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.

Enhancing Cardiorespiratory Fitness Through Sauna Bathing: Insights From the Kuopio Ischemic Heart Disease Prospective Study.

PURPOSE: The physiological adaptations stimulated by a sauna bath(SB) are similar to those produced by moderate- or high-intensity physical activity (PA), but the relationship between SB and cardiorespiratory fitness (CRF) is not clear. The objective of this study was to evaluate the cross-sectional and longitudinal associations between frequency and duration of SB with CRF. METHODS: Baseline SB habits were assessed in 2012 men aged 42 -61 yr. CRF was directly measured using a respiratory gas exchange analyzer during cardiopulmonary exercise testing at baseline and 11 yr later. The associations of SB frequency and duration with baseline and 11-yr levels of CRF were examined using robust regression analyses adjusted for several confounders, including lifestyle factors such as PA. RESULTS: In baseline analysis, a unit increase in sauna sessions/wk was associated with an increase in CRF 0.30 mL/kg/min (standard error [SE]: 0.14; P= .034). Alternatively, compared with a single sauna sessions/wk, 2-3 and 4-7 sauna sessions/wk was each associated with significant increases in levels of CRF: 0.84 mL/kg/min (SE: 0.32; P= .008) and 1.17 mL/kg/min (SE: 0.57; P= .041), respectively. In longitudinal analysis, frequent SB was associated with increases in 11-yr CRF levels, but this was only significant for 2-3 sauna sessions/wk compared with a single sauna sessions/wk: 1.22 mL/kg/min (SE: 0.59; P= .038). Duration of SB was not significantly associated with CRF levels in cross-sectional and longitudinal analyses. CONCLUSIONS: Frequent SB may improve levels of CRF independently of PA. These results warrant replication in robust definitive randomized controlled trials.

Unraveling the link between cardiorespiratory fitness and cancer: a state-of-the-art review.

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.

Frequent sauna bathing and psychosis: Interrelationship with cardiorespiratory fitness.

Frequent sauna bathing and higher cardiorespiratory fitness (CRF) levels may play a role in reducing the risk of mental disorders such as psychosis, however, data on their joint contributions is scanty. We aimed to investigate the interplay between sauna bathing, CRF and psychosis risk using a population-based prospective study. Self-reported frequency of sauna bathing (FSB) and CRF measured by respiratory gas analyses were assessed at baseline in 2221 men aged 42-61 years who had no history of psychosis. Frequency of sauna bathing was categorized as low and high (≤2 and 3-7 sessions/week, respectively) and CRF as tertiles (low, medium and high). Hazard ratios (HRs) with 95% CIs were estimated. During a median follow-up of 25.2 years, 215 psychotic disorders were recorded. Comparing high vs low FSB, the multivariable-adjusted HRs (95% CIs) for psychosis was 0.49 (0.32-0.74), which persisted on further adjustment for CRF 0.50 (0.33-0.75). Compared to low CRF, the multivariable-adjusted HRs (95% CIs) for medium and high CRF levels were 0.65 (0.46-0.90) and 0.75 (0.52-1.07) respectively. Compared to low FSB & low CRF, the HRs (95% CIs) for low FSB & medium-high CRF, high FSB & low CRF, and high FSB & medium-high CRF were 0.62 (0.45-0.84), 0.26 (0.11-0.60), and 0.41 (0.25-0.68) respectively. Frequent sauna baths and medium-high CRF levels appear to each independently decrease psychosis risk. However, frequent sauna bathing may be related to a reduced risk of psychosis irrespective of fitness levels and might be a stronger risk indicator for psychosis than CRF.

Hemodynamic gain index and risk of chronic kidney disease: A prospective cohort study of middle-aged and older men.

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.

Self-reported smoking, urine cotinine, and risk of type 2 diabetes: Findings from the PREVEND prospective cohort study.

BACKGROUND: Smoking is a major risk factor for type 2 diabetes (T2D), but the evidence has mostly relied on self-reports. We aimed to compare the associations of smoking exposure as assessed by self-reports and urine cotinine with T2D. METHODS: Using the PREVEND prospective study, smoking status was assessed at baseline by self-reports and urine cotinine in 4708 participants (mean age, 53 years) without a history of diabetes. Participants were classified as never, former, light current and heavy current smokers according to self-reports and analogous cut-offs for urine cotinine. Hazard ratios (HRs) with 95% CIs were estimated for T2D. RESULTS: During a median follow-up of 7.3 years, 259 participants developed T2D. Compared with self-reported never smokers, the multivariable adjusted HRs (95% CI) of T2D for former, light current, and heavy current smokers were 1.02 (0.75-1.4), 1.41 (0.89-2.22), and 1.30 (0.88-1.93), respectively. The corresponding adjusted HRs (95% CI) were 0.84 (0.43-1.67), 1.61 (1.12-2.31), and 1.58 (1.08-2.32), respectively, as assessed by urine cotinine. Urine cotinine-assessed but not self-reported smoking status improved T2D risk prediction beyond established risk factors. CONCLUSION: Urine cotinine assessed smoking status may be a stronger risk indicator and predictor of T2D compared to self-reported smoking status.

The multifaceted benefits of passive heat therapies for extending the healthspan: A comprehensive review with a focus on Finnish sauna.

Passive heat therapy is characterized by exposure to a high environmental temperature for a brief period. There are several types of passive heat therapy which include hot tubs, Waon therapy, hydrotherapy, sanarium, steam baths, infrared saunas and Finnish saunas. The most commonly used and widely studied till date are the Finnish saunas, which are characterized by high temperatures (ranging from 80-100°C) and dry air with relative humidity varying from 10-20%. The goal of this review is to provide a summary of the current evidence on the impact of passive heat therapies particularly Finnish saunas on various health outcomes, while acknowledging the potential of these therapies to contribute to the extension of healthspan, based on their demonstrated health benefits and disease prevention capabilities. The Finnish saunas have the most consistent and robust evidence regarding health benefits and they have been shown to decrease the risk of health outcomes such as hypertension, cardiovascular disease, thromboembolism, dementia, and respiratory conditions; may improve the severity of musculoskeletal disorders, COVID-19, headache and flu, while also improving mental well-being, sleep, and longevity. Finnish saunas may also augment the beneficial effects of other protective lifestyle factors such as physical activity. The beneficial effects of passive heat therapies may be linked to their anti-inflammatory, cytoprotective and anti-oxidant properties and synergistic effects on neuroendocrine, circulatory, cardiovascular and immune function. Passive heat therapies, notably Finnish saunas, are emerging as potentially powerful and holistic strategies to promoting health and extending the healthspan in all populations.

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.

Does arthroscopic or open washout in native knee septic arthritis result in superior post-operative function? A systematic review and meta-analysis of randomised controlled trials and observational studies.

AIMS: Septic arthritis (SA) of the native knee joint is associated with significant morbidity. This review compared post-operative functional outcomes (patient-reported outcome measures (PROMs) and range of movement (ROM)) following arthroscopic washout (AW) and open washout (OW) amongst adult patients with SA of the native knee. The need for further operative intervention was also considered. METHODS: Electronic databases of PubMed, MEDLINE, Embase, Cochrane, Web of Science and Scopus were searched between 16 February 2023 and 18 March 2023. Randomised controlled trials (RCTs) and comparative observational analytic studies comparing function (reflected in PROMs or ROM) at latest follow-up following AW and OW were included. A narrative summary was provided concerning post-operative PROMs. Pooled estimates for mean ROM and re-operation rates were conducted using the random-effects model. The risk of bias was assessed using the Cochrane risk-of-bias assessment tool-2 for RCTs and the Risk of Bias in Non-Randomized Studies of Interventions tool for observational analytic studies. RESULTS: Of 2580 retrieved citations, 7 articles (1 RCT and 6 cohort studies) met the inclusion criteria. Of these, five had some concerns/moderate risk of bias, and two had serious risk. There was a slight tendency for superior mean PROMs following AW compared with OW, but due to small effect sizes, this was unlikely clinically relevant. Additionally, the use of four different PROMs scales made direct comparisons impossible. AW was associated with superior ROM (mean difference 20.18° (95% CI 14.35, 26.02; p < 0.00001)), whilst there was a tendency for lower re-operation requirements following AW (OR 0.64, 95% CI 0.26, 1.57, p = 0.44). CONCLUSIONS: AW was associated with equivalent to superior post-operative function and lower requirement for further intervention compared with OW. Results need to be interpreted cautiously, taking into consideration the methodological and clinical heterogeneity of the included studies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO 2022, CRD42022364062.

Focal resurfacing of the knee - A systematic review and meta-analysis.

PURPOSE: In order to assess the published validity of focal resurfacing of the knee, a systematic review and meta-analysis were conducted to (i) evaluate revision rates and implant survival of focal resurfacing of the knee; (ii) explore surgical complications; and (iii) evaluate patient reported clinical outcome measures. METHODS: PubMED, Cochrane Library and Medline databases were searched by 2 independent reviewers in February 2022 for prospective and retrospective cohort studies evaluating any of the following implant types: HemiCAP®, UniCAP®, Episealer® or BioBoly®. Data on incidence of revision, complications and various patient reported outcome measures, such as Knee Society Score (KSS) or Knee Injury and Osteoarthritis Outcome Score (KOOS) was sourced. RESULTS: A total of 24 published studies were identified with a total of 1465 enrolled patients. A revision rate of 12.97% over a 5.9 year weighted mean follow-up period was observed across all implant types. However, in one series a Kaplan-Meir survival as high as 92.6% at a 10-year follow-up period was noted. A statistically significant improvement was documented across multiple subjective clinical outcomes scores, for example a mean 4.56 point improvement of the VAS (0-10) pain score. The Kellgren-Lawrence score was used to evaluate the radiological progression of osteoarthritis and showed a small significant reduction in all anatomical locations, hence not supporting the hypothesis that focal femoral implants can lead to the progression of osteoarthritis in the affected compartment. There was a low reported incidence of post-operative complications such as aseptic loosening or deep wound infection. CONCLUSIONS: Focal femoral resurfacing appears to be a viable treatment option for focal symptomatic chondral lesions in patients beyond biological reconstruction, with low revision rates and high patient satisfaction especially at short and medium length follow-up.

Physical activity, exercise and adverse cardiovascular outcomes in individuals with pre-existing cardiovascular disease: a narrative review.

INTRODUCTION: The evidence supporting the cardiovascular health benefits of physical activity and/or exercise training is well-established. While the role of physical activity in primary prevention is unequivocal, its significance in secondary prevention (among those with preexisting cardiovascular disease) is less definitive. Though guidelines universally recommend physical activity as part of the secondary preventive strategy, the empirical evidence underpinning these recommendations is not as robust as that for primary prevention. AREAS COVERED: This review distills the body of available observational and interventional evidence on the relationship between physical activity, exercise, and adverse cardiovascular outcomes among those with preexisting cardiovascular disease. The postulated biologic mechanisms underlying the relationships, areas of prevailing uncertainty, and potential public health implications are also discussed. EXPERT OPINION: A physical activity level of 500 MET-min/week (equivalent to 150 min of moderate-intensity physical activity or 75 min of vigorous-intensity physical activity or an equivalent combination) may be a minimum requirement for patients with preexisting CVD. However, to reap the maximum benefits of physical activity and also minimize adverse effects, physical activity and/or exercise regimens should be tailored to unique factors such as individual's baseline physical activity habits, cardiovascular health status and the specific nature of their cardiovascular disease.

