Urine cotinine versus self-reported smoking and the risk of chronic kidney disease.

BACKGROUND AND HYPOTHESIS: Evidence on the role of smoking in the development of chronic kidney disease (CKD) has mostly relied on self-reported smoking status. We aimed to compare the associations of smoking status as assessed by self-reports and urine cotinine with CKD risk. METHODS: Using the PREVEND prospective study, smoking status was assessed at baseline using self-reports and urine cotinine in 4333 participants (mean age, 52 years) without a history of CKD at baseline. Participants were classified as never, former, light current and heavy current smokers according to self-reports and comparable cut-offs for urine cotinine. Hazard ratios (HRs) with 95% CIs were estimated for CKD. RESULTS: The percentages of self-reported and cotinine-assessed current smokers were 27.5% and 24.0%, respectively. During a median follow-up of 7.0 years, 593 cases of CKD were recorded. In analyses adjusted for established risk factors, the HRs (95% CI) of CKD for self-reported former, light current, and heavy current smokers compared with never smokers were 1.17 (0.95-1.44), 1.48 (1.10-2.00), and 1.48 (1.14-1.93), respectively. On further adjustment for urinary albumin excretion (UAE), the HRs (95% CI) were 1.07 (0.87-1.32), 1.26 (0.93-1.70), and 1.20 (0.93-1.57), respectively. For urine cotinine-assessed smoking status, the corresponding HRs (95% CI) were 0.81 (0.52-1.25), 1.17 (0.92-1.49), and 1.32 (1.02-1.71), respectively, in analyses adjusted for established risk factors plus UAE. CONCLUSION: Self-reported current smoking is associated with increased CKD risk, but dependent on UAE. The association between urine cotinine-assessed current smoking and increased CKD risk is independent of UAE. Urine cotinine-assessed smoking status may be a more reliable risk indicator for CKD incidence than self-reported smoking status.

Differential associations of risk factors with severe and non-severe hypoglycaemia: the Hypoglycaemia Assessment Tool prospective observational study in people with insulin-treated type 1 diabetes and type 2 diabetes.

AIM: To assess the differential association of risk factors with severe and non-severe hypoglycaemia. MATERIALS AND METHODS: The Hypoglycaemia Assessment Tool study evaluated the risk of hypoglycaemia over a 4-week period in patients with type 1 diabetes (T1D) and type 2 diabetes (T2D) on insulin in 24 countries. Negative binomial regressions were applied to examine the associations of several risk factors with severe and non-severe hypoglycaemia. RESULTS: The median age was 41 years in 5949 patients with T1D and 62 years in 12 914 patients with T2D. The 4-week rates of non-severe hypoglycaemic were 5.57 and 1.40 episodes per person in T1D and T2D, respectively; the corresponding rates for severe hypoglycaemia were 0.94 and 0.30. The excess risk was 42% higher for severe than non-severe hypoglycaemia in females versus males with T2D; 27% higher in patients with T2D with versus without a continuous glucose monitoring (CGM); and 47% lower in patients with T1D with versus without an insulin pump. The excess risk also differed across geographical areas and was marginally lower for severe than non-severe hypoglycaemia for higher values of HbA1c in patients with T2D. Associations with severity of hypoglycaemia were not different for age, diabetes and insulin therapy duration, previous hypoglycaemic episodes and insulin regimen. CONCLUSIONS: The risk of severe versus non-severe hypoglycaemia differs in patients with T1D and T2D; sex, the use of a CGM and insulin pump, and geographical areas were differently associated with one type of hypoglycaemia than the other.

Glycaemic control and macrovascular and microvascular outcomes: A systematic review and meta-analysis of trials investigating intensive glucose-lowering strategies in people with type 2 diabetes.

AIM: We aimed to determine the macrovascular and microvascular outcomes of intensive versus standard glucose-lowering strategies in type 2 diabetes (T2D) and investigate the relationships between these outcomes and trial arm glycated haemoglobin (HbA1c) reduction. MATERIALS AND METHODS: In this systematic review and meta-analysis, we identified relevant trials from MEDLINE, Embase, the Cochrane Library, and bibliographies up to August 2023. Macrovascular and microvascular outcomes, along with safety outcomes, were evaluated. Pooled study-specific hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated, and meta-regression was employed to analyse the relationships between outcomes and HbA1c reduction. RESULTS: We included 11 unique RCTs involving 51 469 patients with T2D (intensive therapy, N = 26 691; standard therapy, N = 24 778). Intensive versus standard therapy reduced the risk of non-fatal myocardial infarction (MI) (HR 0.84; 95% CI 0.75-0.94) with no difference in the risk of major adverse cardiovascular events (HR 0.97; 95% CI 0.92-1.03) and other adverse cardiovascular outcomes. Intensive versus standard therapy reduced the risk of retinopathy (HR 0.85; 0.78-0.93), nephropathy (HR 0.71; 0.58-0.87) and composite microvascular outcomes (HR 0.88; 0.77-1.00). Meta-regression analyses showed modest evidence of inverse linear relationships between HbA1c reduction and the outcomes of major adverse cardiovascular events, non-fatal MI, stroke and retinopathy, but these were not statistically significant. CONCLUSIONS: In people with T2D, intensive glucose control was associated with a reduced risk of non-fatal MI and several microvascular outcomes, particularly retinopathy and nephropathy. The lack of an effect of intensive glucose-lowering on most macrovascular outcomes calls for a more comprehensive approach to managing cardiovascular risk factors alongside glycaemic control.

Glycaemic control and macrovascular and microvascular outcomes in type 2 diabetes: Systematic review and meta-analysis of cardiovascular outcome trials of novel glucose-lowering agents.

AIM: Using a systematic review and meta-analysis of placebo-controlled cardiovascular outcome trials (CVOTs) of newer glucose-lowering agents [sodium-glucose cotransporter-2 inhibitors (SGLT-2is), glucagon-like peptide-1 receptor agonists (GLP-1RAs), and dipeptidyl peptidase-4 inhibitors (DPP-4is)] in type 2 diabetes (T2D), we aimed to determine the macrovascular and microvascular outcomes of these agents and clarify the relationships between glycated haemoglobin (HbA1c) reduction and risk of these outcomes. MATERIALS AND METHODS: Randomized controlled trials were identified from MEDLINE, Embase and the Cochrane Library until September 2023. Study-specific hazard ratios with 95% confidence intervals (CIs) were pooled, and meta-regression was used to assess the relationships between outcomes and between trial arm HbA1c reductions. RESULTS: Twenty unique CVOTs (six SGLT-2is, nine GLP-1RAs, five DPP-4is), based on 169 513 participants with T2D, were eligible. Comparing SGLT-2is, GLP-1RAs and DPP-4is with placebo, the hazard ratios (95% CIs) for 3-point major adverse cardiovascular events were 0.88 (0.82-0.94), 0.85 (0.79-0.92) and 1.00 (0.94-1.06), respectively. SGLT-2is and GLP-1RAs consistently reduced the risk of several macrovascular and microvascular complications, particularly kidney events. DPP-4is showed no macrovascular benefits. There was potential evidence of an inverse linear relationship between HbA1c reduction and 3-point major adverse cardiovascular event risk (estimated risk per 1% reduction in HbA1c: 0.84, 95% CI 0.67-1.06; p = .14; R2 = 14.2%), which was driven by the component of non-fatal stroke (R2 = 100.0%; p = .094). There were non-significant inverse linear relationships between HbA1c reduction and the risk of several vascular outcomes. CONCLUSIONS: SGLT-2is and GLP-1RAs showed consistent risk reductions in macrovascular and microvascular outcomes. The vascular benefits of SGLT-2is and GLP-1RAs in patients with T2D extend beyond mere glycaemic control.

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

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

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

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

Alcohol Consumption, High-Density Lipoprotein Particles and Subspecies, and Risk of Cardiovascular Disease: Findings from the PREVEND Prospective Study.

The associations of HDL particle (HDL-P) and subspecies concentrations with alcohol consumption are unclear. We aimed to evaluate the interplay between alcohol consumption, HDL parameters and cardiovascular disease (CVD) risk. In the PREVEND study of 5151 participants (mean age, 53 years; 47.5% males), self-reported alcohol consumption and HDL-P and subspecies (small, medium, and large) by nuclear magnetic resonance spectroscopy were assessed. Hazard ratios (HRs) with 95% CIs for first CVD events were estimated. In multivariable linear regression analyses, increasing alcohol consumption increased HDL-C, HDL-P, large and medium HDL, HDL size, and HDL subspecies (H3P, H4P, H6 and H7) in a dose-dependent manner. During a median follow-up of 8.3 years, 323 first CVD events were recorded. Compared with abstainers, the multivariable adjusted HRs (95% CIs) of CVD for occasional to light, moderate, and heavy alcohol consumers were 0.72 (0.55-0.94), 0.74 (0.54-1.02), and 0.65 (0.38-1.09), respectively. These associations remained consistent on additional adjustment for each HDL parameter. For CVD, only HDL-C was associated with a statistically significant decreased risk of CVD in a fully adjusted analysis (HR 0.84, 95% CI 0.72-0.97 per 1 SD increment). For coronary heart disease, HDL-C, HDL-P, medium HDL, HDL size, and H4P showed inverse associations, whereas HDL-C and HDL size modestly increased stroke risk. Except for H6P, alcohol consumption did not modify the associations between HDL parameters and CVD risk. The addition of HDL-C, HDL size, or H4P to a CVD risk prediction model containing established risk factors improved risk discrimination. Increasing alcohol consumption is associated with increased HDL-C, HDL-P, large and medium HDL, HDL size, and some HDL subspecies. Associations of alcohol consumption with CVD are largely independent of HDL parameters. The associations of HDL parameters with incident CVD are generally not attenuated or modified by alcohol consumption.

