Lowest Tertile Research Articles

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

Microfibrillar-associated protein 4 as a predictive biomarker of treatment response in patients with chronic inflammatory diseases initiating biologics: secondary analyses based on the prospective BELIEVE cohort study.

Currently, there are no reliable biomarkers for predicting treatment response in chronic inflammatory diseases (CIDs). To determine whether serum microfibrillar-associated protein 4 (MFAP4) levels can predict the treatment response to biological therapy in patients with CIDs. The BELIEVE study was originally designed as a prospective, multi-center cohort study of 233 patients with either rheumatoid arthritis, psoriatic arthritis, psoriasis, axial spondyloarthritis, Crohn's disease, or ulcerative colitis, initiating treatment with a biologic agent (or switching to another). Clinical assessment and blood sample collection were performed at baseline and 14-16 weeks after treatment initiation. The primary analyses included participants with available blood samples at baseline; missing data were handled as non-responders. The patients were stratified into the upper tertile of serum MFAP4 (High MFAP4) versus a combined category of middle and lower tertiles (Other MFAP4). The primary outcome was the proportion of patients with clinical response to biologic therapy after 14-16 weeks. 211 patients were included in the primary analysis population. The mean age was 43.7 (SD: 14.8) years, and 120 (59%) were female. Positive treatment response was observed in 41 (59%) and 69 (49%) for High MFAP4 and Other MFAP4, respectively. When adjusting for pre-specified variables (CID, age, sex, smoking status, and BMI), the adjusted OR was 2.28 (95% CI: 1.07 to 4.85) for a positive treatment outcome in the High MFAP4 group. A high MFAP4 status before initiating biological treatment is associated with a positive clinical response, when adjusting for confounding factors.

Associations between neutrophil-percentage-to-albumin ratio level and all-cause mortality and cardiovascular disease-cause mortality in general population: evidence from nhanes 1999-2010

Abstract Introduction Chronic inflammation is a recognized independent risk factor for cardiovascular disease (CVD), highlighting the need for reliable inflammatory indicators to predict CVD(1). As an inflammatory indicator which has been proved to have predictive value for the prognosis of CVDs, neutrophil percentage-to-albumin ratio (NPAR) has obtained increasing attention(2,3), but further research is needed to confirm the relationship with mortality in general population. Purpose To explore whether NPAR can serve as a predictive inflammatory indicator for CVD-cause and all-cause mortality in general population. Methods This prospective cohort study included 21317 individuals who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2010. The baseline NPAR level was calculated as Neutrophil percentage (%) * 100/Albumin (g/dl). Data for CVD and all-cause mortality were acquired by linking the cohort database with the National Death Index through December 31, 2019.Weighted Kaplan–Meier curves with log-rank tests were conducted to access cumulative survival differences across different NPAR results. Restricted cubic spline analyses were employed to examine the nonlinear association. Multivariable Cox proportional hazards regression models were used to compute hazard ratios and 95% CIs. Receiver Operating Characteristic (ROC) curves were used to compare predictive value of NPAR with systemic immune inflammation index (SII) and neutrophils percent. Results In this cohort study, during 270014 person-years of follow-up, 4074 all-cause deaths and 1116 CVD-cause deaths were documented. We found significant associations between elevated NPAR and both CVD-cause and all-cause mortality in Kaplan–Meier curves (both P for log-rank test<0.001). Restricted cubic splines revealed non-linear associations between NPAR level and both CVD-cause (P=0.018 for nonlinearity) and all-cause mortality (P<0.001 for nonlinearity) (Figure 1A and 1B). After adjusting for confounding factors, participants in the highest NPAR tertile had a significantly increased risk of all-cause mortality (HR: 1.46, 95% CI: 1.33-1.61) and CVD-cause mortality (HR: 1.54, 95% CI: 1.32-1.80) compared to those in the lowest tertile, while no association was detected for individuals in the middle tertile (Figure 2). The effect of NPAR was consistent across most subgroups, with no significant interaction with most covariates except for high cholesterol (CVD-cause mortality: P=0.014, all-cause mortality: P=0.022). Further ROC analysis confirmed that NPAR had higher predictive value than neutrophil percent and SII. Conclusions Elevated NPAR level was significantly associated with an increased risk of all-cause and CVD-cause mortality in general population.Given its easy-to-calculate nature and high predictive value, NPAR index, with implications in public health, deserves greater attention in inflammatory assessment and cardiovascular prevention.Figure 1 Nonlinear associationFigure 2 Cox regression table

