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Pubblicazioni recenti - cardiorenal
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SGLT2 Inhibitors and Their Mode of Action in Heart Failure-Has the Mystery Been Unravelled?
Curr Heart Fail Rep2021 Sep;():. doi: 10.1007/s11897-021-00529-8.
Pabel Steffen, Hamdani Nazha, Luedde Mark, Sossalla Samuel,
Abstract
PURPOSE OF REVIEW:
SGLT2 inhibitors (SGLT2i) are new drugs for patients with heart failure (HF) irrespective of diabetes. However, the mechanisms of SGLT2i in HF remain elusive. This article discusses the current clinical evidence for using SGLT2i in different types of heart failure and provides an overview about the possible underlying mechanisms.
RECENT FINDINGS:
Clinical and basic data strongly support and extend the use of SGLT2i in HF. Improvement of conventional secondary risk factors is unlikely to explain the prognostic benefits of these drugs in HF. However, different multidirectional mechanisms of SGLT2i could improve HF status including volume regulation, cardiorenal mechanisms, metabolic effects, improved cardiac remodelling, direct effects on cardiac contractility and ion-homeostasis, reduction of inflammation and oxidative stress as well as an impact on autophagy and adipokines. Further translational studies are needed to determine the mechanisms of SGLT2i in HF. However, basic and clinical evidence encourage the use of SGLT2i in HFrEF and possibly HFpEF.
© 2021. The Author(s).
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Haemodynamic parameters associated with renal function prior to and following heart transplantation.
ESC Heart Fail2021 Sep;():. doi: 10.1002/ehf2.13534.
Baudry Guillaume, Sebbag Laurent, Bourdin Juliette, Hugon-Vallet Elisabeth, Jobbe Duval Antoine, Mewton Nathan, Pozzi Matteo, Rossignol Patrick, Girerd Nicolas,
Abstract
AIMS:
Abnormal renal function is a common feature in patients on heart transplant waiting lists. This study aimed to identify the haemodynamic parameters associated with decreased estimated glomerular filtration rate (eGFR) in patients listed for heart transplantation (HT) and renal function improvement following HT.
METHODS AND RESULTS:
A total of 176 adults (52 years old, 81% men) with available right heart catheterization (RHC) listed in our centre for HT between 2014 and 2019 were studied. Cardiac catheterization measurements were obtained at time of HT listing evaluation. Changes in renal function were assessed between RHC and 6 months after HT. Median eGFR was 63 mL/min/1.73 m at time of RHC. Central venous pressure > 10 mmHg was associated with a two-fold increase in the likelihood of eGFR
CONCLUSIONS:
Central venous pressure is the main haemodynamic parameter associated with eGFR
© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
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Impact of red blood cell distribution width and mean platelet volume in patients with ST-segment elevation myocardial infarction.
Heart Vessels2021 Sep;():. doi: 10.1007/s00380-021-01936-6.
Ebina Toshiaki, Tochihara Shiori, Okazaki Mai, Koike Kazuyo, Tsuto Yuko, Tayama Megumi, Takanami Yukiko, Hirose Haruka, Horii Mutsuo, Okada Kozo, Matsuzawa Yasushi, Maejima Nobuhiko, Iwahashi Noriaki, Hibi Kiyoshi, Kosuge Masami, Tamura Kouichi, Kimura Kazuo,
Abstract
The complete blood cell count is one of the most frequently ordered laboratory tests, and many parameters, including red blood cell distribution width (RDW) and mean platelet volume (MPV), are available. The purpose of this study was to investigate the usefulness of the combination of RDW and MPV in patients with ST-segment elevation myocardial infarction (STEMI). Patients with STEMI who underwent primary percutaneous coronary intervention were retrospectively enrolled (n?=?229). The association between RDW as well as MPV and cardiovascular events was investigated. The median age was 67 years, and males made up 85% of the sample. Median RDW was 13.6%, and median MPV was 8.2 fL. During a median follow-up period of 528 days (IQR 331.5-920.5), 41 patients died or experienced major adverse cardiac and cerebrovascular events (MACCEs). Patients with RDW ? 13.7% had more deaths or MACCEs with marginal significance (p?=?0.0799). Patients with MPV ? 8.3 fL had significantly more deaths or MACCEs (p?=?0.0283). Patients with RDW ? 13.7% and MPV ? 8.3 fL had significantly more deaths or MACCEs (p?=?0.0185). MPV was significantly associated with death or adverse events in patients with STEMI who were treated with primary PCI. RDW had only a weak association with death or adverse events. The results of the combination of MPV and RDW were similar to those of MPV.
