The complementary roles of iron and estrogen in menopausal differences in cardiometabolic outcomes.

Biological hormonal changes are frequently cited as an explanatory factor of sex and menopause differences in cardiometabolic diseases (CMD) and its associated risk factors. However, iron metabolism which varies between sexes and among women of different reproductive stages could also play a role. Recent evidence suggest that iron may contribute to CMD risk by modulating oxidative stress pathways and inflammatory responses, offering insights into the mechanistic interplay between iron and CMD development. In the current review, we provide a critical appraisal of the existing evidence on sex and menopausal differences in CMD, discuss the pitfall of current estrogen hypothesis as sole explanation, and the emerging role of iron in CMD as complementary pathway. Prior to menopause, body iron stores are lower in females as compared to males, but the increase during and after menopause, is tandem with an increased CMD risk. Importantly, basic science experiments show that an increased iron status is related to the development of type 2 diabetes (T2D), and different cardiovascular diseases (CVD). While epidemiological studies have consistently reported associations between heme iron intake and some iron biomarkers such as ferritin and transferrin saturation with the risk of T2D, the evidence regarding their connection to CVD remains controversial. We delve into the factors contributing to this inconsistency, and the limitation of relying on observational evidence, as it does not necessarily imply causation. In conclusion, we provide recommendations for future studies on evaluating the potential role of iron in elucidating the sex and menopausal differences observed in CMD.

Selenium Supplementation in Patients with Hashimoto Thyroiditis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Background: Hashimoto thyroiditis (HT) is the most common cause of hypothyroidism in iodine-sufficient areas. Selenium is an essential trace element required for thyroid hormone synthesis and exerts antioxidant effects. Therefore, it may be of relevance in the management of HT. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the effect of selenium supplementation on thyroid function (thyrotropin [TSH], free and total thyroxine [fT4, T4], free and total triiodothyronine [fT3, T3]), thyroid antibodies (thyroid peroxidase antibodies [TPOAb], thyroglobulin antibodies [TGAb], thyrotropin receptor antibody [TRAb]), ultrasound findings (echogenicity, thyroid volume), immune markers, patient-reported outcomes, and adverse events in HT. The study protocol was registered on PROSPERO (CRD42022308377). We systematically searched MEDLINE, Embase, CINHAL, Web of Science, Google Scholar, and the Cochrane CENTRAL Register of Trials from inception to January 2023 and searched citations of eligible studies. Two independent authors reviewed and coded the identified literature. The primary outcome was TSH in patients without thyroid hormone replacement therapy (THRT); the others were considered secondary outcomes. We synthesized the results as standardized mean differences (SMD) or odds ratio (OR), assessed risk of bias using the Cochrane RoB 2 tool, and rated the evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Results: We screened 687 records and included 35 unique studies. Our meta-analysis found that selenium supplementation decreased TSH in patients without THRT (SMD -0.21 [confidence interval, CI -0.43 to -0.02]; 7 cohorts, 869 participants; I2 = 0%). In addition, TPOAb (SMD -0.96 [CI -1.36 to -0.56]; 29 cohorts; 2358 participants; I2 = 90%) and malondialdehyde (MDA; SMD -1.16 [CI -2.29 to -0.02]; 3 cohorts; 248 participants; I2 = 85%) decreased in patients with and without THRT. Adverse effects were comparable between the intervention and control groups (OR 0.89 [CI 0.46 to 1.75]; 16 cohorts; 1339 participants; I2 = 0%). No significant changes were observed in fT4, T4, fT3, T3, TGAb, thyroid volume, interleukin (IL)-2, and IL-10. Overall, certainty of evidence was moderate. Conclusions: In people with HT without THRT, selenium was effective and safe in lowering TSH, TPOAb, and MDA levels. Indications for lowering TPOAb were found independent of THRT.

Impact of Persistent Medication Adherence and Compliance with Lifestyle Recommendations on Major Cardiovascular Events and One-Year Mortality in Patients with Type 2 Diabetes and Advanced Stages of Atherosclerosis: Results From a Prospective Cohort Study.

