Highest Tertile Research Articles

Association between cardiometabolic index and frailty among patients with diabetes mellitus: a cross-sectional study

BackgroundCardiometabolic index (CMI) is a novel marker that can assess metabolic status. Studies have found that people with diabetes mellitus (DM) are at high risk of developing frailty. However, there is a lack of evidence between CMI and the risk of frailty in patients with DM. Therefore, the aim of this study was to investigate the association between CMI and frailty in patients with DM.MethodsThis study utilized data from the 2005-2018 National Health and Nutrition Examination Survey (NHANES). Weighted multivariate logistic regression was conducted in this study to explore the association between CMI and frailty status in patients with DM. In addition, subgroup analyses and interaction analyses were conducted to assess heterogeneity between different subgroups. Subsequently, restricted cubic spline (RCS) was also used to test for non-linear relationships.ResultsThis study ultimately included 2,761 patients with DM. Weighted multivariate logistic regression showed that, after adjusting all covariates, an increase in the level of CMI was associated with an increased risk of being in a frailty status in patients with DM (OR = 1.12, 95% CI = 1.04–1.22, p = 0.005). Dividing CMI into tertiles, the risk of frailty in patients in the highest tertile (Q3) was higher than that of patients in Q1 (OR = 1.56, 95% CI = 1.18–2.07, p = 0.002). The non-linear relationship between CMI and the risk of frailty in DM patients was further confirmed by RCS analysis.ConclusionThis study found that the higher the CMI, the higher the risk of frailty in DM patients. Maintaining a healthy low-fat dietary pattern and properly controlling blood lipid levels may reduce the risk of frailty in patients with DM.

Metabolic syndrome in association with novel dietary index, metabolic parameters, nesfatin-1 and omentin-1

BackgroundMetabolic syndrome is a prevalent and common health problem and numerous studies have revealed the role of diet and lifestyle change in prevention of metabolic syndrome. However, the novel dietary index, cardioprotective index (CPI) and its association with metabolic syndrome is not investigated yet. In the current study, we evaluated the association between metabolic syndrome and its components, CPI, Nesfatin-1 and Omentin-1in a cross-sectional study.MethodsThree hundred forty eight overweight and obese individuals with metabolic syndrome were recruited. Subjects underwent anthropometric and laboratory assays including metabolic markers, Nesfatin-1 and Omentin-1 with commercial kits.ResultsThose at the first tertile of CPI had lower high density lipoprotein concentrations (HDL) and higher low density lipoprotein concentrations (LDL), triglyceride (TG), systolic and diastolic blood pressures (SBP, DBP) levels compared with those at the highest tertiles (P < 0.05). After adjustment for the confounding effects of age, sex, body mass index, physical activity and total calorie intake, LDL lost its significance across CPI tertiles. Moreover, serum total cholesterol, insulin and insulin resistance were not significant across CPI tertiles neither in crude nor in adjusted models (P > 0.05). Additionally, being at the third tertile of CPI was accompanied with significantly higher Nesfatin-1 and Omentin-1 levels compared with lowest tertiels (P < 0.05) in crude and confounder – adjusted models. Conclusions: To our findings, CPI was in positive relationship with metabolic parameters, blood pressure, Nesfatin-1 and Omentin-1 levels in metabolic syndrome. Further future studies will help to elaborate the causality.Clinical trial numberNot applicable.

Association of lower serum sclerostin levels with elevated risk for increased arterial stiffness: The JPOS Cohort Study.

Studies on the relationship between serum sclerostin, a Wnt/β-catenin pathway inhibitor, and atherosclerosis have yielded inconsistent results. We aim to longitudinally investigate the relationship between serum sclerostin levels and the risk of increased arterial stiffness in Japanese community-dwelling women. Of 1044 women aged ≥50 years whose brachial-ankle pulse wave velocity (baPWV) value was available in a baseline survey in 2011-2012, we excluded 374 whose baPWVs were ≥1800 cm/s, set as the cutoff for increased arterial stiffness, and eight with missing data. Of the remaining 662 women, we included in the analysis 556 followed in the 4- to 5-year follow-up study. The coefficient of variation of the sclerostin measurement was 3.45%. We obtained odds ratios (ORs) for sclerostin at baseline categorized by tertiles, with the high tertile as reference for increased arterial stiffness. Ninety-four women showed increased arterial stiffness during a mean follow-up of 4.0 years. The increased arterial stiffness rates in the low, medium, and high tertiles were 22.2%, 16.1%, and 12.4%, respectively (trend test p = 0.013). The ORs for the medium and low tertiles for increased arterial stiffness were 1.58 (p = 0.205) and 2.16 (p = 0.027), respectively, after adjusting for age and baseline baPWV. After further adjustment for baseline BMI, hypertension, hyperlipidemia, diabetes mellitus, eGFR, and BMC at whole body, the ORs for the medium and low tertiles were 1.65 (p = 0.181) and 2.50 (p = 0.014), respectively. Lower serum sclerostin levels were associated with elevated risks for increased arterial stiffness in Japanese community-dwelling women.

Associations of Circulating Platelet Endothelial Cell Adhesion Molecule-1 Levels With Progression of Cerebral Small-Vessel Disease, Cognitive Decline, and Incident Dementia.