© 2021. Springer Japan KK, part of Springer Nature.
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The Role of Cell-Free Plasma DNA in Patients with Cardiorenal Syndrome Type 1.
Cardiorenal Med2021 Sep;():1-8. doi: 10.1159/000518553.
Virzì Grazia Maria, Clementi Anna, Milan Manani Sabrina, Castellani Chiara, Battaglia Giovanni Giorgio, Angelini Annalisa, Vescovo Giorgio, Ronco Claudio,
Abstract
BACKGROUND:
Recent research highlighted the potential role of circulating cell-free DNA (cfDNA), resulted by apoptosis or cell necrosis, as a prognostic marker in the setting of different clinical conditions. Cardiorenal syndrome type 1 (CRS type 1) is characterized by a rapid worsening of cardiac function leading to acute kidney injury (AKI). Apoptosis of renal epithelial cells is proposed as a mechanism involved in CRS type 1. In this study, we investigated cfDNA levels in patients with acute heart failure (AHF) and CRS type 1 and the possible correlation between cfDNA levels and inflammatory and apoptotic parameters.
METHODS:
We enrolled 17 AHF patients and 15 CRS type 1 who exhibited AKI at the time of admission (caused by AHF) or developed AKI during the first 48 h from admission. cfDNA was extracted from plasma and quantified by real-time polymerase chain reaction. Plasma levels of NGAL, tumor necrosis factor-?, interleukin (IL)-6, IL-18, and caspase-3 were measured.
RESULTS:
We observed significantly higher levels of cfDNA in patients with CRS type 1 than patients with AHF. Caspase-3, IL-6, IL-18, and NGAL levels resulted significantly increased in patients with CRS type 1. Moreover, a positive correlation between cfDNA levels and caspase-3 levels was found, as well as between cfDNA levels and IL-6 and renal parameters.
CONCLUSION:
Our study explores the premise of cfDNA as a marker for apoptosis and inflammation in CRS type 1 patients. cfDNA could potentially serve as an index for noninvasive monitoring of tissue damage and apoptosis in patients with AKI induced by AHF.
© 2021 The Author(s). Published by S. Karger AG, Basel.
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Impact of sarcopenic obesity on long-term clinical outcomes after ST-segment elevation myocardial infarction.
Atherosclerosis2021 Aug;():. doi: S0021-9150(21)01294-6.
Sato Ryosuke, Okada Kozo, Akiyama Eiichi, Konishi Masaaki, Matsuzawa Yasushi, Nakahashi Hidefumi, Minamimoto Yugo, Kimura Yuichiro, Maejima Nobuhiko, Iwahashi Noriaki, Hibi Kiyoshi, Kosuge Masami, Ebina Toshiaki, Tamura Kouichi, Kimura Kazuo,
Abstract
BACKGROUND AND AIMS:
Both low appendicular skeletal muscle index (ASMI) and specific abdominal fat composition [i.e., increased visceral to subcutaneous (V/S) fat ratio] have been associated with cardiovascular events. However, the combined impact of these 2 components on long-term outcomes remains unclear, especially in patients with ST-segment elevation myocardial infarction (STEMI).
METHODS:
In 303 patients with STEMI, ASMI and V/S fat ratio were assessed using dual-energy X-ray absorptiometry and abdominal computed tomography. Based on the criteria of the Asian Working Group for Sarcopenia and median of V/S fat ratio, sarcopenic obesity (SO) pattern was defined as low ASMI with high V/S fat ratio. The primary endpoint was composite outcomes of all-cause death, myocardial infarction, ischemic stroke, hospitalization for heart failure and unplanned revascularization.
RESULTS:
During a median follow-up of 3.9 years, primary endpoint occurred in 67 patients. Patients with an SO pattern showed significantly lower event-free survival rate compared with those without (p=0.006 by log-rank). Notably, when stratified by median age (67 years), this trend was particularly prominent in the younger-age group (p
CONCLUSIONS:
Low ASMI with high V/S fat ratio, or so-called sarcopenic obesity, was associated with poor prognosis after STEMI, particularly in younger-age patients. The combined assessment of skeletal muscle with abdominal fat distribution may help stratify the risk among patients with STEMI, rather than each component alone.
Copyright © 2021 Elsevier B.V. All rights reserved.
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Apela inhibits systemic and renal inflammatory reactions in mice with type I cardiorenal syndrome.
FASEB J2021 Oct;35(10):e21907. doi: 10.1096/fj.202101030R.
Jin Liangli, Li Quanyi, Li Jing, Pan Yang, Zou Jue, Wu Xiaoyuan, Wang Zhi,
Abstract
This study investigated the effect of apela on renal function and anti-inflammatory effect on whole body and kidney tissue in mice with type I cardiorenal syndrome (CRS). The murine type I CRS model was established and apela was subcutaneously infused for two weeks. Cardiac and renal functions were evaluated by echocardiography and blood biochemistry, respectively. The systemic and renal inflammatory responses were examined with molecular biological and histological methods. Human renal glomerular endothelial cells (RGECs) were used to evaluate the adhesion effect of monocytes in vitro. Compared to mice from the control group (CRS + vehicle), the plasma levels of N-terminal pro-brain natriuretic peptide, blood urea nitrogen and creatinine were significantly decreased, while the mean left ventricular ejection fraction was increased in apela-treated CRS mice at the 4th week. The expression of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-? (TNF-?) in the circulation and kidney was decreased in apela-treated mice compared with control mice, and apela improved cardio-renal pathology in mice with type I CRS. Additionally, Apela significantly suppressed the expression of MCP-1, TNF-?, intercellular adhesion molecule-1 and vascular intercellular adhesion molecule-1 in RGECs induced by angiotensin II (Ang II), and inhibited the promoting effect of Ang II on the adhesion of THP-1 cells to RGECs. Western blot results showed that the expression of phosphorylated nuclear factor kappa B (phospho-NF?B) in CRS mice was increased, but the expression of phospho-NF?B was down-regulated after apela treatment. Furthermore, apela significantly inhibited the Ang II-mediated increase in phospho-NF?B expression in RGECs in vitro, but the administration of an apelin peptide jejunum receptor (APJ) inhibitor blocked the inhibitory effect of apela. This study revealed that apela improves cardiorenal function and reduces systemic and renal inflammatory response in type I CRS mice and the apela/APJ system may alleviate renal inflammatory responses by inhibiting the NF?B signalling pathway.
© 2021 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.
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The Association of Pre-Kidney Transplant Dialysis Modality with de novo Posttransplant Heart Failure.
Cardiorenal Med2021 Sep;():1-9. doi: 10.1159/000518535.
Lenihan Colin R, Liu Sai, Airy Medha, Walther Carl, Montez-Rath Maria E, Winkelmayer Wolfgang C,
Abstract
BACKGROUND:
Heart failure (HF) after kidney transplantation is a significant but understudied problem. Pretransplant dialysis modality could influence incident HF risk through differing cardiac stressors. However, whether pretransplant dialysis modality is associated with the development of posttransplant HF is unknown.
METHODS:
We used the US Renal Data System to assemble a cohort of 27,701 patients who underwent their first kidney transplant in the USA between the years 2005 and 2012 and who had Medicare fee-for-service coverage for >6 months preceding their transplant date. Patients with any HF diagnosis prior to transplant were excluded. Detailed baseline patient characteristics and comorbidities were abstracted. The outcome of interest was de novo posttransplant HF. Pretransplant dialysis modality was defined as the dialysis modality used at the time of transplant. We conducted time-to-event analyses using Cox regression. Death was treated as a competing risk in the study's primary analysis. Graft failure was included as a time-varying covariate.
RESULTS:
Among eligible patients, 81% were treated with hemodialysis prior to transplant, and hemodialysis patients were more likely to be male, had a shorter dialysis vintage, and had more diabetes and vascular disease diagnoses. When adjusted for all available demographic and clinical data, pretransplant treatment with hemodialysis (vs. peritoneal dialysis) was associated with a 19% increased risk in de novo posttransplant HF, with sub-distribution HR 1.19 (95% CI: 1.09-1.29).
CONCLUSIONS:
Our results suggest that choice of pretransplant dialysis modality may impact the development of posttransplant HF.
© 2021 The Author(s) Published by S. Karger AG, Basel.
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Editorial.
Cardiorenal Med -
Mineralocorticoid Receptor Antagonism in Chronic Kidney Disease.
Kidney Int Rep2021 Sep;6(9):2281-2291. doi: 10.1016/j.ekir.2021.05.027.