Background: The aim of this study was to evaluate the impact of single and combined effects of persistent medication adherence and compliance with lifestyle recommendations on the incidence of major adverse cardiovascular events (MACE) and one-year all-cause mortality in patients with type 2 diabetes (T2D) and peripheral artery disease (PAD) after partial foot amputation (PFA), representing a unique cohort of patients with advanced stages of atherosclerosis. Methods: This is a prospective cohort study of 785 consecutive patients (mean age 60.9 ± 9.1 years; 64.1% males). Medication adherence was evaluated by using the proportion of days covered (PDC) measure calculation and was defined as a PDC ≥80%. It derived as an average of PDCs of the following four classes of drugs: a) antidiabetics (oral hypoglycemic medications and/or insulin); b) ACEI or ARBs; c) Statins; d) antiplatelet drugs. Lifestyle compliance was defined as a PDC ≥80% comprising of PDCs of a) physical activity of ≥30 minutes per day; b) healthy nutrition and weight management; c) non-smoking. Cox proportional hazard models adjusted for confounders were used. Results: Total all-cause mortality was 16.9% (n = 133) at one-year follow-up. After adjusting for confounders, compared to adherent/compliant patients (n = 432), non-adherent and/or non-compliant patients had an increased risk of one-year mortality: HR = 8.67 (95% CI [5.29, 14.86] in non-adherent/non-compliant patients (n = 184), p < 0.001; HR = 3.81 (95% CI [2.03, 7.12], p < 0.001) in adherent/non-compliant patients (n = 101) and HR = 3.14 (95% CI [1.52, 6.45] p = 0.002) in non-adherent/compliant patients (n = 184). The incidence of MACE followed similar pattern (HR = 9.66 (95% CI [6.55, 14.25] for non-adherence/non-compliance; HR = 3.48 (95% CI [2.09, 5.77] and HR = 3.35 (95% CI [1.89, 5.91], p < 0.001 for single adherence or compliance. Conclusions: Medication adherence and compliance to lifestyle recommendations have shown to be equally effective to reduce the incidence of MACE and one-year mortality in patients with diabetes and PAD after PFA representing a population with highly advanced stages of atherosclerotic disease. Our findings underline the necessity to give lifestyle intervention programs a high priority and that costs for secondary prevention medications should be covered for patients under these circumstances. Lay Summary: This study analyzed the single and combined effects of medication adherence and compliance with lifestyle recommendations on cardiovascular events and mortality in patients with type 2 diabetes and advances stages of atherosclerosis over a period of one year.Evaluation of medication adherence included antidiabetics, statins, dual antiplatelets and ACEI/ARBs, whereas lifestyle recommendations included healthy nutrition, physical activity and smoking cessation.Persistent medication adherence and lifestyle changes have shown to be equally effective to reduce the incidence of MACE and one-year mortality in patients representing a population with highly advanced stages of atherosclerotic disease, and positive effects added up to a double effect if patients were persistently adherent and compliant with both interventions.

Changes in fasting plasma glucose and subclinical atherosclerosis: A cohort study from VIPVIZA trial.

BACKGROUND AND AIMS: Studies on the influence of fasting plasma glucose (FPG) on the development of carotid plaque (CP) and intima media thickness (CIMT) mainly focused on single FPG measures. We investigated whether changes in FPG (ΔFPG) are associated with incident CP and CIMT change (ΔCIMT) over time. METHODS: Analyses were based on information from 1896 participants from the VIPVIZA trial (Visualization of asymptomatic atherosclerotic disease for optimum cardiovascular prevention), with baseline and 3-year follow-up data on FPG, ultrasonographic CP (none or ≥1 lesion/s) and CIMT assessments. We studied the association between baseline FPG (prior to intervention) or 3-year ΔFPG (mmol/L) and incident CP (logistic regression) or ΔCIMT (linear regression). Analyses were adjusted for multiple potential confounders. RESULTS: 1896 and 873 individuals, respectively, were included in the analysis on incident CP and ΔCIMT. Participants were 60 years old at baseline and 61% and 54% were females, in the CP and CIMT analyses, respectively. Every mmol/L increase in FPG was associated with an increased odds of incident CP (odds ratio: 1.42, 95% confidence interval [CI]: 1.17, 1.73), but there was no association with ΔCIMT (mean difference: 0.002 mm, 95% CI: -0.003, 0.008) after 3 years. Baseline FPG was not associated with incident CP nor ΔCIMT progression. CONCLUSIONS: In middle-aged individuals with low to moderate risk for cardiovascular diseases, 3-year ΔFPG was positively associated with the risk of incident CP, but not with ΔCIMT. Single measures of FPG may not be sufficient in estimating cardiovascular risk among individuals with low to moderate risk.