Mid-regional pro-adrenomedullin is an independent predictor of cardiovascular outcomes in cardiac surgery, a prospective cohort study in 500 patients

Abstract Background MR-proADM (mid-regional pro-adrenomedullin) is a stable pro-peptide of Adrenomedullin, which is expressed in various cell types such as heart, lung, and renal tissue. It is a prognostic parameter for heart failure (HF) and sepsis as well as all-cause and cardiovascular (CV) mortality. Purpose Considering the characteristics of MR-proADM as a reliable biomarker for adverse events, we aimed to investigate the prognostic impact of MR-proADM in patients undergoing elective cardiac surgery. Methods We prospectively enrolled patients undergoing elective cardiac bypass and/or valve surgery at the department of cardiac surgery between May 2013 and August 2018. Blood samples were taken one day prior to surgery. MR-proADM was measured using an automated immunofluorescence assay. Patients were followed prospectively until endpoints were reached. The primary endpoint was the composite of hospitalization for heart failure (HHF) or CV mortality, the secondary endpoint was postoperative atrial fibrillation (POAF). The multivariate regression model was adjusted for age, sex, NT-proBNP, type of surgery, and CRP-level at baseline. Results A total of 500 patients (146 female [29.2%]; median age 69.8 years [IQR 60.6-75.5]) were followed over a median of 4.6 years (IQR 3.0–5.8). Valve surgery was performed in 214 (42.8%) patients, 160 (32%) underwent a bypass operation and 126 (25.2%) a combined valve and bypass surgery. The median MR-proADM value of the entire study population was 0.58 nmol/L (IQR: 0.44-0.79 nmol/L). Patients were stratified in risk categories based on their MR-proADM values (Low Risk ≤0.63nmol/L, Intermediate Risk 0.63-0.83nmol/L, High Risk >0.84nmol/L). Patients in the highest category presented with higher rates of diabetes mellitus (p <0.001), COPD (p <0.001), HF (p=0.009) and either bypass surgery (p=0.039) or the combination of bypass and valve surgery (p=0.008), compared to patients in the lowest tertile. We observed a significant increase in 5-year’s event rates for HHF/ CV Mortality in patients in higher risk groups (Low Risk 8.6% vs High Risk 37.7%, p <0.001, Figure 1). The adjusted Cox regression model found that MR-pro ADM was independently associated with a risk increase for HHF/ CV Mortality (adjusted HR of 4.45, 95% CI 2.55-8.09; p<0.001, Figure 2) comparing the High Risk to the Low Risk Group. A comparable risk increase could be observed in POAF, with an adjusted HR of 2.61 (High Risk Group vs Low Risk Group, 95% CI 1.46-4.67, p<0.001). Conclusion Within the prospective investigation, MR-pro ADM was found to be an independent predictor for HHF and CV mortality in patients undergoing cardiac bypass and/or valve surgery. Furthermore, there was a consistent predictive potential for POAF. In the era of personalized medicine, preoperative MR-pro ADM levels could help to identify patients at risk for serious adverse events, in order to apply intensified secondary prevention and reduce mortality and morbidity.

Impact of glucose metabolism status on the relationship between remnant cholesterol and ischemic risk after percutaneous coronary intervention: a large-scale long-term cohort study from real-world

Abstract Background Elevated remnant cholesterol (RC) is considered a risk factor for ischemic events in patients with coronary artery disease (CAD). Recently evidence demonstrates a close connection between RC and cardiometabolic disorders, particularly diabetes mellitus (DM). However, it remains unclear whether different glucose metabolism statuses modify the association between RC and ischemic risk after percutaneous coronary intervention (PCI). Purpose This study aims to explore whether glucose metabolism statuses alter the relationship between RC and ischemic risk in CAD patients undergoing PCI. Methods This prospective study enrolled consecutive 10,724 CAD patients undergoing PCI throughout 2013. Patients were categorized into three groups: DM, pre-DM, and normal glucose regulation (NGR) group. Fasting RC was calculated as total cholesterol minus low-density lipoprotein cholesterol and high-density lipoprotein cholesterol, and was analyzed based on tertile levels (low, middle, and high). The clinical endpoint was major adverse cardiovascular and cerebrovascular events (MACCE, including cardiac mortality, revascularization and stroke). Results A total of 9,406 PCI patients were ultimately included, among whom the average age was 58.44 ± 10.26 years and 2,142 (22.80%) were female. During 5-year follow-up, 1,876 (19.9%) patients experienced MACCE. In the overall cohort, the highest RC tertile was associated with a higher risk of MACCE (hazard ratio [HR]: 1.129, 95% confidence interval [CI]: 1.006-1.267) compared to those in the lowest tertile (Figure 1). Importantly, a significant interaction was observed between RC levels and glucose metabolism statuses (P for interaction = 0.032). In the DM group, multivariate Cox regression analysis revealed that the highest tertile of RC significantly increased a 1.172-fold risk of MACCE (HR:1.172, 95% CI:1.004-1.369). However, neither the pre-DM nor NGR groups showed any significant association between RC and MACCE (both P > 0.05). Further subgroup analysis found that the correlation between the highest tertile of RC and an increased MACCE risk was only in the DM group, which was prominent among females (Figure 2). Conclusions In a large-scale 5-year follow-up study, we are the first to demonstrate that RC-related ischemic risk may be exacerbated by diabetes in CAD patients undergoing PCI, highlighting the potential benefits of intensifying RC-lowering treatments for PCI patients combined with DM.

Circulating secretoneurin concentrations predict cardiovascular death in ambulatory patients with heart failure

Abstract Background Secretoneurin (SN) is a novel biomarker, which predicts cardiovascular (CV)-related mortality in patients with acute dyspnea and sepsis. Higher SN concentrations have also been found associated with all-cause death in outpatients with heart failure (HF), but whether SN primarily reflects cardiovascular (CV)-related mortality in HF outpatients is not known. Objectives To evaluate the relation between SN concentrations and CV- & non-CV death in ambulatory patients with HF. Methods We studied 184 consecutive patients who attended our HF clinic for routine follow up and had stored blood samples available for SN analysis. SN concentrations were measured with a CE-marked SN ELISA assay. We assessed the associations between SN concentrations and CV & non-CV death. Mortality was ascertained using medical records, autopsy reports and death certificates, and CV deaths included sudden cardiac deaths or mortality due to myocardial infarction, HF or stroke. We assessed association with CV & non-CV death by Kaplan-Meier curves and by Cox proportional hazard regression analysis. Results Median age was 76 years (range: 38-94 years) and two thirds were male. Sixty-three percent had HF with reduced ejection fraction, 22% had NYHA III/IV symptoms and median NT-proBNP was 1079 (interquartile range: 462-2347) ng/L. Median SN level was 60 (range: 21-134) pmol/L. In multivariable linear regression analysis, impaired renal function and lower body-mass index were significantly associated with increasing (log)SN concentration. During median follow up of 540 days, there were 18 CV deaths, including 15 HF deaths, and 7 non-CV deaths. A higher SN concentration was associated with higher risk of CV death, while we did not find statistically significant association between SN concentrations and non-CV deaths (Figure). Patients with SN concentration in the top tertile had 15-fold increased risk of CV death compared to patients with SN concentration in the lowest tertile. In multivariable Cox regression analysis that adjusted for age, NYHA functional class, frailty status, increasing SN concentrations were independently associated with CV death: hazard ratio per logSN (95% CI): 3.01 (1.02-8.90), p=0.04. Conclusion In ambulatory patients with HF, circulating SN concentrations were predictive of CV death. Higher SN concentrations in ambulatory HF patients seemed to be linked to impaired renal function and lower body-mass index. Figure: Kaplan Meier curves illustrating the relation between SN tertiles and (A) CV mortality (B) Non-CV mortality.

