Yicong Ye

Angiotensin II plasma levels are linked to disease severity and predict fatal outcomes in H7N9-infected patients

A novel influenza A (H7N9) virus of avian origin emerged in eastern China in the spring of 2013. This virus causes severe disease in humans, including acute and often lethal respiratory failure. As of January 2014, 275 cases of H7N9-infected patients had been reported, highlighting the urgency of identifying biomarkers for predicting disease severity and fatal outcomes. Here, we show that plasma levels of angiotensin II, a major regulatory peptide of the renin–angiotensin system, are markedly elevated in H7N9 patients and are associated with disease progression. Moreover, the sustained high levels of angiotensin II in these patients are strongly correlated with mortality. The predictive value of angiotensin II is higher than that of C-reactive protein and some clinical parameters such as the PaO2/FiO2 ratio (partial pressure of arterial oxygen to the fraction of inspired oxygen). Our findings indicate that angiotensin II is a biomarker for lethality in flu infections. Supplementary information The online version of this article (doi:10.1038/ncomms4595) contains supplementary material, which is available to authorized users.

Impact of thyroid function on serum cystatin C and estimated glomerular filtration rate: a cross-sectional study.

OBJECTIVE To determine the relationship between thyroid-stimulating hormone (TSH) and cystatin C (CysC) and estimated glomerular filtration rate calculated by Cys C (eGFR(CysC)). METHODS We conducted a cross-sectional study including 8,126 male participants. Serum creatinine (Cr), CysC, eGFR calculated by Cr (eGFR(Cr)), and eGFR(CysC) were determined and compared in euthyroid and subclinical thyroid dysfunction patients. Relationships between TSH and Cr, cystatin C, eGFR(Cr), and eGFR(CysC) were assessed by linear and quadratic trend analyses. Odds ratios (ORs) of chronic kidney disease (CKD; eGFR<60 mL/min/1.73 m2) were calculated according to categories of thyroid function using TSH values of 2.01-3.00 mIU/L as a reference. RESULTS Serum CysC level was significantly elevated, and eGFR(CysC) was significantly reduced in both subclinical hypothyroidism and subclinical hyperthyroidism. TSH was negatively and linearly associated with Cr and eGFR(Cr) (P<.001). Quadratic trends were found between TSH and cystatin C or eGFR(CysC) (P<.001). Compared with individuals with TSH of 2.01-3.00 mIU/L, the prevalence of CKD(CysC) was significantly higher in subjects with TSH<0.40 mIU/L, 3.01-4.00 mIU/L, and 4.01-7.00 mIU/L, while the prevalence of CKD(Cr) was only significantly higher in subjects with TSH>7.0 mIU/L. CONCLUSIONS Despite only studying male subjects and using eGFR rather than standard GFR, we conclude that thyroid function differentially affects serum CysC and Cr concentrations. Subclinical hypothyroidism and subclinical hyperthyroidism are both associated with elevated CysC, reduced eGFR(CysC), and higher prevalence of CKDCysC. Assessment of renal function with CysC should be avoided in patients with thyroid dysfunction.

The oral glucose tolerance test for the diagnosis of diabetes mellitus in patients during acute coronary syndrome hospitalization: a meta-analysis of diagnostic test accuracy.

BackgroundThe appropriateness of the routine performance of an oral glucose tolerance test (OGTT) to screen for diabetes mellitus (DM) during acute coronary syndrome hospitalization is still under debate.MethodsA systematic search of databases (MEDLINE [1985 to March 2012], EMBASE [1985 to March 2012]) was conducted. All prospective cohort studies assessing the accuracy or reproducibility of an OGTT in ACS or non-ACS individuals were included. A bivariate model was used to calculate the pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR). Heterogeneity was explored using subgroup analysis and meta-regression.ResultsFifteen studies with 8,027 participants were included (10 ACS and 5 non-ACS studies). The pooled results on SEN, SPE, PLR, NLR, and DOR were 0.70 (95% CI, 0.60-0.78), 0.91 (95% CI, 0.86-0.94), 7.6 (95% CI, 4.9-11.7), 0.33 (95% CI, 0.25-0.45), and 23 (95% CI, 12–41), respectively. The OGTT has a slightly lower SPE in diagnosing DM in ACS than in non-ACS patients (0.86 [95% CI 0.81-0.92] versus 0.95 [95% CI 0.93-0.98], p<0.01), while the SEN values are comparable (0.71 [95% CI 0.60-0.82] versus 0.67 [95% CI 0.54-0.81], p=0.43). After adjusting the interval between repeated tests and age, the meta-regression did not show a difference in DOR between ACS and non-ACS studies.ConclusionsDespite the discrepancy in the interval between the two OGTTs, performing an OGTT in patients with ACS provides accuracy that is similar to that in in non-ACS patients. It is reasonable to screen patients hospitalized for ACS for previously undiagnosed DM using an OGTT.

Effect of high-dose statin versus low-dose statin plus ezetimibe on endothelial function: a meta-analysis of randomized trials.

Background: Combining low-dose statin and ezetimibe reduces the low-density lipoprotein cholesterol (LDL-C) similar to high-dose statin. However, whether there is a difference in the effect of these 2 lipid-lowering regimes on endothelial function is still controversial. Methods: We performed a systematic search of databases (MEDLINE [1950 to September 2011], EMBASE [1966 to September 2011]) and references of identified studies. Completely published randomized controlled trials comparing the effect of high-dose statin with low-dose stain plus ezetimibe on endothelial function (flow-mediated dilation [FMD] method) were included in this study. Results: Six trials with a total of 213 participants were included in the meta-analysis. The pooled weighted mean difference of FMD did not differ between the 2 lipid-lowering regimes (0.22%; 95% confidence interval [CI]: −0.85%-1.29%, P = .68). Furthermore, no significant reduction in LDL-C and C-reactive protein (CRP) occurred with high-dose statin versus low-dose statin plus ezetimibe (pooled weighted mean differences of LDL-C and CRP were −4.12 mg/dL, 95% CI: −9.54-1.12 mg/dL, P = .12, and −0.02 mg/L, 95% CI: −0.31-0.27 mg/L, P = .89, respectively). Conclusions: Based on the currently available evidence, combining a low-dose statin with ezetimibe may provide similar beneficial effects on endothelial function as high-dose statin.

Efficacy and safety of biodegradable polymer biolimus-eluting stents versus durable polymer drug-eluting stents: a meta-analysis.

Backgrounds Drug-eluting stents (DES) with biodegradable polymers have been developed to address the risk of thrombosis associated with first-generation DES. We aimed to determine the efficacy and safety of biodegradable polymer biolimus-eluting stents (BES) versus durable polymer DES. Methods Systematic database searches of MEDLINE (1950 to June 2013), EMBASE (1966 to June 2013), the Cochrane Central Register of Controlled Trials (Issue 6 of 12, June 2013), and a review of related literature were conducted. All randomized controlled trials comparing biodegradable polymer BES versus durable polymer DES were included. Results Eight randomized controlled trials investigating 11,015 patients undergoing percutaneous coronary interventions were included in the meta-analysis. The risk of major adverse cardiac events did not differ significantly between the patients treated with the biodegradable polymer BES and the durable polymer DES (Relative risk [RR], 0.970; 95% CI, 0.848–1.111; p = 0.662). However, biodegradable polymer BES was associated with reduced risk of very late ST compared with the durable polymer DES, while the risk of early or late ST was similar (RR for early or late ST, 1.167; 95% CI 0.755–1.802; p = 0.487; RR 0.273; 95% CI 0.115–0.652; p = 0.003; p for interaction = 0.003). Conclusions In this meta-analysis of randomized controlled trials, treatments with biodegradable polymer BES did not significantly reduce the risk of major adverse cardiac events, but demonstrated a significantly lower risk of very late ST when compared to durable polymer DES. This conclusion requires confirmation by further studies with long-term follow-up. PROSPERO register number http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42013004364#.UnM2lfmsj6J

Association Between Subclinical Hypothyroidism and Blood Pressure - A Meta-Analysis of Observational Studies

OBJECTIVE This meta-analysis aimed to examine the relationship between subclinical hypothyroidism (SCH) and blood pressure (BP). METHODS A systematic search of MEDLINE and EMBASE databases was performed to identify all related cross-sectional studies and baseline data in prospective cohort studies in the general population. Weighted mean differences (WMDs) of systolic blood pressure (SBP) and diastolic blood pressure (DBP) between SCH and euthyroid groups were calculated. Subgroup analyses and meta-regression were used to explore potential heterogeneities among studies. RESULTS Twenty studies with 50,147 individuals were included. The WMDs of SBP and DBP were 1.47 mm Hg (95% confidence interval [CI] 0.54-2.39 mm Hg, P = .002) and 0.44 mm Hg [95% CI: -0.15-1.02 mm Hg, P = .142] between SCH and euthyroid groups, respectively. Significant heterogeneity was indentified among the included studies. Subgroup analysis showed that differences in study design, gender, and thyroid-stimulating hormone (TSH) cutoff level were not associated with the WMD of SBP, except for age difference between SCH and euthyroid groups. Meta-regression revealed a significant association between WMDs of SBP and age difference between the 2 groups (P = .015). CONCLUSION In this meta-analysis, SCH was associated with slightly higher SBP, which could be attributed to the age difference between SCH and euthyroid groups in the general population. However, this study could not exclude an association between SCH and BP. Prospective studies are needed to confirm these findings.

Percutaneous coronary intervention in left main coronary artery disease with or without intravascular ultrasound: A meta-analysis

This meta-analysis compared IVUS-guided with angiography-guided PCI to determine the effect of IVUS on the mortality in patients with LM CAD. Current guidelines recommend intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) in patients with left main coronary artery disease (LM CAD; Class IIa, level of evidence B). A systematic search of the MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases was conducted to identify randomized or non-randomized studies comparing IVUS-guided PCI with angiography-guided PCI in LM CAD. Ten studies (9 non-randomized and 1 randomized) with 6,480 patients were included. The primary outcome was mortality including all-cause death and cardiac death. Compared with angiography-guide PCI, IVUS-guided PCI was associated with significantly lower risks of all-cause death (risk ratio [RR] 0.60, 95% confidence interval [CI] 0.47–0.75, p<0.001), cardiac death (RR 0.47, 95% CI 0.33–0.66, p<0.001), target lesion revascularization (RR 0.43, 95% CI 0.25–0.73, p = 0.002), and in-stent thrombosis (RR 0.28, 95% CI 0.12–0.67, p = 0.004). Subgroup analyses indicated the beneficial effect of IVUS-guide PCI was consistent across different types of studies (unadjusted non-randomized studies, propensity score-matched non-randomized studies, or randomized trial), study populations (Asian versus non-Asian), and lengths of follow-up (<3 years versus ≥3 years). IVUS-guided PCI in LM CAD significantly reduced the risks of all-cause death by ~40% compared with conventional angiography-guided PCI. PROSPERO registration number: CRD 42017055134.

Use of atorvastatin in lipid disorders and cardiovascular disease in Chinese patients.