Association between dietary phytochemical index, cardiometabolic risk factors and metabolic syndrome in Switzerland. The CoLaus study.

BACKGROUND AND AIMS: Plant-based diets are associated with reduced cardiometabolic risk factors (CRFs) and lower risk of metabolic syndrome (MetS), probably via phytochemicals acting synergistically. However, dietary phytochemical content estimation is challenging; therefore, the dietary phytochemical index (DPI) was proposed as a practical way to assess total dietary phytochemical content from phytochemical-rich foods (PRFs). We evaluated the association between DPI with CRFs and MetS and its components. METHODS AND RESULTS: Cross-sectional analysis of 2009-2012 data of Colaus cohort study (Lausanne, Switzerland), including 3879 participants (mean age 57.6 ± 10.4 years, 53.5% women). Dietary intake was assessed via a validated food frequency questionnaire. DPI was calculated as the total energy intake percentage obtained from PRFs consumption and assessed as quartiles. Associations were determined using multivariable linear and logistic regression for CRFs and MetS, respectively. Median DPI value was 25.5 (interquartile range: 17.7-34.6). After multivariable-adjusted analyses, significant inverse associations were observed between the last two highest DPI quartiles and waist circumference (WC), body mass index (BMI), insulin, leptin, and hs-CRP. No significant associations were observed for MetS or its components except for central obesity, as subjects in the highest DPI quartile had lower odds (OR: 0.78; 95% CI: 0.62, 0.97) than those in lowest quartile. CONCLUSION: A diet high in PRFs assessed via DPI is associated with lower WC, BMI, insulin, leptin, hs-CRP values, and lower odds of central obesity, indicating a potential protective effect of phytochemical intake on these CRFs and highlighting the importance of high PRFs intake in promoting cardiometabolic health.

Impact of type 2 diabetes on life expectancy and role of kidney disease among inpatients with heart failure in Switzerland: an ambispective cohort study.

BACKGROUND: Type 2 diabetes (T2D) is expected to worsen the prognosis of inpatients with heart failure (HF) but the evidence from observational studies is inconsistent. We aimed to compare mortality outcomes and life expectancy among inpatients with HF with or without T2D and explored whether chronic kidney disease (CKD) influenced these associations. METHODS: We collected hospital and civil registry records of consecutive inpatients from a tertiary hospital in Switzerland with a diagnosis of HF from the year 2015 to 2019. We evaluated the association of T2D with mortality risk using Cox regression and adjusted for confounders. RESULTS: Our final cohort consisted of 10,532 patients with HF of whom 27% had T2D. The median age (interquartile range [IQR]) was 75 [68 to 82] and 78 [68 to 86] for the diabetes and non-diabetes groups, respectively. Over a median follow-up [IQR] of 4.5 years [3.3 to 5.6], 5,347 (51%) of patients died. T2D patients had higher risk of all-cause mortality (hazard ratio [HR] 1.21, 95% confidence interval [CI] 1.14 to 1.29). Compared to control (i.e. no T2D nor CKD), average life expectancy (95% CI) among T2D patients, CKD, or both was shorter by 5.4 months (95% CI 1.1 to 9.7), 9.0 months (95% CI 8.4 to 9.6), or 14.8 months (95% CI 12.4 to 17.2), respectively. No difference by sex or ejection fraction category was observed. CONCLUSIONS: T2D is associated with a significantly higher risk of all-cause mortality and shorter life expectancy compared to those without among middle-aged and elderly inpatients with HF; presence of CKD may further increase these risks.

A 7-Step Guideline for Qualitative Synthesis and Meta-Analysis of Observational Studies in Health Sciences.

Objectives: To provide a step-by-step, easy-to-understand, practical guide for systematic review and meta-analysis of observational studies. Methods: A multidisciplinary team of researchers with extensive experience in observational studies and systematic review and meta-analysis was established. Previous guidelines in evidence synthesis were considered. Results: There is inherent variability in observational study design, population, and analysis, making evidence synthesis challenging. We provided a framework and discussed basic meta-analysis concepts to assist reviewers in making informed decisions. We also explained several statistical tools for dealing with heterogeneity, probing for bias, and interpreting findings. Finally, we briefly discussed issues and caveats for translating results into clinical and public health recommendations. Our guideline complements "A 24-step guide on how to design, conduct, and successfully publish a systematic review and meta-analysis in medical research" and addresses peculiarities for observational studies previously unexplored. Conclusion: We provided 7 steps to synthesize evidence from observational studies. We encourage medical and public health practitioners who answer important questions to systematically integrate evidence from observational studies and contribute evidence-based decision-making in health sciences.