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.

Cut-off values for estimated cardiorespiratory fitness in terms of physical functioning among middle-aged to older adults.

Cardiorespiratory fitness is linked to various health outcomes. This study aimed to establish cut-off values for estimated cardiorespiratory fitness associated with poor physical functioning in middle-aged to older adults. A total of 2638 participants (1083 males), aged 40-69 years, performed a 6-min walking test (6MWT) to estimate cardiorespiratory fitness (VO<inf>2max)</inf> and completed a health-related questionnaire. Physical functioning was assessed using four outcomes: perceived health, perceived fitness, difficulties in 2-km walking, and difficulties in climbing several stairs. Receiver operator characteristics (ROC) curves were used to determine cut-off values for estimated VO<inf>2max</inf> and 6MWT distance linked to poor physical functioning based on the four outcomes. Analyses were done separately for males and females, and for 40- to 49-, 50- to 59-, and 60- to 69-year-old groups. Multinomial regression was used to analyze differences between fitness thirds in outcome variables. ROC analyses were significant for all outcomes (AUC 0.686-0.834, P<0.001). In the total group, cut-off values for estimated VO<inf>2max</inf> were 29.9-30.2 mL/kg/min, and for walking distance, 588.0-599.5 m. Cut-off values decreased with age, and mean differences between males and females were 3.3 mL/kg/min and 33 m. All cut-off values were within ±1.3 mL/kg/min of the lower fitness tertile. The odds ratios of having poor physical functioning in the middle and high fitness thirds were less than 0.50 compared to low fitness third. VO<inf>2max</inf> of 30 mL/kg/min and 600-m walking distance seemed reasonable cut-off values for poor physical functioning. Exceeding the currently proposed thresholds is a desirable goal to avoid consequences of insufficient fitness.

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.

Association between the composite dietary antioxidant index and sarcopenia among United States adults: A cross-sectional study.

Diets high in antioxidants are associated with decreased prevalence of sarcopenia. This study aimed to investigate whether the composite dietary antioxidant index (CDAI) and sarcopenia have an underlying relationship. We used the data from the National Health and Nutrition Examination Survey 2011-2018. According to dietary antioxidant intake, the CDAI was calculated for each individual. Appendicular skeletal muscle mass index was employed to determine sarcopenia. Multivariate weighted logistic models and restricted cubic spline regression analysis was undertaken to determine the association between CDAI and sarcopenia. A total of 7012 participants were enrolled in this study, including 473 with sarcopenia (weighted percentage, 5.6%). Compared with the lowest tertile, those in the highest tertile of the CDAI exhibited a greater likelihood of being male, with lower body mass index, higher education level and economic standard, and more chance of being single or separated. In multivariate weighted logistic models, model 3 revealed a noteworthy inverse association between the CDAI and sarcopenia (odds ratio = 0.94; 95% CI, 0.91-0.98; P = 0.003). Compared with the lowest tertile, the highest tertile of CDAI was associated with a 0.57-fold risk of sarcopenia (95% CI, 0.42-0.77; P < 0.001). The inverse association between CDAI and sarcopenia strengthened in the participants with elevated education levels (P for interaction = 0.003). The CDAI was inversely correlated with the prevalence of sarcopenia. As a comprehensive measurement representing antioxidant status, the CDAI may help manage and prevent sarcopenia.

Association between malnutrition and adverse renal outcomes in patients with type 2 diabetes.