Objective: Statins are still underused for the prevention of cardiovascular disease (CVD) in China. Hence, we conducted a systemic review on the pharmacology, clinical efficacy, and adverse events of atorvastatin, as well as on patient adherence. Data Sources: We conducted a systemic search in PubMed with the following keywords: “atorvastatin” (Supplementary concept) or “atorvastatin” (All field) and (“China” [AD] or “China” [all field] or “Chinese” [All field]). Study Selection: Clinical or basic research articles on atorvastatin were included. Results: Atorvastatin is a reversible and competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, decreasing the de novo cholesterol synthesis. The pharmacokinetics of atorvastatin among Chinese is similar to those in Caucasians, and several gene polymorphisms have proved to be associated with the metabolism of atorvastatin in the Chinese population. Several international multiple-center randomized control trials have demonstrated the benefit of atorvastatin for primary and secondary prevention of CVD. None of them, however, included the Chinese, and current evidence in the population is still inadequate, due to the small sample size, low study quality, short study duration, and the use of surrogate endpoints instead of clinical endpoints. The overall incidence of adverse events observed with atorvastatin did not increase in the 10–80 mg dose range, and was similar to that observed with placebo and in patients treated with other statins, which makes atorvastatin well-tolerated in the Chinese population. Moreover, high patient adherence was observed in clinical studies. Conclusions: Based on the current available evidence, there is no significant difference between Chinese and non-Chinese population in term of pharmacology and clinical efficacy/safety. High-quality evidence is still needed to support the use of atorvastatin in high-risk Chinese population.

Optimal Oral Antithrombotic Regimes for Patients with Acute Coronary Syndrome: A Network Meta-Analysis

Objective We performed a network meta-analysis to investigate the optimal antithrombotic regime by indirectly comparing new antithrombotic regimes (new P2Y12 inhibitors plus aspirin or novel oral anticoagulants on top of traditional dual antiplatelet therapy [DAPT]) in patients with acute coronary syndrome (ACS). Methods A systematic search of MEDLINE, EMBASE, and the Cochrane databases was performed to identify all phase 3 randomized controlled trials (RCTs) involving novel oral anticoagulants or oral P2Y12 inhibitors in patients with ACS. Major adverse cardiac events (MACE) were regarded as the efficacy endpoint, and thrombolysis in myocardial infarction (TIMI) major bleeding events were used as the safety endpoint. The net clinical benefit was calculated as the sum of MACE and TIMI major bleeding events. Results Five phase 3 RCTs with 64,476 ACS patients were included. Although there were no significant differences among new antithrombotic regimes, rivaroxaban 5 mg twice daily plus traditional DAPT might be the most effective in reducing the incidence of MACE, accompanying the highest risk of TIMI major bleeding. Ticagrelor plus aspirin presented slight advantage on the net clinical benefit over other new antithrombotic regimes, with the highest probability of being the best regimes for net clinical benefit (35.0%), followed by prasugrel plus aspirin (28.0%), and rivaroxaban 2.5 mg twice daily plus traditional DAPT (19.5%). Conclusion Novel antithrombotic regime with ticagrelor plus aspirin brings a larger clinical benefit in comparison with other regimes, suggesting that it may be the optimal antithrombotic regime for patients with ACS.

Arginine methylation dysfunction increased risk of acute coronary syndrome in coronary artery disease population: A case-control study

Abstract The plasma levels of asymmetric dimethylarginine (ADMA) had been proved to be an independent cardiovascular risk factor. Few studies involved the entire arginine methylation dysfunction. This study was designed to investigate whether arginine methylation dysfunction is associated with acute coronary syndrome risk in coronary artery disease population. In total 298 patients undergoing coronary angiography because of chest pain with the diagnosis of stable angina pectoris or acute coronary syndrome from February 2013 to June 2014 were included. Plasma levels of free arginine, citrulline, ornithine, and the methylated form of arginine, ADMA, and symmetric dimethylarginine (SDMA) were measured with high-performance liquid chromatography coupled with tandem mass spectrometry. We examined the relationship between arginine metabolism-related amino acids or arginine methylation index (AMI, defined as ratio of [arginine + citrulline + ornithine]/[ADMA + SDMA]) and acute coronary events. We found that plasma ADMA levels were similar in the stable angina pectoris group and the acute coronary syndrome group (P = 0.88); the AMI differed significantly between 2 groups (P < 0.001). Multivariate logistic regression demonstrated that AMI was an independent risk factor of acute coronary events in patients with coronary artery disease (OR = 0.975, 95% confidence interval 0.956–0.993; P = 0.008). Our study suggested that ADMA levels were very similar in the stable angina and acute coronary syndrome patients; AMI might be an independent risk factor of acute coronary events in coronary artery disease population.