Rapid kidney function decline and increased risk of heart failure in patients with type 2 diabetes: findings from the ACCORD cohort : Rapid kidney function decline and heart failure in T2D.

BACKGROUND: Impaired kidney function and albuminuria are associated with increased risk of heart failure (HF) in patients with type 2 diabetes (T2D). We investigated whether rapid kidney function decline over time is an additional determinant of increased HF risk in patients with T2D, independent of baseline kidney function, albuminuria, and other HF predictors. METHODS: Included in the study were 7,539 participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study with baseline urinary albumin-to-creatinine ratio (UACR) data, who had completed 4 years of follow-up and had ≥ 3 eGFR measurements during that period (median eGFR/year = 1.9, IQR 1.7-3.2). The association between rapid kidney function decline (eGFR loss ≥ 5 ml/min/1.73 m2/year) and odds of HF hospitalization or HF death during the first 4 years of follow-up was estimated by logistic regression. The improvement in risk discrimination provided by adding rapid kidney function decline to other HF risk factors was evaluated as the increment in the area under the Receiving Operating Characteristics curve (ROC AUC) and integrated discrimination improvement (IDI). RESULTS: Over 4 years of follow-up, 1,573 participants (20.9%) experienced rapid kidney function decline and 255 (3.4%) experienced a HF event. Rapid kidney function decline was associated with a ~ 3.2-fold increase in HF odds (3.23, 95% CI, 2.51-4.16, p < 0.0001), independent of baseline CVD history. This estimate was not attenuated by adjustment for potential confounders, including eGFR and UACR at baseline as well as at censoring (3.74; 95% CI 2.63-5.31). Adding rapid kidney function decline during follow-up to other clinical predictors (WATCH-DM score, eGFR, and UACR at study entry and end of follow-up) improved HF risk classification (ROC AUC = + 0.02, p = 0.027; relative IDI = + 38%, p < 0.0001). CONCLUSIONS: In patients with T2D, rapid kidney function decline is associated with a marked increase in HF risk, independent of starting kidney function and/or albuminuria. These findings highlight the importance of serial eGFR measurements over time to improve HF risk estimation in T2D.

Prognostic Role of Polyvascular Involvement in Patients with Symptomatic Peripheral Artery Disease.

Background: Statin therapy is recommended for patients with peripheral artery disease (PAD). However, PAD patients with polyvascular (PV) extent remain threatened by an increased residual cardiovascular (CV) risk. Purpose: To investigate the association of prescribed statin therapy and mortality in PAD patients with or without PV extent. Methods: A single-center retrospective longitudinal observational study originating from a consecutive registry with 1380 symptomatic PAD patients over a mean observational time of 60 ± 32 months. The association of atherosclerotic extent and statin use (PAD, plus one additional region (CAD or CeVD, [+1 V]), +2 vascular regions (+CAD and CeVD [+2 V]) with the risk of all-cause mortality was evaluated using Cox proportional hazard models adjusted for potential confounding factors. Results: The mean age of the study's participants was 72.0 ± 11.7 years, with 36% being female. PAD patients with PV extent [+1 V] and [+2 V] were older and suffered from diabetes, hypertension, or dyslipidemia more often; they, too, had more severely impaired kidney function (all p < 0.0001) compared to patients with PAD only. PAD patients with PV [+1 V] and [+2 V] received better statin medication and reached the recommended LDL-C target compared to PAD-only patients (p < 0.001). Despite better statin treatment, the rate of all-cause mortality was higher in PV patients than in PAD-only patients (PAD only: 13%; [+1 V]: 22%; [+2 V]: 35%; p < 0.0001). Conclusion: PV patients receive better statin therapy than PAD-only patients but nevertheless still have higher mortality rates. Future studies are needed to explore whether more aggressive LDL-lowering treatment for PAD patients may be translated into better prognosis.

Early menopause and cardiovascular risk factors: a cross-sectional and longitudinal study.

