The association between Coronary Artery Calcification (CAC) and osteoporosis has been reported but not fully understood. Therefore, using an original bioinformatic framework we analyzed ...transcriptomic profiles of 20 elderly women with high CAC score and 31 age- and sex-matching controls from São Paulo Ageing & Health study (SPAH). We integrated differentially expressed microRNA (miRNA) and long-noncoding RNA (lncRNA) interactions with coding genes associated with CAC, in the context of bone-metabolism genes mined from literature. Top non-coding regulators of bone metabolism in CAC included miRNA 497-5p/195 and 106a-5p, and lncRNA FAM197Y7. Top non-coding RNAs revealed significant interplay between genes regulating bone metabolism, vascularization-related processes, chromatin organization, prostaglandin and calcium co-signaling. Prostaglandin E2 receptor 3 (PTGER3), Fibroblasts Growth Factor Receptor 1 (FGFR1), and One Cut Homeobox 2 (ONECUT2) were identified as the most susceptible to regulation by the top non-coding RNAs. This study provides a flexible transcriptomic framework including non-coding regulation for biomarker-related studies.
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•The novel scoring system identified CAC key genes associated with bone metabolism•DE bone metabolism genes affect vascularization, prostaglandin, and Ca2+ signaling•The most affected by the non-coding regulation in CAC are PTGER3, FGFR1 and ONECUT2•CAC associated miRNAs and lncRNAs regulate distinct calcification-related processes•R package wizbionet developed for this study can be utilized in biomarker discovery
CONTEXT Perioperative red blood cell transfusion is commonly used to address anemia, an independent risk factor for morbidity and mortality after cardiac operations; however, evidence regarding ...optimal blood transfusion practice in patients undergoing cardiac surgery is lacking. OBJECTIVE To define whether a restrictive perioperative red blood cell transfusion strategy is as safe as a liberal strategy in patients undergoing elective cardiac surgery. DESIGN, SETTING, AND PATIENTS The Transfusion Requirements After Cardiac Surgery (TRACS) study, a prospective, randomized, controlled clinical noninferiority trial conducted between February 2009 and February 2010 in an intensive care unit at a university hospital cardiac surgery referral center in Brazil. Consecutive adult patients (n = 502) who underwent cardiac surgery with cardiopulmonary bypass were eligible; analysis was by intention-to-treat. INTERVENTION Patients were randomly assigned to a liberal strategy of blood transfusion (to maintain a hematocrit ≥30%) or to a restrictive strategy (hematocrit ≥24%). MAIN OUTCOME MEASURE Composite end point of 30-day all-cause mortality and severe morbidity (cardiogenic shock, acute respiratory distress syndrome, or acute renal injury requiring dialysis or hemofiltration) occurring during the hospital stay. The noninferiority margin was predefined at −8% (ie, 8% minimal clinically important increase in occurrence of the composite end point). RESULTS Hemoglobin concentrations were maintained at a mean of 10.5 g/dL (95% confidence interval CI, 10.4-10.6) in the liberal-strategy group and 9.1 g/dL (95% CI, 9.0-9.2) in the restrictive-strategy group (P < .001). A total of 198 of 253 patients (78%) in the liberal-strategy group and 118 of 249 (47%) in the restrictive-strategy group received a blood transfusion (P < .001). Occurrence of the primary end point was similar between groups (10% liberal vs 11% restrictive; between-group difference, 1% 95% CI, −6% to 4%; P = .85). Independent of transfusion strategy, the number of transfused red blood cell units was an independent risk factor for clinical complications or death at 30 days (hazard ratio for each additional unit transfused, 1.2 95% CI, 1.1-1.4; P = .002). CONCLUSION Among patients undergoing cardiac surgery, the use of a restrictive perioperative transfusion strategy compared with a more liberal strategy resulted in noninferior rates of the combined outcome of 30-day all-cause mortality and severe morbidity. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01021631
Background
Vertebral fractures (VFs) are the most common clinical manifestation of osteoporosis associated with high morbimortality. A personal/familiar history of fractures increases the risk of ...fractures. The purpose of this study is to identify possible molecular markers associated with osteoporotic VFs in elderly women from community.
Methods
Transcriptomic analysis using Affymetrix HTA2 microarray was performed using whole blood samples of 240 subjects from a population‐based survey (Sao Paulo Ageing & Health SPAH study). Only elderly women with osteoporosis diagnosis by densitometry were analyzed, and divided in two groups: VF: women with osteoporosis and VFs versus no vertebral fracture (NVF): women with osteoporosis and NVFs. They were matched for age, chronic disease, medication use, and bone mineral density (BMD). The logistic regression model adjusted for age was applied for transcriptome data analysis. SYBR green‐based quantitative polymerase chain reaction (qPCR) was used to validate the most significant expression changes obtained in the microarray experiment.
