Epicardial adipose tissue (EAT) volume is related to subclinical atherosclerosis and major adverse cardiovascular events (MACE) in asymptomatic subjects

Introduction Epicardial adipose tissue (EAT) is an emerging cardiovascular risk marker. It has been suggested to be an inflammatory mediator with a role in subclinical atherosclerosis and coronary artery disease. However, its prognostic relevance in hard clinical outcomes remains thoroughly unexplored in the literature. Purpose Evaluate the prognostic relevance of EAT, regarding the occurrence of major adverse cardiovascular events (MACE) in an asymptomatic population. Methods 895 asymptomatic volunteers were prospectively enrolled in a single Portuguese center (mean age 51.9±7.7, 78.5% male) and underwent a median follow-up time of 3.7 years (IQR 5.0). EAT volume was measured by Cardiac Computed Tomography (CCT) using a modified simplified method. Participants were distributed into two groups, above and below the EAT-volume median. We compared both groups regarding the occurrence of MACE through univariate analysis, Kaplan-Meier Survival curves and log-rank test. Association to subclinical atherosclerosis was addressed using correlation between EAT volume and calcium score (Agatson). Results There is a strong correlation between EAT volume and calcium score (r=0.205, p<0.0001), sustaining that it may play an important role in mediating coronary artery disease and subclinical atherosclerosis. Patients with higher EAT volume, were exposed to higher occurrence of MACE on follow-up [70.4% (19 of 27) vs 49.4% (429 of 868), p=0.032] with a clearer separation of the curves after 5.7 years. Conclusion In an asymptomatic population, EAT volume seems to be related to subclinical atherosclerosis and to the occurrence of adverse cardiovascular events on long-term follow-up. Our study addresses some unanswered questions, such as the prognostic relevance of EAT as an emerging cardiovascular risk marker. FUNDunding Acknowledgement Type of funding sources: None.

Prognostic impact of liver fibrosis and steatosis by transient elastography for cardiovascular and mortality outcomes in individuals with nonalcoholic fatty liver disease and type 2 diabetes: the Rio de Janeiro Cohort Study

Background Liver stiffness measurement (LSM, which reflects fibrosis) and controlled attenuation parameter (CAP, which reflects steatosis), two parameters derived from hepatic transient elastography (TE), have scarcely been evaluated as predictors of cardiovascular complications and mortality in individuals with type 2 diabetes and nonalcoholic fatty liver disease (NAFLD). Methods Four hundred type 2 diabetic patients with NAFLD had TE examination (by Fibroscan®) performed at baseline. Multivariate Cox analyses evaluated the associations between TE parameters and the occurrence of cardiovascular events (CVEs) and mortality. TE parameters were assessed as continuous variables and dichotomized at low/high values reflecting advanced liver fibrosis (LSM > 9.6 kPa) and severe steatosis (CAP > 296 or > 330 dB/m). Improvements in risk discrimination were assessed by C-statistic and by the relative Integrated Discrimination Improvement (IDI) index. Results During a median follow-up of 5.5 years, 85 patients died (40 from cardiovascular causes), and 69 had a CVE. As continuous variables, an increasing LSM was a risk marker for total CVEs (hazard ratio [HR]: 1.05; 95% CI: 1.01–1.08) and all-cause mortality (HR: 1.04; 95% CI: 1.01–1.07); whereas an increasing CAP was a protective factor for both outcomes (HR: 0.93; 95% CI: 0.89–0.98; and HR: 0.92; 95% CI: 0.88–0.97; respectively). As dichotomized variables, a high LSM remained a risk marker of adverse outcomes (with HRs ranging from 2.5 to 3.0) and a high CAP was protective (with HRs from 0.3 to 0.5). The subgroup of individuals with low-LSM/high-CAP had the lowest risks while the opposite subgroup with high-LSM/low-CAP had the highest risks. Both LSM and CAP improved risk discrimination, with increases in C-statistics up to 0.037 and IDIs up to 52%. Conclusions Measured by hepatic TE, advanced liver fibrosis is a risk marker and severe steatosis is a protective factor for cardiovascular complications and mortality in individuals with type 2 diabetes and NAFLD.

Analysis of Telomere Maintenance Related Genes Reveals NOP10 as a New Metastatic-Risk Marker in Pheochromocytoma/Paraganglioma

One of the main problems we face with PPGL is the lack of molecular markers capable of predicting the development of metastases in patients. Telomere-related genes, such as TERT and ATRX, have been recently described in PPGL, supporting the association between the activation of immortalization mechanisms and disease progression. However, the contribution of other genes involving telomere preservation machinery has not been previously investigated. In this work, we aimed to analyze the prognostic value of a comprehensive set of genes involved in telomere maintenance. For this study, we collected 165 PPGL samples (97 non-metastatic/63 metastatic), genetically characterized, in which the expression of 29 genes of interest was studied by NGS. Three of the 29 genes studied, TERT, ATRX and NOP10, showed differential expression between metastatic and non-metastatic cases, and alterations in these genes were associated with a shorter time to progression, independent of SDHB-status. We studied telomere length by Q-FISH in patient samples and in an in vitro model. NOP10 overexpressing tumors displayed an intermediate-length telomere phenotype without ALT, and in vitro results suggest that NOP10 has a role in telomerase-dependent telomere maintenance. We also propose the implementation of NOP10 IHC to better stratify PPGL patients.