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Pubblicazioni recenti - cardiorenal
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Glucagon Like Peptide-1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors for Diabetes After Solid Organ Transplantation.
Transpl Int2021 Apr;():. doi: 10.1111/tri.13883.
Ertuglu Lale A, Porrini Esteban, Hornum Mads, Demiray Atalay, Afsar Baris, Ortiz Alberto, Covic Adrian, Rossing Peter, Kanbay Mehmet,
Abstract
Post-transplant diabetes mellitus (PTDM) is a common complication of solid organ transplantation and a major cause of increased morbidity and mortality. Additionally, solid organ transplant patients may have pre-existent type 2 diabetes mellitus (T2DM). While insulin is the treatment of choice for hyperglycemia in the first weeks after transplantation, there is no preferred first line agent for long-term management of PTDM or pre-existent T2DM. Glucagon like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter 2 (SGLT2) inhibitors improve glycemic control, lower body weight and blood pressure, are recommended after lifestyle and metformin as initial therapy for diabetic patients with cardiovascular or kidney comorbidities regarding their cardiorenal benefits. Furthermore, the mechanisms of action of GLP-1RA may counteract some of the driving forces for PTDM, as calcineurin-induced ? cell toxicity as per preclinical data, and improve obesity. However, their use in the treatment of PTDM is currently limited by a paucity of data. Retrospective observational and small exploratory studies suggest that GLP-1RA effectively improve glycemic control and induce weight loss in patients with PTDM without interacting with commonly used immunosuppressive agents, although randomized controlled clinical trials are required to confirm their safety and efficacy. In this narrative review, we evaluate the risk factors and pathogenesis of PTDM and compare the potential roles of GLP-1RA and SGLT2 inhibitors in PTDM prevention and management as well as in pre-existent T2DM, and providing a roadmap for evidence generation on newer antidiabetic drugs for solid organ transplantation.
This article is protected by copyright. All rights reserved.
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Impaired perfusion in the myocardial microcirculation in asymptomatic patients with Stages 1-4 chronic kidney disease with intrarenal arterial lesions.
Nephrol Dial Transplant2020 Dec;():. doi: gfaa245.
Xiao Fei, Zhang Weiwei, He Ya-Ni, Yang Jie, Liu Xinghong, Wang Ling, Zhang Jianguo, Dai Huanzi,
Abstract
BACKGROUND:
Even mild renal disease is a powerful cardiovascular risk factor. However, the association between these pathophysiologic processes (especially in the early asymptomatic stage) is not known.
METHODS:
We recruited 243 asymptomatic patients with Stages 1-4 chronic kidney disease (CKD) without obstructive coronary artery disease (CAD). We distinguished different degrees of severity of intrarenal arterial lesions (IALs) according to the Oxford classification. Myocardial microcirculation perfusion was measured using single-photon emission computed tomography (SPECT). Summed scores of 17 stress and rest image segments produced the summed stress score (SSS) and summed rest score (SRS), respectively. The summed difference score (SDS) was calculated as the difference between the SSS and SRS. Coronary microvascular disease (CMD) was defined as abnormal SPECT (SSS ?4 or SDS ?2) in the absence of obstructive CAD.
RESULTS:
Participants showed a stepwise increase in CMD severity with IAL aggravation. SSS of no/mild/moderate/severe IALs was 1.64?±?1.08, 2.56?±?1.35, 4.42?±?2.17 and 6.48?±?3.52, respectively (P?
CONCLUSIONS:
We demonstrated, for the first time, that impaired perfusion in the myocardial microcirculation in asymptomatic patients with Stages 1-4 CKD with IALs. Renal arteriolar hyalinization may be a useful marker of CMD in CKD.
© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
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Predictive effect of salt intake on patient and kidney survival in non-dialysis CKD: competing risk analysis in older versus younger patients under nephrology care.
Nephrol Dial Transplant2020 Dec;():. doi: gfaa252.
Garofalo Carlo, Provenzano Michele, Andreucci Michele, Pisani Antonio, De Nicola Luca, Conte Giuseppe, Borrelli Silvio,
Abstract
BACKGROUND:
The optimal level of salt intake remains ill-defined in non-dialysis chronic kidney disease (CKD) patients under regular nephrology care. This unanswered question becomes critical in older patients who are exposed to higher risk of worsening of cardiorenal disease due to volemic changes.
METHODS:
In this pooled analysis of four prospective studies in CKD, we compared the risk of all-cause mortality and end-stage kidney disease (ESKD) between patients ?65 and >65?years of age stratified by salt intake level (<6, 6-8 and >8?g/day) estimated from two measurements of 24-h urinary sodium.
