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.

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.

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.

Association Between Ultra-Processed Food Intake and All-Cause Mortality: A Systematic Review and Meta-Analysis.

Consumption of ultra-processed foods (UPF) has increased worldwide during the last decades because they are hyperpalatable, cheap, and ready-to-consume products. However, uncertainty exists about their impact on health. We conducted a systematic review and meta-analysis evaluating the association of UPF consumption with all-cause mortality risk. Five bibliographic databases were searched for relevant studies. Random effects models were used to calculate pooled relative risks (RRs) and 95% confidence intervals (CIs). Of 6,951 unique citations, 40 unique prospective cohort studies comprising 5,750,133 individuals were included; publication dates ranged from 1984 to 2021. Compared with low consumption, highest consumption of UPF (RR = 1.29, 95% CI: 1.17, 1.42), sugar-sweetened beverages (RR = 1.11, 95% CI, 1.04, 1.18), artificially sweetened beverages (RR = 1.14, 95% CI, 1.05, 1.22), and processed meat/red meat (RR = 1.15, 95% CI, 1.10, 1.21) were significantly associated with increased risk of mortality. However, breakfast cereals were associated with a lower mortality risk (RR = 0.85, 95% CI, 0.79, 0.92). This meta-analysis suggests that high consumption of UPF, sugar-sweetened beverages, artificially sweetened beverages, processed meat, and processed red meat might increase all-cause mortality, while breakfast cereals might decrease it. Future studies are needed to address lack of standardized methods in UPF categorization.

Effect of oat supplementation interventions on cardiovascular disease risk markers: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: Oat supplementation interventions (OSIs) may have a beneficial effect on cardiovascular disease (CVD) risk. However, dietary background can modulate such effect. This systematic review assesses the effects of OSIs on CVD risk markers among adults, accounting for different dietary backgrounds or control arms. METHODS: We included randomized clinical trials (RCTs) that assessed the effect of oat, oat beta-glucan-rich extracts or avenanthramides on CVD risk markers. RESULTS: Seventy-four RCTs, including 4937 predominantly hypercholesterolemic, obese subjects, with mild metabolic disturbances, were included in the systematic review. Of these, 59 RCTs contributed to the meta-analyses. Subjects receiving an OSI, compared to control arms without oats, had improved levels of total cholesterol (TC) [weighted mean difference and (95% CI) - 0.42 mmol/L, (- 0.61; - 0.22)], LDL cholesterol [- 0.29 mmol/L, (- 0.37; - 0.20)], glucose [- 0.25 nmol/L, (- 0.36; - 0.14)], body mass index [- 0.13 kg/m2, (- 0.26; - 0.01)], weight [- 0.94 kg, (- 1.84: - 0.05)], and waist circumference [- 1.06 cm, (- 1.85; - 0.27)]. RCTs on inflammation and/or oxidative stress markers were scarce and with inconsistent findings. RCTs comparing an OSI to heterogeneous interventions (e.g., wheat, eggs, rice, etc.), showed lowered levels of glycated haemoglobin, diastolic blood pressure, HDL cholesterol and apolipoprotein B. The majority of included RCTs (81.1%) had some concerns for risk of bias. CONCLUSION: Dietary OSIs resulted in lowered levels of blood lipids and improvements in anthropometric parameters among participants with predominantly mild metabolic disturbances, regardless of dietary background or control. Further high-quality trials are warranted to establish the role of OSIs on blood pressure, glucose homeostasis and inflammation markers.

Association of diabetes with atrial fibrillation types: a systematic review and meta-analysis.

BACKGROUND: Atrial fibrillation (AF) is a common arrhythmia classified as paroxysmal and non-paroxysmal. Non-paroxysmal AF is associated with an increased risk of complications. Diabetes contributes to AF initiation, yet its role in AF maintenance is unclear. We conducted a systematic review and meta-analysis to summarize the evidence regarding the association of diabetes with AF types. METHODS: We searched 5 databases for observational studies investigating the association of diabetes with the likelihood of an AF type (vs another type) in humans. Study quality was evaluated using the Newcastle-Ottawa Scale. Studies classifying AF types as paroxysmal (reference) and non-paroxysmal were pooled in a meta-analysis using random effects models. RESULTS: Of 1997 articles we identified, 20 were included in our systematic review. The population sample size ranged from 64 to 9816 participants with mean age ranging from 40 to 75 years and percentage of women from 24.8 to 100%. The quality of studies varied from poor (60%) to fair (5%) to good (35%). In the systematic review, 8 studies among patients with AF investigated the cross-sectional association of diabetes with non-paroxysmal AF (vs paroxysmal) of which 6 showed a positive association and 2 showed no association. Fourteen studies investigated the longitudinal association of diabetes with "more sustained" AF types (vs "less sustained") of which 2 showed a positive association and 12 showed no association. In the meta-analysis of cross-sectional studies, patients with AF and diabetes were 1.31-times more likely to have non-paroxysmal AF than those without diabetes [8 studies; pooled OR (95% CI), 1.31 (1.13-1.51), I2 = 82.6%]. The meta-analysis of longitudinal studies showed that for patients with paroxysmal AF, diabetes is associated with 1.32-times increased likelihood of progression to non-paroxysmal AF [five studies; pooled OR (95% CI), 1.32 (1.07-1.62); I2 = 0%]. CONCLUSIONS: Our findings suggest that diabetes is associated with an increased likelihood of non-paroxysmal AF rather than paroxysmal AF. However, further high quality studies are needed to replicate these findings, adjust for potential confounders, elucidate mechanisms linking diabetes to non-paroxysmal AF, and assess the impact of antidiabetic medications on AF types. These strategies could eventually help decrease the risk of non-paroxysmal AF among patients with diabetes.

Menopausal Transition Is Not Associated with Dietary Change in Swiss Women.

BACKGROUND: Adherence to a healthy diet could contribute to maintaining adequate health throughout the menopausal transition, but data are scarce. OBJECTIVE: We evaluated the association between menopausal status and changes in dietary intake in Swiss adult women. METHODS: Cross-sectional (n = 2439) and prospective analyses (n = 1656) were conducted between 2009 and 2012 (first follow-up) among women (mean age ± SD, 58.2 ± 10.5 y) living in Lausanne, Switzerland. In both visits, dietary intake was assessed using a validated FFQ, and menopausal status was classified based on the presence or absence of menstruations. Multivariable linear and logistic regression models were used to investigate the cross-sectional association of menopausal status (postmenopausal compared with premenopausal) at the first follow-up with food intake and dietary recommendations. To examine whether menopausal status (premenopausal as reference group, menopausal transition, and postmenopausal) during 5 y of follow-up was associated with longitudinal changes in diet, including adherence to dietary Swiss recommendations, we applied multivariable linear and logistic mixed models adjusted for several covariates. RESULTS: At the first follow-up, postmenopausal women consumed less (P < 0.002) meat [median (IQR) 57.2 (35-86.2) compared with 62.5 (41.2-95.2) g/d], pasta [61.8 (37.5-89.2) compared with 85 (57.8-128) g/d], and added sugar [0.1 (0-4) compared with 0.7 (0-8) g/d] and more dairy products [126 (65.4-214) compared with 109 (64.5-182) g/d] and fruit [217 (115-390) compared with 174 (83.2-319) g/d] than premenopausal women. However, linear regression analysis adjusted for potential confounding factors showed no independent (cross-sectional) associations of menopausal status with total energy intake (TEI) and individual macro- or micronutrient intakes. In the prospective analysis, compared with women who remained premenopausal during follow-up (n = 244), no differences were found in changes in TEI, dietary intakes, or adherence to the Swiss dietary recommendations in women transitioning from premenopausal to postmenopausal (n = 229) and who remained postmenopausal (n = 1168). CONCLUSION: The menopausal transition is not associated with changes in dietary habits among Swiss women.

Thyroid function and life expectancy with and without noncommunicable diseases: A population-based study.

BACKGROUND: Variations in thyroid function within reference ranges are associated with increased risk of diseases and death. However, the impact of thyroid function on life expectancy (LE) with and without noncommunicable diseases (NCDs) remains unknown. We therefore aimed to investigate the association of thyroid function with total LE and LE with and without NCD among euthyroid individuals. METHODS AND FINDINGS: The study was embedded in the Rotterdam Study, a prospective population-based study carried out in the Netherlands. In total, 7,644 participants without known thyroid disease and with thyroid-stimulating hormone (TSH) and free thyroxine (FT4) levels within reference ranges were eligible. NCDs were defined as presence of cardiovascular disease, diabetes mellitus type 2, or cancer. We used the demographic tool of multistate life tables to calculate LE estimates at the age of 50 years, using prevalence, incidence rates, and hazard ratios for three transitions (healthy to NCD, healthy to death, and NCD to death). The total LE and LE with and without NCD among TSH and FT4 tertiles were calculated separately in men and women. Analyses were adjusted for sociodemographic and cardiovascular risk factors. The mean (standard deviation) age of the participants was 64.5 (9.7) years, and 52.3% were women. Over a median follow-up of 8 years (interquartile range 2.7-9.9 years), 1,396 incident NCD events and 1,422 deaths occurred. Compared with those in the lowest TSH tertile, men and women in the highest TSH tertile were expected to live 1.5 years (95% confidence interval [CI] 0.8-2.3, p < 0.001) and 1.5 years (CI 0.8-2.2, p < 0.001) longer, respectively, of which 1.4 years (CI 0.5-2.3, p = 0.002) and 1.3 years (CI 0.3-2.1, p = 0.004) with NCD. Compared with those in the lowest FT4 tertile, the difference in LE for men and women in the highest FT4 tertile was -3.7 years (CI -5.1 to -2.2, p < 0.001) and -3.3 years (CI -4.7 to -1.9, p < 0.001), respectively, of which -1.8 years (CI -3.1 to -0.7, p = 0.003) and -2.0 years (CI -3.4 to -0.7, p = 0.003) without NCD. A limitation of the study is the observational design. Thus, the possibility of residual confounding cannot be entirely ruled out. CONCLUSIONS: In this study, we found that people with low-normal thyroid function (i.e., highest tertile of TSH and lowest tertile of FT4 reference ranges) are expected to live more years with and without NCD than those with high-normal thyroid function (i.e., lowest tertile of TSH and highest tertile of FT4 reference ranges). These findings provide support for a re-evaluation of the current reference ranges of thyroid function.

Thyroid Function and the Risk of Atherosclerotic Cardiovascular Morbidity and Mortality: The Rotterdam Study.

RATIONALE: Thyroid hormones have been linked with various proatherogenic and antiatherogenic processes. However, the relationship of thyroid function with manifestations of atherosclerosis remains unclear. OBJECTIVE: To investigate the association of thyroid function with atherosclerosis throughout its spectrum; that is, subclinical atherosclerosis, incident atherosclerotic cardiovascular (ASCV) events, and ASCV mortality. METHODS AND RESULTS: This population-based study was embedded within the Rotterdam Study. The risk of atherosclerosis was evaluated by measuring (1) presence of subclinical atherosclerosis, assessed by coronary artery calcification score >100 AU; (2) ASCV events, defined as fatal and nonfatal myocardial infarction, other coronary heart disease mortality, or stroke; (3) ASCV mortality, defined as death because of coronary heart disease and cerebrovascular or other atherosclerotic diseases. Associations of thyroid-stimulating hormone and free thyroxine with the outcomes were assessed through logistic regression and Cox proportional hazard models, adjusted for potential confounders, including cardiovascular risk factors. A total of 9420 community-dwelling participants (mean age±SD, 64.8±9.7 years) were included. During a median follow-up of 8.8 years (interquartile range, 4.5-11.8 years), 934 incident ASCV events and 612 ASCV deaths occurred. Free thyroxine levels were positively associated with high coronary artery calcification score (odds ratio, 2.28; 95% confidence interval, 1.30-4.02) and incident ASCV events (hazard ratio, 1.87; confidence interval, 1.34-2.59). The risk of ASCV mortality increased in a linear manner with higher free thyroxine levels (hazard ratio, 2.41; confidence interval, 1.68-3.47 per 1 ng/dL) and lower thyroid-stimulating hormone levels (hazard ratio, 0.92; confidence interval, 0.84-1.00 per 1 logTSH). Results remained similar or became stronger among euthyroid participants. CONCLUSIONS: Free thyroxine levels in middle-aged and elderly subjects were positively associated with atherosclerosis throughout the whole disease spectrum, independent of cardiovascular risk factors.

Achieved systolic blood pressure in older people: a systematic review and meta-analysis.

BACKGROUND: It remains unclear into which level the systolic blood pressure (SBP) should be lowered in order to provide the best cardiovascular protection among older people. Hypertension guidelines recommendation on attaining SBP levels <150 mmHg in this population is currently based on experts' opinion. To clarify this issue, we systematically reviewed and quantified available evidence on the impact of achieving different SBP levels <150 mmHg on various adverse outcomes in subjects aged ≥60 years old receiving antihypertensive drug treatment. METHODS: We searched 8 databases to identify randomized controlled trials (RCTs) and post-hoc analyses or subanalyses of RCTs reporting the effects of attaining different SBP levels <150 mmHg on the risk of stroke, acute myocardial infarction, heart failure, cardiovascular mortality and all-cause mortality in participants aged ≥60 years. We performed random-effects meta-analyses stratified by study design. RESULTS: Eleven studies (> 33,600 participants) were included. Compared with attaining SBP levels ≥140 mmHg, levels of 130 to <140 mmHg were not associated with lower risk of outcomes in the meta-analysis of RCTs, whereas there was an associated reduction of cardiovascular mortality (RR 0.72, 95% CI 0.59-0.88) and all-cause mortality (RR 0.86, 95% CI 0.75-0.99) in the meta-analysis of post-hoc analyses or subanalyses of RCTs. Limited and conflicting data were available for the SBP levels of <130 mmHg and 140 to <150 mmHg. CONCLUSIONS: Among older people, there is suggestive evidence that achieving SBP levels of 130 to <140 mmHg is associated with lower risks of cardiovascular and all-cause mortality. Future trials are required to confirm these findings and to provide additional evidence regarding the <130 and 140 to <150 mmHg SBP levels.