Nutritional management is crucial in patients with chronic kidney disease. Therefore, it is important to assess nutritional status and detect malnutrition, especially in patients with diabetes. However, there is currently a lack of evidence regarding the relationship between nutritional indices and renal function in patients with type 2 diabetes. This study investigated whether the geriatric nutritional risk index (GNRI) is related to renal prognosis in type 2 diabetes patients. The study included 946 type 2 diabetes patients enrolled in the Fukushima Cohort Study. The primary endpoint of this study was a renal event, defined as a combination of a 50% decline in eGFR from baseline and end-stage kidney disease. All-cause death and new cardiovascular events were also measured as secondary outcomes. The association between GNRI and these endpoints was assessed using Cox regression analysis. The median patient age was 66 years, 57% were men, the median eGFR was 67.9 mL/min/1.73 m2, and the median GNRI was 100.0. Compared to patients in the highest GNRI tertile, patients in the lowest tertile had a significantly increased risk of therenal event (HR 5.15, 95% CI 2.51-10.6) and all-cause death (HR 2.30, 95% CI 1.20-4.42). A significant association was not observed between GNRI levels and cardiovascular events. We observed an association between poor nutritional status, assessed by GNRI, and adverse outcomes in patients with type 2 diabetes. Nutritional status assessment has potential utility as a prognostic tool for individuals with type 2 diabetes.

Healthy and unhealthy dietary patterns and sperm quality from the Led-Fertyl study.

Dietary patterns may affect sperm quality, but the scientific evidence is limited. To evaluate the association between adherence to different a-priori dietary patterns and sperm quality parameters in healthy reproductive-age men. A cross-sectional analysis was conducted using data from 200 young men enrolled in the Led-Fertyl study. Tertiles of six a-priori dietary patterns were estimated: four healthy dietary patterns [Mediterranean Diet Adherence Screener (MEDAS), Dietary Approaches to Stop Hypertension (DASH), Healthful Plant-Based Diet Index (hPDI) and EAT-Lancet Score], and two unhealthy dietary patterns [Western Diet and Unhealthful Plant-Based Diet Index (uPDI)]. Sperm quality parameters (count, concentration, vitality, total and progressive motility, and normal morphology) were considered the main outcomes. Compared with the lowest tertile, participants in the highest MEDAS tertile had higher total sperm count (β=3.2;95%CI: 1.0, 5.5) and concentration (β=1.8;95%CI: 0.6, 3.0), and total (β=8.2;95%CI: 1.3, 15.1) and progressive motility (β=7.1;95%CI: 0.2, 14.0). Similarly, participants in the highest hPDI tertile had higher total sperm count (β=3.4;95%CI: 1.4, 5.5) and concentration (β=1.2;95%CI: 0.0, 2.3) compared with those in the lowest tertile. When these dietary patterns were modelled as continuous variables (for each 1-point increment in the specific score), an inverse association was found between the uPDI and Western and total sperm count [(β=-2.7;95%CI: -4.8, -0.7) and (β=-3.8;95%CI: -5.8, -1.7), respectively] and sperm concentration [(β=-1.2;95%CI: -2.4, -0.1) and (β=-1.7;95%CI: -2.8, -0.5), respectively]. Compared with participants in the lowest tertile, those in the highest uPDI tertile presented higher odds of abnormal sperm concentration (OR: 4.6;95%CI: 1.0, 19.9) and one or more seminogram abnormalities (OR: 2.3;95%CI: 1.1, 5.0). Our findings suggest that higher adherence to healthy dietary patterns (Mediterranean and healthful plant-based diet) was positively associated with better sperm quality parameters, in contrast, greater adherence to unhealthy dietary patterns was inversely associated.

