Dataset Information

Renin Feedback Is an Independent Predictor of Outcome in HFpEF.

ABSTRACT: Drugs which interact with the renin angiotensin aldosterone system (RAAS) aim to reduce the negative effects of angiotensin (Ang) II. Treatment with these drugs anticipate a compensatory up-regulation of renin; however, it has been shown that there is a large variability in circulating plasma renin (PRA), even in patients with optimal medical therapy in patients with heart failure (HF) with reduced ejection fraction (HFrEF). Our aim was to measure plasma renin activity (PRA-S), its response to RAAS inhibitor (RAASi) therapies and its effects on outcome in patients with HF with preserved ejection fraction (HFpEF). For this purpose, 150 HFpEF patients were included into a prospective single-center registry. Equilibrium (eq) angiotensin metabolites were measured from serum samples using mass spectroscopy. PRA-S (eqAng I + eqAng II) was calculated and compared in respect to the primary endpoint defined as all-cause death. PRA-S in patients with RAASi therapy was not significantly higher than in patients without RAASi (p = 0.262). Even after adjusting for confounding factors, PRA-S remained predictive for all-cause death in the multivariable model with a hazard ratio of 2.14 (95%CI 1.20-3.82, p = 0.010). We conclude that high PRA-S is associated with poor prognosis in patients with HFpEF, regardless of RAASi treatment, which could ultimately result in hyperactivated RAAS and consecutive negative effects on the cardiovascular and renal system, leading to poor outcome in patients with HFpEF.

SUBMITTER: Binder C

PROVIDER: S-EPMC8147649 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Renin Feedback Is an Independent Predictor of Outcome in HFpEF.

Binder Christina C Poglitsch Marko M Duca Franz F Rettl René R Dachs Theresa Marie TM Dalos Daniel D Schrutka Lore L Seirer Benjamin B Ligios Luciana Camuz LC Capelle Christophe C Eslam Roza Badr RB Qin Hong H Hengstenberg Christian C Bonderman Diana D

Journal of personalized medicine 20210503 5

Drugs which interact with the renin angiotensin aldosterone system (RAAS) aim to reduce the negative effects of angiotensin (Ang) II. Treatment with these drugs anticipate a compensatory up-regulation of renin; however, it has been shown that there is a large variability in circulating plasma renin (PRA), even in patients with optimal medical therapy in patients with heart failure (HF) with reduced ejection fraction (HFrEF). Our aim was to measure plasma renin activity (PRA-S), its response to R ...[more]

PMID: 34063595

Similar Datasets

Project description:Spindle Apparatus Coiled-Coil Protein 1 (SPDL1) is a relatively recently identified coiled-coil domain containing protein and an important determinant of DNA fidelity by ensuring faithful mitosis. Hence, SPDL1 is suspected to underlie genomic (in-)stability in human cancers, yet its exact roles in these diseases remain largely underexplored. Given that genomic instability (GIN) is a crucial feature in colorectal cancer (CRC), we primarily asked whether the expression of this protein may account for differences in clinicopathological features and survival rates of CRC patients. Protein expression was evaluated by immunohistochemistry in the institutional tissue microarray (TMA), and gene expression by the analysis of publicly available datasets. To place the prognostic relevance in a predicted biological context, gene co-expression set around SPDL1 identified by public data mining was annotated and assessed for enrichment in gene ontology (GO) categories, BRITE hierarchies, and Reactome pathways. The comparison with adjacent normal tissue revealed a high expression of SPDL1 protein in a subset of tumor cases (48.84%), and these had better prognosis than the SPDL1-low expression counterpart even after adjustment for multiple confounders. SPDL1-high expression within tumors was associated with a median 56-month survival advantage, but not with any clinicopathological characteristics of our cohort. In the TCGA cohort, SPDL1 was overexpressed in tumor tissue and positively associated with improved survival, chromosome instability phenotype, and various GIN markers. In addition to the genes critically involved in the cell cycle and mitosis, a gene set co-expressed with SPDL1 contained checkpoint members of both chromosome segregation and DNA replication, as well as those associated with defective DNA repair, and retrograde vesicle-mediated transport. In conclusion, SPDL1 is an independent predictor of CRC patient survival in a possible connection with chromosomal instability.