OBJECTIVE: The aim of the study is to evaluate the cross-sectional and longitudinal association of early natural menopause with changes in cardiovascular risk factors (CVRFs). METHODS: Postmenopausal women from the Swiss CoLaus study, reporting age at natural menopause (ANM) and having CVRFs measurements (blood lipids, blood pressure, glucose, homeostatic model assessment for insulin resistance [HOMA-IR], and inflammatory markers) at baseline (2003-2006) and first follow-up (2009-2012) were eligible for analysis. Age at natural menopause was analyzed as a continuous variable and in categories (ANM <45 and ≥45 y old). Linear regression analysis and linear mixed models were used to assess whether ANM is associated cross-sectionally and longitudinally with changes in CVRFs. Models were adjusted for demographic characteristics, lifestyle-related factors, time since menopause, medication, and clinical conditions. RESULTS: We analyzed 981 postmenopausal women. The cross-sectional analysis showed that women with ANM younger than 45 years had lower diastolic blood pressure (ß = -3.76 mm Hg; 95% confidence interval [CI] = -5.86 to -1.65) compared with women whose ANM was 45 years or older. In the longitudinal analysis, ANM younger than 45 years was associated with changes in log insulin (ß = 0.26; 95% CI = 0.08 to 0.45) and log homeostatic model assessment for insulin resistance levels (ß = 0.28; 95% CI = 0.08 to 0.48). No associations were found between ANM and other CVRFs. CONCLUSIONS: Early menopause may be associated with changes in glucose metabolism, while it may have little to no impact on other CVRFs. Larger longitudinal studies are needed to replicate our findings.

Clinical evidence for high-risk medical devices used to manage diabetes: protocol for a systematic review and meta-analysis.

INTRODUCTION: Medical devices, including high-risk medical devices, have greatly contributed to recent improvements in the management of diabetes. However, the clinical evidence that is submitted for regulatory approval is not transparent, and thus a comprehensive summary of the evidence for high-risk devices approved for managing diabetes in Europe is lacking. In the framework of the Coordinating Research and Evidence for Medical Devices group, we will, therefore, perform a systematic review and meta-analysis, which will evaluate the efficacy, safety and usability of high-risk medical devices for the management of diabetes. METHOD AND ANALYSIS: This study has been reported according to the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. We will search Embase (Elsevier), Medline All (Ovid), Cochrane Library (Wiley), Science Citation Index Expanded and Emerging Sources Citation Index (Web of Science) to identify interventional and observational studies that evaluate the efficacy and/or safety and/or usability of high-risk medical devices for the management of diabetes. No language or publication dates' limits will be applied. Animal studies will be excluded. In accordance with the Medical Device Regulation in European Union, high-risk medical devices are those in classes IIb and III. The following medical devices for diabetes management are considered as having a high risk: implantable continuous glucose monitoring systems, implantable pumps and automated insulin delivery devices. Selection of studies, data extraction and quality of evidence assessment will be performed independently by two researchers. Sensitivity analysis will be performed to identify and explain potential heterogeneity. ETHICS AND DISSEMINATION: No ethical approval is needed for this systematic review, as it is based in already published data. Our findings will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42022366871.

Comparison of different software for processing physical activity measurements with accelerometry.

Several raw-data processing software for accelerometer-measured physical activity (PA) exist, but whether results agree has not been assessed. We examined the agreement between three different software for raw accelerometer data, and associated their results with cardiovascular risk. A cross-sectional analysis conducted between 2014 and 2017 in 2693 adults (53.4% female, 45-86 years) living in Lausanne, Switzerland was used. Participants wore the wrist-worn GENEActive accelerometer for 14 days. Data was processed with the GENEActiv manufacturer software, the Pampro package in Python and the GGIR package in R. For the latter, two sets of thresholds "White" and "MRC" defining levels of PA and two versions (1.5-9 and 1.11-1) for the "MRC" threshold were used. Cardiovascular risk was assessed using the SCORE risk score. Time spent (mins/day) in stationary, light, moderate and vigorous PA ranged from 633 (GGIR-MRC) to 1147 (Pampro); 93 (GGIR-White) to 196 (GGIR-MRC); 19 (GGIR-White) to 161 (GENEActiv) and 1 (GENEActiv) to 26 (Pampro), respectively. Spearman correlations between results ranged between 0.317 and 0.995, while concordance coefficients ranged between 0.035 and 0.968. With some exceptions, the line of perfect agreement was not in the 95% confidence interval of the Bland-Altman plots. Compliance to PA guidelines varied considerably: 99.8%, 98.7%, 76.3%, 72.6% and 50.2% for Pampro, GENEActiv, GGIR-MRC v.1.11-1, GGIR-MRC v.1.4-9 and GGIR-White, respectively. Cardiovascular risk decreased with increasing time spent in PA across most software packages. We found large differences in PA estimation between software and thresholds used, which makes comparability between studies challenging.