Results
Microarray analysis identified 142 differentially expressed genes (DEGs, p < .01), 57 upregulated and 85 downregulated, compared VF versus NVF groups. The DEG with the greatest expression difference was the Gamma2‐Syntrophin (SNTG2) (β = 31.88, p = .005). Validation by qPCR confirmed increased expression in VF group of Syntrophin (SNTG2, fold change = 2.79, p = .009), TRAF3 Interacting Protein2 (TRAF3IP2, fold change = 2.79, p = .020), and Integrin Subunit Alpha 6 (ITGA6, fold change = 2.86, p = .038).
Conclusion
Our data identified and validated the association of SNTG2 (608715), TRAF3IP2 (607043), and ITGA6 (147556) with osteoporotic VF in elderly women, independently of BMD. These results suggest that these transcripts have potential clinical significance and may help to explain the molecular mechanisms and biological functions of vertebral fracture.
Our data identified and validated the association of SNTG2, TRAF3IP2, and ITGA6 with osteoporotic vertebral fracture (VF) in elderly women, independently of bone mineral density. These results suggest that these transcripts have potential clinical significance and may help to explain the molecular mechanisms and biological functions of VF.
Coronary artery bypass graft surgery with cardiopulmonary bypass is a safe, routine procedure. Nevertheless, significant morbidity remains, mostly because of the body's response to the ...nonphysiological nature of cardiopulmonary bypass. Few data are available on the effects of off-pump coronary artery bypass graft surgery (OPCAB) on cardiac events and long-term clinical outcomes.
In a single-center randomized trial, 308 patients undergoing coronary artery bypass graft surgery were randomly assigned: 155 to OPCAB and 153 to on-pump CAB (ONCAB). Primary composite end points were death, myocardial infarction, further revascularization (surgery or angioplasty), or stroke. After 5-year follow-up, the primary composite end point was not different between groups (hazard ratio 0.71, 95% CI 0.41 to 1.22; P=0.21). A statistical difference was found between OPCAB and ONCAB groups in the duration of surgery (240±65 versus 300±87.5 minutes; P<0.001), in the length of ICU stay (19.5±17.8 versus 43±17.0 hours; P<0.001), time to extubation (4.6±6.8 versus 9.3±5.7 hours; P<0.001), hospital stay (6±2 versus 9±2 days; P<0.001), higher incidence of atrial fibrillation (35 versus 4% of patients; P<0.001), and blood requirements (31 versus 61% of patients; P<0.001), respectively. The number of grafts per patient was higher in the ONCAB than the OPCAB group (2.97 versus 2.49 grafts/patient; P<0.001).
No difference was found between groups in the primary composite end point at 5-years follow-up. Although OPCAB surgery was related to a lower number of grafts and higher episodes of atrial fibrillation, it had no significant implications related to long-term outcomes. Clinical Trial Registration-URL: http://www.controlled-trials.com. Unique identifier: ISRCTN66068876.
Despite the well-established association of gene expression deregulation with low muscle mass (LMM), the associated biological mechanisms remain unclear. Transcriptomic studies are capable to ...identify key mediators in complex diseases. We aimed to identify relevant mediators and biological mechanisms associated with age-related LMM. LMM-associated genes were detected by logistic regression using microarray data of 20 elderly women with LMM and 20 age and race-matched controls extracted from our SPAH Study (GSE152073). We performed weighted gene co-expression analysis (WGCNA) that correlated the identified gene modules with laboratorial characteristics. Gene enrichment analysis was performed and an LMM predictive model was constructed using Support Vector Machine (SVM). Overall, 821 discriminating transcripts clusters were identified (|beta coefficient| >1;
-value <0.01). From this list, 45 predictors of LMM were detected by SVM and validated with 0.7 of accuracy. Our results revealed that the well-described association of inflammation, immunity and metabolic alterations is also relevant at transcriptomic level. WGCNA highlighted a correlation of genes modules involved in immunity pathways with vitamin D level (R = 0.63,
= 0.004) and the Agatston score (R = 0.51,
= 0.02). Our study generated a predicted regulatory network and revealed significant metabolic pathways related to aging processes, showing key mediators that warrant further investigation.
•Vertebral fractures (VF) are a hallmark of osteoporosis and important cause of morbidity and mortality.•Moderate/severe VF fractures were associated with trabecular volumetric bone density using ...HR-pQCT at tibia in older women.•Moderate/severe VF were associated with femoral neck areal bone mineral density in older men from community.
Many vertebral fractures (VF) occur in individuals classified by DXA as being at low risk of fragility fractures. The aim of this study was to verify the association between VF and peripheral bone microarchitecture and strength parameters (SP) using, in addition to DXA, high-resolution peripheral quantitative computed tomography (HR-pQCT) and axial bone microarchitecture using the trabecular bone score (TBS).
Cross-sectional study of 276 community-dwelling subjects aged ≥65 years from the SPAH study cohort.
Lateral DXA scans of the spine were analyzed to assess VF. HR-pQCT was performed at the radius and tibia. TBS was determined using DXA.