Project description:Purpose Atrial fibrillation (AF) is a significant independent risk factor for 1-year mortality in patients with first acute ischemic stroke (AIS). The CHA2DS2-VASc score was initially developed to assess the risk of stroke in patients with AF. Recently, this scoring system has been demonstrated to have clinical value for predicting long-term clinical outcomes in AIS but the evidence is insufficient. This large-scale prospective cohort study investigated the independent predictive value of the score in such patients. Methods We included patients with AIS from the Taiwan Stroke Registry (TSR) during 2006–2016 as the present study population. Patients were divided into those with high (≥2) and low (<2) CHA2DS2-VASc scores. We further analyzed and classified patients according to the presence of AF. The clinical endpoint was major adverse cardiac and cerebrovascular events (MACCEs) at 1 year after the index AIS. Results A total of 62,227 patients with AIS were enrolled. The median age was 70.3 years, and 59% of the patients were women. After confounding factors were controlled, patients with high CHA2DS2-VASc scores had significantly higher incidence of 1-year MACCEs (adjusted hazard ratio [HR] = 1.63; 95% confidence interval [CI] = 1.52, 1.76), re-stroke (adjusted HR = 1.28; 95% CI = 1.16, 1.42), and all-cause mortality (adjusted HR = 2.03; 95% CI = 1.83, 2.24) than those with low CHA2DS2-VASc scores did. In the comparison between AF and non-AF groups, the AF group had increased MACCEs (adjusted HR = 1.74; 95% CI = 1.60, 1.89), myocardial infarction (adjusted HR = 4.86; 95% CI = 2.07, 11.4), re-stroke (adjusted HR = 1.47; 95% CI = 1.26, 1.71), and all-cause mortality (adjusted HR = 1.90; 95% CI = 1.72, 2.10). The Kaplan–Meier curve revealed that both CHA2DS2-VASc scores and AF were independent risk predictors for 1-year MACCEs and mortality. Conclusions The CHA2DS2-VASc score and AF appeared to consistently predict 1-year MACCEs of AIS patients and provide more accurate risk stratification. Therefore, increased use of the CHA2DS2-VASc score may help improve the holistic clinical assessment of AIS patients with or without AF.

Project description:BackgroundDuodenal cytochrome b (DCYTB) is a ferrireductase that functions together with divalent metal transporter 1 (DMT1) to mediate dietary iron reduction and uptake in the duodenum. DCYTB is also a member of a 16-gene iron regulatory gene signature (IRGS) that predicts metastasis-free survival in breast cancer patients. To better understand the relationship between DCYTB and breast cancer, we explored in detail the prognostic significance and molecular function of DCYTB in breast cancer.MethodsThe prognostic significance of DCYTB expression was evaluated using publicly available microarray data. Signaling Pathway Impact Analysis (SPIA) of microarray data was used to identify potential novel functions of DCYTB. The role of DCYTB was assessed using immunohistochemistry and measurements of iron uptake, iron metabolism, and FAK signaling.ResultsHigh DCYTB expression was associated with prolonged survival in two large independent cohorts, together totaling 1610 patients (cohort #1, p = 1.6e-11, n = 741; cohort #2, p = 1.2e-05, n = 869; log-rank test) as well as in the Gene expression-based Outcome for Breast cancer Online (GOBO) cohort (p < 1.0e-05, n = 1379). High DCYTB expression was also associated with increased survival in homogeneously treated groups of patients who received either tamoxifen or chemotherapy. Immunohistochemistry revealed that DCYTB is localized on the plasma membrane of breast epithelial cells, and that expression is dramatically reduced in high-grade tumors. Surprisingly, neither overexpression nor knockdown of DCYTB affected levels of ferritin H, transferrin receptor, labile iron or total cellular iron in breast cancer cells. Because SPIA pathway analysis of patient microarray data revealed an association between DCYTB and the focal adhesion pathway, we examined the influence of DCYTB on FAK activation in breast cancer cells. These experiments reveal that DCYTB reduces adhesion and activation of focal adhesion kinase (FAK) and its adapter protein paxillin.ConclusionsDCYTB is an important predictor of outcome and is associated with response to therapy in breast cancer patients. DCYTB does not affect intracellular iron in breast cancer cells. Instead, DCYTB may retard cancer progression by reducing activation of FAK, a kinase that plays a central role in tumor cell adhesion and metastasis.

Dataset Information

Renin Feedback Is an Independent Predictor of Outcome in HFpEF.

Publications

Renin Feedback Is an Independent Predictor of Outcome in HFpEF.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets