Elevated circulating follistatin associates with increased risk of mortality and cardiometabolic disorders.

BACKGROUND AND AIMS: Previous study showed that elevated circulating hepatokine follistatin (FST) associates with an increased risk of type 2 diabetes by inducing adipose tissue insulin resistance. Here we explore further the relationships between plasma FST levels with mortality and health outcomes. METHODS AND RESULTS: The population-based Malmö Diet Cancer cardiovascular cohort (n = 4733, age 45-68 years) was used to study plasma FST in relation to incidence of health outcomes, by linkage with national patient registers. Cox regression analysis was used to assess the associations of plasma FST and outcomes, with adjustments for multiple potential confounding factors. During the mean follow-up time of 22.64 ± 5.84 years in 4,733 individuals, 526 had incident stroke, 432 had ischemic stroke, 530 had incident coronary events (CE), 339 had incident heart failure (HF), 320 had incident chronic kidney disease (CKD) and 1,843 individuals died. Hazard ratio (HR) per standard deviation increase in FST levels adjusted for multiple risk factors was 1.05 (95%CI: 1.00-1.11, p = 0.036) for mortality; 1.10 (95%CI: 1.00-1.20, p = 0.042) for stroke; 1.13 (95%CI: 1.03-1.25, p = 0.014) for ischemic stroke; 1.16 (95%CI: 1.03-1.30, p = 0.015) for HF; and 1.38 (95%CI: 1.12-1.70, p = 0.003) for a diagnosis of CKD. In MDC-CC individuals without prevalent or incident diabetes, the association between FST and stroke, CE and CKD remained significant; but not with mortality or HF. CONCLUSIONS: Elevated circulating FST associates with an increased risk of mortality and HF, which partly may be mediated by diabetes. FST also associated with stroke, ischemic stroke, CE and CKD, independently of established risk factors including diabetes.

Red cell distribution width and its polygenic score in relation to mortality and cardiometabolic outcomes.

Introduction: Elevated red cell distribution width (RDW) has been associated with a range of health outcomes. This study aims to examine prognostic and etiological roles of RDW levels, both phenotypic and genetic predisposition, in predicting cardiovascular outcomes, diabetes, chronic kidney disease (CKD) and mortality. Methods: We studied 27,141 middle-aged adults from the Malmö Diet and Cancer study (MDCS) with a mean follow up of 21 years. RDW was measured with a hematology analyzer on whole blood samples. Polygenic scores for RDW (PGS-RDW) were constructed for each participant using genetic data in MDCS and published summary statistics from genome-wide association study of RDW (n = 408,112). Cox proportional hazards regression was used to assess associations between RDW, PGS-RDW and cardiovascular outcomes, diabetes, CKD and mortality, respectively. Results: PGS-RDW was significantly associated with RDW (Pearson's correlation coefficient = 0.133, p < 0.001). RDW was significantly associated with incidence of stroke (hazard ratio (HR) per 1 standard deviation = 1.06, 95% confidence interval (CI): 1.02-1.10, p = 0.003), atrial fibrillation (HR = 1.09, 95% CI: 1.06-1.12, p < 0.001), heart failure (HR = 1.13, 95% CI: 1.08-1.19, p < 0.001), venous thromboembolism (HR = 1.21, 95% CI: 1.15-1.28, p < 0.001), diabetes (HR = 0.87, 95% CI: 0.84-0.90, p < 0.001), CKD (HR = 1.08, 95% CI: 1.03-1.13, p = 0.004) and all-cause mortality (HR = 1.18, 95% CI: 1.16-1.20, p < 0.001). However, PGS-RDW was significantly associated with incidence of diabetes (HR = 0.96, 95% CI: 0.94-0.99, p = 0.01), but not with any other tested outcomes. Discussion: RDW is associated with mortality and incidence of cardiovascular diseases, but a significant association between genetically determined RDW and incident cardiovascular diseases were not observed. However, both RDW and PGS-RDW were inversely associated with incidence of diabetes, suggesting a putative causal relationship. The relationship with incidence of diabetes needs to be further studied.

The relationships between the plasma metabolome and orthostatic blood pressure responses.