Buckwheat and Cardiometabolic Health: A Systematic Review and Meta-Analysis.

Buckwheat (BW) is suggested to have beneficial effects, but evidence on how it affects cardiometabolic health (CMH) is not yet established. We aimed to assess the effects of BW and/or its related bioactive compounds on cardiovascular disease (CVD) risk markers in adults. Five databases were searched for eligible studies. Observational prospective studies, nonrandomized or randomized trials were considered if they assessed BW, rutin or quercetin-3-glucoside intake and CVD risk markers. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for reporting. We selected 16 human studies based on 831 subjects with mild metabolic disturbances, such as hypercholesterolemia, diabetes and/or overweight. Eight studies, investigating primarily grain components, were included in the meta-analyses (n = 464). High study heterogeneity was present across most of our analyses. Weighted mean difference (WMD) for subjects receiving BW supplementation, compared to controls, were - 0.14 mmol/L (95% CI: -0.30; 0.02) for total cholesterol (TC), -0.03 mmol/L (95% CI: -0.22; 0.16) for LDL cholesterol, -0.14 kg (95% CI: -1.50; 1.22) for body weight, -0.04 mmol/L (95% CI: - 0.09;0.02) for HDL cholesterol, -0.02 mmol/L (95% CI: -0.15; 0.11) for triglycerides and -0.18 mmol/L (95% CI: -0.36; 0.003) for glucose. Most of the studies (66.7%) had concerns of risk of bias. Studies investigating other CVD markers were scarce and with inconsistent findings, where available. Evidence on how BW affects CMH is limited. However, the available literature indicates that BW supplementation in mild dyslipidaemia and type 2 diabetes may provide some benefit in lowering TC and glucose, albeit non-significant. Our work highlights the need for more rigorous trials, with better methodological rigor to clarify remaining uncertainties on potential effects of BW on CMH and its utility in clinical nutrition practice.

Sex and N-terminal pro B-type natriuretic peptide: The potential mediating role of iron biomarkers.

Background: Levels of N-terminal pro B-type natriuretic peptide (NT-proBNP), a marker of heart failure and cardiovascular risk, are generally higher in women than men. We explored whether iron biomarkers mediate sex differences in NT-proBNP levels. Methods: We included 5,343 community-dwelling individuals from the Prevention of Renal and Vascular Endstage Disease study. With linear regression analyses, we investigated the association of sex and iron biomarkers with NT-proBNP levels, independent of adjustment for potential confounders. The assessed iron biomarkers included ferritin, transferrin saturation (TSAT), hepcidin, and soluble transferrin receptor (sTfR). Next, we performed mediation analyses to investigate to which extent iron biomarkers influence the association between sex and NT-proBNP. Results: Of the included 5,343 participants, the mean standard deviation age was 52.2 ± 11.6 years and 52% were females. After adjustment for potential confounders, women compared to men, had higher NT-proBNP (ß = 0.31; 95%CI = 0.29, 0.34), but lower ferritin (ß = -0.37; 95%CI = -0.39, -0.35), hepcidin (ß = -0.22, 95%CI = -0.24, -0.20), and TSAT (ß = -0.07, 95% CI = -0.08, -0.06). Lower ferritin (ß = -0.05, 95%CI = -0.08, -0.02), lower hepcidin (ß = -0.04, 95%CI = -0.07, -0.006), and higher TSAT (ß = 0.07; 95%CI = 0.01, 0.13) were associated with higher NT-proBNP. In mediation analyses, ferritin and hepcidin explained 6.5 and 3.1% of the association between sex and NT-proBNP, respectively, while TSAT minimally suppressed (1.9%) this association. Conclusion: Our findings suggest that iron biomarkers marginally explain sex differences in levels of NT-proBNP. Future studies are needed to explore causality and potential mechanisms underlying these pathways.

Coronary artery calcium score and coronary computed tomography angiography predict one-year mortality in patients with type 2 diabetes and peripheral artery disease undergoing partial foot amputation.

