Aims Sacubitril-valsartan has been shown to have superior effects over angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in patients with heart failure (HF) and hypertension. The efficacy and safety of sacubitril-valsartan in patients with HF are controversial. We performed a meta-analysis of randomized controlled trials to assess and compare the effect and adverse events of sacubitril-valsartan, valsartan, and enalapril in patients with HF. Methods and results We conducted a systematic search using PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov. Randomized controlled trials involving the use of sacubitril-valsartan in patients with HF were included. We assessed the pooled odds ratio (OR) of all-cause mortality, cardiovascular mortality, and hospitalization for HF in fixed-effects models and the pooled risk ratio (RR) of symptomatic hypotension, worsening renal function, and hyperkalaemia in fixed-effects models. Of the 315 identified records, six studies involving 14 959 patients were eligible for inclusion. Sacubitril-valsartan reduced the endpoints of all-cause mortality and cardiovascular mortality in patients with HF with reduced ejection fraction (HFrEF) in three trials with pooled ORs of 0.83 (P = 0.0006) and 0.78 (P < 0.0001), respectively. Regarding the composite outcome of hospitalization for HF in five trials, the pooled OR was 0.79 (P < 0.00001). Compared with enalapril or valsartan, sacubitril-valsartan was associated with a high risk of symptomatic hypotension (RR 1.47, P < 0.00001), low risk of worsening renal function (RR 0.81, P = 0.005), and low rate of serious hyperkalaemia (≥6.0 mmol/L) (RR 0.76, P = 0.0007) in all six trials. Conclusions Compared with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, sacubitril-valsartan significantly decreased the risk of death from all causes or cardiovascular causes in HFrEF and hospitalization for HF in both patients with HFrEF and HF with preserved ejection fraction. Sacubitril-valsartan reduced the risk of renal dysfunction and serious hyperkalaemia but was associated with more symptomatic hypotension.

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One of the pathological functions of heat shock protein 22 (HSP22) is the association with inflammatory diseases and atherosclerosis. However, the effects of a high-fat diet (HFD) or oxidized low-density lipoprotein (ox-LDL) combined with atorvastatin (ATV) on HSP22 expression are entirely unknown. The present study investigated the effects of ATV on HSP22 expression in HFD-induced atherosclerotic apolipoprotein E-deficient (ApoE−/−) mice and in ox-LDL-induced human umbilical vein endothelial cells (HUVECs). Furthermore, the influence of HSP22-knockdown on the HFD- or ox-LDL-induced atherosclerotic model was also examined. It was found that HFD or ox-LDL treatment significantly increased HSP22 expression in the serum and aorta, accompanied by decreased phosphorylated (p)-endothelial nitric oxide synthase (p-eNOS) activity and activated p38 mitogen-activated protein kinase (MAPK). However, these effects were suppressed by treatment with ATV. Furthermore, HSP22-knockdown showed reduced ox-LDL-induced lesions, evidenced by increased p-eNOS activity and inactivated p38 MAPK, while suppression of cell proliferation inhibition and cell cycle arrest were also observed. Taken together, the results of this study suggest that HFD or ox-LDL increased the expression of HSP22 and p-p38 MAPK, and decreased the p-eNOS activity in vitro and in vivo, and ATV could reduce the effects by downregulating HSP22 expression.

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