Aldosterone Synthase Inhibitors for Cardiorenal Protection: Ready for Prime Time?

Background: Aldosterone is the principal mineralocorticoid hormone and the final effector of the renin-angiotensin-aldosterone system. This hormone is primarily synthesized by the CYP11B2 enzyme and produced by the adrenal zona glomerulosa. Through genomic and non-genomic effects, it plays an important role in cardiovascular and renal disease.

Treatment of hypertension in the elderly: target the lowest well-tolerated blood pressure.

Introduction: Antihypertensive treatment provides substantial benefits in older people. However, many challenges remain, including the ideal blood pressure (BP) target to be achieved. Because the elderly population is particularly vulnerable to adverse events, BP control should be carefully managed.

Changes in 24-hour blood pressure profile after 12 weeks of dapagliflozin treatment in patients with diabetic kidney disease: an Italian multicenter prospective study.

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) lower ambulatory blood pressure (ABP) in patients with type 2 diabetes mellitus; whether the same holds true in diabetic kidney disease (DKD) is unknown. This information is critical to the knowledge of mechanisms of nephroprotection and safety of this therapy.

Methods: This multicenter prospective study evaluates the changes in ABP after 12 weeks of dapagliflozin 10 mg/day in a cohort of patients with type 2 DKD and glomerular filtration rate (GFR) >25 mL/min/1.

Rationale and design of ELIXIR, a randomized, controlled trial to evaluate efficacy and safety of XyloCore, a glucose-sparing solution for peritoneal dialysis.

Peritoneal dialysis adoption and technique survival is affected by limitations related to peritoneal membrane longevity and metabolic alterations. Indeed, almost all peritoneal dialysis fluids exploit glucose as an osmotic agent that rapidly diffuses across the peritoneal membrane, potentially resulting in metabolic abnormalities such as hyperglycemia, hyperinsulinemia, obesity, and hyperlipidemia. Moreover, glucose-degradation products generated during heat sterilization, other than glucose itself, induce significant morphological and functional changes in the peritoneum leading to ultrafiltration failure.

Serum Uric Acid, Hypertriglyceridemia, and Carotid Plaques: A Sub-Analysis of the URic Acid Right for Heart Health (URRAH) Study.

High levels of serum uric acid (SUA) and triglycerides (TG) might promote high-cardiovascular-risk phenotypes, including subclinical atherosclerosis. An interaction between plaques xanthine oxidase (XO) expression, SUA, and HDL-C has been recently postulated. Subjects from the URic acid Right for heArt Health (URRAH) study with carotid ultrasound and without previous cardiovascular diseases (CVD) (n = 6209), followed over 20 years, were included in the analysis.

Prognostic impact of hypertension grading.

Background: Most Hypertension Guidelines grade hypertension according to various cut-off values. We sought to investigate the prognostic impact of Grades 1 (140-159 and/or 90-99 mmHg), 2 (160-179 and/or 100-109 mmHg) and 3 (≥180 and/or ≥110 mmHg).

Methods: We followed for an average of 10 years a cohort of 3,150 initially untreated hypertensive patients (mean age 50 years, 44 % women) with no previous cardiovascular disease at entry.

Molecular Targets of Novel Therapeutics for Diabetic Kidney Disease: A New Era of Nephroprotection.

Diabetic kidney disease (DKD) is a chronic microvascular complication in patients with diabetes mellitus (DM) and the leading cause of end-stage kidney disease (ESKD). Although glomerulosclerosis, tubular injury and interstitial fibrosis are typical damages of DKD, the interplay of different processes (metabolic factors, oxidative stress, inflammatory pathway, fibrotic signaling, and hemodynamic mechanisms) appears to drive the onset and progression of DKD. A growing understanding of the pathogenetic mechanisms, and the development of new therapeutics, is opening the way for a new era of nephroprotection based on precision-medicine approaches.

Serum Uric Acid/Serum Creatinine Ratio and Cardiovascular Mortality in Diabetic Individuals-The Uric Acid Right for Heart Health (URRAH) Project.

Several studies have detected a direct association between serum uric acid (SUA) and cardiovascular (CV) risk. In consideration that SUA largely depends on kidney function, some studies explored the role of the serum creatinine (sCr)-normalized SUA (SUA/sCr) ratio in different settings. Previously, the URRAH (URic acid Right for heArt Health) Study has identified a cut-off value of this index to predict CV mortality at 5.

[Non-inferiority trials].

Superiority trials are designed to test the hypothesis that a given diagnostic or therapeutic strategy is better than (i.e. "superior to") placebo or an active control.

Triglyceride-glucose Index and Mortality in a Large Regional-based Italian Database (Urrah Project).