Whereas autonomic dysfunction and the metabolic syndrome are clinically associated, the relationships with the plasma metabolome is unknown. We explored the association between orthostatic blood pressure responses and 818 plasma metabolites in middle-aged subjects from the general population. We included 3803 out of 6251 subjects (mean age, 57 years; 52% women) from the Malmö sub-cohort of The Swedish CardioPulmonary bioImage Study with information on smoking habits, diabetes, antihypertensive drug treatment, anthropometrics, hemodynamic measurements and 818 plasma metabolites (mass-spectrometry). The associations between each metabolite and orthostatic systolic blood pressure responses were determined using multivariable linear regression analysis and p values were corrected using the Bonferroni method. Six amino acids, five vitamins, co-factors and carbohydrates, nine lipids and two xenobiotics were associated with orthostatic blood pressure after adjusting for age, gender and systolic blood pressure. After additional adjustments for BMI, diabetes, smoking and antihypertensive treatment, the association remained significant for six lipids, four amino acids and one xenobiotic. Twenty-two out of 818 plasma metabolites were associated with orthostatic blood pressure responses. Eleven metabolites, including lipids in the dihydrosphingomyelin and sphingosine pathways, were independently associated with orthostatic systolic blood pressure responses after additional adjustment for markers of cardio-metabolic disease.

The 8-year single-center experience of telescoping flow diverter for complex intracranial aneurysms treatment.

OBJECTIVE: Treatment of complex intracranial aneurysms (IAs) is still a challenging thing and this study aims to summarize the experience of telescoping flow diverters (FDs) in treating complex intracranial aneurysms. METHOD: Between April 2013 to November 2020, 381 IA cases treated by flow diverters (FD) were retrieved from the database of 4988 IA cases, and finally 20 cases treated by telescoping FDs were enrolled for further analysis. RESULT: Among 20 patients, 15 patients (75.0%) received Tubridge telescoping while 5 patients (25.0%) received PED telescoping. The technical success rate was 100%. The immediate occlusion results were: 7 cases of OKM grade A (35.0%), 11 cases of OKM grade B (55.0%), and 2 cases of OKM grade C (10.0%). No perioperative complications occurred. The clinical follow-up was available in 20 patients (100%) and the follow-up time was 6-96 months. One patient developed massive infarction and the other 19 patients were range between 0 and 2. The angiographic follow-up was available in 17 patients (85%) and the follow-up time was 6-27 months. The occlusion results were: 1 case of OKM grade B (5.9%), 6 cases of OKM grade C (35, 0.3%), and 10 cases of OKM grade D (58.8%). 2 patients (11.8%) developed occlusion of the patent artery. CONCLUSION: Telescoping flow diverters showed low perioperative complications and high IA occlusion rate when treating complex intracranial aneurysms in follow-up time, which provides an alternative manner beyond conventional strategy for neurosurgeons.

Proteomic Profiles of Body Mass Index and Waist-to-Hip Ratio and Their Role in Incidence of Diabetes.

CONTEXT: It is unclear to what extent the plasma proteome of abdominal fat distribution differs from that of body mass index, and whether the differences have clinical implications. OBJECTIVE: To evaluate the difference between the plasma proteomic profiles of body mass index (BMI) and waist-to-hip ratio (WHR), and then examine the identified BMI- or WHR-specific proteins in relation to incidence of diabetes. METHODS: Data were obtained from the Malmö Diet and Cancer-Cardiovascular Cohort study in the general community. Participants (n = 4203) with no previous diabetes (aged 57.2 ±â€…6.0 years, 37.8% men) were included. Plasma proteins (n = 136) were measured by the Proseek proximity extension method. BMI- and WHR-specific proteins were identified at baseline using a 2-step iterative resampling approach to optimize internal replicability followed by ß coefficient comparisons. The identified proteins were considered internally replicated and were then studied in relation to incident diabetes by Cox proportional hazards regression analysis. The main outcome measure was incident diabetes over a mean follow-up of 20.3 ±â€…5.9 years. RESULTS: After excluding 21 overlapping proteins and proteins that did not show significantly different associations with BMI vs WHR, 10 internally replicated proteins were found to be specific to BMI, and 22 were found to be specific to WHR (false discovery rate-adjusted P < .05). Of the WHR-specific proteins, 18 remained associated with diabetes risk after multivariate adjustments, whereas none of the BMI-specific proteins showed associations with diabetes risk. CONCLUSION: Abdominal fat distribution was associated with some unique characteristics of the plasma proteome that potentially could be related to its additional risk of diabetes beyond general obesity.

Skin autofluorescence, a measure of tissue accumulation of advanced glycation end products, is associated with subclinical atherosclerosis in coronary and carotid arteries.