The association between platelet endothelial cell adhesion molecule-1 (PECAM-1) with cerebral small-vessel disease and cognition in dementia-free subjects remains uninvestigated. A prospective cohort of dementia-free subjects was recruited from memory clinics and followed up for 5 years. Annual neurocognitive assessments and twice-yearly brain magnetic resonance imaging scans were performed. Associations of baseline plasma PECAM-1 levels with cerebral small-vessel disease, cognitive decline (Montreal Cognitive Assessment scores and executive function Z scores), and incident dementia were evaluated. Of 213 subjects (aged 70.2±7.7 years, 51.2% men), median PECAM-1 levels were 0.790 (interquartile range, 0.645-0.955 ng/mL). Compared with the highest tertile, subjects within the lowest PECAM-1 tertile had greater cross-sectional white matter hyperintensity volume (β=4.84 [95% CI, 0.67-9.01]; P=0.023), age-related white matter change scores (β=1.39 [95% CI, 0.12-2.67]; P=0.033), and cerebral microbleeds (Adjusted risk ratio, 2.59 [95% CI, 1.19-5.62]; P=0.016). Of the 204 participants with follow-up data (median, 60.0 [interquartile range, 60.0-60.0] months), 24 (11.8%) developed incident dementia. Compared with the highest tertile, subjects within the lower tertiles of PECAM-1 had a higher risk of incident dementia (first tertile: adjusted hazard ratio [AHR], 4.52 [95% CI, 1.35-15.13]; P=0.024; second tertile: AHR, 3.28 [95% CI, 1.02-10.60]; P=0.047). The lowest PECAM-1 tertile was associated with greater progression of white matter hyperintensity volume (β=4.15 [95% CI, 0.06-8.24]; P=0.047), cerebral microbleeds (incident relative risk [IRR], 2.21 [95% CI, 1.05-4.65]; P=0.036), and decline in executive function (β=-0.45 [95% CI, -0.76 to -0.14]; P=0.004), and Montreal Cognitive Assessment (β=-1.32 [95% CI, -2.30 to -0.35]; P=0.008) scores. In dementia-free subjects, lower circulating PECAM-1 levels are associated with greater cerebral small-vessel disease progression and cognitive decline, thus warranting future study as a potential therapeutic target.

Primary Open-Angle Glaucoma Polygenic Risk Score and Risk of Disease Onset

Primary open-angle glaucoma (POAG) is a heritable disease. A polygenic risk score (PRS) threshold may be used to identify individuals at low risk of disease onset. To assess the utility of a POAG PRS to identify ocular hypertensive individuals at low risk of disease onset. This is a post hoc analysis of the Ocular Hypertension Treatment Study (OHTS), a multicenter randomized clinical trial across 22 centers in the US conducted among 1636 participants with ocular hypertension from February 1994 to April 2019 with available genetic data. Of the 1636 original participants, 1077 had available genetic data; after excluding 67 for missing data, data quality concerns, or ancestry other than European or African, 1010 were included in the present analysis. Data for this report were analyzed from November 2023 to June 2024. From 1994-2002, participants were randomized to receive topical intraocular pressure (IOP)-lowering medications. From 2002 onwards, all participants were given topical IOP-lowering medications. Twenty-year conversion rates by POAG PRS threshold, baseline randomization status, and OHTS clinical risk tertile. Among the 1010 participants in this study, 563 (65.8%) were female, and the mean (SD) age was 55.9 (9.4) years. In a mixed-effects logistic regression model adjusted for OHTS risk factors for conversion to POAG and randomization status, a PRS under the 48th percentile was associated with a 1.49 times higher likelihood of disease-free status after 20 years of follow-up (95% CI, 1.04-2.15; P = .03; unadjusted hazard ratio [HR], 1.64; 95% CI, 1.13-2.38; P = .009), compared with high polygenic risk. When we stratified the trial cohort into nongenetic OHTS clinical risk tertiles, the largest differences in survival probability at 20 years based on PRS threshold was observed in eyes in the highest tertile, initial observation group (20-year conversion rate: 61.1% in the high polygenic risk group vs 23.8% in the low polygenic risk group; 95% CI, -63.0 to -11.6; P = .01), with randomization to early treatment partially mitigating the effect of high genetic risk (20-year conversion rate: 37.3% in the high polygenic risk group vs 24.1% in the low polygenic risk group; 95% CI, -35.6 to 9.3%; P = .32). These findings support considering use of a POAG PRS threshold to identify individuals at low risk of disease onset, with those below the PRS threshold more likely to have lower conversion rates over 20 years. Among those considered at highest risk based on the OHTS clinical risk model, early treatment may partially offset the association with high genetic risk but provide limited benefit for those with low genetic risk. ClinicalTrials.gov Identifier: NCT00000125.

Primary Care Practice Telehealth Use and Low-Value Care Services

The rapid expansion of telehealth transformed how primary care practices deliver care; however, uncertainties about the quality of telehealth-delivered care compared with in-person care remain. While there are concerns that increased telehealth may introduce wasteful care, how telehealth affects the delivery of low-value care is unknown. To examine whether a primary care practice's level of telehealth use is associated with changes in the rates of low-value care. This retrospective cohort study using a difference-in-differences study design was conducted from January 1, 2019, to December 31, 2022, using Medicare fee-for-service claims data. Participants were Medicare beneficiaries attributed to primary care practices in Michigan. Low, medium, or high tertile of practice-level telehealth use. Low-value care was assessed using 8 claims-based measures relevant to primary care, grouped into 4 main categories: office-based, laboratory-based, imaging-based, and mixed-modality services. Poisson regression models were used to estimate the association between practice-level telehealth use and rates of low-value care services, controlling for practice-level characteristics. A total of 577 928 beneficiaries (332 100 [57%] women; mean [SD] age, 76 [8] years) attributed to 2552 primary care practices were included in the study. After adjusting for practice-level characteristics and baseline differences in low-value care rates between telehealth use groups, high practice-level telehealth use was associated with lower rates of low-value cervical cancer screening (-2.9 [95% CI, -5.3 to -0.4] services per 1000 beneficiaries) and lower rates of low-value thyroid testing (-40 [95% CI, -70 to -9] tests per 1000 beneficiaries) compared with low practice-level telehealth use. Of the other 6 outcomes examined, there was no association between practice-level telehealth use and rates of low-value care services. In this cohort study of Medicare fee-for-service beneficiaries who received care from primary care practices in Michigan, some low-value care services (ie, cervical cancer screening among women older than 65 years and low-value thyroid testing) were lower among practices with high telehealth use, and there was no association between practice-level telehealth use in rates of most other low-value care services not delivered in the office. As telehealth continues to be an important part of care delivery, evaluating how it may encourage or discourage low-value care services is critical to understanding its impact on quality of care.

Impacto clínico de la adiposidad visceral en la mortalidad a largo plazo de pacientes sometidos a revascularización coronaria

Introduction and objectives: Although visceral adiposity increases cardiovascular risk in the general population, the obesity paradox has been reported in critically ill patients. However, evidence for its prognostic role in patients undergoing coronary artery bypass grafting (CABG) is limited. This study evaluated the prognostic implications of visceral adiposity in patients who underwent CABG using computed tomography-based measurement of visceral fat.Methods: A total of 2810 patients who underwent CABG from 2007 to 2017 were analyzed. The study population was classified into 3 groups according to visceral fat area index (VFAI) tertiles. VFAI was calculated as visceral fat area (cm2)/height2 (m2) at the L3 level. The primary outcome was all-cause mortality during follow-up.Results: Patients in the low VFAI group (lowest tertile) were younger and had a lower body mass index and less subcutaneous fat than those in the high VFAI group (highest tertile). During a median 8.7-year follow-up, VFAI was significantly associated with the risk of mortality in restricted cubic spline curve analysis (HR, 0.94 per 10 increases; 95%CI, 0.91-0.97; P < .001). Patients in the low VFAI group had a higher incidence of long-term mortality than those in the intermediate and high VFAI groups (T1 36.1%, T2 27.2%, and T3 29.1%; T1 vs T2; adjusted HR, 1.36; 95%CI, 1.15-1.61; P < .001; T1 vs T3; adjusted HR, 1.37; 95%CI, 1.16-1.62; P < .001). Similar results were obtained after inverse probability treatment-weighting analysis.Conclusions: Low visceral adiposity was associated with an increased risk of long-term mortality in patients who underwent CABG.

Serum total bilirubin is a risk factor of metabolic syndrome and its components in obese Egyptians.

The link between serum total bilirubin and metabolic syndrome and its components has been previously proposed. However, it is unknown whether total bilirubin is a risk factor of metabolic syndrome and its components in obese Egyptians. Therefore, this study was conducted to clarify the association of total bilirubin levels with metabolic syndrome and its components in obese Egyptians. A total of 200 adults with obesity were enrolled in this study. Obese participants were evaluated for metabolic syndrome; there were 92 obese participants with metabolic syndrome and 108 obese participants without metabolic syndrome. Anthropometric measurements, fasting blood glucose (FBG), fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), HOMA-β (%), lipid profile, uric acid, alanine aminotransferase, aspartate aminotransferase, and serum total bilirubin were assessed. Total bilirubin was significantly lower in obese participants with metabolic syndrome than in those without metabolic syndrome. Compared with middle bilirubin tertile, high and low bilirubin tertiles were independently associated with metabolic syndrome. Regarding metabolic syndrome components, a significant positive association between low bilirubin tertile and hypertension was found independent of the all studied confounding factors, whereas the association of total bilirubin level with waist circumference (WC), FBG, high-density lipoprotein cholesterol, and triglycerides was dependent on body mass index (BMI), HOMA-IR, and high sensitive C-reactive protein (hs-CRP). Total bilirubin is an independent risk factor of metabolic syndrome in obese Egyptians. We have found an independent association between high bilirubin level and reduced risk of metabolic syndrome, whereas low bilirubin level was associated with increased risk of metabolic syndrome. Bilirubin is also independently associated with hypertension, but its association with other components of metabolic syndrome is mainly dependent on BMI, HOMA-IR, and hs-CRP.