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.

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.

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 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.

Outcomes of Octogenarian Patients Treated with Tafamidis for Transthyretin Amyloid Cardiomyopathy.

Patients with transthyretin amyloid cardiomyopathy (ATTR-CM) benefit from disease-modifying agents such as tafamidis. However, the survival benefit of tafamidis in elderly patients (age ≥80 years) is not reported. This study aimed to assess the survival of patients with ATTR-CM aged 80 years and older who were treated with tafamidis compared with patients aged <80 years. We conducted a retrospective analysis of patients with ATTR-CM who underwent tafamidis treatment, aged 45 to 97 years at the time of diagnosis between January 1, 2008, and May 31, 2021. A total of 484 patients were included, with 208 in the ≥80 years group and 276 in the <80 years group. The cohort was followed up for mortality outcomes, and hazard ratios with 95% confidence intervals were calculated. After a median follow-up of 18.5 months, 72 deaths were recorded in the entire cohort. Kaplan-Meier curves showed no differences in survival probability between the 2 groups at 30 months (p for log-rank test = 0.76). The survival rates for patients aged ≥80 years who underwent treatment at 1, 2, 3, 4, and 5 years were 94.7%, 86.0%, 77.0%, 77.0%, and 38.5%, respectively. The corresponding rates for patients aged <80 years who underwent treatment were 93.2, 84.8, 74.4, 68.2, and 64.6%, respectively. In the multivariable analysis, the hazard ratio (95% confidence interval) of the mortality comparing treatment patients aged ≥80 years with those aged <80 years was 0.81 (0.41 to 1.61). In conclusion, tafamidis treatment is associated with similar reductions in mortality in older and younger patients with ATTR-CM.

Baseline and usual triglyceride-glucose index and the risk of chronic kidney disease: a prospective cohort study.

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.

Sex disparities in physical activity domains and hypertension prevalence.

BACKGROUND: This study aimed to examine the associations of leisure time physical activity (LTPA) and occupational physical activity (OPA) with the prevalence of hypertension, while exploring the sex disparities in these associations. METHODS: A cross-sectional study was conducted using data from the Korea National Health and Nutrition Examination Survey between 2014 and 2019 (n = 26,534). Hypertension was defined as the use of antihypertensive drugs or systolic and diastolic blood pressure ≥ 140/90 mm Hg. Self-reported physical activity (PA), assessed by the global PA questionnaire, was categorized into three domains: total PA, LTPA and OPA. Each PA domain was classified based on METs-min/wk and intensity. RESULTS: In a multivariable adjusted model, the odds ratio (OR) with 95% confidence intervals (CIs) for the prevalence of hypertension in the active versus inactive group, based on METs, was 0.92 (95% CI 0.85-0.99) for total PA, 0.90 (95% CI 0.83-0.98) for LTPA and 1.21 (95% CI 1.05-1.38) for OPA. Compared to the inactive group, moderate to vigorous intensity was associated with a lower odds of hypertension for total PA and LTPA (total PA: OR 0.95, 95% CI 0.89-1.00 and LTPA: OR 0.92, 95% CI 0.86-0.98), but a higher odd for OPA (OR 1.17, 95% CI 1.05-1.30). Subgroup analyses showed significant evidence of effect modification by sex on the associations of total PA and LTPA (METs and intensity) with hypertension prevalence (p-values for interaction < 0.01); the associations were generally stronger for women. OPA was associated with a higher prevalence of hypertension in women, but not in men (p-value for interaction > 0.05). CONCLUSIONS: Higher levels of total PA and LTPA were associated with lower prevalence of hypertension in both men and women, with slightly stronger associations for women. However, higher OPA was associated with a higher prevalence of hypertension in women. These findings support the PA health paradox hypothesis and highlight the sex disparities in the association between OPA and hypertension prevalence.