RESULTS:
The cohort included 1785 patients. The estimated glomerular filtration rate was 37?±?21?mL/min/1.73?m2 overall, 41?±?25 in younger patients and 34?±?16 in older patients (P?8?g?sodium chloride/day in 21.9, 26.2 and 52.0% of older patients and 18.6, 25.2 and 56.2% in younger patients, respectively (P?=?0.145). During a median follow-up of 4.07?years we registered 383 ESKD and 260 all-cause deaths. In the whole cohort, the risks of ESKD and all-cause death did not differ by salt intake level. In older patients, ESKD risk [multi-adjusted hazard ratio (HR) and 95% confidence interval (CI)] was significantly lower at salt intakes of 6-8?g/day [HR 0.577 (95% CI 0.361-0.924)] and >8?g/day [HR 0.564 (95% CI 0.382-0.833)] versus the reference group (<6?g/day). Mortality risk was higher in older versus younger patients, with no difference across salt intake categories. No effect of salt intake on ESKD and mortality was observed in younger patients.
CONCLUSIONS:
CKD patients under nephrology care show a moderate salt intake (8.4?g/day) that is lower in older versus younger patients. In this context, older patients are not exposed to higher mortality across different levels of salt intake, while salt intake <6?g/day poses a greater risk of ESKD.
© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
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Cardiorenal Protection in Diabetic Kidney Disease.
Endocrinol Metab (Seoul)2021 Apr;():. doi: 10.3803/EnM.2021.987.
Lee Jason F, Berzan Ecaterina, Sridhar Vikas S, Odutayo Ayodele, Cherney David Z I,
Abstract
Over the last 5 years there have been many new developments in the management of diabetic kidney disease. Glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium-glucose cotransporter-2 (SGLT2) inhibitors were initially used for glycemic control, but more recent studies have now shown that their benefits extend to cardiovascular and kidney outcomes. The recent addition of data on the novel mineralocorticoid receptor antagonist (MRA) gives us another approach to further decrease the residual risk of diabetic kidney disease progression. In this review we describe the mechanism of action, key studies, and possible adverse effects related to these three classes of medications. The management of type 2 diabetes now includes an increasing number of medications for the management of comorbidities in a patient population at significant risk of cardiovascular disease and progression of chronic kidney disease. It is from this perspective that we seek to outline the rationale for the sequential and/or combined use of SGLT2 inhibitors, GLP-1 RA and MRAs in patients with type 2 diabetes for heart and kidney protection.
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The Role of Serum Chloride in Acute and Chronic Heart Failure: A Narrative Review.
Cardiorenal Med2021 Apr;():1-12. doi: 10.1159/000515604.
Rivera Frederick Berro, Alfonso Pia, Golbin Jem Marie, Lo Kevin, Lerma Edgar, Volgman Annabelle Santos, Kazory Amir,
Abstract
Clinical guidelines include diuretics for the treatment of heart failure (HF), not to decrease mortality but to decrease symptoms and hospitalizations. More attention has been paid to the worse outcomes, including mortality, associated with continual diuretic therapy due to hypochloremia. Studies have revealed a pivotal role for serum chloride in the pathophysiology of HF and is now a target of treatment to decrease mortality. The prognostic value of serum chloride in HF has been the subject of much attention. Mechanistically, the macula densa, a region in the renal juxtaglomerular apparatus, relies on chloride levels to sense salt and volume status. The recent discovery of with-no-lysine (K) (WNK) protein kinase as an intracellular chloride sensor sheds light on the possible reason of diuretic resistance in HF. The action of chloride on WNKs results in the upregulation of the sodium-potassium-chloride cotransporter and sodium-chloride cotransporter receptors, which could lead to increased electrolyte and fluid reabsorption. Genetic studies have revealed that a variant of a voltage-sensitive chloride channel (CLCNKA) gene leads to almost a 50% decrease in current amplitude and function of the renal chloride channel. This variant increases the risk of HF. Several trials exploring the prognostic value of chloride in both acute and chronic HF have shown mostly positive results, some even suggesting a stronger role than sodium. However, so far, interventional trials exploring serum chloride as a therapeutic target have been largely inconclusive. This study is a review of the pathophysiologic effects of hypochloremia in HF, the genetics of chloride channels, and clinical trials that are underway to investigate novel approaches to HF management.
© 2021 The Author(s) Published by S. Karger AG, Basel.
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ADEQUATE BLOOD PRESSURE CONTROL UNATTAINABLE WITHOUT ADEQUATE RECOGNITION AND TREATMENT OF PRIMARY ALDOSTERONISM.