Assessing management factors limiting yield and starch content of cassava in the western Brazilian Cerrado

AbstractCassava (Manihot esculenta Crantz) was declared the “crop of the 21st century” by the Food and Agriculture Organization of the United Nations due to its high starch content and low input requirements. The management factors that govern yields and starch content in cassava in Brazil are still unclear. The aim of this study was to identify the main factors that limit the yield and starch content of cassava fields in Brazilian Cerrado. The data were collected as part of a survey covering 300 cassava fields in two growing seasons (2020–2021 and 2021–2022). Throughout the development cycle, management practices, yield, and percentage starch content in the roots were described. The database was divided into high and low yield tertiles. Mean comparison tests, regression tree analyses, and boundary functions were applied. The importance of genetics, environment, and associated crop constraints on cassava production (yields and starch content) was assessed. The yield gap in cassava was 44.6 Mg ha−1. The most important factors leading to yield and starch losses were variety, planting date, and potassium fertilization. By adapting optimal practices, it is possible to produce an additional 1.5 million tons of cassava on the current cultivation area in the western Brazilian Cerrado, which corresponds to 8.3% of total production in Brazil and could increase the production of cassava starch by more than 400,000 Mg.

The association between dietary quality index- international and metabolic risk factors in RaNCD cohort study

BackgroundNon-communicable diseases (NCDs) are the leading cause of death around the world. The Dietary Quality Index-International (DQI-I) is one of the indicators that shows changes in diet and its association with NCDs. The aim of this study is to measure the association between the DQI-I and major metabolic risk factors.MethodsThis study is a cross-sectional study based on data collected in the first phase of the prospective cohort study on Ravansar non-communicable diseases (RaNCD). To perform clinical and biochemical tests such as lipid profile, blood glucose and liver enzymes, blood samples were collected using standard vacutainer blood collection techniques. Information from the food frequency questionnaire containing 118 food items was used to score each person’s DQI-I. Binary logistic regression was used to determine the association between the DQI-I tertile and the metabolic risk factors. Linear regression was also used for the association between subgroups of DQI-I score and the metabolic risk factors.ResultsThe total number of subjects in this study was 7,115, with a mean age of 47.14 ± 8.29 years. Dietary quality was generally poor, with 37.03% in the lowest tertile. Men had better dietary quality than women. Anthropometric measures, blood pressure, triglycerides and blood glucose were lower in the lowest tertile of dietary quality. A one-unit increase in the total DQI-I resulted in a 0.19 decrease in total cholesterol. Higher dietary quality was associated with a 22% increased risk of high triglycerides, a 19% increased risk of low high-density density lipoprotein, a 5% decreased risk of elevated low-density lipoprotein, a 42% increased risk of high blood pressure, and a 99% increased risk of high fasting blood glucose. Higher dietary quality was also associated with a 33% increased risk of overweight/obesity.ConclusionThe study found that participants had poor dietary quality, with some favorable metabolic outcomes in the lowest tertile, but concerning associations in the highest tertile, including increased risk for high triglycerides, blood pressure, and obesity. The complex associations suggest that balanced, multifaceted interventions are needed.

Decreased neutrophils are associated with reduced risk of Type 2 Diabetes Incidence: Results from the CORDIOPREV study.

Numerous studies have reported an association between neutrophils and T2DM, although this relationship remains unclear. This study aims to investigate the interaction of neutrophils and a dietary intervention on T2DM incidence after 60 months of follow-up. A comprehensive analysis was conducted on the framework of the CORDIOPREV study, which included 462 patients without T2DM at the beginning of the study. They were randomly assigned to either a Mediterranean or a low-fat diet, of whom 107 developed T2DM. Absolute neutrophil counts and other related-ratio, were measured. Kaplan-Meier curves showed that the lowest tertile of basal neutrophils was associated with a reduced likelihood of T2DM incidence when compared to the middle [HR=0.499 (95%CI, 0.287-0.866)] and the highest tertiles [HR=0.442 (95%CI, 0.255-0.768)] in overall population, after adjusting for clinical variables. This association only remained significant in patients who follow a Mediterranean diet when compared the lowest to the middle [HR=0.423 (95% CI, 0.213-0.842)] and the highest tertiles [HR=0.371 (95% CI, 0.182-0.762)]. The predictive capacity yielded an AUC of 0.711 (95%CI: 0.652-0.769), being neutrophils the most important variable in the in the model. Decrease in neutrophils over the 60 months were associated with increased insulin sensitivity index (ISI) (R=-0.31; p=0.019), particularly in patients who followed the Mediterranean diet. These findings suggest that monitoring neutrophils can help prevent the development of T2DM, as a reduction in neutrophil counts could be associated with improved insulin sensitivity. Following a Mediterranean diet might be a potential strategy to reduce the incidence of T2DM by lowering neutrophil levels. Further research is necessary to gain a deeper understanding regarding this mechanism.

Prognostic value of C-reactive protein / albumin ratio for amputation and/or mortality after lower extremity revascularization in haemodialysis patients with peripheral artery disease

