Finerenone attenuates myocardial apoptosis, metabolic disturbance and myocardial fibrosis in type 2 diabetes mellitus

Abstract Background Finerenone is a third-generation mineralocorticoid receptor antagonists, which has shown good cardiac function improvement in patients with type 2 diabetes in large-scale clinical trials. However, its specific role in diabetic cardiomyopathy remains unclear. We explored the potential functions and mechanisms of finerenone in diabetic cardiomyopathy. Methods The type 2 diabetic rat model was induced by high-fat diet and low-dose streptozotocin (n = 6, each group). Next the drug group was treated with finerenone (1 mg/kg/day) for 8 weeks. Then we detected the cardiac structure and function and relevant indicators. Neonatal rat cardiomyocytes were used for in vitro culture to determine the direct effect of finerenone on cardiomyocytes stimulated by high glucose and high fatty acid. Results Compared with the control group, rats in the type 2 diabetes group exhibited hyperglycemia, hyperlipidemia, and impaired cardiac function. Myocardium showed increased fibrosis and apoptosis. Finerenone attenuated these impairments without changing blood glucose levels. In neonatal rat cardiomyocytes, the stimulation of high concentrations of palmitic acid increased fatty acid uptake, as well as increased reactive oxygen species and apoptosis. Finerenone significantly improved fatty acid metabolism, reduced cellular inflammation levels, and decreased apoptosis. Conclusions By blocking the mineralocorticoid receptor, finerenone attenuates cardiac steatosis, myocardial fibrosis and apoptosis, and subsequent myocardial remodeling and diastolic dysfunction in type II diabetic rats

Effects of Rosuvastatin and Atorvastatin on Renal Function

Background: Several clinical trials have reported inconsistent findings for the effects of rosuvastatin (RSV) and atorvastatin (AN) on renal function. The aim of this meta-analysis was to investigate the effects of these 2 statins on glomerular filtration rate (GFR) and proteinuria respectively, and determine which is better. Methods and Results: PubMed, CENTRAL, Web of Knowledge, and ClinicalTrials.gov website were searched for randomized controlled trials. Eligible studies reported GFR and/or proteinuria during treatment with RSV or ATV compared with control (placebo, no statins, or usual care), or RSV compared with AN head to head. Trials that enrolled dialysis participants and teenagers were excluded. Statistical heterogeneity was assessed using the 12 statistic, and pooled results using the random-effects model. The standardized mean differences (SMD) and ratio of means (ROM) were measured, respectively, to analyze GFR and proteinuria. Sixteen trials with a total number of 24,278 participants were identified. Compared with control, changes in the SMD of GFR were 0.04 (95% confidence interval [CI]: 0.01-0.07) and 0.59 (95%CI: 0.12-1.06) for RSV and ATV, respectively. The ROMs of proteinuria were 0.59 (95%CI: 0.46-0.74) for RSV vs. the control group, and 1.23 (95%CI: 1.05-1.43) in the head-to-head comparison. Conclusions: Both RSV and ATV improve GFR, and ATV seems to be more effective in reducing proteinuria. The validity and clinical significance require high-quality intensive studies with composite clinic endpoints of kidney and death. (Circ J 2012; 76: 1259-1266)http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000303369800032&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Cardiac & Cardiovascular SystemsSCI(E)21ARTICLE51259-12667

Association between low serum magnesium level and major adverse cardiac events in patients treated with drug-eluting stents for acute myocardial infarction.

OBJECTIVES: We investigated the association of serum magnesium (Mg) levels and major adverse cardiac events (MACEs) after drug-eluting stent (DES) implantation. BACKGROUND: Mg depletion plays a key role in the pathphysiologic features of diabetes mellitus, hypertension, thrombosis, arrhythmias and coronary artery disease. Whether the depletion is related to the long-term prognosis of DES implantation is not known. METHODS: From 2008 to 2011, we enrolled 414 consecutive patients <50 years old who underwent DES implantation for acute coronary syndrome. Serum Mg level was analyzed and patients were followed up for a median of 24 months (interquartile range 14-32 months) for the occurrence of MACEs defined as death, myocardial infarction, stroke, and any revascularization. RESULTS: For patients with unstable angina, no significant association between serum Mg level and MACEs was found in the multivariate model. For patients with myocardial infarction, after adjusting for age, positive family history, smoking status, hypertension, hypercholesterolemia, and diabetes at baseline, the risk was 8.11-fold higher for patients with quartile 1 than 4 Mg level (95% confidence interval 1.7-38.75; P<0.01). In addition, when tested as a continuous variable, serum magnesium was a significant predictor for MACEs of acute myocardial infarction (HR [per 0.1 mM increase], 0.35 [95% CI, 0.19-0.63], p< 0.01), after adjustment for other confounders. CONCLUSIONS: Low serum level of Mg may be an important predictor of MACEs with DES implantation for acute myocardial infarction. Further research into the effectiveness of Mg supplementation for these patients is warranted

Relative risk by quartiles of serum Mg level according to different clinical presentation.

<p>95% CI, 95% confidence interval.</p><p>*<i>P</i><0.05, **<i>P</i><0.01.</p><p># adjusted for age, positive family history, smoking status, hypertension, hypercholesterolemia, and diabetes at baseline.</p

Factors of major adverse cardiac events (MACEs) and relative risk by quartiles of serum Mg level.

<p>PCI, percutaneous coronary intervention; 95% CI, 95% confidence interval.</p><p>*<i>P</i><0.05.</p><p># adjusted for positive family history, smoking status, hypertension, hypercholesterolemia, and diabetes at baseline.</p

Cumulative major adverse cardiac event-free survival in 414 patients by quartiles of serum magnesium level.

<p>Cumulative major adverse cardiac event-free survival in 414 patients by quartiles of serum magnesium level.</p

Clinical characteristics of patients with acute coronary syndrome by quartiles of serum Mg level.

<p>Data are no. (%) unless indicated.</p

Risk factors of coronary artery disease by quartile (Q) of serum magnesium (Mg) level.

<p>BMI, body mass index; CAD, coronary artery disease.</p><p>Data are no. (%) unless indicated.</p