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.

Depression and anxiety symptoms are underestimated risk factors for postoperative prognosis in patients with Type 2 diabetes and peripheral artery disease undergoing partial foot amputation: Results from a prospective cohort study.

OBJECTIVE: The aim of this study was to evaluate the prevalence and impact of depression and anxiety symptoms on post-operative prognosis and 1-year all-cause mortality in a large unique cohort of patients with Type 2 diabetes (T2D) and peripheral artery disease (PAD) after partial foot amputation (PFA). METHODS: Prospective cohort study with 1-year follow-up of 785 consecutive patients (mean age 60.9 ± 9.1 years; 64.1% males) with T2D and PAD after PFA. Depressive symptoms were assessed by Patient Health Questionnaire-9 (PHQ-9) and anxiety symptoms by Hamilton Anxiety Rating Scale (HARS). We used multivariable Cox proportional hazard models to examine the association of depression and anxiety with all-cause mortality. RESULTS: One-year all-cause mortality was 16.9% (n = 133). 331 (42.1%) patients had PHQ-9 score ≥ 10 indicating major depressive disorder. After adjusting for confounders, PHQ-9 score ≥ 10 was associated with an increased risk of 1-year all-cause mortality (HR = 1.68 (95%CI[1.16-2.44], p = 0.006). Depression dimensions of negative self-feeling and suicidal ideations were independently associated with 1-year mortality (HR = 1.26 (95%CI[1.24-1.55], p = 0.029 and HR = 2.37 (95%CI[1.89-2.96], p < 0.001, respectively). Compared to no depression, severe depressive symptoms (cut-off≥20) were associated with increased all-cause mortality (HR = 3.9 (95%CI [1.48-10.29], p = 0.006). Compared to no anxiety, severe anxiety symptoms (cut-off>30) were associated with increased 1-year mortality (HR = 2.25(95%CI [1.26-4.05], p = 0.006). CONCLUSION: Depressive symptoms and severe anxiety have shown independently increased risk of 1-year all-cause mortality in patients with T2D and PAD requiring PFA. Our results indicate that screening for anxiety and depression should be considered under these circumstances to identify patients at increased risk to allow appropriate intervention.

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.

Potential Mediating Role of Iron Biomarkers in the Association of Sex With Glucose, Insulin, and Type 2 Diabetes.

Context: Sex-specific prevalence and incidence of type 2 diabetes (T2D) have been reported, but the underlying mechanisms are uncertain. Objective: In this study, we aimed to investigate whether iron biomarkers mediate the association between biological sex and glucose metabolism and the incidence of T2D. Methods: We used data from the general population enrolled in the prospective Prevention of REnal and Vascular ENd-stage Disease study in Groningen, The Netherlands. We measured ferritin, transferrin saturation (TSAT), hepcidin, soluble transferrin receptor (sTfR), fasting plasma glucose (FPG), fasting plasma insulin (FPI) levels, and incidence of T2D. We used multivariable regression and mediation analyses to investigate our hypothesis. All iron biomarkers, FPG, and FPI were log-transformed. Results: The mean (SD) age of the 5312 (51.3% female) individuals was 52.2 (11.6) years. Compared with males, females had lower FPG (ß = -.01; 95% CI -0.02, -0.01) and FPI (ß = -.03; 95% CI -0.05, -0.02) levels. Ferritin, hepcidin, and sTfR showed potential mediating effects on the association between sex and FPG, 21%, 5%, and 7.1%, respectively. Furthermore, these variables mediated 48.6%, 5.7%, and 3.1% of the association between sex and FPI, respectively. Alternatively, TSAT had a suppressive mediating role in the association of sex with FPG and FPI. The incidence of T2D was lower in females than in males (hazard ratio 0.58; 95% CI 0.44, 0.77), with 19.2% of this difference being mediated by ferritin. Conclusion: Iron biomarkers may partially mediate the association between sex and glucose homeostasis. Future studies addressing the causality of our findings are needed.

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.

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.

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.

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.

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.