduced risk of a range of cancers, including head and neck, lung, breast, gastrointestinal, particularly pancreatic and colorectal, bladder, overall cancer incidence and mortality, and potentially stomach and liver, bile duct, and gall bladder cancers. These inverse associations between CRF and cancer risk do not generally differ across age groups, sex, race, or adiposity, suggesting a universal protective effect of CRF. Nonetheless, evidence linking CRF with skin, mouth and pharynx, kidney, and endometrial cancers is limited and inconclusive. Conversely, higher CRF levels may be potentially linked to an increased risk of prostate cancer and hematological malignancies, such as leukemia and myeloma, although the evidence is still not conclusive. CRF appears to play a significant role in reducing the risk of several cancers through various biological mechanisms, including inflammation reduction, immune system enhancement, hormonal regulation, and metabolic improvements. Overall, enhancing CRF through regular physical activity offers a vital, accessible strategy for reducing cancer risk and extending the health span. Future research should aim to fill the existing evidence gaps regarding specific cancers and elucidate the detailed dose–response relationships between CRF levels and cancer risk. Studies are also needed to elucidate the causal relationships and mechanistic pathways linking CRF to cancer outcomes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Triglyceride-glucose (TyG) index is an emerging marker of adverse cardiometabolic conditions such as cardiovascular disease and type 2 diabetes. The long-term relevance of TyG index to chronic kidney disease (CKD) is uncertain. We aimed to assess the association of TyG index with CKD risk and its utility in risk prediction in a prospective study. The TyG index was calculated using fasting triglycerides and fasting plasma glucose (FPG) levels measured in 2362 men aged 42–61 years with normal kidney function using the formula: Ln (fasting triglycerides [mg/dL] × FPG [mg/dL]/2). Multivariable adjusted hazard ratios (HRs) (95% confidence intervals, CIs) were estimated for CKD. Correction for within-person variability was made using data from repeat measurements of triglycerides and FPG taken 11 years after baseline. Over a median follow-up duration of 17.5 years, 223 CKD cases were recorded. The age-adjusted regression dilution ratio for the TyG index was 0.54 (95% CI, 0.48–0.60). The risk of CKD increased continuously with increasing TyG index across the range 9.3 to 11.6 (p value for nonlinearity<.001). In analysis adjusted for established risk factors, a unit higher TyG index was associated with an increased risk of CKD (HR 1.59, 95% CI 1.24–2.05). Comparing extreme tertiles of the TyG index, the corresponding adjusted HR (95% CI) for CKD was 1.61 (1.15–2.27). Addition of the TyG index to a CKD risk prediction model containing established risk factors improved risk discrimination and reclassification (p value for difference in −2 log likelihood<.001; NRI=47.66%, p=.014; IDI=0.0164, p<.001). Higher TyG index is associated with an increased risk of CKD and improves the prediction and classification of CKD beyond established risk factors. Using single baseline estimations of the TyG index to investigate its association with CKD risk could considerably under-estimate the true association. [ABSTRACT FROM AUTHOR]

Previous findings on the association between high-density lipoprotein cholesterol (HDL-C) and fracture have yielded inconsistent results and it is unclear if the association varies with age and sex. We sought to evaluate the prospective association between HDL-C levels and fracture risk and assess if the association is modified by age and sex. Circulating HDL-C levels were measured at baseline in a population-based sample of 2,448 men aged 42–61 years. Cox regression was used to estimate hazard ratios (HRs) and 95% CIs. Incident fractures (n = 134) occurred during a median follow-up of 25.7 years. In analysis adjusted for several risk factors, the HR (95% CI) for fractures was 1.00 (0.85–1.20) per 1 standard deviation (SD) increase in HDL-C levels. Comparing the extreme tertiles of HDL-C levels, the corresponding adjusted HR (95% CI) was 0.94 (0.62–1.45). In a meta-analysis of eight cohort studies (including the current study) comprising 74,378 participants and 4,621 fracture cases, the fully-adjusted risk estimate (95% CI) for fracture was 1.03 (0.96–1.10) per 1SD increase in HDL-C levels and 1.05 (0.92–1.20) comparing extreme tertiles of HDL-C. The pooled risk estimate (95% CIs) for fracture per 1SD increase were 1.09 (1.01–1.17) and 0.98 (0.93–1.04) for age groups ≥ 60 and < 60 years, respectively, and the corresponding risks comparing the extreme tertiles of HDL-C levels were 1.21 (1.09–1.33) and 0.95 (0.85–1.07) (p-value for interaction < 0.05). Age may modify the association between HDL-C levels and fracture risk – an increased fracture risk associated with increased HDL-C levels is only evident in older age (≥ 60 years). [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is a global public health burden but is largely preventable. Few studies have reported an association between high levels of cardiorespiratory fitness (CRF) and decreased risk of CKD. However, some relevant aspects of the association, such as the dose-response relationship and the long-term relevance of CRF levels to CKD, have yet to be addressed. We, therefore, aimed to quantify the nature and magnitude of the association between CRF and CKD in a cohort of 2099 men aged 42-61 years with normal kidney function at baseline. CRF was directly measured using a respiratory gas exchange analyzer during cardiopulmonary exercise testing. Hazard ratios (HRs) (95% CIs) were estimated for the incidence of CKD. Correction for within-person variability was made using data from repeat measurements of CRF taken 11 years after baseline. A total of 197 CKD events were recorded during a median follow-up of 25.8 years. The age-adjusted regression dilution ratio for CRF was 0.59 (95% CI: 0.53-0.65). The risk of CKD decreased in a graded fashion with increasing CRF. Comparing extreme tertiles of CRF, the HR (95% CI) for CKD was 0.67 (0.46-0.97) following adjustment for several established and emerging risk factors. The corresponding adjusted HR (95% CI) was 0.51 (0.27-0.96) following correction for within-person variability. In a meta-analysis of five population-based cohort studies (including the current study) comprising 32,447 participants and 4,043 CKD cases, the fully-adjusted risk ratios (95% CIs) for CKD comparing extreme tertiles of baseline and long-term CRF values were 0.58 (0.46-0.73) and 0.40 (0.27-0.59), respectively. Findings from a new prospective study and pooled analysis of previous studies plus the new study indicate that high CRF levels are strongly and independently associated with a reduced risk of CKD and consistent with a linear dose-response relationship. Using single baseline measurements of CRF to investigate the association between CRF and CKD risk could considerably underestimate the true association. [ABSTRACT FROM AUTHOR]