Trends Cardiovasc Med2021 Apr;():. doi: S1050-1738(21)00047-5.
Ruilope Luis M, Ruiz-Hurtado Gema, Tamargo Juan,
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Undernutrition - thirty years of the Regional Basic Diet: the legacy of Naíde Teodósio in different fields of knowledge.
Nutr Neurosci2021 Apr;():1-22. doi: 10.1080/1028415X.2021.1915631.
Jannuzzi Larissa B, Pereira-Acacio Amaury, Ferreira Bruna S N, Silva-Pereira Debora, Veloso-Santos João P M, Alves-Bezerra Danilo S, Lopes Jarlene A, Costa-Sarmento Glória, Lara Lucienne S, Vieira Leucio D, Abadie-Guedes Ricardo, Guedes Rubem C A, Vieyra Adalberto, Muzi-Filho Humberto,
Abstract
Undernutrition is characterized by an imbalance of essential nutrients with an insufficient nutritional intake, a disorder in which the clinical manifestations in most cases are the result of the economic and social context in which the individual lives. In 1990, the study by the medical and humanitarian Naíde Teodósio (1915-2005) and coworkers, which formulated the Regional Basic Diet (RBD) model for inducing undernutrition, was published. This diet model took its origin from the observation of the dietary habits of families that inhabited impoverished areas from the Pernambuco State. RBD mimics an undernutrition framework that extends not only to the Brazilian population, but to populations in different regions worldwide. The studies based on RBD-induced deficiencies provide a better understanding of the impact of undernutrition on the pathophysiological mechanisms underlying the most diverse prevalent diseases. Indexed papers that are analyzed in this review focus on the importance of using RBD in different areas of knowledge. These papers reflect a new paradigm in translational medicine: they show how the study of pathology using the RBD model in animals over the past 30 years has and still can help scientists today, shedding light on the mechanisms of prevalent diseases that affect impoverished populations.
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Lipid effects of sodium-glucose cotransporter 2 inhibitors.
Curr Opin Lipidol2021 Apr;():. doi: 10.1097/MOL.0000000000000751.
Lazarte Julieta, Kanagalingam Tharsan, Hegele Robert A,
Abstract
PURPOSE OF REVIEW:
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are widely used antihyperglycemic drugs that show remarkable cardiorenal protective effects in patients with or without type 2 diabetes. Furthermore, they are effective among patients across a wide range of baseline renal and cardiac function. Numerous mechanisms have been evaluated to understand these remarkable clinical benefits. From an early stage, these agents were noted to affect the plasma lipid profile. Here we review lipid profile alterations attributable to SGLT2 inhibitors and also some mechanisms explored in model systems and human studies.
RECENT FINDINGS:
SGLT2 inhibitors given to patients with diabetes as monotherapy shift substrate utilization from carbohydrates to lipids, and have mild effects on the lipid profile. Increased LDL cholesterol appears to be associated with increased hepatic production and decreased catabolism. Increased HDL cholesterol and decreased triglycerides appear to be associated with improved insulin sensitivity and increased lipolysis. Lipid effects of SGLT2 inhibitors are further modulated by background therapy with other diabetes medications and statins.
SUMMARY:
The minor lipid profile alterations observed in patients treated with SGLT2 inhibitors are offset by the staggering range of beneficial pleiotropic mechanisms that likely explain the marked cardiorenal benefits of these agents.
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
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Homozygous Familial Hypercholesterolemia.
J Atheroscler Thromb2021 Apr;():. doi: 10.5551/jat.RV17050.
Nohara Atsushi, Tada Hayato, Ogura Masatsune, Okazaki Sachiko, Ono Koh, Shimano Hitoshi, Daida Hiroyuki, Dobashi Kazushige, Hayashi Toshio, Hori Mika, Matsuki Kota, Minamino Tetsuo, Yokoyama Shinji, Harada-Shiba Mariko, ,
Abstract
Familial hypercholesterolemia (FH) is an inherited disorder with retarded clearance of plasma LDL caused by mutations of the genes involved in the LDL receptor-mediated pathway and most of them exhibit autosomal dominant inheritance. Homozygotes of FH (HoFH) may have plasma LDL-C levels, which are at least twice as high as those of heterozygous FH (HeFH) and therefore four times higher than normal levels. Prevalence of HoFH had been estimated as 1 in 1,000,000 before but more recent genetic analysis surveys predict 1 in 170,000 to 300,000. Since LDL receptor activity is severely impaired, HoFH patients do not or very poorly respond to medications to enhance activity, such as statins, and have a poorer prognosis compared to HeFH. HoFH should therefore be clinically distinguished from HeFH. Thorough family studies and genetic analysis are recommended for their accurate diagnosis. Fatal cardiovascular complications could develop even in the first decade of life for HoFH, so aggressive lipid-lowering therapy should be initiated as early as possible. Direct removal of plasma LDL by lipoprotein apheresis has been the principal measure for these patients. However, this treatment alone may not achieve stable LDL-C target levels and combination with drugs should be considered. The lipid-lowering effects of statins and PCSK9 inhibitors substantially vary depending on the remaining LDL receptor activity of individual patients. On the other hand, the action an MTP inhibitor is independent of LDL receptor activity, and it is effective in most HoFH cases. This review summarizes the key clinical issues of HoFH as well as insurance coverage available under the Japanese public healthcare system.
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Emergency TAVI in cardiogenic shock and cardiorenal syndrome secondary to severe bicuspid aortic stenosis.
BMJ Case Rep2021 Apr;14(4):. doi: e239003.
Byrne Luke, Wheen Peter, O'Connor Stephen,
Abstract
A 78-year man with severe aortic stenosis awaiting elective surgical aortic valve replacement presented with worsening New York Heart Association IV shortness of breath. Despite appropriate heart failure treatment, he deteriorated and developed cardiogenic shock and cardiorenal syndrome which progressed despite inotropic support. A non-contrast-gated CT coronary angiogram was arranged in light of acute renal failure which revealed a bicuspid aortic valve. Three-dimensional transoesophageal echocardiography guidance was used to assist annulus sizing. An emergency transcatheter aortic valve replacement (eTAVI) was carried out 5?days into admission with a 34?mm Core Valve Evolut Pro valve with a no contrast technique. The patient's blood pressure and urine output improved and no procedural complications were encountered. He was discharged after 21 days and has remained well subsequently. This case highlights the utility of eTAVI and demonstrates the feasibility of a no contrast approach.
© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.
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Klotho: a possible mechanism of action of SGLT2 inhibitors preventing episodes of acute kidney injury and cardiorenal complications of diabetes.
Drug Discov Today2021 Apr;():. doi: S1359-6446(21)00194-X.
Kale Ajinath, Sankrityayan Himanshu, Anders Hans-Joachim, Bhanudas Gaikwad Anil,
Abstract
Diabetes and cardiorenal comorbidities are major global health concerns, with high economic burdens and mortality rates. Sodium glucose co-transporter-2 inhibitors (SGLT2is) are novel US Food and Drug Administration (FDA)-approved antihyperglycemics with unexpected protective potential against cardiorenal diseases in patients with or without type 2 diabetes mellitus (T2DM). Despite initial concerns, the incidence of episodes of acute kidney injury (AKI) was significantly lower in patients taking SGLT2i compared with other therapies or placebo. Evolving data suggest a link between SGLT2is and the anti-aging protein Klotho in the amelioration of diabetes and cardiorenal diseases. Here, we consider Klotho and SGLT2is as a novel therapeutic approach for the management of AKI and other cardiorenal complications in patients with or without diabetes.
Copyright © 2021 Elsevier Ltd. All rights reserved.
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Renal hemosiderosis presenting with acute kidney Injury and macroscopic hematuria in Immunoglobulin A nephropathy: a case report.
BMC Nephrol2021 Apr;22(1):132. doi: 10.1186/s12882-021-02334-w.
Taguchi Shinya, Hidaka Sumi, Yanai Mitsuru, Ishioka Kunihiro, Matsui Kenji, Mochida Yasuhiro, Moriya Hidekazu, Ohtake Takayasu, Kobayashi Shuzo,
Abstract
BACKGROUND:
Macroscopic hematuria-associated acute kidney injury (AKI) is a well-known complication of immunoglobulin A (IgA) nephropathy. In such cases, intratubular obstruction by red blood cell (RBC) casts and acute tubular necrosis are mainly observed pathologically. Herein, we report the case of a patient with IgA nephropathy presenting with AKI following an episode of macrohematuria. The patient presented with severe renal tubular hemosiderosis and acute tubular necrosis and without any obvious obstructive RBC casts.
CASE PRESENTATION:
A 68-year-old woman, who was diagnosed with IgA nephropathy on renal biopsy 6 years ago, was admitted to our hospital after an episode of macroscopic glomerular hematuria and AKI following upper respiratory tract infection. Renal biopsy showed mesangial proliferation of the glomeruli, including crescent formation in 17?% of the glomeruli, and acute tubular necrosis without obvious hemorrhage or obstructive RBC casts. The application of Perls' Prussian blue stain showed hemosiderin deposition in the renal proximal tubular cells. Immunofluorescence showed granular mesangial deposits of IgA and C3. Based on these findings, she was diagnosed with acute tubular necrosis with a concurrent IgA nephropathy flare-up. Moreover, direct tubular injury by heme and iron was considered to be the cause of AKI. She was treated with intravenous pulse methylprednisolone followed by oral prednisolone. Thereafter, the gross hematuria gradually faded, and her serum creatinine levels decreased.
CONCLUSIONS:
IgA nephropathy presenting with acute kidney injury accompanied by macrohematuria may cause renal hemosiderosis and acute tubular necrosis without obstructive RBC casts. Hemosiderosis may be a useful indicator for determining the pathophysiology of macroscopic hematuria-associated AKI. However, renal hemosiderosis may remain undiagnosed. Thus, Perls' Prussian blue iron staining should be more widely used in patients presenting with hematuria.
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Right Ventricular Dysfunction and Adverse Outcomes after Renal Transplantation.
Cardiorenal Med2021 Apr;():1-10. doi: 10.1159/000515124.
Joseph Megan S, Tinney Francis, Naik Abhijit, Parasuraman Raviprasenna, Samaniego-Picota Milagros, Bhave Nicole M,
Abstract
INTRODUCTION:
Pulmonary hypertension is common among patients with end-stage renal disease, although data regarding the impact of right ventricular (RV) failure on postoperative outcomes remain limited. We hypothesized that echocardiographic findings of RV dilation and dysfunction are associated with adverse clinical outcomes after renal transplant.
METHODS:
A retrospective review of adult renal transplant recipients at a single institution from January 2008 to June 2010 was conducted. Patients with transthoracic echocardiograms (TTEs) within 1 year leading up to transplant were included. The primary end point was a composite of delayed graft function, graft failure, and all-cause mortality.
RESULTS:
Eighty patients were included. Mean follow-up time was 9.4 ± 0.8 years. Eight patients (100%) with qualitative RV dysfunction met the primary end point, while 39/65 patients (60.0%) without RV dysfunction met the end point (p = 0.026). Qualitative RV dilation was associated with a significantly shorter time to all-cause graft failure (p = 0.03) and death (p = 0.048). RV systolic pressure was not measurable in 45/80 patients (56%) and was not associated with outcomes in the remaining patients.
CONCLUSION:
RV dilation and dysfunction are associated with adverse outcomes after renal transplant. TTE assessment of RV size and function should be a standard part of the pre-kidney transplant cardiovascular risk assessment.
© 2021 The Author(s) Published by S. Karger AG, Basel.
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The Kidney-Heart Connection in Obesity.
Nephron2021 Apr;():1-5. doi: 10.1159/000515419.
García-Carrasco Almudena, Izquierdo-Lahuerta Adriana, Medina-Gómez Gema,
Abstract
There is a strong relationship between the kidney and the heart, where if one of these organs fails, so does the other, in the so-called cardiorenal syndrome (CRS). Besides, there are also interactions with the rest of the body leading to a metabolic state that establishes a feedback loop that is perpetuated. The CRS is characterized by hemodynamic changes, activation of neuro-humoral systems, natriuretic peptides, and changes in mineral metabolism. In this scenario, the kidney and heart, connected by a dysfunctional endothelium, inevitably fail. In obesity, this syndrome is exacerbated due to the complications of adipose tissue dysfunction, in the so-called cardiorenal metabolic syndrome (CRMetS). Obesity promotes adipose tissue dysfunction because it exceeds lipid storage capacity and leads to a lipotoxic state, characterized by inflammation, hypertension, insulin resistance and dyslipidemia, oxidative stress, and hyperuricemia, among others, that affect different organs other than the adipose tissue. In addition, the pro-inflammatory gut microbiota present in obese patients releases uremic toxins, contributing to oxidative stress and inflammation, perpetuating and accelerating the progression of this pathology. In this article, we describe the contribution of obesity, the factors and mechanisms implicated in the development of the CRMetS. Despite the great knowledge about the CRS, more research is needed to characterize the CRMetS given the global obesity epidemic.
© 2021 S. Karger AG, Basel.
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Empagliflozin Inhibits Proximal Tubule NHE3 Activity, Preserves GFR, and Restores Euvolemia in Nondiabetic Rats with Induced Heart Failure.
J Am Soc Nephrol2021 Apr;():. doi: ASN.2020071029.
Borges-Júnior Flávio A, Silva Dos Santos Danúbia, Benetti Acaris, Polidoro Juliano Z, Wisnivesky Aline C T, Crajoinas Renato O, Antônio Ednei L, Jensen Leonardo, Caramelli Bruno, Malnic Gerhard, Tucci Paulo J, Girardi Adriana C C,
Abstract
BACKGROUND:
SGLT2 inhibitors reduce the risk of heart failure (HF) mortality and morbidity, regardless of the presence or absence of diabetes, but the mechanisms underlying this benefit remain unclear. Experiments with nondiabetic HF rats tested the hypothesis that the SGLT2 inhibitor empagliflozin (EMPA) inhibits proximal tubule (PT) NHE3 activity and improves renal salt and water handling.
METHODS:
Male Wistar rats were subjected to myocardial infarction or sham operation. After 4 weeks, rats that developed HF and sham rats were treated with EMPA or untreated for an additional 4 weeks. Immunoblotting and quantitative RT-PCR evaluated SGLT2 and NHE3 expression. Stationary microperfusion measured PT NHE3 activity.
RESULTS:
EMPA-treated HF rats displayed lower serum B-type natriuretic peptide levels and lower right ventricle and lung weight to tibia length than untreated HF rats. Upon saline challenge, the diuretic and natriuretic responses of EMPA-treated HF rats were similar to those of sham rats and were higher than those of untreated HF rats. Additionally, EMPA treatment prevented GFR decline and renal atrophy in HF rats. PT NHE3 activity was higher in HF rats than in sham rats, whereas treatment with EMPA markedly reduced NHE3 activity. Unexpectedly, SGLT2 protein and mRNA abundance were upregulated in the PT of HF rats.
CONCLUSIONS:
Prevention of HF progression by EMPA is associated with reduced PT NHE3 activity, restoration of euvolemia, and preservation of renal mass. Moreover, dysregulation of PT SGLT2 may be involved in the pathophysiology of nondiabetic HF.
Copyright © 2021 by the American Society of Nephrology.
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Prediction of fatal and non-fatal cardiovascular events in young and middle-aged healthy workers: The IberScore model.
Eur J Prev Cardiol2021 04;28(2):177-186. doi: 10.1177/2047487319894880.
Fernández-Labandera Carlos, Calvo-Bonacho Eva, Valdivielso Pedro, Quevedo-Aguado Luis, Martínez-Munoz Paloma, Catalina-Romero Carlos, Ruilope Luis M, Sánchez-Chaparro Miguel A,
Abstract
AIMS:
Our primary objective was to improve risk assessment for fatal and non-fatal cardiovascular events in a working population, mostly young and healthy.
METHODS:
We conducted a prospective cohort study to derive a survival model to predict fatal and non-fatal 10-year cardiovascular risk. We recruited 992,523 workers, free of diagnosed cardiovascular disease at entry, over six years, from 2004-2009. We divided the sample into two independent cohorts: a derivation one (626,515 workers; from 2004-2006) and a temporal validation one (366,008 workers; over 2007-2009). Then, we followed both cohorts over 10 years and registered all fatal and non-fatal cardiovascular events. We built a new risk calculator using an estimation of cardiovascular biological age as a predictor and named it IberScore. There were remarkable differences between this new model and Systematic Coronary Risk Evaluation (SCORE) (in both the specification and the equation).
RESULTS:
Over the 10-year follow-up, we found 3762 first cardiovascular events (6?) in the derivation cohort. Most of them (80.3%) were non-fatal ischaemic events. If we had been able to use our model at the beginning of the study, we had classified in the 'high-risk' or 'very high-risk' groups 82% of those who suffered a cardiovascular event during the follow-up. All the post-estimation tests showed superior performance (true positive rate: 81.8% vs 11.8%), higher discrimination power and better clinical utility (standardised net benefit: 58% vs 13%) for IberScore when compared to SCORE.
CONCLUSION:
Risk assessment of fatal and non-fatal cardiovascular events in young and healthy workers was improved when compared to the previously used model (SCORE). The latter was not reliable to predict cardiovascular risk in our sample. The new model showed superior clinical utility and provided four useful measures for risk assessment. We gained valuable insight into cardiovascular ageing and its predictors.
Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.
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Lower heart failure and chronic kidney disease risks associated with sodium-glucose cotransporter-2 inhibitor use in Japanese type 2 diabetes patients without established cardiovascular and renal diseases.
Diabetes Obes Metab2021 Apr;23 Suppl 2():19-27. doi: 10.1111/dom.14119.