The association between dietary inflammatory index with risk rheumatoid arthritis: A case-control study

Diet represents an important set of potential risk factors for rheumatoid arthritis (RA), a known inflammatory condition. This case-control study examined the association between the inflammatory potential of diet, as determined by the dietary inflammatory index (DII®), and RA risk in an Iranian population. The present Case–control study was conducted on 100 RA patients and 200 age- and sex-matched controls in Isfahan, Iran. The presence of RA was determined by expert Rheumatologist assessment based on the American College of Rheumatology definitions. A 168-item food frequency questionnaire was used to collect dietary intake from which DII scores were computed. Odds ratios (OR) and 95 % confidence intervals (CI) for the association between the DII, expressed in tertiles, and RA risk were estimated by two multivariable logistic regression models, one crude model and one in which we controlled for important potential confounders. In the crude model, individuals in the top DII tertile (most pro-inflammatory diet) had more than triple the risk of RA compared to those in the lowest tertile (ORtertile3vs1= 3.57; 95 % CI, 1.95–6.53; p< 0.001). The association was essentially unchanged after controlling for potential confounders (OR tertile3vs1 = 3.83; 95 % CI, 1.66–8.81; p<0.001). We found that a pro-inflammatory diet is associated with increased risk of RA. Higher volume studies are needed to confirm the results.

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.

Free fatty acids: independent predictors of long-term adverse cardiovascular outcomes in heart failure patients

BackgroundThe association between plasma free fatty acid (FFA) and the outcomes in the heart failure (HF) patients remains unclear.MethodsA cohort study among HF patients was performed. Plasma FFA was analyzed as both a continuous and a categorical variable (grouped by tertiles) to assess its association with composite cardiovascular (CV) death and HF hospitalization (CV death & HHP), CV death alone, and all-cause mortality (ACM) using Cox regression models. Subgroup analyses of HF patients with preserved ejection fraction (HFpEF) and mildly reduced/reduced ejection fraction (HFmrEF/HFrEF) were performed. This work also assessed the effectiveness of combining FFA and NT-pro BNP biomarkers for risk stratification by calculating the concordance index (C-index).ResultsAmong the 4,109 HF patients, FFA levels exceeding 0.4–0.42 mmol/L were associated with increased risks of the three outcomes. Patients in the highest FFA tertile faced greater risks than those in the lowest tertile. Adjusted hazard ratios were 1.32 (95% CI: 1.11–1.58) for CV death & HHP, 1.45 (95% CI: 1.16–1.82) for CV death, and 1.39 (95% CI: 1.15–1.68) for ACM, with a maximum follow-up of 8 years (median: 25 months). Subgroup analyses revealed that elevated FFA levels consistently predicted worse outcomes in both HFmrEF/HFrEF and HFpEF patients. The C-index for predicting outcomes was significantly greater when NT-pro BNP and FFA were combined than when NT-pro BNP was used alone (P < 0.01).ConclusionIncreased plasma FFA concentrations were independently associated with greater risks of CV death & HHP, CV death, and ACM among HF patients, irrespective of the ejection fraction. The combination of FFA and NT-pro BNP biomarkers significantly improved risk stratification in HF patients.

Does growing up in a physical activity-friendly neighborhood increase the likelihood of remaining active during adolescence and early adulthood?

BackgroundThe SOPHYA-cohort-study investigated whether the objectively characterized and perceived residential neighborhood of Swiss youth predict accelerometer-measured physical activity and activity in specific domains (participation in a sports club and cycling) five years later.MethodsAt baseline in 2014, 1230 children and adolescents aged 6 to 16 years participated and wore accelerometers for 7 days. Of these children, 447 participated again in the follow-up study in 2019 and provided longitudinal accelerometer measurements. Sociodemographic factors and perceptions of the local neighbourhood were assessed by questionnaire. Specific objective environmental data (e.g. built environment or social environment) was modelled to the children’s address at baseline. Multivariate linear and logistic regression models were applied to identify short- and long-term characteristics that are associated with accelerometer-based physical activity, cycling and participation in organised sport.ResultsIf the neighborhood-score as perceived by the parents in 2014 was in the middle or lowest tertile, children were significantly less active cross-sectionally in 2014 (-41.1 (-78.0;-4.2) and -52.4 (-88.6;-16.2) counts per minute, cpm), and five years later (-52.4 (-88.6;-16.2) and 48.1 (-86.6;-9.7) cpm). In addition, they were also less likely to accumulate active minutes above the median at both measuring points compared to peers of the same age and sex. Using objective environmental data modeled around the children’s residential address, similar associations were found: In the tertile with the lowest proportion of green space children achieved less cpm in 2014, while a high main street density and a low socioeconomic environment, respectively, hindered physical activity tracking above the median longitudinally. Also for cycling and participation in a sport club, the associations with the perceived and objective environment were more pronounced in the longitudinal analyses.ConclusionThe results suggest that growing up in a physical activity friendly neighborhood increases the likelihood of remaining active during adolescence and early adulthood. Interventions should be implemented to ensure that children growing up in an unfavorable neighborhood do not fall behind at an early stage.

Absence of Kidney Tubular Injury in Patients With Acute Heart Failure With Acute Kidney Injury.

Worsening renal function (WRF) is common in hospitalized patients being treated for acute heart failure. However, discriminating clinically significant WRF remains challenging. In patients hospitalized with acute heart failure, we evaluated if blood and urine biomarkers of cardiac and kidney dysfunction were associated with adverse outcomes. We identified 175 of 927 participants in the AKINESIS study (Acute Kidney Neutrophil Gelatinase-Associated Lipocalin Evaluation of Symptomatic Heart Failure Study) who met criteria for stage 1 or 2 Kidney Disease: Improvement Global Outcomes acute kidney injury during the first 3 days of hospitalization. We measured 24 blood and urine biomarkers from specimens collected within 24 hours of meeting acute kidney injury criteria. The primary composite outcome consisted of worsening WRF (higher acute kidney injury stage), need for dialysis, or death at 30 days. Biomarkers' association with the composite outcome was assessed with logistic regression by tertiles and area under the curve (AUC). Of the 175 participants, 32 (18%) developed the primary composite outcome. Only history of chronic kidney disease was significantly different between those with and without the composite outcome. The highest tertile of plasma Gal-3 (galectin-3) and urine epidermal growth factor were associated with increased odds of the composite outcome compared with the lowest tertile in unadjusted analyses. After adjusting for serum creatinine, systolic blood pressure, and blood urea nitrogen, only the highest tertile of Gal-3 was associated with greater odds of the composite outcome (odds ratio, 4.6 [95% CI, 1.4-16.0). Gal-3 had the highest AUC (0.70 [95% CI, 0.58-0.82]), while epidermal growth factor had a lower AUC (0.63 [95% CI, 0.53-0.74]). Notably, urine biomarkers of kidney tubule injury were not associated with the composite outcome. Tubular injury does not occur in most patients with acute heart failure experiencing WRF, consistent with the functional mechanisms of WRF in this patient population. URL: https://www.clinicaltrials.gov/study/NCT01291836?term=NCT01291836&rank=1; Unique identifier: NCT01291836.

Oxidative stress and inflammation mediate the association between elevated oxidative balance scores and improved sleep quality: evidence from NHANES.

The association between oxidative stress, as measured by the Oxidative Balance Score (OBS), and sleep quality remains unclear. The primary objective of this investigation was to clarify this relationship and to explore the potential involvement of oxidative stress and inflammation. Data from 15,198 participants in the National Health and Nutrition Examination Survey 2007-2014 were analyzed. Sleep quality indicators, including sleep disorder, trouble, and duration, were assessed. The OBS, comprising information on 16 dietary nutrients and 4 lifestyle factors, was then calculated. Multivariable logistic and linear regression models were employed to investigate the correlation between OBS and sleep quality. Additionally, mediation analyses were conducted to evaluate the potential effects of oxidative stress and inflammation. We demonstrated a correlation between an elevated OBS and reduced sleep disorders (OR, 0.72; 95% CI, 0.58-0.91; p = 0.0055), reduced sleep trouble (OR, 0.81; 95% CI, 0.69-0.96; p = 0.0174), and prolonged sleep duration (β 0.009; 95% CI, 0.0002-0.0160; p = 0.015) when comparing the highest and lowest tertiles. Dietary factors exhibited autonomous correlations with sleep duration, whereas lifestyle factors displayed independent associations with sleep trouble and sleep disorders. Moreover, the relationships between OBS and both sleep disorders and trouble were influenced by albumin, γ-glutamyl transferase, total bilirubin, and white blood cells, with combined mediation effects of 34.66 and 29.54%, respectively (both p < 0.001). Sensitivity analyses revealed a significant association between OBS and sleep disorder (p < 0.001). This study revealed a positive correlation between an elevated OBS and improved sleep quality, manifested by decreased sleep disorders, mitigated sleep trouble, and prolonged sleep duration. This is potentially mediated by oxidative stress and inflammation. Therefore, the study underscores the importance of adopting a diet rich in antioxidants and healthy lifestyle choices to address sleep-related concerns, providing a novel avenue for enhancing overall sleep quality.