METHODS: This is a single-center prospective cohort study including 199 consecutive patients with T2D, PAD (mean age 62.3 ± 7.2 years; 62.8% males), and preoperative CACS and CCTA undergoing PFA and followed-up over 1 year. RESULTS: Over a period of 1 year follow-up, a total of 35 (17.6%) participants died. The area under ROC curve to predict mortality for the CACS was 0.835 (95% CI:0.769-0.900), for CCTA 0.858 (95% CI:0.788-0.927). After adjustment for confounders, compared to no-stenosis on CCTA (reference), the risk of all-cause mortality in non-obstructive coronary atery disease (CAD) increased (HR = 1.38, 95% CI [0.75-12.86], p = .284), 1-vessel obstructive CAD (HR = 8.13, 95% CI [0.87-75.88], p = .066), 2-vessels (HR = 10.94, 95% CI [1.03-115.8], p = .047), and 3-vessels (HR = 45.73, 95% CI [4.6-454.7], p = .001) respectively. Increasing levels of CACS tended to be associated with increased risk of all-cause mortality (HR = 1.002, 95% CI [1.0-1.003], p = .061). 61/95 patients with obstructive CAD underwent coronary revascularization. CONCLUSIONS: Coronary artery calcium score and CCTA have a high predictive value for 1-year all-cause mortality in T2D patients undergoing minor amputations and may be considered for preoperative risk assessment allowing timely preventive interventions.

Objectively measured adherence to physical activity among patients with coronary artery disease: Comparison of the 2010 and 2020 World Health Organization guidelines and daily steps.

Background: Tailored recommendations for patients after percutaneous coronary interventions (PCI) need physical activity (PA) to be objectively measured and assessed for adherence to guidelines. The recent WHO guidelines removed the daily recommended bout duration, while the potential impact of this change on patients after PCI remains unclear. Aim: We evaluated prevalence estimates of adherence to PA recommendations among patients after PCI across the 2010 [≥30 min moderate- to vigorous-intensity PA (MVPA) at ≥ 10-min bout duration] and 2020 WHO guidelines (≥30 min of MVPA of any bout duration), as well as 7,500 and 10,000 steps. Methods: We conducted an observational longitudinal single-center study with patients after PCI for chronic or acute coronary syndrome (ACS); maximal age 80 years. Wrist-worn accelerometers recorded participants' PA data from the evening of hospital discharge over the next 18 days. Results: We analyzed data from 282 participants with sufficient minimum wear time (7 days of ≥12 h), including 45 (16%) women; and 249 (88%) with ACS. Median wear time was 18 (17, 18) days. Median participant age was 62 (55, 69) years. Fifty-two participants (18.4%) fulfilled 2010 WHO guidelines and 226 (80.1%) fulfilled the 2020 WHO guidelines. Further, 209 (74.1%) participants achieved ≥7,500 steps/day and 155 (55.0%) performed ≥10,000 steps/day. Conclusion: Among participants after PCI, most MVPA was accumulated in bouts <10 min, leading to a fourfold discrepancy between participants fulfilling the 2010 and 2020 WHO PA recommendations. The number of steps/day may be a valid proxy to recent WHO PA recommendations as it is not dependent on the bout-length definition. Clinical trial registration: [ClinicalTrials.gov], identifier [NCT04663373].

Prognostic impact of physical activity patterns after percutaneous coronary intervention. Protocol for a prospective longitudinal cohort. The PIPAP study.

Introduction: Current guidelines recommend wearable activity trackers to detect insufficient physical activity (PA) and help increase PA to prevent or ameliorate cardiovascular disease. However, there is a paucity of data regarding how objectively measured PA trajectories, patterns, and sedentary time, are associated with mortality and recurrent events after percutaneous coronary intervention (PCI) in patients with established coronary artery disease (CAD). Additionally, it remains unclear if early PA and sedentary time after PCI are associated with such outcomes. Therefore, in the present study (ClinicalTrials.gov Identifier: NCT04663373), we aim to establish the associations of objectively measured PA with major adverse cardiac events and mortality at one-year follow-up. Methods and analysis: In this single-centre observational study, patients with CAD will be prospectively recruited immediately after PCI. All the information from the clinical history, baseline characteristics, and outcomes during follow-up will be obtained from the CARDIOBASE registry. Accelerometer data will be collected for 18 days following hospital discharge and 14 days at one-year follow-up. PA trajectories will be identified by group-based trajectory modeling. Major adverse cardiac events and mortality will be prospectively monitored up to 1 year after PCI. All data will be collected using Research Electronic Data Capture.