Objectives: Elevated systolic blood pressure (SBP) is associated with an increased risk of cardiovascular disease (CVD) mortality, whereas frequent sauna bathing reduces the risk. Whether frequent sauna bathing mitigates CVD mortality among adults with elevated SBP has not been previously investigated. Design and Setting: We examined the interactions between SBP and frequency of sauna bathing (FSB) with the risk of CVD mortality in a cohort of Caucasian men. Participants: The Kuopio Ischaemic Heart Disease Study cohort comprising of 2,575 men aged 42–61 years at baseline was employed for this prospective study analysis. Measurements: Resting blood pressure was measured using a standardized protocol and sauna bathing habits were assessed by a self-administered questionnaire. Systolic blood pressure was categorized as normal and high (<140 and ≥140 mmHg, respectively) and FSB as low and high (defined as ≤ 2 and 3–7 sessions/week, respectively). Results: A total of 744 CVD deaths were recorded during a median follow-up of 27.8 yr. Comparing high vs normal SBP, the multivariable-adjusted HR (95% CI) for CVD mortality was 1.44 (1.23–1.68). Comparing low vs high FSB, the multivariable-adjusted HR (95% CI) for CVD mortality was 1.24 (1.03–1.51). The associations persisted following mutual adjustment for each exposure. Compared with men with normal SBP-high FSB, high SBP-low FSB was associated with an increased risk of CVD mortality 1.81 (1.39–2.36), with attenuated but persisting evidence of an association for men with high SBP and high FSB 1.52 (1.06–2.16). When SBP was categorized as normal and high (<130 and ≥130 mmHg, respectively), there was no evidence of an association for men with high SBP and high FSB 1.11 (0.77–1.61). Conclusion: There might be an interaction between SBP, sauna bathing and CVD mortality risk in middle-aged and older Caucasian males. Frequent sauna baths may offset the increased risk of CVD mortality in men with high-normal SBP but not elevated SBP. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Few studies have investigated whether higher cardiorespiratory fitness (CRF) or favourable body composition are related to lower arterial stiffness in women. We therefore investigated the associations of CRF, body fat percentage (BF%), fat free mass index (FFMI), and mean arterial pressure (MAP) with arterial stiffness in 146 women aged 16–58 years. CRF was assessed by a maximal exercise test with respiratory gas analysis either on a cycle ergometer or a treadmill. Aortic pulse wave velocity (PWVao), augmentation index (AIx%), and MAP were assessed by a non-invasive oscillometric device and BF% and FFMI by a bioelectrical impedance or DXA device. CRF was inversely associated with PWVao (β = − 0.004, 95% CI − 0.005 to − 0.002) and AIx% (β = − 0.075, 95% CI − 0.102 to − 0.048) and these associations remained similar after adjustment for BF% or MAP, but not after the adjustment for age. FFMI was inversely associated with PWVao (β = − 0.010, 95% CI − 0.019 to − 0.002) and MAP directly associated with PWVao (β = 0.005, 95% CI 0.003 to 0.006) and AIx% (β = 0.092, 95% CI 0.069 to 0.116) and the associations with PWVao also remained after further adjustments for BF% and age. In conclusion, a higher FFMI and a lower MAP were independently associated with lower arterial stiffness. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Handgrip strength (HGS), a measure of muscular strength, might be a risk indicator for cognitive functioning, but the evidence is not consistent. Using a new prospective study and meta-analysis of published observational cohort studies, we aimed to evaluate the prospective associations of HGS with poor cognitive outcomes including cognitive impairment, dementia and Alzheimer's disease (AD). Handgrip strength, measured using a Martin-Balloon-Vigorimeter, was assessed at baseline in a population-based sample of 852 men and women with good cognitive function in the Kuopio Ischemic Heart Disease cohort. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated for cognitive outcomes. Relevant published studies were sought in MEDLINE, Embase and Web of Science from inception until October 2021 and pooled using random effects meta-analysis. During a median follow-up of 16.6 years, 229 dementia cases were recorded. Comparing extreme tertiles of HGS, the multivariable adjusted HR (95% CI) for dementia, AD and vascular dementia was 0.77 (0.55–1.07), 0.75 (0.52–1.10) and 0.49 (0.16–1.48), respectively. In a meta-analysis of 16 population-based prospective cohort studies (including the current study) comprising 180,920 participants, the pooled multivariable adjusted relative risks (95% CIs) comparing the top vs bottom thirds of HGS levels were as follows: 0.58 (0.52–0.65) for cognitive impairment; 0.37 (0.07–1.85) for cognitive decline; 0.73 (0.62–0.86) for dementia; 0.68 (0.53–0.87) for AD; and 0.48 (0.32–0.73) for vascular dementia. GRADE quality of evidence ranged from low to very low. Meta-analysis of aggregate prospective data suggests that HGS may be a risk indicator for poor cognitive outcomes such as cognitive impairment, dementia and AD. Systematic review registration: PROSPERO 2021: CRD42021237750. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The beneficial effects of regular physical activity in promoting health and preventing chronic diseases are well documented. The relationship between regular physical activity and the risk of pneumonia is uncertain. We aimed to evaluate the magnitude and specificity of the prospective association between regular physical activity and the risk of pneumonia using a systematic review and meta-analysis of published observational cohort studies in general populations. Relevant studies with at least 1 year of follow-up were sought from inception until 15 September 2021 in MEDLINE, Embase, Web of Science, and manual search of relevant articles. Relative risks (RRs) with 95% confidence intervals (CIs) for the maximum versus the minimal amount of physical activity groups were pooled using fixed effects meta-analysis. The quality of the evidence was evaluated using the GRADE tool. A total of 10 prospective cohort studies comprising 1,044,492 participants and 7681 events were eligible. The pooled multivariable-adjusted RR (95% CI) of pneumonia comparing the most versus the least physically active groups was 0.69 (0.64–0.74). This association was significantly modified by type of outcome (p-value for meta-regression =.002): 0.82 (0.72–0.93) for incident pneumonia and 0.64 (0.59–0.70) for pneumonia-related mortality. There was no evidence of heterogeneity and publication bias. The GRADE quality of the evidence ranged from moderate to low. Aggregate analysis of 10 cohort studies shows that regular physical activity is associated with lowered risk of incident pneumonia and pneumonia-related mortality in the general population. Physical activity types that are attractive to and feasible for high-risk populations need to be identified and encouraged. Systematic review registration: PROSPERO 2021: CRD42021277514. [ABSTRACT FROM AUTHOR]