Georgianos Panagiotis I, Agarwal Rajiv,
Abstract
The overactivation of the mineralocorticoid receptor (MR) in animal models of chronic kidney disease (CKD) increases sodium retention and hypertension and provokes inflammation and fibrosis in the kidneys, blood vessels, and the heart; these processes play an important role in the progression of cardiorenal disease. Accordingly, blockade of the MR is an attractive therapeutic intervention to retard the progression of CKD and improve cardiovascular morbidity and mortality. Finerenone is a novel, nonsteroidal MR antagonist (MRA) with a unique mode of action that is distinct from currently available steroidal MRAs. In animal models of CKD, finerenone has a more favorable benefit/risk ratio as compared with the steroidal MRAs such as spironolactone and eplerenone. In patients with type 2 diabetes and heart and/or kidney disease, phase II trials have revealed that compared with spironolactone, eplerenone, or placebo, finerenone displays benefits that exceed the risks of MR antagonism. In patients with CKD and type 2 diabetes, a large phase III trial has shown that, compared with placebo, finerenone improved kidney failure and cardiovascular outcomes. In the first part of this article, we explore the safety and efficacy of spironolactone and eplerenone in early- and late-stage CKD. In the second part, we describe the mechanism of action of finerenone and discuss the promising role of this nonsteroidal MRA as a novel therapeutic opportunity to improve clinical outcomes in patients with CKD.
© 2021 International Society of Nephrology. Published by Elsevier Inc.
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Sodium-Glucose Cotransporter 2 (SGLT-2) Inhibitors: Delving Into the Potential Benefits of Cardiorenal Protection Beyond the Treatment of Type-2 Diabetes Mellitus.
Cureus2021 Aug;13(8):e16868. doi: 10.7759/cureus.16868.
Srinivas Natasha, Sarnaik Mubashira K, Modi Srimy, Pisipati Yasaswi, Vaidya Sarayoo, Syed Gaggatur Naqvi, Sange Aliya H, Sange Ibrahim,
Abstract
Diabetes mellitus is a leading cause of morbidity and mortality and a significant risk factor for the early onset of chronic kidney disease and heart disease. Hyperglycemia and insulin resistance are key factors that play a role in the pathogenesis of type 2 diabetes. Renal glucose reabsorption is a critical component of glycemic regulation. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, commonly known as gliflozins, lower blood sugar levels by inhibiting glucose absorption in the proximal tubule of the kidney. SGLT2 inhibitors are currently used primarily as antidiabetic medications; however, their advantages go well beyond just glycemic control. This article has reviewed the mechanisms behind cardiac and renal involvement in type 2 diabetes and their inseparable interconnections. This article has also discussed the pharmacokinetic and pharmacodynamic profile of different SGLT2 inhibitors available in the market. Finally, this review has provided a perspective on the outcome trials, which provide evidence supporting a potential benefit of SGLT2 inhibitors in reducing cardiovascular and renal risks and possible mechanisms that mediate the renal and cardiovascular protection conferred.
Copyright © 2021, Srinivas et al.
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Preface: Cardiorenal Considerations for Type 2 Diabetes-Time to Exit the Dark Ages.
Diabetes Spectr -
Prognostic value of NT-proBNP and CA125 across glomerular filtration rate categories in acute heart failure.
Eur J Intern Med2021 Sep;():. doi: S0953-6205(21)00297-1.
de la Espriella Rafael, Bayés-Genís Antoni, Llàcer Pau, Palau Patricia, Miñana Gema, Santas Enrique, Pellicer Mauricio, González Miguel, Górriz José Luis, Bodi Vicent, Sanchis Juan, Núñez Julio,
Abstract
BACKGROUND:
This study aimed to evaluate whether glomerular filtration rate (eGFR) during admission modifies the predictive value of plasma amino-terminal pro-brain natriuretic peptide (NT-proBNP) and carbohydrate antigen 125 (CA125) in patients hospitalized for acute heart failure (AHF).
METHODS:
We retrospectively evaluated 4595 patients consecutively discharged after admission for AHF at three tertiary-care hospitals from January 2008 through October 2019. To investigate the effect of kidney function on the association of NT-proBNP and CA125 with 1-year mortality (all-cause and cardiovascular mortality), we stratified patients according to four eGFR categories:
RESULTS:
At 1-year follow-up, 748 of 4595 (16.3%) patients died after discharge (of all deaths, 575 [12.5%] were cardiovascular). After multivariate adjustment, both NT-proBNP and CA125 remained independently associated with a higher risk of death when modeled as main effects (P
CONCLUSIONS:
In patients with AHF and severely reduced eGFR, CA125 outperforms NT-proBNP in predicting 1-year mortality.