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

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

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

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

Physical activity and risk of chronic kidney disease: systematic review and meta-analysis of 12 cohort studies involving 1,281,727 participants.

The role of regular physical activity in preventing vascular and non-vascular disease is well established. Chronic kidney disease (CKD) is a major cause of global morbidity and mortality and largely preventable, but it is uncertain if regular physical activity can reduce the risk of CKD. Using a systematic review and meta-analysis of published observational cohort studies in the general population, we sought to assess the association between physical activity and CKD risk. Relevant studies with at least one-year of follow-up were sought from inception until 02 May 2022 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 random effects meta-analysis. The quality of the evidence was evaluated using the GRADE tool. A total of 12 observational cohort studies comprising 1,281,727 participants and 66,217 CKD events were eligible for the analysis. The pooled multivariable-adjusted RR (95% CI) of CKD comparing the most versus the least physically active groups was 0.91 (0.85-0.97). The association was consistent across several study level subgroups. Exclusion of any single study at a time from the meta-analysis did not change the direction or significance of the association. There was no evidence of small study effects among contributing studies. The GRADE quality of the evidence was low. In the general population, individuals who are most physically active have a lowered risk of CKD compared to those who are not or least physically active. CRD42022327640.

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

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

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

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

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

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

Rehabilitation for revision total knee replacement: survey of current service provision and systematic review.

BACKGROUND: Revision total knee replacement (TKR) is a major operation with a long recovery period and many patients report suboptimal outcomes. Rehabilitation has the potential to improve outcomes. The aim of this study was to understand current provision of rehabilitation for revision TKR in England and evaluate the existing evidence. METHODS: Phase 1: An online national survey of education and rehabilitation provision for patients receiving revision TKR was completed by physiotherapy staff at 22 hospitals across England that were high volume for revision TKR (response rate of 34%). Phase 2: Systematic review to identify studies evaluating rehabilitation programmes for revision joint replacement. Searches were conducted in MEDLINE, EMBASE, PsycINFO, CINAHL, and Cochrane databases from inception to 15th June 2022. Randomised controlled trials (RCTs) and observational studies that evaluated post-operative rehabilitation for adults undergoing revision joint replacement were included. Screening, data extraction and quality assessment was undertaken by two reviewers. RESULTS: Phase 1: Pre-operative education which aimed to prepare patients for surgery and recovery was provided in most hospitals, predominately involving a single session delivered by a multidisciplinary team. Inpatient physiotherapy commonly commenced on post-operative day 1 and was provided twice daily, with most hospitals also providing occupational therapy. Rehabilitation was often provided in the first four weeks after hospital discharge, either in an outpatient, community or home setting. In most hospitals, the education and rehabilitation provided to patients receiving revision TKR was the same as that provided to patients undergoing primary TKR. Phase 2: Of the 1,445 articles identified, three retrospective cohort studies based on hospital records review were included. The studies evaluated intensive inpatient rehabilitation programmes, consisting of 2-3 h of daily group or individual physiotherapy, with additional occupational therapy in one study. All three studies reported improvement in functional outcomes for patients undergoing rehabilitation after revision TKR. All studies were limited by their retrospective design, short duration of follow-up and lack of sample size calculation. No RCTs evaluating effectiveness of rehabilitation for revision TKR were identified. CONCLUSION: This study identified the need for future research to develop and evaluate tailored rehabilitation to optimise patient outcomes following revision TKR.

The impact of physical activity changes on exercise capacity and health-related quality of life in young patients with CHD: a 3-year follow-up study.