There is limited information on the association of body mass index (BMI) with left ventricular (LV) remodeling corresponding to severity of reduced lung function in patients with chronic obstructive pulmonary disease (COPD). Therefore, we investigated whether BMI is associated with cardiac atrial and ventricular dimensions according to severity of lung functional impairment in Chinese COPD elderly. A total of 563 hospitalized COPD patients with lung function impairment and 184 patients with non-COPD (aged 65–92 years) were collected retrospectively in a cross-sectional study in a university affiliated tertiary hospital in China. BMI and cardiac echocardiographic parameters were compared according to severity of lung functional impairment in COPD patients. BMI was 22.9 ± 3.9 kg/m2 in COPD patients, 24.0 ± 4.1 kg/m2 in non-COPD patients respectively. Reduced BMI, LV mass index, LV wall thickness and left atrial diameter, and dilated right ventricle (RV) existed in COPD patients with severe lung dysfunction as compared the COPD patients with mild to moderate lung functional reduction and non-COPD patients (P < 0.05), while there were no differences in BMI and echocardiographic parameters between the COPD patients with mild to moderate lung functional decline and non-COPD patients (P > 0.05). Logistic regression analysis showed that low BMI (BMI < 18.5 kg/m2) was correlated with reduced LV mass and wall thickness, dilated RV and reduced lung function in the COPD patients with severe lung dysfunction. In conclusion, this study demonstrates that lower BMI is associated not only with dilated RV and impaired pulmonary function, but also it is related to reduced LV mass in Asian COPD elderly with severe lung dysfunction. [ABSTRACT FROM AUTHOR]

Evolving debate suggests that handgrip strength, a measure of muscular strength, might be associated with the risk of fractures; however, the evidence is conflicting. We aimed to assess the association of handgrip strength with the risk of fracture in the general population. Handgrip strength, measured using a dynamometer, was assessed at baseline in a population-based sample of 853 men and women aged 61–73 years in the Kuopio Ischemic Heart Disease prospective cohort. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated for incident fractures. Incident fractures (hip, humeral, or wrist) (n = 159) occurred during a median follow-up of 16.7 years. Comparing extreme tertiles of handgrip strength, the age- and sex-adjusted hazard ratio (95% CI) for fractures was 0.80 (0.55–1.18). The association remained similar on further adjustment for other potential confounders: HR (95% CI) of 0.82 (0.55–1.21). In a meta-analysis of 19 population-based prospective cohort studies (including the current study) comprising 220,757 participants and 9199 fractures (including 1302 hip fractures), the fully adjusted relative risk (RR) (95% confidence interval, CI) for incident fractures was 0.70 (0.61–0.80) comparing the top versus bottom thirds of handgrip strength. The association remained significant after trim-and-fill correction for publication bias. The corresponding RR (95% CI) for hip fractures (9 studies) was 0.61 (0.54–0.70). Handgrip was only modestly associated with fracture risk in the primary analysis, which may be driven by the low event rate. Pooled prospective cohort evidence suggests that elevated handgrip strength is associated with reduced future fracture risk. [ABSTRACT FROM AUTHOR]

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 [ABSTRACT FROM AUTHOR]