BACKGROUND AND AIMS: Skin autofluorescence (AF), a measure of tissue accumulation of advanced glycation end products (AGEs), has been associated with diabetes and cardiovascular disease. However, the association of skin AF with subclinical coronary atherosclerosis in the general population is largely unknown. Our study aimed to examine the associations between skin AF and subclinical atherosclerosis in coronary and carotid arteries in a middle-aged population. METHODS: Skin AF and subclinical atherosclerosis were measured in 4416 subjects (aged 50-64 years) from the Swedish CArdioPulmonary bioImage Study (SCAPIS). Skin AF was measured non-invasively using an autofluorescence reader. Subclinical atherosclerosis was assessed by ultrasonography of carotid arteries for evaluation of carotid plaques and computed tomography for the evaluation of the coronary artery calcium score (CACS). RESULTS: A total of 615 (13.9%) individuals had CACS >100 and 1340 (30.3%) subjects had bilateral carotid plaques (median total plaque area: 8 mm2). After controlling for confounding factors, there were significant associations between skin AF (per 1 standard deviation (SD) increase) and CACS >100: odds ratio (OR) = 1.17, 95% confidence interval (CI): 1.06-1.29, p = 0.001. Total carotid plaque area and occurrence of bilateral carotid plaques (OR per 1 SD increase: 1.10, 95%CI: 1.01-1.19, p = 0.02) were similarly associated with skin AF after multivariable adjustments. CONCLUSIONS: Elevated skin AF was significantly associated with subclinical atherosclerosis in coronary and carotid arteries independently of conventional risk factors. Skin AF, a measure of accumulation of AGEs, could be a marker for the identification of middle-aged subjects with elevated atherosclerotic risk.

Associations of Red Cell Distribution Width With Coronary Artery Calcium in the General Population.

Red cell distribution width (RDW) is a measure of the variability of erythrocyte volumes. RDW has been associated with incidence of cardiovascular diseases. However, the underlying mechanisms for the increased cardiovascular risk are still unclear. This study aimed to examine associations of RDW and coronary atherosclerosis in the general population. Computed tomography was performed and RDW was measured in fresh blood from 5772 subjects (aged 50-64 years) from the Swedish CArdioPulmonary bioImage Study (SCAPIS). Multinomial logistic regression was conducted to examine the associations between RDW and coronary artery calcium score (CACS). A total of 3902 (67.6%) individuals had low CACS (≤10), 18.6% had moderate CACS (>10 and ≤100) and 13.8% had high CACS (>100). The proportion with high CACS was 11.7%, 12.7%, 13.7% and 18.3%, respectively, in quartile 1-4 of RDW. After controlling for traditional risk factors, there were significant associations between RDW and high CACS: odds ratio = 1.51, 95% confidence interval: 1.18-1.94, and P = .001, for 4th vs 1st quartile of RDW. Elevated RDW is associated with coronary artery calcification in the middle-aged general population. RDW could be a reproducible and easily assessable biomarker of coronary calcification and cardiovascular risk.

The associations between red cell distribution width and lung function measures in a general population.

BACKGROUND: Red cell distribution width (RDW) reflects heterogeneity of the erythrocyte volumes. High RDW is a novel risk marker, which has been associated with mortality and morbidity both from cardiovascular and respiratory diseases, but the association between RDW and measures of lung function in the general population remains unclear. METHODS: The associations of RDW with spirometry, diffusing capacity (DLCO) and impulse oscillometry (IOS) were investigated among 5767, 5496 and 5598 subjects (aged 50-64 years), respectively, from the Swedish CArdioPulmonary bioImage Study (SCAPIS). Multiple linear regression and general linear models were performed to examine the relationships of lung function measures and RDW, with adjustment for potential confounding factors. RESULTS: Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC were significantly and inversely associated with RDW after multivariate adjustments. For 1- standard deviation (SD) increase in RDW, FEV1 decreased with 0.034 L (95%CI: -0.046 to -0.022 L), p < 0.001; FVC with 0.031 L (95%CI: -0.045 to -0.017 L), p < 0.001; and FEV1/FVC with 0.003 (95%CI: -0.004 to -0.001), p = 0.002. Significant associations of RDW and DLCO were only found among smokers. For IOS, pulmonary reactance rather than resistance was significantly associated with RDW: X5 decreased 0.002 kPa/(L/s) (95%CI: -0.003 to -0.0002 kPa/(L/s)), p = 0.025, per 1-SD higher RDW. CONCLUSIONS: We found significant negative associations between RDW and measures of lung function. However, the effect sizes are small and RDW is not likely to be a sensitive marker of impaired lung function in middle-aged individuals from the general population.

The associations between red cell distribution width and plasma proteins in a general population.

BACKGROUND: High red cell distribution width (RDW) has been increasingly recognized as a risk factor for cardiovascular diseases (CVDs), but the underlying mechanisms remain unknown. Our aim was to explore the associations between RDW and plasma proteins implicated in the pathogenesis of CVD using a targeted proteomics panel. METHODS: RDW and 88 plasma proteins were measured in a population-based cohort study (n = 4726), Malmö Diet and Cancer-Cardiovascular Cohort (MDC-CC). A random 2/3 of the cohort was used as discovery sample and remaining 1/3 was used for replication. Multiple linear regression was used to assess the associations between RDW and plasma proteins, with adjustments for age, sex, and other potential confounders. Proteins with Bonferroni-corrected significant associations with RDW in the discovery sub-cohort were validated in the replication cohort. RESULTS: Thirteen of 88 plasma proteins had significant associations with RDW in the discovery sample, after multivariate adjustments. Eleven of them were also significant in the replication sample, including SIR2-like protein 2 (SIRT2), stem cell factor (SCF, inversely), melusin (ITGB1BP2), growth differentiation factor-15 (GDF-15), matrix metalloproteinase-7 (MMP-7), hepatocyte growth factor (HGF), chitinase-3-like protein 1 (CHI3L1), interleukin-8 (IL-8), CD40 ligand (CD40-L), urokinase plasminogen activator surface receptor (U-PAR) and matrix metalloproteinase-3 (MMP-3). CONCLUSIONS: Several proteins from this targeted proteomics panel were associated with RDW in this cohort. These proteins could potentially be linked to the increased cardiovascular risk in individuals with high RDW.

Red Cell Distribution Width is Associated with Future Incidence of Abdominal Aortic Aneurysm in a Population-Based Cohort Study.

Red cell distribution width (RDW) has been suggested to have a predictive potential for several cardiovascular diseases, but its association with abdominal aortic aneurysm (AAA) is unknown. We examined whether RDW is associated with the risk of AAA among 27,260 individuals from the population-based Malmö Diet and Cancer Study cohort. Data of baseline characteristics were collected during 1991-1996. Cox regression was used to estimate hazard ratios (HR) with 95% confidence intervals (CI) for AAA across quartiles of RDW. During a median follow-up of 21.7 years, 491 subjects developed AAA. After adjustment for other confounding factors, participants in the highest quartile of RDW experienced 61% increased risk of AAA as compared to those with the lowest quartile (HR = 1.61, CI = 1.20, 2.12). RDW showed similar relationship with severe (i.e. ruptured or surgically repaired) AAA or non-severe AAA (adjusted HR 1.58 and 1.60, respectively). The observed association between RDW and AAA risk was significant in current smokers (adjusted HR = 1.68, CI = 1.18, 2.38) but not in former smokers (adjusted HR = 1.13, CI = 0.72, 1.79), or never-smokers (adjusted HR = 1.77, CI = 0.74, 4.22). Elevated RDW is associated with increased future incidence of AAA, however the causal and pathophysiological mechanisms remain to be explored.

The preattentive change detection in preschool children with attention deficit hyperactivity disorder: a mismatch negativity study.

To investigate the preattentive change detection in preschool children with attention deficit hyperactivity disorder (ADHD), we compared the mismatch negativity (MMN) and P3a of event-related potentials (ERPs) between preschool ADHD and normal children using three-stimulus oddball paradigm. Analyzing MMN and P3a components, we found that MMN elicited by deviants and P3a elicited by novelty were significantly reduced in patients than in controls. In addition, the P3a amplitude was positive correlated to IQ and negatively correlated to hyperactivity, antagonistic defiance and conduct problems in Swanson, Nolan, and Pelham IV Rating Scale, parent version. These data provided new neurophysiological evidence for the dysfunction of preattentive change detection and attentional shift in ADHD children.

The relationship between red cell distribution width and all-cause and cause-specific mortality in a general population.

Red Cell Distribution Width (RDW) could be a risk factor for developing various chronic diseases, and seems to be a prognostic marker in patients with cardiovascular disease (CVD) or cancer. Our aim was to explore the association between RDW and all-cause and cause-specific mortality in a general population. RDW was measured in 27,063 participants (aged 45-73 years) from the population-based Malmö Diet and Cancer cohort. After a follow-up of 19.8 ± 5.5 years, Cox proportional hazards regression analysis was used to study the relationship between RDW and all-cause and cause-specific mortality, with adjustment for confounding factors. A total of 9388 individuals (4715 men and 4673 women) died during the follow up. High RDW was significantly associated with all-cause mortality (HR, 4th vs. 1st quartile: 1.34, 95%CI: 1.24-1.45), cancer mortality (HR: 1.27, 95%CI: 1.12-1.44), CVD mortality (HR: 1.39, 95%CI: 1.21-1.59), and respiratory disease mortality (HR: 1.47, 95%CI: 1.06-2.03). The C-statistic increased significantly from 0.732 to 0.737 when adding RDW to a model adjusted for age and sex. There was a significant interaction between RDW and BMI with respect to all-cause mortality. We concluded that RDW is associated with mortality and propose that high RDW is a significant, but non-specific marker of mortality risk in the general population.

