A prospective study of hepatic safety of statins used in very elderly patients.

BACKGROUND: Statins play an important role in the care of patients with cardiovascular disease and have a good safety record in clinical practice. Hepatotoxicity is a barrier that limits the ability of primary care physicians to prescribe statins for patients with elevated liver transaminase values and/or underlying liver disease. However, limited population-based data are available on the use of statin therapy and on the hepatotoxicity of statins in very elderly patients. This prospective study evaluated the liver enzyme elevation during statin therapy in very elderly patients (≥80 years old). METHODS: Patients with hypercholesterolemia (LDL-C levels ≥3.4 and < 5.7 mmol/L), atherosclerosis, coronary heart disease (CHD), or a CHD-risk equivalent were enrolled and received once-daily statin treatment. Multivariate logistic regression models were used to study the impact of age, gender, hepatitis B infection, fatty liver disease, biliary calculus, other chronic diseases, drug kinds, alcohol abuse, statin variety, and statin dose variables. RESULTS: A total of 515 consecutive patients ranging from 80 to 98 years old were included in the analysis. These patients were treated with simvastatin, fluvastatin, pravastatin, rosuvastatin, or atorvastatin. Twenty-four patients (4.7, 95% CI 2.7-6.6) showed an increase in their hepatic aminotransferase levels. No significant difference of hepatic aminotransferase elevation rates was observed in different statin treatment groups. The incidence of mild, moderate, and severe elevation of aminotransferase levels was 62.5% (15/24), 29.2% (7/24), and 8.3% (2/24), respectively. None of the patients developed hepatic failure. Nine patients with moderate or severe aminotransferase elevations discontinued therapy. The time of onset of hepatic aminotransferase elevation ranged from 2 weeks to 6 months after statin treatment. The onset of hepatic aminotransferase elevation was within 1 month for 70.8% of patients. The patients took 2 weeks to 3 months to recover their liver function after statin therapy cessation. Multivariate analysis identified chronic hepatitis B infection and alcohol consumption as independent factors associated with the hepatic response to statins: OR, 12.83; 95% CI (4.36-37.759) and OR, 2.736; 95% CI (1.373-5.454), respectively. CONCLUSION: The prevalence of elevated transaminases was higher than published data in very elderly patients. Overall, statin treatment is safe for patients ≥80 years old.

Combined Use of Circulating miR-133a and NT-proBNP Improves Heart Failure Diagnostic Accuracy in Elderly Patients.

BACKGROUND Circulating microRNAs (miRNAs) are emerging as novel biomarkers for detecting cardiovascular diseases. Here, circulating miR-133a and miR-221 were investigated as potential diagnostic biomarkers for heart failure (HF) patients, particularly in elderly patients. MATERIAL AND METHODS A total of 94 elderly HF patients (mean age=77.4 years old) and 31 healthy controls (age- and sex-matched) participated in this study. Plasma NT-proBNP levels were measured using an electrochemiluminescence immunoassay, and circulating miR-133a and miR-221 levels were examined using real-time quantitative PCR, with diagnostic efficacies determined for each independently and in combination. RESULTS MiR-133a expression increased by 4.6-fold (P<0.001) and miR-221 expression increased by 2.0-fold (P<0.001) in the elderly HF patients relative to the healthy controls. ROC curves were generated and AUC values of 0.863 for miR-133a (CI95%: 0.800-0.927), 0.718 for miR-221 (CI95%: 0.622-0.813), and 0.895 for NT-proBNP (CI95%: 0.841-0.948) were obtained. Unlike NT-proBNP, miR-133a and miR-221 were found to be unaffected by age, BMI, renal function, albumin, or Hb levels. More importantly, the diagnostic value of NT-proBNP was found to be improved when combined with any of the examined miRNA biomarkers alone or in a panel. When combining miR-133a with NT-proBNP, an AUC value of 0.975 (CI95%: 0.950-0.999) was obtained, which was significantly higher than for NT-proBNP alone (z=2.395, P=0.016). CONCLUSIONS miR-133a and miR-221 can serve as potential HF diagnostic biomarkers in elderly patients. Moreover, the diagnostic accuracy of NT-proBNP can be improved by the addition of miR-133a.

Lnc-SGK1 induced by Helicobacter pylori infection and highsalt diet promote Th2 and Th17 differentiation in human gastric cancer by SGK1/Jun B signaling.

Serum and glucocorticoid-inducible kinase (SGK) 1can be triggered in several malignancies. Most research on SGK1has focused on its role in cancer cells, and we sought to investigate its potential upstream non-coding RNA nominated as Lnc-SGK1, and their expression and diagnostic value in T cells in human gastric cancer (GC). Excessive expression of Lnc-SGK1 and SGK1 were observed in T cell either within the tumor or peripheral T cells, and furthermore associated with Helicobacter pylori infection and high-salt diet (HSD). Within T cells, Helicobacter pylori (Hp) infection and high-salt dietcan up-regulated SGK1 expression and in turn enhance expression of Lnc-SGK1 through JunB activation. And expression of Lnc-SGK1 can further enhance transcription of SGK1 through cis regulatory mode. Lnc-SGK1 can induce Th2 and Th17 and reduce Th1 differentiation via SGK1/JunB signaling. Serum Lnc-SGK1 expression in combination with H. pylori infection and/or HSD in T cells was associated with poor prognosis of GC patients, and could be an ideal diagnostic index in human GC.

Atorvastatin inhibits the expression of RAGE induced by advanced glycation end products on aortas in healthy Sprague-Dawley rats.

BACKGROUND: Atorvastatin can downregulate the expression of receptor for advanced glycation end products (RAGE) in the aortas of diabetic rats. However, its effect on healthy rats remains unclear. The aim of this study was to observe the direct impact of atorvastatin on advanced glycation end products- (AGEs) induced RAGE expression in healthy Sprague Dawley (SD) rats. METHODS: SD rats received AGE-BSA (20 mg/kg/day or 40 mg/kg/day), dual treatment (AGE-BSA 40 mg/kg/day and atorvastatin 20 mg/kg/day) or no treatment for 12 and 24 weeks, respectively. The deposition of AGEs and expression of RAGE in the animals' aortas were assessed by Quantitative RT-PCR, immunohistochemistry, and western-blot tests. Serum levels of AGEs were measured using ELISA. RESULTS: AGE-BSA upregulated the serum level of AGEs, deposition of AGEs, and expression of RAGE in aortas in a time- and dose-dependent way that can accelerate the development and progression of atherosclerosis. These upregulations could be significantly attenuated by atorvastatin in the absence of its lipid-lowering effects. These data provide further evidence for the novo mechanism of atorvastatin's pleiotropic effect. CONCLUSION: Atorvastatin has a direct inhibitory effect on AGEs-RAGE expression in healthy SD rats. These potential pleiotropic vasculoprotective effects are independent of effects on glucose and lipid control.