Amiodarone, one of the most widely prescribed antiarrhythmic drugs to treat both ventricular and supraventricular arrhythmias, has been identified as a candidate drug for use against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We present the rationale of using amiodarone in the COVID-19 scenario, as well as whether or not amiodarone administration represents a potential strategy to prevent SARS-CoV-2 infection, rather than simply used to treat patients already symptomatic and/or with severe coronavirus disease 2019 (COVID-19), based on current evidence. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Emerging evidence suggests that sauna bathing is associated with reduced risk of cardiovascular and all-cause mortality events. However, the biochemical pathways by which sauna bathing might confer its effects on cardiovascular function are not certain. We aimed to study the acute effects of Finnish sauna bathing on various blood-based cardiovascular biomarkers. The study included 102 non-naive sauna users (54% male) with mean age of 51.9 years, who had at least one cardiovascular risk factor. Participants underwent a 30-min single sauna session (mean temperature, 73 °C). Biochemical profiling was conducted before, immediately after sauna and 30-min post-sauna. Overall median N-terminal pro-B-type natriuretic peptide (NT-proBNP) level (n = 20 participants) was 46.0 ng/L before sauna exposure, which increased to 50.5 ng/l immediately after sauna (median change, + 12.00%; p < 0.001) and remained persistent at 30-min post-sauna (median change from pre-sauna to post-30-min sauna, + 13.93%; p < 0.001). The changes were more evident in males compared with females. There were no significant changes in overall levels of high sensitivity C-reactive protein, creatine kinase, high sensitivity troponin I, and creatine kinase-MBm. However, levels of creatine kinase increased in males (median change immediately after sauna, + 2.99%; p = 0.024). Levels of NT-proBNP increased after sauna exposure. The increase in levels of creatine kinase was more evident in males. Long-term interventional studies are warranted to evaluate if these biomarkers are involved in pathways underlying the associations of sauna bathing with cardiovascular outcomes. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the associations of peak oxygen uptake ([Formula: see text]) and [Formula: see text] at ventilatory threshold ([Formula: see text] at VT) with arterial stiffness in adolescents.Methods: The participants were 55 adolescents (36 girls, 19 boys) aged 16-19 years. Aortic pulse wave velocity (PWVao) and augmentation index (AIx%) were measured by non-invasive oscillometric device from right brachial artery level. [Formula: see text] was directly measured during a maximal ramp test on a cycle ergometer. [Formula: see text] at VT was determined using the equivalents for ventilation ([Formula: see text]/[Formula: see text] and [Formula: see text]/[Formula: see text]). [Formula: see text] and [Formula: see text] at VT were normalised for body mass (BM) and lean mass (LM). Data were analysed using linear regression analyses and analysis of covariance adjusted for age and sex.Results: [Formula: see text] normalised for BM (β = - 0.445, 95% CI - 0.783 to - 0.107) and [Formula: see text] normalised for LM (β = - 0.386, 95% CI - 0.667 to - 0.106) were inversely associated with PWVao. A higher [Formula: see text] at VT normalised for BM (β = - 0.366, 95% CI - 0.646 to - 0.087) and LM (β = - 0.321, 95% CI - 0.578 to - 0.064) was associated with lower PWVao. Adolescents in the lowest third of [Formula: see text] by LM (6.6 vs. 6.1 m/s, Cohen's d = 0.33) and [Formula: see text] at VT by LM (6.6 vs. 6.0 m/s, Cohen's d = 0.33) had a higher PWVao than those in the highest third of [Formula: see text] or [Formula: see text] at VT by LM.Conclusions: Higher [Formula: see text] and [Formula: see text] at VT by BM and LM were related to lower arterial stiffness in adolescents. Normalising [Formula: see text] and [Formula: see text] at VT for LM would provide the most appropriate measure of cardiorespiratory fitness in relation to arterial stiffness. [ABSTRACT FROM AUTHOR]

Purpose: The Mediterranean diet is associated with decreased morbidity and mortality from various chronic diseases. Adherence to a Mediterranean-style diet has been suggested to have protective effects on bone health and decreases the incidence of bone fractures, but the evidence is not clear. We conducted a systematic review and meta-analysis of available observational studies to quantify the association between adherence to a Mediterranean-style diet, as assessed by the Mediterranean Diet Score (MDS), and the risk of fractures in the general population.Methods: Relevant studies were identified in a literature search of MEDLINE, EMBASE, Web of Science, and reference lists of relevant studies to October 2016. Relative risks (RRS) with 95% confidence intervals (CIs) were aggregated using random-effects models.Results: Five observational studies with data on 353,076 non-overlapping participants and 33,576 total fractures (including 6,881 hip fractures) were included. The pooled fully adjusted RR (95% CI) for hip fractures per 2-point increment in adherence to the MDS was 0.82 (0.71-0.96). Adherence to the MDS was not associated with the risk of any or total fractures based on pooled analysis of only two studies.Conclusion: Limited observational evidence supports a beneficial effect of adherence to a Mediterranean-style diet on the incidence of hip fractures. Well-designed intervention studies are needed to elucidate the relationship between adherence to a Mediterranean-style diet and the risk of adverse bone health outcomes such as fractures. [ABSTRACT FROM AUTHOR]

Serum gamma-glutamyltransferase (GGT) has been linked with the risk of adverse health outcomes. We aimed to assess the prospective association of GGT activity with pneumonia risk. Serum GGT was measured at baseline in 2400 middle-aged men. Within-person variability in GGT values was corrected for using data from repeat measurements. During a median follow-up of 25.3 years, 409 pneumonia cases were recorded. The age-adjusted regression dilution ratio of GGT was 0.68 (95% CI 0.63-0.73). Gamma-glutamyltransferase was approximately log-linearly associated with pneumonia risk. In analysis adjusted for several major pneumonia risk factors, the hazard ratio (95% CI) for pneumonia per 1 standard deviation increase in GGT was 1.14 (1.02-1.28). The association was however attenuated on additional adjustment for high-sensitivity C-reactive protein (hsCRP) 1.08 (0.96-1.22). There is an approximately log-linear positive association between GGT activity and future risk of pneumonia in a middle-aged male population, which is partly dependent on hsCRP. [ABSTRACT FROM AUTHOR]

Sauna bathing has been linked with numerous health benefits. Sauna bathing may reduce the risk of respiratory diseases; however, no prospective evidence exists to support this hypothesis. We aimed to assess the association of frequency of sauna bathing with risk of respiratory diseases (defined as chronic obstructive pulmonary disease, asthma, or pneumonia). Baseline sauna bathing habits were assessed in a prospective cohort of 1935 Caucasian men aged 42-61 years. During a median follow-up of 25.6 years, 379 hospital diagnosed incident cases of respiratory diseases were recorded. In adjustment for several major risk factors for respiratory conditions and other potential confounders, the hazard ratios (HRs) 95% confidence intervals (CIs) of respiratory diseases were 0.73 (0.58-0.92) and 0.59 (0.37-0.94) for participants who had 2-3 and ≥4 sauna sessions per week respectively compared with participants who had ≤1 sauna session per week. The multivariate adjusted HR (95% CI) for pneumonia was 0.72 (0.57-0.90) and 0.63 (0.39-1.00) for participants who had 2-3 and ≥4 sauna sessions per week respectively. Frequent sauna baths may be associated with a reduced risk of acute and chronic respiratory conditions in a middle-aged male Caucasian population. [ABSTRACT FROM AUTHOR]

