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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.

Objective The aim was to investigate the role and potential mechanism of geranylgeranylacetone (GGA) in the development of atherosclerosis, and to explore the role of heat shock protein 22 (HSP22) in mediating GGA effect. Methods Human coronary artery endothelial cell (HCAEC) was used for in vitro study. RNA interference was applied to suppress HSP22 in the cells. Cellular apoptosis and intracellular level of reactive oxygen species (ROS) were detected by flow cytometer, and proteins of HSP22, NF-κB, eNOS, and ICAM-1 were assessed by immunoblotting. HSP22 -/- //ApoE -/- , and HSP22 +/+ //ApoE -/- mice were used to investigate the effect of GGA in the animal model of atherosclerosis. Atherosclerotic lesion of the mice aortas was evaluated by Oil Red O staining and H&E staining. Results GGA significantly inhibited HCAEC apoptosis in response to oxidized-LDL (ox-LDL), but stimulated HSP22 synthesis in the cells. Transfection of HSP22-siRNA in the cells resulted in complete blockage of the GGA effect on apoptosis. GGA also significantly inhibited ROS, NF-κB, and ICAM-1 in the cells transfected control siRNA, but not in the cells transfected with HSP22-siRNA. Atherosclerotic plaque in the aorta was significantly less in the wild type (WT) animals treated with GGA as stained either by Oil Red O or by H&E staining, but not in the HSP22-KO mice. GGA significantly inhibited expression of NF-κB and ICAM-1 in the WT mice, but not in the HSP22-KO mice. Conclusion GGA-induced HSP22, and inhibited ox-LDL-induced apoptosis as well as expression of NF-κB and ICAM-1 in the HCAECs. GGA also attenuated formation of atherosclerotic plaques in mice aorta. Suppression of HSP22 by siRNA resulted in blockage of the GGA inhibition on apoptosis or stimulation on NF-κB and ICAM-1. These findings suggested that GGA protects endothelial cells from injury in response to ox-LDL and block atherosclerotic development in mice aorta through induction of HSP22.

Objective: Recent studies have reported that neutrophil-to-lymphocyte ratio (NLR) is associated with cardiovascular disease. The aim of the present study was to investigate the prognostic value of NLR in aortic disease. Methods: We systematically searched electronic databases (Cochrane, PubMed, Elsevier, Medline, and Embase) from their inception to March 2020. Observational studies that evaluated the relationship between NLR and aortic disease were eligible for critical appraisal. Data were extracted from applicable articles, risk ratio (RR), weighted mean differences (MD) and 95% confidence intervals (CI) were calculated by RevMan 5.3, and statistical heterogeneity was assessed by the I 2 statistic. Results: Fourteen studies enrolling 4066 individuals were included in the meta-analysis. Compared with the control group, NLR was significantly higher in the aortic disease group (MD 3.44, 95%CI: 0.81-6.07, P = 0.01, I 2 = 99%). The NLR was also significantly higher in non-survivors with aortic disease, compared to the survivors (MD 4.62, 95%CI: 2.75-6.50, P < 0.00001, I 2 = 60%). Compared with the aortic disease patients with a low NLR, mortality was significantly higher in those with a high NLR (RR 2.63, 95%CI: 1.79-3.86, P < 0.00001, I 2 = 67%). Conclusion: Based on current evidence, an elevated NLR was associated with aortic disease and in-hospital mortality. Raised NLR also demonstrated a significantly increased the risk of mortality after surgical repair in aortic disease patients. NLR may be a good prognostic biomarker in aortic disease and deserve further research in this area.

Immune checkpoint inhibitors (ICIs)-related myocarditis is a rare but severe side effect that is often accompanied by elevated levels of cardiac troponin I, making it difficult to distinguish from acute myocardial infarction (AMI). Our study aims to explore the differences in blood protein profiles between ICIs-related myocarditis and AMI, and to identify potential biomarkers. We performed plasma proteomics on 15 plasma samples from 5 pairs with ICIs-related myocarditis at treatment baseline and diagnosis, and 5 cases of AMI confirmed by coronary angiography. A total of 1521 plasma proteins were identified, with 1325 quantifiable plasma proteins across all 15 plasma samples. Our study observed that ICIs-related myocarditis group showed differential expressed protein (DEPs) involved in myocardial contraction, immunoregulation, proteasome, arginine and proline metabolism, and cysteine and methionine metabolism. We also identified that MYOM3, Galectin-1, and CSF1 are highly expressed in ICIs-related myocarditis compared with other groups by plasma proteomics analysis, and utilized more AMI plasma samples, as well as animal models of ICIs-related myocarditis and AMI to further validate these findings. These results have the potential to provide valuable predictive information for future clinical research.

The relationship between weight-adjusted-waist index (WWI, a newly developed obesity index) and peripheral arterial disease (PAD) is unclear. We aimed to explore the association between WWI and the prevalence of PAD in US adults. A total of 7,344 participants (males: 50.60%; females: 49.40%) from the 1999–2004 National Health and Nutrition Examination Survey (NHANES) were included in this study. WWI was calculated as waist circumference (WC) divided by the square root of weight. PAD was defined as an ankle-brachial index < 0.90 in either leg. The prevalence of PAD was 7.84%, which was respectively 3.72%, 7.23%, and 12.58% in WWI tertiles 1–3 (P < 0.001). WWI was positively associated with an elevated likelihood of PAD (OR = 1.25, 95% CI: 1.06–1.48), and the association was robust in stratified subgroups (all P for trend > 0.05). For male participants, there was a nearly linear relationship between WWI and PAD (OR = 1.35, 95% CI: 1.01–1.82). However, non-linear positive relationships were detected in females with an inflection point of 10.98 cm/√kg. A positive association was observed on the left of the inflection point (OR = 2.71, 95% CI: 1.27–5.78), while the association on the right was of no statistical significance (OR = 1.01, 95% CI: 0.77–1.33). In summary, WWI was significantly associated with an increased likelihood of PAD in US adults, with a differential association between males and females.