Komuro Issei, Kadowaki Takashi, Bodegård Johan, Thuresson Marcus, Okami Suguru, Yajima Toshitaka,
Abstract
AIMS:
To examine heart failure (HF) and chronic kidney disease (CKD) risks reduction associated with sodium-glucose cotransporter-2 inhibitors (SGLT-2i) compared to other glucose-lowering drugs (oGLD) in the early stage of type 2 diabetes patients without established cardiovascular or renal diseases (CVRD-free T2D).
MATERIALS AND METHODS:
We performed an observational cohort study using a Japanese hospital claims registry, Medical Data Vision. CVRD-free T2D patients were identified between 1 April 2014 and 30 September 2018. SGLT-2i and oGLD new users (and dipeptidyl peptidase 4 inhibitors [DPP-4i] separately) were subjected to 1:1 propensity-score matching analysis. Hazard ratios (HRs) of cardiorenal disease (HF and/or CKD), HF, CKD, stroke, myocardial infarction (MI), and all-cause mortality, were estimated using unadjusted Cox regression.
RESULTS:
A total of 108?362 CVRD-free patients including 54?181 SGLT-2i and 54?181 oGLD users were matched. Baseline characteristics were well balanced (mean age 59.1?years, 63% male, and follow-up 1.50?years [162?970 patient-years]). Compared to oGLD group, SGLT-2i group had lower risk of cardiorenal disease, HF, CKD, stroke, and all-cause mortality with HRs (95% confidence intervals) 0.55 (0.49-0.61), 0.73 (0.61-0.87), 0.45 (0.39-0.52), 0.69 (0.59-0.81), and 0.52 (0.46-0.58), respectively, while no difference in MI. These were consistent in 1:1 propensity-score matching analysis between SGLT-2i and DPP-4i users (n = 17?232 in each group).
CONCLUSIONS:
In Japanese CVRD-free T2D patients, SGLT-2i initiation was associated with lower risk of cardiorenal diseases, stroke, and all-cause mortality compared to oGLD, suggesting preventive effect of SGLT-2i treatment in the early stage of T2D patients without CVRD manifestation.
© 2021 John Wiley & Sons Ltd.
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Association of aldosterone and blood pressure with the risk for cardiovascular events after treatments in primary aldosteronism.
Atherosclerosis2021 Mar;324():84-90. doi: S0021-9150(21)00154-4.
Haze Tatsuya, Hirawa Nobuhito, Yano Yuichiro, Tamura Kouichi, Kurihara Isao, Kobayashi Hiroki, Tsuiki Mika, Ichijo Takamasa, Wada Norio, Katabami Takuyuki, Yamamoto Koichi, Oki Kenji, Inagaki Nobuya, Okamura Shintaro, Kai Tatsuya, Izawa Shoichiro, Yamada Masanobu, Chiba Yoshiro, Tanabe Akiyo, Naruse Mitsuhide,
Abstract
BACKGROUND AND AIMS:
We used a dataset from a Japanese nationwide registry of patients with primary aldosteronism, to determine which of the parameters of hyperaldosteronism and blood pressure before or after treatments for primary aldosteronism (i.e., surgical adrenalectomy or a medication treatment) are important in terms of cardiovascular prognosis.
METHODS:
We assessed whether plasma aldosterone-to-renin ratio and pulse pressure levels before treatment and 6 months after treatment were associated with composite cardiovascular disease events during the 5-year follow-up period.
RESULTS:
The cohort included 1987 patients (mean age was 53.2 years, 52.0% were female, 37.2% had undergone surgical treatment, and the remainder had been treated with mineralocorticoid receptor antagonists). In the Cox proportional hazard model, the covariate-adjusted hazard ratio (95% confidence interval) for the composite cardiovascular disease events risk for each one-standard-deviation increase in the aldosterone-to-renin ratio or pulse pressure before treatment, those after treatment, or the duration of hypertension were 1.24 (1.05, 1.48), 0.74 (0.54, 1.02), and 1.07 (0.79, 1.44), 1.43 (1.07, 1.92), and 1.52 (1.19, 1.95), respectively. Patients with a high pre-treatment aldosterone-to-renin ratio of more than 603 and a large post-treatment pulse pressure of more than 49 mmHg showed approximately three-fold higher hazard ratios for cardiovascular events risk compared to those with a lower aldosterone-to-renin ratio and smaller pulse pressure.
CONCLUSIONS:
Higher aldosterone-to-renin ratio before treatments, higher pulse pressure after treatments, and longer duration of hypertension were prognostic factors for cardiovascular diseases. Early intervention may be important for preventing cardiovascular disease among patients with primary aldosteronism.
Copyright © 2021 Elsevier B.V. All rights reserved.
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Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs) improve biomarkers of inflammation and oxidative stress: A systematic review and meta-analysis of randomised controlled trials.