The renin-angiotensin system (RAS) represents an important target of antihypertensive medications. Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB), which are widely-used RAS inhibiting drugs, have been suggested to have beneficial effects on bone tissue. We aimed to assess the associations of use of ACEIs and/or ARBs with the risk of fractures using a population-based prospective cohort and a meta-analysis of published prospective cohort studies. Information on antihypertensive medication use (including both ACEIs and ARBs) were assessed in 1743 men and women of the Kuopio Ischemic Heart Disease prospective cohort study. Hazard ratios (HRs) [95% confidence intervals (CI)] of ACEIs or ARBs use with incident fractures were calculated. A total of 203 composite (hip, humeral, and wrist) fractures occurred during a median follow-up of 14.8 years. In multivariate adjusted analysis, the HR for composite fractures comparing users of ACEIs or ARBs with non-users was 1.00 (0.59-1.69). The corresponding adjusted HR for hip fractures comparing users versus non-users of ACEIs or ARBs was 0.89 (0.32-2.47). Including the current study, a total of 11 observational cohort studies involving 3526,319 participants and >323,355 fractures were included in a meta-analysis. Comparing ACEI users with non-users and ARB users with non-users, the HRs for composite fractures were 1.09 (0.89-1.33) and 0.87 (0.76-1.01) respectively. The corresponding HRs for hip fractures were 0.91 (0.86-0.95) and 0.80 (0.75-0.85) respectively. Use of RAS inhibitors was not associated with long-term risk of composite fractures in both primary and pooled analyses. Pooled evidence however suggests a beneficial effect of RAS blockers on hip fracture risk. [ABSTRACT FROM AUTHOR]

Cardiorespiratory fitness (CRF), an index of cardiac and respiratory functioning, is strongly associated with a reduced risk of adverse health outcomes. We aimed to assess the prospective association of CRF with the risk of respiratory diseases (defined as chronic obstructive pulmonary disease, pneumonia, or asthma). Cardiorespiratory fitness, as measured by maximal oxygen uptake, was assessed in 1974 middle-aged men. During a median follow-up of 25.7 years, 382 hospital diagnosed respiratory diseases were recorded. Cardiorespiratory fitness was linearly associated with risk of respiratory diseases. In analysis adjusted for several established and potential risk factors, the hazard ratio (HR) (95% CI) for respiratory diseases was 0.63 (0.45-0.88), when comparing extreme quartiles of CRF levels. The corresponding multivariate adjusted HR (95% CI) for pneumonia was 0.67 (0.48-0.95). Our findings indicate a graded inverse and independent association between CRF and the future risk of respiratory diseases in a general male Caucasian population. [ABSTRACT FROM AUTHOR]

Evolving debate suggests that C-reactive protein (CRP) might be associated with the development of venous thromboembolism (VTE); however, the evidence is conflicting. We aimed to assess the prospective association of CRP with VTE risk. C-reactive protein was measured in serum samples at baseline from 2420 men aged 42-61 years, from the Kuopio Ischemic Heart Disease study. Within-person variability in CRP levels was corrected for using repeat measurements of CRP taken 11 years after baseline. Incident VTE events (n = 119) were recorded during a median follow-up of 24.7 years. The age-adjusted regression dilution ratio for log CRP was 0.57 [95% confidence interval (CIs): 0.51-0.64]. In age-adjusted Cox regression analysis, the hazard ratio (95% CIs) for VTE per 1 standard deviation (SD) increase in log baseline CRP was 1.17 (0.98-1.40). Further adjustment for several established and emerging risk factors did not alter the association. In a meta-analysis of nine population-based studies (including the current study) comprising 81,625 participants and 2225 VTE cases, the fully-adjusted risk estimate for VTE was 1.14 (1.08-1.19) per SD increase in log baseline CRP. In a pooled dose-response analysis, a linear association between CRP and VTE risk was suggested ( P for nonlinearity = 0.272). The pooled risk estimate for VTE per 5 mg/l increment in CRP levels was 1.23 (1.09-1.38). C-reactive protein was only modestly associated with VTE risk in the primary analysis. Pooled evidence, however, suggests that elevated CRP is associated with greater VTE risk, consistent with a linear dose-response relationship. [ABSTRACT FROM AUTHOR]

Magnesium, which is an essential trace element that plays a key role in several cellular processes, is a major component of bone; however, its relationship with risk of major bone fractures is uncertain. We aimed to investigate the association of baseline serum magnesium concentrations with risk of incident fractures. We analyzed data on 2245 men aged 42-61 years in the Kuopio Ischemic Heart Disease prospective cohort study, with the assessment of serum magnesium measurements and dietary intakes made at baseline. Hazard ratios [95% confidence intervals (CI)] for incident total (femoral, humeral, and forearm) and femoral fractures were assessed. During a median follow-up of 25.6 years, 123 total fractures were recorded. Serum magnesium was non-linearly associated with risk of total fractures. In age-adjusted Cox regression analysis, the hazard ratio (HR) (95% CIs) for total fractures in a comparison of the bottom quartile versus top quartile of magnesium concentrations was 2.10 (1.30-3.41), which persisted on adjustment for several established risk factors 1.99 (1.23-3.24). The association remained consistent on further adjustment for renal function, socioeconomic status, total energy intake, and several trace elements 1.80 (1.10-2.94). The corresponding adjusted HRs for femoral fractures were 2.56 (1.38-4.76), 2.43 (1.30-4.53) and 2.13 (1.13-3.99) respectively. There was no evidence of an association of dietary magnesium intake with risk of any fractures. In middle-aged Caucasian men, low serum magnesium is strongly and independently associated with an increased risk of fractures. Further research is needed to assess the potential relevance of serum magnesium in the prevention of fractures. [ABSTRACT FROM AUTHOR]

Lipoprotein(a) [Lp(a)]-an established risk factor for vascular disease, has been suggested to be associated with risk of dementia, however no prospective evidence exists to support this finding. We aimed to assess the association of Lp(a) with dementia risk. Lp(a) concentration was assessed at baseline in a prospective cohort of 2532 men aged 42-61 years. During a median follow-up of 24.9 years, 228 new cases of dementia were recorded. Lp(a) was approximately log-linearly associated with dementia risk. In age-adjusted analysis, the hazard ratio for dementia in a comparison of extreme quartiles of Lp(a) levels was 0.68 (95 % CI: 0.47-0.99), which persisted after adjustment for several physical measures, history of coronary heart disease, smoking status, history of diabetes, serum lipids, alcohol consumption, and socio-economic status 0.68 (0.46-0.99). Lp(a) is protective of future dementia risk in a middle-aged male Caucasian population. Further research is needed replicate these findings. [ABSTRACT FROM AUTHOR]

Serum magnesium is an essential intracellular cation involved in processes that regulate cardiovascular function and has been linked to the risk of several cardiovascular disease outcomes. We aimed to investigate the association of serum magnesium concentrations with risk of incident heart failure (HF). We studied 2181 middle-aged men without prevalent HF (aged 42-61 years) enrolled in the finnish Kuopio Ischemic Heart Disease prospective cohort study with serum magnesium measurements made at baseline. Hazard ratios (95 % confidence intervals [CI]) for HF were assessed. During a median follow-up of 24.8 years, 278 HF events occurred. Baseline serum magnesium was weakly and inversely associated with several clinical markers and was continuously associated with risk of HF. The age-adjusted HR (95 % CIs) for HF per 1 standard deviation (SD) higher serum magnesium levels was 0.86 (0.76-0.97). The HR (95 % CIs) was 0.87 (0.76-0.98) after controlling for measures of adiposity, socio-economic variables, medical history, blood pressure, renal function, alcohol consumption, and lipids. These findings remained consistent in analyses accounting for incident coronary heart disease. The results were comparable across several clinically relevant subgroups and analyses with atrial fibrillation as a competing risk yielded similar results. Serum magnesium was continuously, inversely and independently associated with future risk of HF. Further research is needed to assess any potential relevance of serum magnesium in HF prevention. [ABSTRACT FROM AUTHOR]

We aimed to investigate whether frequency of sauna bathing is associated with the levels of serum C-reactive protein. C-reactive protein is a leading blood marker of systemic inflammation. The study consisted of 2084 men (42-60 years) without acute or chronic inflammation. A total of 533 (25.6%), 1368 (65.6%), and 183 (8.8%) participants reported having a sauna bath once a week, 2-3 times, and 4-7 times per week; mean serum C-reactive protein levels were 2.41 (standard deviation 2.91), 2.00 (2.41), 1.65 (1.63) mmol/L, respectively. In a multivariable analysis adjusted for baseline age, body mass index, systolic blood pressure, smoking, type 2 diabetes, previous myocardial infarction, and serum low density lipoprotein cholesterol, alcohol consumption and physical activity, there was a significant inverse association between the frequency of sauna bathing and the level of C-reactive protein. Further studies are warranted to investigate the relationship between sauna bathing and systemic inflammation. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: In nondiabetic individuals, low values of fasting plasma glucose (FPG) have been associated with an increased risk of cardiovascular events. Identification of the potential mechanisms behind this association could help to elucidate the relationship between glycaemia and cardiovascular disease. We aimed to determine the association between FPG and ventricular arrhythmias. Methods: FPG and other cardiometabolic risk factors were measured in a population-based cohort of 2,482 men without a known history of type 2 diabetes mellitus at baseline. Associations between FPG levels and incident cases of ventricular arrhythmias (ventricular tachycardia or fibrillation events ascertained using the National Hospital Discharge Register) were estimated using Cox regression analysis adjusted for potential confounders. Results: During a median follow-up of 23.3 (interquartile range 18.5-25.3) years, 74 (2.9%) incident events were recorded. In a multivariable analysis adjusted for age, systolic BP, smoking status, LDL- and HDL-cholesterol, and C-reactive protein, the HR for ventricular arrhythmia per 1 mmol/l higher baseline FPG was 0.58 (95% CI 0.34, 0.98); this estimate did not materially change after further adjustment for BMI, alcohol consumption, triacylglycerols and history of ischaemic heart disease (0.50 [95% CI 0.28, 0.89]). Conclusions/interpretation: In this nondiabetic male population, FPG was inversely associated with incident risk of ventricular arrhythmias. While our results could help clarify the relationship between low glucose levels and cardiovascular risk, further studies are required to confirm these findings in other populations. [ABSTRACT FROM AUTHOR]