Abstract Background Hypoalbuminemia, a manifestation of protein-energy wasting (PEW) or malnutrition, which is commonly observed in patients with chronic kidney disease, is associated with increasing cardiovascular risk. Recently, C-reactive protein (CRP) / albumin ratio has been developed as a newly surrogate marker of the PEW because the PEW seems to result not only from an inadequate diet but also rather be induced by chronic inflammatory status. The aim of this study was to clarify whether pre-procedural CRP/albumin ratio levels could predict amputation and/or mortality after lower extremity revascularization for peripheral artery disease (PAD) in patients on haemodialysis (HD). Methods A total of consecutive 1,850 HD patients successfully undergoing lower extremity revascularization (494 bypass surgery and 1,356 endovascular therapy) were enrolled in this study. Patients were divided into tertiles according to pre-procedural CRP/albumin ratio levels; low (&amp;lt;0.6, n=619), middle (0.6-3.7, n=609) and high tertile (&amp;gt;3.7, n=622). They were followed up for up to 8-year. The primary endpoint was defined as amputation and/or mortality. Results During follow-up period (median of 53 months), 162 major amputation (8.8%) was performed and 508 patients (27.5%) died. Cumulative incidence rates of amputation and/or mortality at 8-year were 47.4%, 56.2% and 70.0% in low, middle and high tertile of CRP/albumin ratio, respectively (p&amp;lt;0.0001). After adjustment for male, age, traditional risk factors, body mass index, history of coronary artery disease or stroke, procedure (bypass vs. endovascular therapy), infrapopliteal disease and ulcer/gangrene, the CRP/albumin ratio was identified as an independent predictor for amputation and/or mortality [adjusted hazard ratio (aHR) 1.39, 95% confidence interval (CI) 1.12-1.72, p=0.0028 for middle vs. low tertile, and aHR 2.53, 95% CI 2.07-3.09, p&amp;lt;0.0001 for high vs. low tertile, respectively]. Similar results were also observed even for major amputation and mortality, respectively (aHR 2.73, 95% CI 1.77-4.31 for amputation and aHR 2.32, 95% CI 1.82-2.97 for mortality with p&amp;lt;0.0001 for high vs. low tertile in both, respectively, Figure). Conclusion Pre-procedural CRP/albumin ratio could predict both of amputation and mortality after lower extremity revascularization, and could stratify the risk in HD patients with PAD. Measurement of CRP/albumin ratio in such high-risk population may be useful because this newly surrogate marker of the PEW is simple and can be easily obtained in daily practice.

Impact of differences in body mass index, body surface area and lean body mass on clinical outcomes in patients with atrial fibrillation receiving edoxaban: 4-year follow-up data from ETNA-AF-Europe

Abstract Background In patients with atrial fibrillation (AF) treated with non-vitamin K antagonist oral anticoagulants, extremes in body weight and its anthropometric correlates (body mass index [BMI], body surface area [BSA] and lean body mass [LBM]) may affect drug exposure and the occurrence of thromboembolic or haemorrhagic events. Purpose To investigate the association of BMI, BSA and LBM with clinical outcomes according to sex in edoxaban-treated patients with AF using 4-year data from ETNA-AF-Europe (NCT02944019). Methods The prospective, observational ETNA-AF-Europe study followed patients with AF receiving edoxaban for up to 4 years. In this subanalysis, patients were categorised into tertiles (low, middle, and high) for BMI, BSA and LBM and stratified by sex. Baseline characteristics and rates of any thromboembolic and haemorrhagic events per 100 patient-years ([%]/100PY) are reported using 4-year follow-up data. Results Of 13,164 patients, 7461 were men and 5703 were women. Table 1 shows the ranges of BMI, BSA and LBM, defining the low, middle, and high tertiles, and their corresponding baseline characteristics. Irrespective of sex, patients in the low tertile for BMI, BSA and LBM were older and more likely to have renal impairment, history of stroke, and to receive appropriate edoxaban 30mg or non-appropriate edoxaban 60mg. Patients in the high tertile were more likely to have diabetes and hypertension. Overall, the rate (%)/100PY of any thromboembolic event was slightly lower (0.8 vs 1.1%), whereas the corresponding rate of any haemorrhagic event was slightly higher (1.9 vs 1.7%) in men vs women (Figure 1). For BMI, BSA and LBM in men, rates (%)/100PY of any thromboembolic event were similar among tertiles (low, middle, high; BMI, 0.9, 0.8 and 0.8%; BSA, 0.9, 0.8 and 0.8%; LBM, 0.9, 0.7 and 0.9%). For BMI, rates (%)/100PY of any haemorrhagic event were similar among tertiles in men (BMI, 1.9, 1.8 and 2.0%), but highest in the low tertile for BSA and LBM (BSA, 2.4, 1.8 and 1.5%; LBM, 2.4, 1.8 and 1.5%). In women, rates (%)/100PY of any thromboembolic event were similar for all tertiles of BMI but were highest in the low tertile for BSA and LBM (low, middle, high; BMI, 1.3, 1.1 and 1.1%; BSA, 1.4, 1.1 and 1.0%; LBM, 1.4, 1.2 and 0.9%; Figure 1). For BMI, BSA and LBM, rates (%)/100PY of any haemorrhagic event were highest in the low tertile in women (low, middle, high; BMI, 2.1, 1.6 and 1.6%; BSA, 2.2, 1.7 and 1.4%; LBM, 2.3, 1.5 and 1.5%). Conclusions At the 4-year follow-up in this real-life registry, low rates (%/100PY) of any thromboembolic event ([0.7–1.4%]) were observed regardless of patients' BMI, BSA, LBM, or sex. However, higher rates of any haemorrhagic events were observed in the low ([2.2–2.4%]) vs middle ([1.5–1.8%]) and high ([1.4–1.5%]) tertiles for BSA and LBM, suggesting that these variables, more than BMI, should be considered when analysing outcomes in patients with AF treated with edoxaban.Baseline characteristicsFigure 1

Comparative assessment of extracellular volume metrics in predicting adverse outcomes in patients with transthyretin amyloid cardiomyopathy