Diabetes Obes Metab2021 Apr;():. doi: 10.1111/dom.14399.
Bray Jonathan J H, Foster-Davies Harri, Salem Ahmed, Hoole Amy L, Obaid Daniel R, Halcox Julian P J, Stephens Jeffrey W,
Abstract
AIMS:
Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs) have cardiorenal protective properties in patients with type 2 diabetes (T2DM) that are not fully understood. Inflammation and oxidative stress play a role in the pathogenesis of T2DM and its associated cardiorenal complications. Anti-inflammatory and antioxidant properties may contribute towards explaining the beneficial effects of GLP-1RAs. This meta-analysis and systematic review examines the effects of GLP-1RAs on clinical biomarkers of inflammation and oxidative stress.
METHODS:
Medline, Embase and The Cochrane Library were searched for randomised controlled trials (RCTs) that examined changes with GLP-1RAs in a priori selected biomarkers of inflammation:- c-reactive protein (CRP), adiponectin, tumour necrosis factor-alpha (TNF-?), plasminogen activator inhibitor-1 (PAI-1), interleukin-6 (IL6), leptin; and oxidative stress:- malondialdehyde (MDA), 8-iso-prostaglandin F2? (8-iso-PGF2?), and 8-hydroxy-2'-deoxyguanosine (8-OHdG). (PROSPERO: CRD42020182116) RESULTS: We included 40 eligible RCTs (n=6749) with a median follow-up of 6 months, mean participant age of 53.1?years, 56.3% females, HbA1c 7.24%, body mass index (BMI) 28.8kg/m and diabetes duration of 7.46?years. Analysis of GLP-1RAs versus standard diabetes therapies or placebo revealed significant reductions in CRP, TNF? and MDA, and significant increases in adiponectin for (mean difference -0.54mg/L [-0.75, -0.34]; standard mean difference (SMD) -0.39 [-0.62, -0.15]; SMD -0.84 [-1.61, -0.06] and SMD 0.30 [0.12, 0.49], respectively). Systolic blood pressure decreased significantly and was significantly and strongly correlated with a reduction in CRP. HOMA-IR was also significantly correlated with a reduction in CRP, but glycated haemoglobin was not.
CONCLUSIONS:
There is strong evidence supporting clinically relevant anti-inflammatory and antioxidant effects of GLP-1RAs. This may be used to guide future targeted clinical use of GLP-1RAs and in the development of medications seeking to target the cardioprotective properties of GLP-1RAs. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
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CA125 but not NT-proBNP predicts the presence of a congestive intrarenal venous flow in patients with acute heart failure.
Eur Heart J Acute Cardiovasc Care2021 Apr;():. doi: zuab022.
Núñez-Marín Gonzalo, de la Espriella Rafael, Santas Enrique, Lorenzo Miguel, Miñana Gema, Núñez Eduardo, Bodí Vicent, González Miguel, Górriz José Luis, Bonanad Clara, Sanchis Juan, Bayés-Genís Antoni, Núñez Julio,
Abstract
BACKGROUND:
Intrarenal venous flow (IRVF) measured by Doppler ultrasound has gained interest as a potential surrogate marker of renal congestion and adverse outcomes in heart failure. In this work, we aimed to determine if antigen carbohydrate 125 (CA125) and plasma amino-terminal pro-B-type natriuretic peptide (NT-proBNP) are associated with congestive IRVF patterns (i.e., biphasic and monophasic) in acute heart failure (AHF).
METHODS AND RESULTS:
We prospectively enrolled a consecutive cohort of 70 patients hospitalized for AHF. Renal Doppler ultrasound was assessed within the first 24-h of hospital admission. The mean age of the sample was 73.5?±?12.3?years; 47.1% were female, and 42.9% exhibited heart failure with preserved ejection fraction. The median (interquartile range) for NT-proBNP and CA125 were 6149 (3604-12 330) pg/mL and 64 (37-122) U/mL, respectively. The diagnostic performance of both exposures for identifying congestive IRVF patterns was tested using the receiving operating curve (ROC). The cut-off for CA125 of 63.5?U/mL showed a sensibility and specificity of 67% and 74% and an area under the ROC curve of 0.71. After multivariate adjustment, CA125 remained non-linearly and positively associated with congestive IRVF (P-value?=?0.008) and emerged as the most important covariate explaining the variability of the model (R2: 47.5%). Under the same multivariate setting, NT-proBNP did not show to be associated with congestive IRVF patterns (P-value?=?0.847).
CONCLUSIONS:
CA125 and not NT-proBNP is a useful marker for identifying patients with AHF and congestive IRVF patterns.
Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.
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