Serum total osteocalcin, a marker of bone formation, may regulate glucose metabolism and influence the risk of developing adverse metabolic outcomes. We conducted a systematic review and meta-analysis of published observational evidence, to assess and quantify the associations of serum total osteocalcin with type 2 diabetes and intermediate metabolic phenotypes [e.g., metabolic syndrome (MetS)]. Relevant studies were identified in a literature search of MEDLINE, EMBASE, Web of Science, and reference lists of relevant studies to May 2015. Mean differences and risk estimates (odds ratios or relative risks) with 95 % CIs were aggregated using random-effects models. Fifty-two observational (38 cross-sectional, eight cohort, five case-control, and one both cross-sectional and cohort) studies with data on 46,998 non-overlapping participants were included. Baseline serum total osteocalcin levels were significantly lower in type 2 diabetes compared with non-type 2 diabetes and in MetS compared with non-MetS in pooled analysis of cross-sectional evidence. Pooled risk estimates (95 % CIs) for type 2 diabetes in a comparison of extreme fourths of total osteocalcin levels were 0.23 (95 % CI 0.12, 0.46) and 0.89 (95 % CI 0.78, 1.01) for cross-sectional and cohort studies respectively. The corresponding estimate was 0.39 (0.27, 0.56) for MetS from cross-sectional evidence. In both cross-sectional and cohort studies, a unit increase in serum total osteocalcin levels was associated with a significant mean increase in HOMA-B and mean reduction in HbA1c; with significant mean reductions in fasting plasma glucose levels, HOMA-IR, and body mass index in only cross-sectional studies. Available evidence-mainly from cross-sectional studies, supports inverse associations of serum total osteocalcin with risk of adverse metabolic outcomes. Large-scale prospective studies are needed to establish whether serum total osteocalcin may be useful in the prevention of adverse metabolic outcomes such as type 2 diabetes. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Serum albumin concentrations may be associated with future risk of type 2 diabetes, but the epidemiological evidence is limited and uncertain. We prospectively assessed the association between baseline values of serum albumin and incident type 2 diabetes risk in the Kuopio Ischaemic Heart Disease population-based cohort study. Methods: We analysed the data of 1,785 men aged 42-61 years with no known history of diabetes at baseline. Participants' serum albumin concentrations were measured at baseline. HRs and 95% CIs for type 2 diabetes events were subsequently assessed. Results: During a mean follow-up of 20.4 years, 382 participants developed diabetes. Serum albumin concentrations were weakly correlated with several established risk factors for diabetes. Serum albumin was approximately linearly associated with type 2 diabetes risk. In analyses adjusted for several conventional risk factors, the HR for type 2 diabetes per 1 SD increase in serum albumin was 1.15 (95% CI 1.03, 1.28; p = 0.016), which persisted after further adjustment for triacylglycerol, C-reactive protein, γ-glutamyltransferase, estimated glomerular filtration rate and total energy intake (HR 1.15; 95% CI 1.02, 1.29; p = 0.018). The findings were generally consistent across several clinical subgroups. Addition of information on serum albumin to a diabetes risk prediction model containing conventional risk factors led to no significant change in C-index (0.0126; 95% CI −0.0055, 0.0306; p = 0.17). Conclusions/interpretation: A near linear, positive and independent association was found between serum albumin and type 2 diabetes, but this did not improve event discrimination. Further work is warranted to evaluate the causal relevance of these findings. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine whether serum fructosamine is associated with the risk of type 2 diabetes mellitus (T2DM) in a cohort of middle-age Finnish men. Fructosamine and other cardiometabolic risk factors were measured in a sample of 2,520 subjects from the population-based Kuopio Ischemic Heart Disease study. Associations between baseline fructosamine levels and risk of T2DM involved Cox-regression analyses, progressively adjusted for potential confounders and mediators. Mean baseline age and fructosamine levels were 53 years and 267 µmol/L, respectively. During a median follow-up of 23 years (interquartile range 18-25 years), 153 (6.1 %) new cases of T2DM were recorded. We observed an approximately 'J-shaped' association between fructosamine values and T2DM risk, with a nadir at about 250 µmol/L. In subjects with fructosamine ≥250 µmol/L, the hazard ratios per 1 standard deviation (28 µmol/L) higher fructosamine levels resulted 1.20 (95 % CI 1.00-1.44; p = 0.046) in a model adjusted for age, body mass index, systolic blood pressure, serum high-density lipoprotein-cholesterol and family history T2DM. This association did not materially change upon further adjustment for C-reactive protein, physical activity, serum triglyceride and insulin resistance. However, no association was found when adjusting for baseline fasting plasma glucose (FPG). In this cohort of middle-age Finnish men, we found a 'J-shaped' relationship between fructosamine and risk of T2DM, with a higher risk in subjects with baseline levels of fructosamine ≥250 µmol/L. Such an increased risk, however, was not independent from baseline FPG levels. [ABSTRACT FROM AUTHOR]

Whether glucose and insulin are differently associated with the risk of coronary heart disease (CHD) mortality is unclear. We aimed to estimate the association between insulin resistance (estimated by the homeostasis model assessment for insulin resistance, HOMA-IR), fasting serum insulin (FI) and fasting plasma glucose (FPG) with incident CHD mortality in a prospective study including middle-aged nondiabetic Finnish men. During an average follow-up of 20 years, 273 (11 %) CHD deaths occurred. In a multivariable Cox regression analysis adjusted for age, body mass index, systolic blood pressure, serum LDL-cholesterol, cigarette smoking, history of CHD, alcohol consumption, blood leukocytes and plasma fibrinogen, the hazard ratios (HRs) for CHD mortality comparing top versus bottom quartiles were as follows: 1.69 (95 % CI: 1.15-2.48; p = 0.008) for HOMA-IR; 1.59 (1.09-2.32; p = 0.016) for FI; and 1.26 (0.90-1.76; p = 0.173) for FPG. These findings suggest that IR and FI, but not FPG, are independent risk factors for CHD mortality. Further studies could help clarify these results in terms of screening and risk stratification, causality of the associations, and therapeutical implications. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: We validated the metabolic syndrome (MetS) score by confirmatory factor analysis (CFA) in children, middle-aged men, and older women and men and by investigating the relationships of the MetS score to incident type 2 diabetes, myocardial infarction, and cardiovascular and overall death in middle-aged men. Methods: We assessed the core features of MetS, calculated the MetS score using z scores for waist circumference, insulin, glucose, triacylglycerols, HDL-cholesterol and blood pressure, and carried out CFA to investigate whether MetS represents a single entity in population samples of 491 children, 1,900 middle-aged men, 614 older women and 555 older men from Finland. We also followed-up incident type 2 diabetes for 11 years and other outcomes for 17-18 years in middle-aged men. Results: We carried out second-order CFAs in which the MetS was represented by a second-order latent variable underlying four latent variables characterised by abdominal obesity, insulin resistance, dyslipidaemia and raised blood pressure in different age groups. These second-order factors and factors derived from first-order CFA using previously proposed models were strongly associated with a composite MetS score in all age groups ( r = 0.84-0.94) and similarly predicted type 2 diabetes, cardiovascular outcomes and mortality in middle-aged men. The risk of type 2 diabetes, myocardial infarction, cardiovascular death and overall death increased 3.67-, 1.38-, 1.56- and 1.44-fold, respectively, for a 1 SD increase in the MetS score. Conclusions: The MetS can be described as a single entity in all age groups. The MetS score is a valid tool for research evaluating cardiometabolic risk in different age groups. Further research is needed to define cut-off points for risk estimation in clinical practice. [ABSTRACT FROM AUTHOR]

