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International audience; BACKGROUND:To assess the prognostic value of mineralocorticoid receptor antagonist (MRA) initiation and change in serum potassium (K+ ) during follow-up in patients post-acute myocardial infarction with left ventricular dysfunction or chronic heart failure (HF) and reduced ejection fraction (HFrEF).METHODS AND RESULTS:Risk scores for predicting cardiovascular death (primary outcome), hospitalization for HF and all-cause death were developed. K+ and other relevant time-updated clinical and biological variables were added to conventional prognostic factors when constructing these new models. EPHESUS (n = 6632) was the derivation cohort, while EMPHASIS-HF (chronic HF, n = 2737) was used as external validation cohort. The final cardiovascular death risk score included medical history, clinical and biological parameters (e.g. K+ , below or above the normal range of 4-5 mmol/L, estimated glomerular filtration rate, and anaemia), as well as aspects of treatment (any diuretic usage, MRA use or discontinuation, and beta-blocker use). The risk score performed well in both the derivation and validation cohorts and outperformed the MAGGIC score. A web-based calculator was created to allow easy determination of the risk score (http://cic-p-nancy.fr/CardiovascularriskscoreCalculator/).CONCLUSION:Adding time-updated variables, including K+ and MRA treatment, improved risk prediction of cardiovascular death (on top of the MAGGIC score) in patients with HF eligible for renin-angiotensin system inhibitors and MRA therapy. This new risk score including MRA usage and K+ may be of value in helping physicians to better use MRAs, avoid unnecessary and potentially detrimental permanent discontinuations, and therefore improving cardiovascular outcomes in patients with chronic HFrEF or HF after acute myocardial infarction with left ventricular dysfunction.© 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiology.

Introduction: In everyday practice, angiotensin converting enzyme inhibitors and beta-blockers are cornerstone treatments in patients with (cardio-)vascular disease. Clear data that evaluate the effects of the combination of these agents on morbidity and mortality are lacking. Methods: In this retrospective pooled analysis of three large perindopril outcome trials (ADVANCE, EUROPA, PROGRESS), clinical outcomes were evaluated in 29,463 patients with vascular disease. Multivariate Cox regression analyses were performed in patients randomized to a perindopril-based regimen or placebo (treatment effect), and data were stratified according to background beta-blocker treatment. The primary endpoint was a composite of cardiovascular mortality, non-fatal myocardial infarction, and stroke. Results: The cumulative incidence of the primary endpoint over mean follow-up of 4.0 years (Sd 1.0) was significantly lower in the beta-blocker/perindopril group (9.6%; 545/5700 patients) as compared to beta-blocker/placebo (11.8%; 676/5718 patients) (p < 0.01). Adding perindopril to existing beta-blocker treatment reduced the relative risk of the primary endpoint by 20% (hazard ratio (HR) 0.80; 95% confidence interval (CI) 0.71–0.90), non-fatal myocardial infarction by 23% (HR 0.77; 95% CI 0.65–0.91), and all-cause mortality by 22% (HR 0.78; 95% CI 0.68–0.88) as compared to placebo. Significant treatment benefit was not observed for stroke (HR 0.93; 95% CI 0.75–1.15). Significance was maintained for the primary endpoint and cardiovascular endpoints when data were further stratified by baseline hypertension. However, the mortality benefit was only observed in patients with hypertension with background beta-blocker use. Conclusions: These data suggest that the beneficial cardioprotective effects of perindopril treatment are additive to the background beta-blockers use.

The discovery of the intrarenal renin-angiotensin system (iRAS), which regulates angiogenesis, cell differentiation and proliferation, has opened new perspectives in the knowledge of kidney carcinogenesis. In this study we analyzed the immunohistochemical expression and fluorimetric activity of four key peptidases of iRAS in tumor tissue (n = 144) and serum samples (n = 128) from patients with renal neoplasms. Neutral endopeptidase (NEP/CD10), Angiotensin-converting enzyme-2 (ACE2), and aminopeptidase A (APA) were expressed in tumor cells whilst Angiotensin-converting enzyme (ACE) was expressed in the endothelial cells of intratumor blood vessels. The expression of ACE, ACE2 and NEP/CD10 was highest in clear cell renal cell carcinoma (CCRCC) and papillary renal cell carcinoma (PRCC). The expression of these enzymes correlated with CCRCC aggressiveness. In addition, NEP/CD10 correlated with 15-year overall survival. On the other hand, APA expression was decreased in CCRCC with higher grade and stage. The loss of expression of APA independently correlated with a worse 15-year overall survival. Serum activity of ACE2, NEP/CD10 and APA was significantly higher in renal tumor patients than in healthy subjects. Serum ACE activity was lower in high grade and metastatic CCRCC patients, and NEP/CD10 activity was negatively correlated with UISS (UCLA Integrated Staging System) and SSIGN (Mayo Clinic stage, size, grade and necrosis model) scores and with overall survival of CCRCC patients. These results suggest a metabolic imbalance of iRAS in renal tumors. This finding should be taken into account in the search of new diagnostic, prognostic and therapeutic tools for this disease. This work was partially funded by Grant SAF2013-48812-R from Ministerio de Economia y Competitividad (Spain), IT 8-11/13 from de Basque Government and UFI 11/44 from de University of the Basque Country (UPV/EHU). The current work has been developed as PhD project of PE and MB, who are recipients of a Predoctoral Fellowship from the Basque Government (Exp no PRE_2013_1_762 and PRE_2015_2_0148). This work was partially funded by Grant SAF2013-48812-R from Ministerio de Economia y Competitividad (Spain), IT 8-11/13 from de Basque Government and UFI 11/44 from de University of the Basque Country (UPV/EHU). The current work has been developed as PhD project of PE and MB, who are recipients of a Predoctoral Fellowship from the Basque Government (Exp no PRE_2013_1_762 and PRE_2015_2_0148)

Previous preclinical research suggests that angiotensin system inhibitors may have a direct anti-angiogenic effect that may be synergistic with the currently available angiogenesis inhibitors. In this retrospective study, we reviewed 303 patients with metastatic renal cell carcinoma treated with first-line angiogenesis inhibitors. Our results demonstrate a longer overall and progression-free survival for angiotensin system inhibitor users among patients with treatment-related hypertension. If validated, these results may guide the choice of antihypertensive medication among patients being treated with angiogenesis inhibitors. Background: Research suggests that baseline use of angiotensin system inhibitors (ASIs) improves outcome in patients with metastatic renal cell carcinoma (mRCC), but it remains unknown whether the type of antihypertensive medication used to initiate management at onset of treatment-induced hypertension (HTN) is associated with outcome. We evaluated the association of ASIs and outcome among patients with mRCC treated with first-line tyrosine kinase inhibitors (TKIs). Patients and Methods: We identified 303 consecutive patients with mRCC who were treated with sunitinib or pazopanib in a single university hospital cancer center. Statistical analyses were performed using the Kaplan-Meier method and Cox regression adjusted for known risk factors. Results: Progression-free survival (PFS) and overall survival (OS) were similar among patients with baseline HTN (n = 197; 65%) versus patients with no baseline HTN (n = 106; 35%) (PFS; P = .72) (OS; P = .54). There was a significant difference between patients with treatment-induced HTN (n = 110) versus patients with no treatment-induced HTN (n = 193) for PFS (15.6 vs. 6.4 months, respectively; P