Neuropsychological Profile Related with Executive Function of Chinese Preschoolers with Attention-Deficit/Hyperactivity Disorder: Neuropsychological Measures and Behavior Rating Scale of Executive Function-Preschool Version.

BACKGROUND:: Previous studies have found that schoolchildren with attention-deficit/hyperactivity disorder (ADHD) showed difficulties in neuropsychological function. This study aimed to assess neuropsychological function in Chinese preschoolers with ADHD using broad neuropsychological measures and rating scales and to test whether the pattern and severity of neuropsychological weakness differed among ADHD presentations in preschool children. METHODS:: The 226 preschoolers (163 with ADHD and 63 controls) with the age of 4-5 years were included and assessed using the Behavior Rating Scale of Executive Function-Preschool Version (BRIEF-P) and a series of tests to investigate neuropsychological function. RESULTS: Preschoolers with ADHD showed higher scores in all domains of the BRIEF-P (inhibition: 30.64 ± 5.78 vs.20.69 ± 3.86, P < 0.001; shift: 13.40 ± 3.03 vs.12.41 ± 2.79, P = 0.039; emotional control:15.10 ± 3.53 vs.12.20 ± 2.46, P < 0.001; working memory: 28.41 ± 4.99 vs.20.95 ± 4.60, P < 0.001; plan/organize: 17.04 ± 3.30 vs.13.29 ± 2.40, P < 0.001) and lower scores of Statue (23.18 ± 7.84 vs.28.27 ± 3.18, P = 0.001), Word Generation (15.22 ± 6.52 vs.19.53 ± 7.69, P = 0.025), Comprehension of Instructions (14.00 ± 4.44 vs.17.02 ± 3.39, P = 0.016), Visuomotor Precision (P < 0.050), Toy delay (P = 0.048), and Matrices tasks (P = 0.011), compared with normal control. In terms of the differences among ADHD subtypes, all ADHD presentations had higher scores in several domains of the BRIEF-P (P < 0.001), and the ADHD-combined symptoms (ADHD-C) group had the poorest ratings on inhibition and the ability to Plan/Organize. For neuropsychological measures, the results suggested that the ADHD-C group had poorer performances than the ADHD-predominantly inattentive symptoms (ADHD-I) group on Statue tasks (F = 7.34, η2 = 0.12, P < 0.001). Furthermore, the ADHD-hyperactive/impulsive symptoms group had significantly poorer performances compared to the ADHD-C group in the Block Construction task (F = 4.89, η2 = 0.067, P = 0.003). However, no significant group differences were found between the ADHD-I group and normal control. CONCLUSION:: Based on the combined evaluation of performance-based neuropsychological tests and the BRIEF-P, preschoolers with ADHD show difficulties of neuropsychological function in many aspects.

Comparative studies of products produced from four different biomass samples via deoxy-liquefaction.

The objective of this study is to investigate the distribution of products, i.e. gas, liquid oil and char from four different biomass samples (legume straw, corn stalk, cotton stalk and wheat straw) and analysis of the oil for the differences in the hydrocarbon composition with respect to the materials by deoxygenate liquefaction (abbr. deoxy-liquefaction). GC/MS was used to analyze the gas and oil components. According to the similarity of the natural petroleum and bio-petroleum, a new standard for bio-petroleum was established in this paper. The striking characteristic of the bio-petroleum was H/C>1.5, oxygen content <6% and the HHV>40 MJ/kg, containing mainly alkanes, cycloalkanes and aromatic hydrocarbons. In this paper, only the oil produced from legume straw and corn stalk could be called bio-petroleum. The oil derived from different samples contained almost the same compounds, while the relative content varied based on the different content of the main biomass components (lignin and holocellulose). The gaseous products were carbon dioxide, carbon monoxide, methane and hydrogen. In addition, small amount of ethylene, ethane and propane was also observed in gas. The major gas product was carbon dioxide (81.29-86.33%) for all samples.