Increased thyroid hormone sensitivity is correlated with visceral obesity in patients with type 2 diabetes

ObjectiveThe study aimed to assess whether thyroid hormone (TH) sensitivity is related to visceral fat area (VFA) and visceral obesity in euthyroid subjects with type 2 diabetes (T2D).Methods750 euthyroid patients with T2D were enrolled. A VFA of 80 cm2 or more was considered visceral obesity. Central TH sensitivity was conducted using thyrotrophic thyroxine resistance index (TT4RI), thyrotropin index (TSHI), and thyroid feedback quantile-based index (TFQI). Free triiodothyronine to free thyroxine (FT3/FT4) was utilized for assessing peripheral TH sensitivity.ResultsThe subjects had a mean age of 51.5 ± 11.1 years, and 540 (72.0%) of them were men. In multivariable regression analyses, there was a positive correlation of FT3/FT4 tertile with visceral obesity, after full adjustment for confounding variables (P < 0.05). The middle and highest FT3/FT4 tertiles were correlated with a 134% [95% CI (1.24, 4.44)] and 98% [95% CI (1.04, 3.78)] higher prevalence of visceral obesity than the lowest tertile, respectively. Conversely, elevated TFQI levels were linked to a decreased prevalence of visceral obesity. Stratified analysis revealed that these associations were particularly pronounced in participants who are neither overweight nor obese and those aged less than 60 years (all P < 0.05).ConclusionsHigher TH sensitivity is correlated with visceral obesity and elevated VFA in euthyroid patients with T2D, particularly among those younger than 60 years and individuals who are neither overweight nor obese.

Association between dietary fatty acids and depressive symptoms in Chinese haemodialysis patients: a cross-sectional study.

Depression is highly prevalent in haemodialysis patients, and diet might play an important role. Therefore, we conducted this cross-sectional study to determine the association between dietary fatty acids (FA) consumption and the prevalence of depression in maintenance haemodialysis (MHD) patients. Dietary intake was assessed using a validated FFQ between December 2021 and January 2022. The daily intake of dietary FA was categorised into three groups, and the lowest tertile was used as the reference category. Depression was assessed using the Patient Health Questionnaire-9. Logistic regression and restricted cubic spline (RCS) models were applied to assess the relationship between dietary FA intake and the prevalence of depression. As a result, after adjustment for potential confounders, a higher intake of total FA [odds ratio (OR)T3 vs. T1 = 1·59, 95 % confidence interval (CI) = 1·04, 2·46] and saturated fatty acids (SFA)(ORT3 vs. T1 = 1·83, 95 % CI = 1·19, 2·84) was associated with a higher prevalence of depressive symptoms. Significant positive linear trends were also observed (P < 0·05) except for SFA intake. Similarly, the prevalence of depression in MHD patients increasedby 20% (OR = 1.20, 95% CI = 1.01-1.43)foreach standard deviation increment in SFA intake. RCS analysis indicated an inverse U-shaped correlation between SFA and depression (P nonlinear > 0·05). Additionally, the sensitivity analysis produced similar results. Furthermore, no statistically significant association was observed in the subgroup analysis with significant interaction. In conclusion, higher total dietary FA and SFA were positively associated with depressive symptoms among MHD patients. These findings inform future research exploring potential mechanism underlying the association between dietary FA and depressive symptoms in MHD patients.