Physical performance and glycemic control under SGLT-2-inhibitors in patients with type 2 diabetes and established atherosclerotic cardiovascular diseases or high cardiovascular risk (PUSH): Design of a 4-week prospective observational study.

Background: Type 2 diabetes (T2D) is associated with limitation in physical performance. Results from animal studies report enhancement of physical performance in T2D rodents treated with sodium glucose cotransporter 2 inhibitors (SGLT2is). However, in human patients with T2D and established atherosclerotic cardiovascular disease (ASCVD) or high cardiovascular risk, the impact of guideline directed SGLT2i medication on physical performance has not been sufficiently examined. Objectives: The main objectives of this study are thus firstly, to assess the changes in physical performance after 4 weeks of exercise therapy in patients with established ASCVD or high cardiovascular risk categorized into three groups according to their glycemic control at baseline. Secondly, to investigate the association of glycemic control at baseline and new guideline directed antidiabetic treatment (inadequate glycemic control and diabetes + new SGLT2i vs. adequate glycemic control and diabetes vs. no diabetes) with change in physical performance. Methods and design: This is a 4-week prospective observational study of 450 participants with established ASCVD or high cardiovascular risk with or without T2D and without previous SGLT2i medication undergoing exercise therapy during inpatient rehabilitation in a single center in Switzerland. Upon admission, participants are categorized into 3 groups of 150 participants each according to their glycemic control. Group I consisting of participants with inadequately controlled T2D defined as mean fasting plasma glucose (FPG) of ≥7 mmol/L, who are consequently administered new treatment with an SGLT2i. Group II comprises of participants with adequately controlled T2D with mean FPG of <7 mmol/L requiring no antidiabetic medication change. Group III consists of participants with no diabetes and mean FPG of ≤ 5.5 mmol/L. Primary outcomes are 6-min walk distance and rate of perceived exertion. Secondary outcomes are echocardiographic parameters (left ventricular mass index; global longitudinal strain average; end-diastolic volume), fatigue, muscle, metabolic, and anthropometric measures. Ethics and dissemination: This study is conducted in accordance with the Declaration of Helsinki with ethical approval from the Cantonal Ethical Commission of Bern, Switzerland. The results will be published in a peer-reviewed journal. The implementation and reporting will be according to the SPIRIT guidelines. Study protocol registration: https://www.clinicaltrials.gov/, identifier: NCT03422263.

Time-Dependent Effect of Anthracycline-Based Chemotherapy on Central Arterial Stiffness: A Systematic Review and Meta-Analysis.

Background and Aims: Anthracycline-based chemotherapy (ANTH-BC) has been proposed to increase arterial stiffness, however, the time-dependency of these effects remain unclear. This systematic review and meta-analysis aimed to investigate the time-dependent effect of ANTH-BC on markers of central aortic stiffness, namely aortic distensibility (AD) and pulse-wave-velocity (PWV) in cancer patients. Methods: An extensive literature search without language restrictions was performed to identify all studies presenting longitudinal data on the effect of ANTH-BC on either AD and/or central PWV in cancer patients of all ages. An inverse-variance weighted random-effect model was performed with differences from before to after chemotherapy, as well as for short vs. mid-term effects. Results: Of 2,130 articles identified, 9 observational studies with a total of 535 patients (mean age 52 ± 11; 73% women) were included, of which four studies measured AD and seven PWV. Short-term (2-4 months), there was a clinically meaningful increase in arterial stiffness, namely an increase in PWV of 2.05 m/s (95% CI 0.68-3.43) and a decrease in AD (albeit non-significant) of -1.49 mmHg-1 (-3.25 to 0.27) but a smaller effect was observed mid-term (6-12 months) for PWV of 0.88 m/s (-0.25 to 2.02) and AD of -0.37 mmHg-1 (-1.13 to 0.39). There was considerable heterogeneity among the studies. Conclusions: Results from this analysis suggest that in the short-term, ANTH-BC increases arterial stiffness, but that these changes may partly be reversible after therapy termination. Future studies need to elucidate the long-term consequences of ANTH-BC on arterial stiffness, by performing repeated follow-up measurements after ANTH-BC termination. Systematic Review Registration: [www.crd.york.ac.uk/prospero/], identifier [CRD42019141837].