High blood pressure and overweight are risk factors for stroke. The aim of the present study was to examine the association between alcohol consumption and the risk of stroke according to the level of blood pressure and body weight. This study is a population-based sample of men with an average follow-up of 14.9 years from eastern Finland. A total of 2,599 men with no history of stroke at baseline participated. During the follow-up period, 224 strokes occurred, of which 181 were ischemic strokes. After adjustment for age, year of examination, socioeconomic status, serum LDL cholesterol, body mass index, smoking and energy expenditure of physical activity (kcal/day), there was a significant trend of an increased risk for any and ischemic stroke among hypertensive men. Hypertensive (blood pressure of over 140/90 mm Hg) men, who did not consume alcohol had a 1.72-fold (95 % CI 1.12-2.66; p = 0.014) relative risk (RR) for any stroke and a 1.90-fold (95 % CI 1.15-3.13; p = 0.012) RR for ischemic stroke. Among hypertensive men who consumed alcohol RR was 1.86-fold (95 % CI 1.20-2.89; p = 0.005) for any stroke and 2.02-fold (95 % CI 1.21-3.35; p = 0.007) for ischemic stroke. Men who did not consume alcohol with elevated BMI (≥26.4 kg/m) had a 1.63-fold RR (95 % CI 1.11-2.40; p = 0.013) for any stroke and a 1.33-fold RR (95 % CI 0.87-2.04; p = 0.199) for ischemic stroke after adjusting for risk factors. Overweight men (≥26.4 kg/m) who consumed alcohol had a 1.73-fold RR (95 % CI 1.18-2.54; p = 0.005) for any stroke and a 1.71-fold RR (95 % CI 1.14-2.57; p = 0.010) for ischemic stroke after being adjusted for risk factors. In conclusion, this population-based prospective study shows that hypertensive and overweight men who consumed alcohol had an increased risk for stroke. [ABSTRACT FROM AUTHOR]

Systemic inflammation, oxidative stress, and atrial fibrosis are identified as the main mechanisms for atrial fibrillation (AF). Antioxidant micronutrients may have antiarrhythmic benefit in humans. We studied whether plasma carotenoids are related to the risk of AF in elderly subjects. The study population consisted of 1,847 Finnish subjects (620 women and 1,227 men) aged 61-82 years from the Kuopio Ischaemic Heart Disease Risk Factor study cohort. Plasma concentrations of carotenoids were measured by high-performance liquid chromatography. The multivariable-adjusted hazard ratios (HRs) and 95 % confidence intervals (CIs) of plasma carotenoids were analyzed using the Cox proportional hazard's model. During a median follow-up of 2.8 years a total of 105 subjects developed incident AF. The HRs of AF among subjects with levels in the highest through the lowest tertile after adjustment for age, examination year, gender, systolic blood pressure, smoking, alcohol consumption, education, diabetes, use of antihypertensive medication, congestive heart failure, recurrent AF, prevalent coronary heart disease and baseline prevalence of myocardial infarction were 1.70 (95 % CI: 1.01-2.86, p = 0.047) for lutein, 1.99 (95 % CI: 1.14-3.48, p = 0.016) for zeaxanthin. Risk of AF was borderline significant for β-carotene (HR = 1.69, 95 % CI: 1.00-2.87, p = 0.050). Results remained unchanged, when season was added to the multivariable model. Lycopene, β-cryptoxanthin, α-carotene and total carotenoids were not associated with the risk of AF. Results of the present study suggest that low plasma concentrations of lutein and zeaxanthin were associated with an increased risk of AF in elderly population. [ABSTRACT FROM AUTHOR]

Physical fitness and activity status are well-documented risk predictors of cardiovascular and total mortality. The purpose of this article is to show how cardiorespiratory fitness predicts atherosclerotic cardiovascular diseases. Measurement of maximum oxygen consumption (VO2max), defined with or without ventilatory gas analysis during exercise testing, can provide a good estimate for cardiorespiratory fitness, which is an independent marker of the early disease. Low VO2max has been shown to be comparable with elevated systolic blood pressure, smoking, obesity, and diabetes in importance as a risk factor for mortality, as well as a predictor of coronary artery disease and the progression of atherosclerosis. Cardiorespiratory fitness represents one of the strongest predictors of mortality, emphasizing the importance of exercise testing in everyday clinical practice. In the future, well-defined, disease-specific training programs for exercise prescriptions in different risk groups are needed as a clinical tool. [ABSTRACT FROM AUTHOR]

There is limited information on the association of overweight and obesity with cardiac remodeling in elderly population. Therefore, we investigated whether overweight and obesity are associated with cardiac geometric structures and function in Chinese elderly. A total of 1183 hospitalized patients (aged 65–99 years) with primary hypertension were collected retrospectively in a cross-sectional study, and divided into underweight, normal weight, overweight and obesity patient groups according to their body mass index (BMI). Cardiac echocardiographic parameters were compared between the groups. BMI was 17.2 ± 1.2, 21.4 ± 1.2, 25.1 ± 1.2, 30.2 ± 2.6 kg/m2 in underweight, normal weight, overweight and obesity groups respectively. Aortic and left atrial diameter, interventricular septal and left ventricular (LV) posterior wall thickness, LV end-diastolic and end-systolic diameter, and indexed LV mass, and prevalence of E/A reversal were higher, while LV ejection fraction and fractional shortening were lower in elderly with overweight or obesity, as compared with whose with underweight or normal weight separately (All P < 0.05). However, multivariable regression analysis showed that overweight and obesity are independently related to increased LV wall thickness, end-diastolic diameter and mass (All P < 0.05). In conclusions, this study demonstrates that overweight and obesity are associated with increased LV wall thickness, end-diastolic diameter and mass in Asian elderly. [ABSTRACT FROM AUTHOR]