VF was observed in 42.6% of women and 28% of men. At the tibia, women with moderate/severe VF had lower volumetric bone density (vBMD), trabecular number (Tb.N), and SP, and higher trabecular separation (Tb.Sp); and men with VF had lower Tb.N and SP, and higher Tb.Sp. At the radius, women with moderate/severe VF had lower vBMD, trabecular and cortical thickness and SP; and men with VF had lower trabecular vBMD and SP. No associations between TBS and VF were observed in either gender. Logistic regression analysis revealed that trabecular vBMD at the tibia in women (OR:0.980, 95%CI:0.963–0.997, p = 0.022) and femoral neck aBMD in men (OR:0.445, 95%CI:0.212–0.935, p = 0.033) were independently associated with VF.
HR-pQCT images detected differences in bone microstructure in older women with VF independent of aBMD and TBS by DXA, and HR-pQCT could be a useful tool to assess fracture risk. In men, femoral neck aBMD was associated with VF, and DXA continues to be an important tool for predicting VF.
The exchange of lipids with cells and other lipoproteins is a crucial process in HDL metabolism and for HDL antiatherogenic function. Here, we tested a practical method to quantify the simultaneous ...transfer to HDL of phospholipids, free-cholesterol, esterified cholesterol and triacylglycerols and to verify the lipid transfer in patients with coronary artery disease (CAD) or undergoing statin treatment. Twenty-eight control subjects without CAD, 27 with CAD and 25 CAD patients under simvastatin treatment were studied. Plasma samples were incubated with a donor nanoemulsion prepared by ultrasonication of the constituent lipids and labeled with radioactive lipids; % lipids transferred to HDL were quantified in the HDL-containing supernatant after chemical precipitation of non-HDL fractions and the nanoemulsion. The assay was precise and reproducible. Increase of temperature (4-37 °C), of incubation period (5 min to 2 h), of HDL-cholesterol concentration (33-244 mg/dL) and of mass of nanoemulsion lipids (0.075-0.3 mg/μL) resulted in increased lipid transfer from the nanoemulsion to HDL. In contrast, increasing pH (6.5-8.5) and albumin concentration (3.5-7.0 g/dL) did not affect lipid transfer. There was no difference between CAD and control non-CAD with regard to the lipid transfer, but statin treatment reduced the transfer to HDL of all four lipids. The test herein described is a valid and practical tool for exploring an important aspect of HDL metabolism.
This study examined the predictive power of clinical judgment in the incidence of cardiovascular end points in a group of individuals with multivessel coronary artery disease (CAD) followed up in the ...MASS II (Medicine, Angioplasty, or Surgery Study II).
There is still no consensus on the best treatment for patients with stable multivessel CAD and preserved left ventricular function.
Preferred treatment allocation was recorded for each of the 611 randomized patients in the MASS II trial before randomization. We have divided our sample according to physician-guided decision and randomization result into two categories: concordant or discordant. The incidence of the points of cardiac death, myocardial infarction, and refractory angina was compared between concordant and discordant patients.
The number of concordant individuals was 292 (48.2%), and this number was not different between the three studied treatments (p = 0.11). A significant difference (p = 0.02) was disclosed because of an increased incidence of combined end point events in discordant patients. In the multivariate Cox hazard model, clinical judgment was a powerful predictor of outcome (p = 0.01) even after adjustment for other covariates. The main subgroup explaining this difference was a significant shift toward a worse outcome in the subgroup of discordant patients who underwent percutaneous coronary intervention (PCI) (p = 0.003).
Angiographic variables were more often used in making clinical decisions regarding PCI than clinical variables, and the only independent predictor of concordance status in the PCI group was the number of diseased vessels (p = 0.01). Our data are a reminder that physician judgment remains an important predictor of outcomes.
To determine whether information from genetic risk variants for diabetes is associated with cardiovascular events incidence.
From the about 30 known genes associated with diabetes, we genotyped ...single-nucleotide polymorphisms at the 10 loci most associated with type-2 diabetes in 425 subjects from the MASS-II Study, a randomized study in patients with multi-vessel coronary artery disease. The combined genetic information was evaluated by number of risk alleles for diabetes. Performance of genetic models relative to major cardiovascular events incidence was analyzed through Kaplan-Meier curve comparison and Cox Hazard Models and the discriminatory ability of models was assessed for cardiovascular events by calculating the area under the ROC curve.
Genetic information was able to predict 5-year incidence of major cardiovascular events and overall-mortality in non-diabetic individuals, even after adjustment for potential confounders including fasting glycemia. Non-diabetic individuals with high genetic risk had a similar incidence of events then diabetic individuals (cumulative hazard of 33.0 versus 35.1% of diabetic subjects). The addition of combined genetic information to clinical predictors significantly improved the AUC for cardiovascular events incidence (AUC = 0.641 versus 0.610).
Combined information of genetic variants for diabetes risk is associated to major cardiovascular events incidence, including overall mortality, in non-diabetic individuals with coronary artery disease.
Medicine, Angioplasty, or Surgery Study (MASS II). Unique identifier: ISRCTN66068876 URL.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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