Purpose: Recently, a novel index (triglyceride-glucose index-TyG) was considered a surrogate marker of insulin resistance (IR); in addition, it was estimated to be a better expression of IR than widely used tools. Few and heterogeneous data are available on the relationship between this index and mortality risk in non-Asian populations. Therefore, we estimated the predictive role of baseline TyG on the incidence of all-cause and cardiovascular (CV) mortality in a large sample of the general population.

Managing hyperkalemia in patients with heart failure on guideline-directed medical therapy: challenges and opportunities.

Heart failure is a chronic and invalidating syndrome that affects tens of millions of people worldwide with significant socio-economic ramifications for the health care systems. Significant progress in the understanding of the pathophysiology of heart failure has allowed the gradual introduction of several drug classes for the management of such patients. Beta-blockers, mineralocorticoid receptor antagonists, angiotensin receptor neprilysin inhibitors, and sodium-glucose-cotransporter 2 inhibitors are all considered pillars of the guideline-directed medical therapy for heart failure.

Prognostic Value and Relative Cutoffs of Triglycerides Predicting Cardiovascular Outcome in a Large Regional-Based Italian Database.

Background: Despite longstanding epidemiologic data on the association between increased serum triglycerides and cardiovascular events, the exact level at which risk begins to rise is unclear. The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension has conceived a protocol aimed at searching for the prognostic cutoff value of triglycerides in predicting cardiovascular events in a large regional-based Italian cohort.

Methods And Results: Among 14 189 subjects aged 18 to 95 years followed-up for 11.

The lowest well tolerated blood pressure: A personalized target for all?

The optimal blood pressure (BP) target for prevention of cardiovascular complications of hypertension remains uncertain. Most Guidelines suggest different targets depending on age, comorbidities and treatment tolerability, but the underlying evidence is not strong. Results of randomized strategy trials comparing lower (i.

Use of Oral Anticoagulants in Patients with Atrial Fibrillation: Preliminary Data from the Italian Atrial Fibrillation (ITALY-AF) Registry.

Background: Atrial fibrillation (AFIB), the most frequent cardiac arrhythmia, is a major risk factor for stroke, heart failure, and death. Because of the recent advances in AFIB management and the availability of new oral anticoagulants (OACs), there is a need for a systematic and predefined collection of contemporary data regarding its management and treatment.

Methods: The objective of the ongoing ITALY-AFIB registry is to evaluate the long-term morbidity and mortality in patients with AFIB and to verify the implementation of the current guidelines for stroke prevention in these patients.

The Results of the URRAH (Uric Acid Right for Heart Health) Project: A Focus on Hyperuricemia in Relation to Cardiovascular and Kidney Disease and its Role in Metabolic Dysregulation.

The relationship between Serum Uric Acid (UA) and Cardiovascular (CV) diseases has already been extensively evaluated, and it was found to be an independent predictor of all-cause and cardiovascular mortality but also acute coronary syndrome, stroke and heart failure. Similarly, also many papers have been published on the association between UA and kidney function, while less is known on the role of UA in metabolic derangement and, particularly, in metabolic syndrome. Despite the substantial number of publications on the topic, there are still some elements of doubt: (1) the better cut-off to be used to refine CV risk (also called CV cut-off); (2) the needing for a correction of UA values for kidney function; and (3) the better definition of its role in metabolic syndrome: is UA simply a marker, a bystander or a key pathological element of metabolic dysregulation?.

Left ventricular remodeling response to SGLT2 inhibitors in heart failure: an updated meta-analysis of randomized controlled studies.

Background: Randomized controlled trials (RCTs) reported contrasting results about reverse left ventricular remodeling (LVR) after sodium-glucose co-transporter-2 inhibitors (SGLT2i) therapy in patients with heart failure (HF).

Methods And Results: We performed a metanalysis of RCTs of SGLT2i administration in HF outpatients published until June 2022 searching four electronic databases. The protocol has been published in PROSPERO.

Worldwide impact of COVID-19 on hospital admissions for non-ST-elevation acute coronary syndromes (NSTACS): a systematic review with meta-analysis of 553 038 cases.

Background: How coronavirus disease 2019 (COVID-19) impacted non-ST-segment elevation acute coronary syndromes (NSTACS) is an object of controversial reports.

Aim: To systematically review studies reporting NSTACS hospitalizations during the COVID-19 pandemic, and analyse whether differences in COVID-19 epidemiology, methodology of report, or public health-related factors could contribute to discrepant findings.

Methods: Comprehensive search (Medline, Embase, Scopus, Web of Science, Cochrane Register), of studies reporting NSTACS hospitalizations during the COVID-19 pandemic compared with a reference period, following Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines.

Long COVID [post-acute sequelae of coronavirus disease 2019]: experimental drugs for cardiopulmonary complications.

[Figure: see text].