OBJECTIVE: This study examined the relationship between changes in physical activity and their impact on exercise capacity and health-related quality of life over a 3-year span in patients with CHD. METHODS: We evaluated 99 young patients with CHD, aged 13-18 years at the outset. Physical activity, health-related quality of life, and exercise capacity were assessed via questionnaires and peak oxygen uptake measurements at baseline and after 3 years; changes in measures were estimated between the two time points and categorised into quartiles. Participants were stratified according to achieved (active) or not-achieved (inactive) recommended levels of physical activity (≥150 minutes/week) at both time points. RESULTS: Despite increases in physical activity, exercise capacity, and health-related quality of life over 3 years, the changes were not statistically significant (all p > 0.05). However, a positive association was found between physical activity changes and exercise capacity (ß = 0.250, p = 0.040) and health-related quality of life improvements (ß = 0.380, p < 0.001). Those with the most pronounced physical activity increase showed notable exercise capacity (p < 0.001) and health-related quality of life increases (p < 0.001) compared with patients with the largest decline in physical activity. The active-inactive category demonstrated a notable decline in exercise capacity compared to the active-active group, while the inactive-active group showed health-related quality of life improvements. CONCLUSIONS: Over 3 years, increased physical activity was consistently linked to increases in exercise capacity and health-related quality of life in patients with CHD, highlighting the potential of physical activity augmentation as an intervention strategy.

A Meta-Analysis of the Incidence and Temporal Trends of Postoperative Dislocation in Revision Total Hip Arthroplasty Utilizing Constrained Acetabular Components or Dual Mobility Implants.

BACKGROUND: The incidence of dislocation after revision total hip arthroplasty (rTHA) is reported to be up to 25% and remains a common source of failure. Constrained acetabular components and dual mobility implants are two implant classes being utilized to alleviate this burden in patients who have recurrent instability or major intraoperative instability. This meta-analysis evaluated the incidence and temporal trends of dislocation after implantation with constrained acetabular components and dual mobility implants in rTHA. METHODS: Longitudinal studies reporting dislocation after the use of constrained acetabular components or dual mobility implants in rTHA were sought from Medline and Embase to October 2022. Secondary outcomes included re-revision surgery for dislocation and all causes. A total of 75 relevant citations were identified comprising 36 datasets of 3,784 constrained acetabular components and 47 datasets of 10,216 dual mobility implants. RESULTS: For constrained acetabular components, the pooled incidence of dislocation was 9% (95% confidence interval: 7.2, 11.7) (range 0.0%-35.3%) over a weighted mean follow-up of 6 years, in contrast to 3% (95% confidence interval: 2.2, 4.4) (range 0.0%-21.4%) over 5 years for dual mobility implants. Re-revision rates for dislocation after using constrained acetabular components were around 9%, in contrast to 2% for dual mobility implants. Re-revision rates for all causes after using constrained acetabular components were around 19%, in contrast to 8% for dual mobility implants. CONCLUSION: Dual mobility implants in the context of rTHA demonstrate lower incidences of dislocation (3% versus 9%), re-revision for dislocation (2% versus 9%), and rer-evision for any cause (8% versus 19%) in contrast to constrained acetabular components. This must be considered by surgeons when implanting such devices, often selected to treat instability.

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

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

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

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

Cardiovascular and renal outcomes of initial combination therapy with glucose-lowering agents versus a stepwise approach in newly diagnosed or treatment-naïve type 2 diabetes: A systematic review and meta-analysis.

AIM: To evaluate the efficacy and safety of the initial combination therapy versus a stepwise approach in newly diagnosed type 2 diabetes (T2D) by conducting a systematic review and meta-analysis of observational cohort studies and randomized controlled trials (RCTs). METHODS: Studies were identified from MEDLINE, Embase, the Cochrane Library, and through search of bibliographies to January 2022. Study-specific risk ratios (RRs) and mean differences with 95% confidence intervals (CIs) were pooled. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. RESULTS: Eight articles including four unique RCTs (n = 5527 participants) and one observational cohort study (n = 200) that compared initial combination therapy versus stepwise therapy were included. The RR for myocardial infarction comparing initial combination therapy versus stepwise therapy was 1.21 (95% CI 0.74-2.00). Initial combination therapy reduced levels of fasting plasma glucose and glycated haemoglobin: mean differences -0.97 mmol/L (95% CI -1.41, -0.53) and -24.92 mmol/mol (95% CI -25.67, -24.27), respectively. Initial combination therapy versus stepwise therapy reduced lipid levels, blood pressure and intima media thickness, with no differences in body composition variables, neuropathy, retinopathy or adverse events. Single-study results showed that initial combination therapy reduced creatinine levels and urine albumin excretion rate. The quality of the evidence ranged from moderate to very low. CONCLUSIONS: Except for improving cardiometabolic and glycaemic variables, a limited number of studies characterized by small sample sizes show that initial combination therapy for newly diagnosed T2D may be similar in efficacy and safety to stepwise therapy with respect to cardio-renal outcomes. There is a lack of sufficient evidence to recommend initial combination therapy with glucose-lowering agents in newly diagnosed T2D with the aim of preventing cardio-renal outcomes. Definitive RCTs are warranted.

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

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