Copyright © 2021. Published by Elsevier B.V.
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Heme-oxygenase and lipid mediators in obesity and associated cardiometabolic diseases: Therapeutic implications.
Pharmacol Ther2021 Sep;():107975. doi: S0163-7258(21)00177-7.
McClung John A, Levy Lior, Garcia Victor, Stec David E, Peterson Stephen J, Abraham Nader G,
Abstract
Obesity-mediated metabolic syndrome remains the leading cause of death worldwide. Among many potential targets for pharmacological intervention, a promising strategy involves the heme oxygenase (HO) system, specifically its inducible form, HO-1. This review collects and updates much of the current knowledge relevant to pharmacology and clinical medicine concerning HO-1 in metabolic diseases and its effect on lipid metabolism. HO-1 has pleotropic effects that collectively reduce inflammation, while increasing vasodilation and insulin and leptin sensitivity. Recent reports indicate that HO-1 with its antioxidants via the effect of bilirubin increases formation of biologically active lipid metabolites such as epoxyeicosatrienoic acid (EET), omega-3 and other polyunsaturated fatty acids (PUFAs). Similarly, HO-1and bilirubin are potential therapeutic targets in the treatment of fat-induced liver diseases. HO-1-mediated upregulation of EET is capable not only of reversing endothelial dysfunction and hypertension, but also of reversing cardiac remodeling, a hallmark of the metabolic syndrome. This process involves browning of white fat tissue (i.e. formation of healthy adipocytes) and reduced lipotoxicity, which otherwise will be toxic to the heart. More importantly, this review examines the activity of EET in biological systems and a series of pathways that explain its mechanism of action and discusses how these might be exploited for potential therapeutic use. We also discuss the link between cardiac ectopic fat deposition and cardiac function in humans, which is similar to that described in obese mice and is regulated by HO-1-EET-PGC1? signaling, a potent negative regulator of the inflammatory adipokine NOV.
Copyright © 2021. Published by Elsevier Inc.
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Type 1 Cardiorenal Syndrome in Decompensated Heart Failure Patients in a Low-Income Region in Brazil: Incidence of Acute Kidney Injury (AKIN and KDIGO Criteria), Need for Dialysis and Mortality.
Arq Bras Cardiol2021 08;117(2):385-391. doi: S0066-782X2021001000385.
Nascimento Ginivaldo Victor Ribeiro do, Brito Heitor Carlos Domingues de, Lima Carlos Eduardo Batista de,
Abstract
BACKGROUND:
Type 1 cardiorenal syndrome is associated with higher mortality in heart failure patients. However, few studies have compared the diagnostic criteria of acute kidney injury (AKI) in this population.
OBJECTIVE:
To assess clinical and functional features and factors associated AKI in patients with heart failure.
METHOD:
Retrospective, cohort study on patients with decompensated heart failure or recent acute myocardial infarction, conducted in a tertiary hospital in a low-income region of Brazil. Clinical, laboratory and echocardiographic features were compared between patients with and without AKI according to the Acute Kidney Network (AKIN) and Kidney Disease: Improving Global Outcomes (KDIGO) criteria. The level of statistical significance was set at p
RESULTS:
Of 81 patients, 61.73% had AKI. Mean creatinine and urea levels were 1.79±1.0 mg/dL and 81.5±46.0 mg/dL, respectively, and higher in the group with AKI (p
CONCLUSION:
In this population of patients with heart failure, AKI was highly prevalent and considered an independent risk factor for mortality. Cardiac changes were not associated with AKI, and the KDIGO and AKIN criteria showed similar performance.
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The evaluation of noninferiority for renal composite outcomes between sodium-glucose cotransporter inhibitors in Japan.
Prim Care Diabetes2021 Sep;():. doi: S1751-9918(21)00167-4.
Kobayashi Kazuo, Toyoda Masao, Hatori Nobuo, Sato Kazuyoshi, Miyakawa Masaaki, Tamura Kouichi, Kanamori Akira,
Abstract
BACKGROUND:
In Japan, six types of sodium-glucose cotransporter inhibitors (SGLT2Is) are currently in use. Here, we evaluated differences in renal composite outcomes between SGLT2Is with or without evidence of cardio vascular outcome trials (CVOTs).