Abstract Introduction The indexed total extracellular volume of the myocardium (iECV) has recently been proposed to be superior in predicting adverse outcome in severe aortic stenosis as compared to conventional extracellular volume (ECV). So far, no study has assessed the comparative predictive performance of both measures in transthyretin amyloid cardiomyopathy (ATTR-CM). Aim We aimed to assess and compare the predictive performance of conventional ECV against iECV in determining adverse outcomes in patients with ATTR-CM. Methods From 2012 to 2023, patients with ATTR-CM undergoing contrast cardiac magnetic resonance (CMR) imaging prior to any specific treatment were enrolled. Both, conventional ECV and iECV were quantified on CMR alongside left ventricular volumetrics and late gadolinium enhancement. Adverse outcome was defined as a composite endpoint of hospitalization for heart failure and/or death. Results Analysis of 178 patients with ATTR-CM (82% males, mean age 77±8 years) revealed a mean conventional ECV of 47±13% and a mean iECV of 46±21 mL/m2, with a median follow-up of 2.5 years (IQR: 1.00-4.08 years). Conventional ECV was significantly associated with the composite endpoint (HR=1.03, 95%CI=1.01–1.05, p=0.006), outperforming iECV (HR=1.01, 95%CI=1.00–1.02, p=0.010). On multivariate analysis, adjusted for age, sex and left ventricular function, conventional ECV remained associated with the composite endpoint (p=0.002), while iECV demonstrated a slightly less significant association (p=0.003). Kaplan-Meier analysis, stratified by conventional ECV tertiles, revealed that patients in the highest tertile (ECV ≥53%) demonstrated the highest event rate (p = 0.043 by log rank test, see Figure 1A), in contrast to iECV (p=NS, Figure 1B). Conclusions High conventional ECV, among CMR fibrosis markers, is linked to heart failure hospitalizations and death in ATTR-CM, demonstrating superior prognostic value compared to iECV. Conventional ECV measurements may offer enhanced risk stratification for patients with ATTR-CM.

Aortic valve calcium score to mean gradient ratio: a new frontier in aortic stenosis prognostication

Abstract Introduction Aortic stenosis (AS) presents diagnostic challenges, especially in patients with discordant low gradient AS (LGAS), i.e., small aortic valve area (AVA) and low Doppler mean gradient (MG). LGAS is associated with worse outcomes compared to concordant AS. Aortic valve calcium score (AVCS) is a measure of AS severity independent of flow and helps diagnose severe AS. It is unknown if the degree of discordance in AVCS and MG is of any clinical significance. A high AVCS/MG ratio may indicate impaired ventricular function and response to pressure overload despite preserved LVEF, potentially contributing to worse outcomes. Purpose This study aims to elucidate the prognostic significance of the AVCS/MG ratio in patients with severe AS and preserved left ventricular ejection fraction (LVEF) undergoing TAVR. We hypothesized a higher AVCS/MG ratio correlates with increased mortality. Methods Patients who underwent transcatheter aortic valve replacement (TAVR) from 2010 to 2020 for native valve severe AS with LVEF≥50% were identified from an institutional database. AVCS were obtained within 90 days of pre-TAVR echocardiography. Patients were divided into tertiles based on their AVCS/MG ratio. Primary outcome was overall mortality. Results The analysis included 1067 patients (mean age 79±9 years, 43% female); overall AVA was 0.80±0.14 cm², LVEF 63±6%, MG 46±12 mmHg, AVCS 2630±1528 AU, and AVCS/MG ratio 58±31. Patients stratified by AVCS/MG tertiles showed no difference in overall comorbidity index across tertiles (Figure 1). However, the group in the highest tertile was the oldest (80±8 vs 79±8 vs 77±9 years), predominantly male (87% vs 61% vs 24%), with the highest prevalent atrial fibrillation (44% vs 28% vs 25%) and stroke volume index &amp;lt;35 mL/m² (16% vs 11% vs 5%). 9-year survival was 15% vs 25% vs 36% (p&amp;lt;0.001, Figure 2). In multivariate analysis adjusted for age, sex, comorbidities, LVEF and AVA, AVCS/MG ratio was independently associated with increased risk of mortality (HR 1.005; 95% CI [1.001-1.008], p=0.005). Conclusion Higher AVCS/MG discordance is associated with increased risk of mortality following TAVR. Serial AVCS measurements during progressive AS may help identify patients at higher risk who may potentially benefit from earlier aortic valve intervention.

The triglyceride-glucose index, ventricular arrhythmias and major cardiovascular events in patients at high risk of sudden cardiac death

BackgroundThe association between the triglyceride-glucose (TyG) index and ventricular arrhythmias (VAs) is unclear. This study aimed to investigate the relationship between the TyG index, VAs, and major cardiovascular events in patients at high risk of sudden cardiac death (SCD).MethodsWe enrolled 1046 patients at high risk of SCD with an indication for implantable cardioverter-defibrillator (ICD) implantation at the Chinese National Center for Cardiovascular Diseases. The primary outcome was VAs, defined as sustained ventricular tachycardia and ventricular fibrillation documented by the ICD. The secondary outcomes were cardiac mortality, heart transplantation, and rehospitalization for heart failure.ResultsThe mean (± SD) age was 59.6 ± 14.0 years old, and 25.7% were female. During the mean follow-up of 36.1 months, 342 (32.7%) patients had VAs, and 185 (17.7%) patients had major cardiovascular events. The mean fasting glucose and triglyceride levels were 111.9 ± 42.7 mg/dL and 140.0 ± 95.4 mg/L, respectively, with a TyG index range of 6.96–11.8. In the Fine-Gray subdistribution hazard model analysis, an increase in the TyG index was associated with a significant increase in the VAs (per 1 TyG index, hazard ratio [HR] 2.95; 95% confidence interval [CI], 2.29–3.80) and secondary outcome (HR 2.84; 95% CI 1.86–4.34). When stratified into tertiles, the risk of VAs was significantly higher in the highest tertile (HR 4.08; 95% CI, 2.81–5.92) than in the lowest tertile. Analysis of the secondary outcome revealed similar findings (HR 3.18; 95% CI, 1.73–5.85).ConclusionsIn our cohort, the pre-operational TyG index is significantly associated with VAs and major cardiovascular events for patients with high risk of SCD.

Amyloid beta, a marker of vascular aging and cardiovascular disease, is associated with accelerated progression of renal dysfunction

Abstract Background Amyloid-beta (1-40) (Αb1-40), a proinflammatory and pro-atherosclerotic peptide, is involved in Alzheimmer’s disease and vascular aging and is considered an emerging prognostic marker of atherosclerotic cardiovascular disease (ASCVD) and heart failure. Because Ab1-40 clearance is largely dependent on renal function while clinical data consistently associate this peptide with renal function, we hypothesized that Ab1-40 circulating levels would serve as a predictor of progression of renal dysfunction. Purpose To examine the potential cross-sectional and prospective bidirectional association of Ab1-40 levels with renal function in a population with a wide range of ASCVD risk. Methods In the settings of the Athens Cardiometabolic registry, data from consecutively recruited subjects with (n=137) and without clinically overt ASCVD (n=674) with available both Ab1-40 plasma levels and GFR values (total n=811) were analyzed. Αb1-40 was measured by enzyme-linked immunosorbent assay and renal function was assessed by estimation of glomerular filtration rate (GFR). Of these subjects, 182 individuals consented to be followed up and re-assessed after a minimum period of 12 months in order to examine a potential bidirectional link between changes in Ab1-40 levels and GFR. Results Patients with increased Ab1-40 levels at baseline had significantly worse renal function, reflected as lower GFR values, compared with their counterparts with lower Ab1-40 levels (GFR= 74.8 vs 93.3 vs 100.2 ml/min/1.73m2 for high, middle and low tertile of Ab1-40 levels, p&amp;lt;0.001). Elevated Ab1-40 levels were associated with chronic kidney disease (CKD) stage 2 [odds ratio (OR)=2.29, 95% confidence intervals (CI)= 1.58-3.31, p&amp;lt;0.001] and CKD stage 3 (OR=3.67, 95% CI=2.37-5.70, p&amp;lt;0.001) at baseline. Furthermore, increased Ab1-40 at baseline was prospectively associated with accelerated progression of renal dysfunction as assessed by changes in GFR values between baseline and follow-up [mean adjusted rate of decrease=-7.20 (95% CI=-1.33, -13.07) for higher vs lowest tertiles of Ab1-40 levels across a follow-up period of 12 months, p=0.017 for interaction). On the contrary, baseline GFR values were not prospectively associated with Ab1-40 levels at follow-up visits (p&amp;gt;0.05). Conclusion In a population with a wide range of ASCVD risk, high Αb1-40 levels at baseline were associated both with renal function at baseline and with accelerated rate of progression of GFR deterioration at follow-up irrespective of its baseline levels. These findings suggest a mechanistic background for the established association of Ab1-40 with renal function and warrant further research to clarify the clinical value of monitoring its circulating levels as a novel biomarker which could reflect enhanced risk for renal dysfunction.

Role of inflammation and cholesterol efflux in myocardial infarction patients without standard modifiable risk factors

Abstract Background A substantial proportion of ST-segment elevation myocardial infarction (STEMI) patients has no standard modifiable cardiovascular risk factors (SMuRF) at admission. Knowledge on pathogenesis and risk markers of mortality in these patients remain limited. Aims We described the characteristics and prognosis of SMuRF-less patients admitted for a first STEMI in the light of recent prognostic biomarkers. Methods Baseline characteristics including interleukin (IL)-1β, hs-CRP and serum cholesterol efflux capacity were compared between patients with and without SMuRF. Determinants of 1-year all-cause mortality were assessed using univariable and multivariable Cox regression analyses. Results Among the 1604 patients included, 178 (11.1%) were SMuRF-less. SMuRF-less patients were older (66.9 ± 15.3 vs 61.9 ± 13.9, p&amp;lt;0.001), less often men (66.9 vs 75.9%, p&amp;lt;0.001) and had lower body mass index (24.2 ± 3.9 vs 26.0 ± 4.4, p&amp;lt;0.001) compared to patients with ≥1 SMuRFs. SMuRF-less patients presented higher rates of altered LVEF&amp;lt;45% and killip≥2 at admission (31.8% vs 22.8%, p=0.014 and 19 vs 12.9%, respectively, p=0.027) without differences in proportions of late STEMI presenters (symptoms-to-balloon time &amp;gt;360 min) did not differ between groups. SMuRF-less patients had lower rates of revascularization (82 vs 92.3%, p&amp;lt;0.001) and received less guidelines recommended medications (statins, β-blockers or angiotensin-converting enzyme (ACE) inhibitors) at discharge; p&amp;lt;0.001 for all. Compared to patients with SMuRF, SMuRF-less patients had lower serum cholesterol efflux capacity (0.79 ± 0.16 vs 0.83 ± 0.16, respectively, p&amp;lt;0.001), were more often in the highest tertile of IL-1β (28.7% vs 18.9%, respectively, p=0.002) with a trend towards more patients within the highest hs-CRP level tertile (24.7% vs 19.1%, respectively, p=0.077). Crude rates of mortality were more than doubled in the SMuRF-less group (18.5% vs 7.7%, respectively, p&amp;lt;0.001). After multivariable adjustment SMuRF-less status was associated with a higher rate of mortality at one year aHR 1.87 [1.05-2.38], p=0.029) as well as inflammation biomarkers IL-1β (HR 1.81 [1.23-2.66], p=0.003) and high tertiles of hs-CRP (HR 1.87 [1.31-2.66], p&amp;lt;0.001) whereas having a high serum cholesterol efflux capacity was associated with a lower mortality (HR 0.27 [0.09-0.87], p=0.0208). Conclusion In STEMI patients, SMuRF-less patients have higher levels of inflammatory biomarkers and more frequent defective serum cholesterol efflux capacity, are undertreated, and have higher rate of mortality than patients with standard modifiable cardiovascular risk factors. Optimized management of such patients is needed.

Impact of metabolic abnormalities on the association between normal-range urinary albumin-to-creatinine ratio and cardiovascular mortality: evidence from the NHANES 1999–2018

BackgroundThe urinary albumin to creatinine ratio (UACR) is associated with adverse cardiovascular outcomes, even when within the normal range. However, the potential modification of this effect by metabolic abnormalities remains unclear. This study explored whether metabolic abnormalities modify the association between normal-range UACR and cardiovascular mortality.MethodsThis cohort study included 27,298 U.S. adults from the National Health and Nutrition Examination Survey 1999–2018, with mortality follow-up through December 31, 2019. Normal UACR (< 30 mg/g) was considered. Metabolic abnormalities were categorized into three groups based on the number of metabolic abnormality components: metabolic health (0 components), pre-metabolic syndrome (Pre-MetS, 1–2 components), and metabolic syndrome (MetS, 3–5 components). Multivariable Cox proportional hazards regression was used to estimate the association between normal UACR and cardiovascular mortality, stratified by metabolic abnormality groups.ResultsOver a median follow-up of 9.67 years, 764 cardiovascular deaths occurred. In the fully adjusted model, higher normal UACR was associated with an increased risk of cardiovascular death in metabolically abnormal individuals, but not in metabolically healthy individuals. When UACR was divided into tertiles, the highest tertile was associated with a 60% and 79% higher risk of cardiovascular mortality in the Pre-MetS and MetS groups, respectively, compared with the lowest tertile (Pre-MetS: HR, 1.60 [95% CI: 1.19–2.15]; MetS: HR, 1.79 [95% CI: 1.34–2.41]).ConclusionA higher normal UACR was associated with an increased risk of cardiovascular death in metabolically abnormal individuals, underscoring the need for early renal risk management in this population.

Association of Four Dietary Patterns and Stair Climbing with Major Adverse Cardiovascular Events: A Large Population-Based Prospective Cohort Study.

The protective effect of a healthy diet combined with stair climbing on cardiovascular health is unclear. We aimed to assess the independent and joint associations of dietary patterns and stair climbing with major adverse cardiovascular events (MACEs). We included 117,384 participants with information on dietary intake and stair climbing from the UK Biobank (UKBB). We excluded participants with MACEs at baseline and death within two years of follow-up. We used restricted cubic spline (RCS) plots describing the linear or nonlinear associations between dietary patterns (the alternate Mediterranean diet score (AMED), dietary approaches to stop hypertension (DASH), the healthful planted-based diet index (HPDI) and the alternate healthy eating index-2010 (AHEI-2010)) and stair climbing and MACEs. COX regressions estimated the hazard ratios (HRs) for incident MACEs associated with dietary patterns combined with stair climbing, and adjusted for sociodemographic, lifestyle and medical factors. The UKBB documented 9408 MACEs over a median follow-up of 13.3 years. Four dietary patterns were negatively and linearly associated with MACEs (P-nonlinear > 0.05), whereas daily stair climbing was negatively and nonlinearly associated with MACEs (P-nonlinear = 0.011). All of the dietary patterns had significant multiplicative interactions with stair climbing (all p-values < 0.05). The three dietary patterns had the lowest risk ratios for MACEs in the highest tertile (T3) combined with daily stair climbing of 60-100 steps (AMED: 0.78 (0.68, 0.89), DASH: 0.80 (0.70, 0.91) and HPDI: 0.86 (0.75, 0.98)), whereas the AHEI-2010 had the lowest HRs for MACEs in the T1 combined with stair climbing of 110-150 steps (AHEI-2010: 0.81 (0.71, 0.93)). Maintaining healthy dietary patterns and adhering to an average of 60-100 steps of stair climbing per day at home can be effective in preventing cardiovascular health-related events.