METHODS:
We retrospectively surveyed 536 Japanese patients with type 2 diabetes mellitus with chronic kidney disease who received SGLT2Is for more than 1 year. Patients were classified as having received empagliflozin, canagliflozin, or dapagliflozin (n = 270, Evidence (+) group) or as having received ipragliflozin, tofogliflozin, or luseogliflozin (n = 266, Evidence (-) group). The propensity score matching method was performed.
RESULT:
On matched cohort model including 205 cases in each group, there were no significant differences in the incidence of renal composite outcomes (n = 28 [14%] in the Evidence (+) group, n = 21 [10%] in the Evidence (-) group for the matched model; p = 0.29) between groups. Cox hazard analyses in the matched cohort model showed that the risk ratio for renal composite outcomes in the Evidence (-) group was 0.73 (95% confidence interval: 0.40-1.32), which was greater than the noninferiority margin of 1.22.
CONCLUSION:
Three SGLT2Is with no CVOT's evidence did not show noninferiority compared with other SGLT2Is with evidences.
Copyright © 2021 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.
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Renal Hemodynamics and Renin-Angiotensin-Aldosterone System Profiles in Patients with Heart Failure: Heart failure, RAAS, renal hemodynamics.
J Card Fail2021 Sep;():. doi: S1071-9164(21)00356-0.
Lytvyn Yuliya, Burns Kevin D, Testani Jeffrey M, Lytvyn Andriy, Ambinathan Jaya Prakash N, Osuntokun Oluwatosin, Godoy Lucas C, Cherney David, Parker John D,
Abstract
INTRODUCTION:
Understanding cardiorenal pathophysiology in heart failure (HF) is of clinical importance.
OBJECTIVE:
To characterize renal hemodynamic function and the transrenal gradient of the renin-angiotensin-aldosterone system (RAAS) markers in patients with HF and non-HF matched controls.
METHODS:
In this post-hoc analysis, glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and transrenal gradients (arterial-renal vein) of angiotensin converting enzyme (ACE), aldosterone, and plasma renin activity (PRA) were measured in 47 patients with HF and 24 controls. Gomez's equations were used to derive afferent (R) and efferent (R) arteriolar resistances. Transrenal RAAS gradients were also collected in patients treated with intravenous: (1) dobutamine (HF n=11, non-HF n=11) and (2) nitroprusside (HF n=18, non-HF n=5).
RESULTS:
The concentrations of PRA, aldosterone and ACE were higher in the renal vein vs. artery in HF vs. non-HF patients (p
CONCLUSIONS:
A larger transrenal RAAS marker gradient in patients with HF suggests a renal origin for neurohormonal activation associated with a vasoconstrictive renal profile.
Copyright © 2021. Published by Elsevier Inc.
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Mineralcorticoid receptor blockers in chronic kidney disease.
Nefrologia2021 Sep;():. doi: S2013-2514(21)00067-5.
Erraez Sara, López-Mesa Manuel, Gómez-Fernández Pablo,
Abstract
There are many experimental data supporting the involvement of aldosterone and mineralcorticoid receptor (MR) activation in the genesis and progression of chronic kidney disease (CKD) and cardiovascular damage. Many studies have shown that in diabetic and non-diabetic CKD, blocking the renin-angiotensin-aldosterone (RAAS) system with conversion enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARBs) decreases proteinuria, progression of CKD and mortality, but there is still a significant residual risk of developing these events. In subjects treated with ACEi or ARBs there may be an aldosterone breakthrough whose prevalence in subjects with CKD can reach 50%. Several studies have shown that in CKD, the aldosterone antagonists (spironolactone, eplerenone) added to ACEi or ARBs, reduce proteinuria, but increase the risk of hyperkalemia. Other studies in subjects treated with dialysis suggest a possible beneficial effect of antialdosteronic drugs on CV events and mortality. Newer potassium binders drugs can prevent/decrease hyperkalemia induced by RAAS blockade, and may reduce the high discontinuation rates or dose reduction of RAAS-blockers. The nonsteroidal MR blockers, with more potency and selectivity than the classic ones, reduce proteinuria and have a lower risk of hyperkalemia. Several clinical trials, currently underway, will determine the effect of classic MR blockers on CV events and mortality in subjects with stage 3b CKD and in dialysis patients, and whether in patients with type 2 diabetes mellitus and CKD, optimally treated and with high risk of CV and kidney events, the addition of finerenone to their treatment produces cardiorenal benefits. Large randomized trials have shown that sodium glucose type 2 cotransporter inhibitors (SGLT2i) reduce mortality and the development and progression of diabetic and nondiabetic CKD. There are pathophysiological arguments, which raise the possibility that the triple combination ACEi or ARBs, SGLT2i and aldosterone antagonist provide additional renal and cardiovascular protection.
Copyright © 2020 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.
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Glucagon-Like Peptide-1 Receptor Agonists and Brain Vascular Function.
Heart Lung Circ2021 Aug;():. doi: S1443-9506(21)01201-4.
Begic Edin, Causevic Mirsada,
Abstract
Prevention of cardiovascular events and regression of atherosclerotic changes are the primary aims of preventive cardiovascular medicine. Arterial thrombosis is caused by endothelial dysfunction, which disrupts vascular haemostasis. Glucagon-like peptide 1 (GLP-1) receptor agonists have been initially used as glucose lowering agents, but over time have been used for other indications due to their cardiorenal benefit, as well as their benefit in the regression of atherosclerosis process. The aim of this paper is to present the benefits of GLP-1 receptor agonists in the prevention of atherosclerotic changes, in the preservation of brain vascular function, and to show the possible role in the treatment of neurodegenerative diseases.
Copyright © 2021 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.
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Drug Treatment of Heart Failure with Reduced Ejection Fraction: Defining the Role of Vericiguat.
Drugs2021 Sep;():. doi: 10.1007/s40265-021-01586-y.
Coats Andrew J S, Tolppanen Heli,
Abstract
Vericiguat, a novel stimulator of soluble guanylate cyclase (sGC), has shown promising results in patients with heart failure and reduced ejection fraction (HFrEF) in the recent VICTORIA trial. The nitric oxide (NO)-sGC-cyclic guanosine monophosphate (cGMP) signaling pathway is disturbed in heart failure, leading to increased formation of reactive oxygen species and reduced NO bioavailability, and resultant myocardial dysfunction, adverse left ventricular remodeling, and cardiorenal syndrome. Restoration of sufficient NO-sGC-cGMP signaling has been proposed as an important treatment target in heart failure, beyond neurohormonal blockage and afterload reduction. Vericiguat has a dual mode of action on this axis, it both sensitizes sGC to low levels of NO, and can directly stimulate sGC in the absence of any endogenous NO. VICTORIA was a Phase 3 trial that compared vericiguat, at a target dose of 10 mg, with placebo in 5050 patients with HFrEF (ejection fraction
© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.
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Sodium-Glucose Co-transporter 2 Inhibitors Versus Metformin as the First-Line Treatment for Type 2 Diabetes: Is It Time for a Revolution?
Cardiovasc Drugs Ther2021 Sep;():. doi: 10.1007/s10557-021-07249-0.
Koufakis Theocharis, Papazafiropoulou Athanasia, Makrilakis Konstantinos, Kotsa Kalliopi,
Abstract
Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have emerged as a promising therapeutic option for hyperglycemia and its complications. However, metformin remains the first-line pharmacological treatment in most algorithms for type 2 diabetes (T2D). Although metformin is generally believed to exert positive effects on cardiovascular (CV) outcomes, relevant data are mainly observational and potentially overinterpreted. Yet, it exerts numerous pleiotropic actions that favorably affect metabolism and diabetes comorbidities. CV outcome trials have demonstrated cardiorenal protection with SGLT2i among people at high CV risk and mostly on concomitant metformin therapy. However, post hoc analyses of these trials suggest that the cardiorenal effects of gliflozins are independent of background treatment and consistent across the full spectrum of CV risk. Considering the importance of addressing hyperglycemia as a means of preventing diabetic complications and significant knowledge gaps, particularly regarding the cost-effectiveness of SGLT2i in drug-naïve populations with T2D, the position of metformin in the management of people with diabetes at low CV risk remains solid for the moment. On the other hand, available evidence-despite its limitations-suggests that specific groups of people with T2D, particularly those with heart failure and kidney disease, could probably benefit more from treatment with SGLT2i. This narrative mini-review aims to discuss whether current evidence justifies the use of SGLT2i as the first-line treatment for T2D.
© 2021. Springer Science+Business Media, LLC, part of Springer Nature.
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