Hongzhi Xie

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.

Danon disease as a cause of concentric left ventricular hypertrophy in patients who underwent endomyocardial biopsy

BACKGROUND Danon disease is an X-linked dominant disorder; concentric left ventricular hypertrophy (LVH) is one of its manifestations. In this study, we investigated the prevalence of Danon disease in patients with concentric LVH who underwent endomyocardial biopsy (EMB). METHODS AND RESULTS A total of 50 patients with concentric LVH underwent EMB from January 2008 to December 2010. Cardiac amyloidosis was diagnosed in 14 patients; genetic analysis of lysosome-associated membrane protein 2 (LAMP2) was done in the remaining 36 patients. Three novel LAMP2 frameshift mutations were found. They were c.808_809 insG in exon 6, c.320_321 insCATC in exon 3, and c.257_258delCC in exon 3, leading to a premature stop codon on cDNA analysis. The prevalence of Danon disease was seen in 6% (3 of 50) of unselected concentric LVH patients who underwent EMB, or 8% (3 of 36) after excluding cardiac amyloidosis through EMB. All the three patients were male teenagers with a mean age of 15 ± 1 years, and had mild mental retardation, two of the three with Wolff-Parkinson-White (WPW) syndrome and markedly increased left ventricular voltage. All the three patients had increased serum hepatic enzymes and creatine kinase (CK) concentrations. There was no death or cardiovascular hospitalization during 20 ± 15 months of follow-up. CONCLUSIONS Danon disease may account for a number of patients with concentric LVH who underwent EMB. Danon disease should be suspected in the male teenager with concentric LVH, especially with elevated serum hepatic enzymes and CK concentrations, and/or WPW syndrome with markedly increased voltage of the left ventricle. Genetic analysis of LAMP2 can help make the diagnosis.

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

Effect of statins in preventing contrast-induced nephropathy: an updated meta-analysis.

ObjectiveThe effect of statins in preventing contrast-induced nephropathy (CIN) has been reported, with conflicting results. The aim of this study was to carry out an updated meta-analysis to determine whether pretreatment with statins can reduce the risk of CIN and adverse clinical events. Materials and methodsSystematic database searches of MEDLINE (1950 to December 2013), EMBASE (1966 to December 2013), and the Cochrane Central Register of Controlled Trials (Issue 12, December 2013) were performed. All randomized controlled trials assessing the efficacy of statins on CIN were included. ResultsSeventeen studies with 6323 patients were included. Pretreatment with statins before angiography significantly reduced the risk of CIN [relative risk 0.50; 95% confidence interval (CI) 0.35–0.71; P<0.001] and was associated with significantly lower postprocedural serum creatinine levels (weighted mean difference −0.05 mg/dl; 95% CI −0.09 to −0.02 mg/dl; P=0.005). Meanwhile, the use of statins resulted in trends of reduced risks of renal replacement therapy and all-cause death within 30 days (relative risk 0.44; 95% CI 0.18–1.08; P=0.07). Further analyses indicated that high-dose statins were more effective than low-dose statins in reducing the risk of CIN and that different types of statins showed similar effects in preventing CIN. ConclusionPretreatment with statins before angiography is effective in preventing CIN and may reduce the risk of adverse clinical events. However, the optimal dose and duration for statin pretreatment are still unknown.

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.

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.

Renal Dysfunction and hsCRP Predict Long-term Outcomes of Percutaneous Coronary Intervention in Acute Myocardial Infarction

Background:This study assessed the combined utility of estimated glomerular filtration rate (eGFR) and serum high-sensitivity C-reactive protein (hsCRP) levels to predict long-term mortality and cardiovascular outcomes of patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Elevated CRP levels and renal dysfunction have both been shown to independently and jointly predict mortality and cardiovascular outcomes after PCI in the short term. However, long-term results in patients with acute STEMI undergoing PCI have not been reported. Methods:A total of 262 patients with acute STEMI undergoing primary PCI were classified at admission into quartiles according to eGFR (<60, 60–70, 70–80 and ≥80 mL·min−1·1.73 m−2) and hsCRP (<3 and ≥3 mg/L). Mortality, nonfatal myocardial infarction (MI) and major adverse cardiac events (MACEs) were compared among the groups. Results:During a median follow-up of 48.3 months, the composite of all-cause mortality and nonfatal MI (mortality + MI) was significantly higher (35.09%) in the group with the lowest eGFR compared with that of the other 3 eGFR groups (14.29%, 3.77% and 9.43%, respectively, P < 0.0001) and the group with elevated hsCRP (34.29%) versus that with hsCRP <3 mg/L (4.41%, P < 0.0001). A combined analysis showed an exaggerated hazard in patients with the lowest eGFR and highest hsCRP (hazard ratio: 44.658; 95% confidence interval: 5.955–111.890). Conclusions:Renal dysfunction and elevated hsCRP predict a high long-term incidence of MACE in patients with acute STEMI undergoing primary PCI, with the combination being of prognostic significance for long-term mortality and MI in these patients.

Smoking and prasugrel

Recently, clopidogrel has beenproved to be reduced or complete lack of clinical benefit in nonsmokers in post-hoc analysis of several largescale randomized controlled trials (RCTs). These observations raise concerns about the costs and potential risks incurred by treating nonsmokers with clopidogrel [1]. In acute coronary syndrome (ACS) patients with scheduled percutaneous coronary intervention, the thirdgeneration thienopyridine prasugrel was associated with significantly reduced rates of ischemic events compared to clopidogrel in TRITONTIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel) [2]. Thus, we tried to determine the association between prasugrel and smoking habits in patients with ACS. Two largest RCTs comparing prasugrel with clopidogrel (TRITONTIMI 38 [2] and TRILOGY ACS [The Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes] [3,4]) were included in our analysis. In TRITON-TIMI 38, 13,608 patients with moderate-to-high-risk ACS with scheduled percutaneous coronary intervention were randomized to receive prasugrel or clopidogrel for 6 to 15 months. The primary efficacy end point occurred in 12.1% of patients receiving clopidogrel and 9.9% of patients receiving prasugrel (hazard ratio[HR] for prasugrel vs. clopidogrel, 0.81; 95% confidence interval [CI], 0.73 to 0.90; pb0.001). In TRILOGYACS, 9326 patients with unstable angina or myocardial infarction without ST-segment elevation who did not undergo revascularization were randomized to receive prasugrel or clopidogrel. After a median follow-up of 17 months, prasugrel did not significantly reduce the frequency of the primary end point. Both studies were high quality RCTs, and scored 5 using JADAD scale [5]. Both studies used death from cardiovascular causes, myocardial infarction, or stroke as primary end point. Thus, we directly calculated the pooled HR of primary endpoint for both smokers and non-smokers using STATA 11.0 (STATA, TX, USA) with inverse-variance method. The authors of this manuscript have certified that they comply with the

Late acquired double lumina in a sirolimus-eluting stent recanalized chronic total occlusion lesion: Angiographic and optical coherence tomographic findings

clopidogrel pharmacokinetics, pharmacodynamics, and clinical efficacy in postmyocardial infarction patients. Circ Cardiovasc Interv 2011;4(5):422–8. [5] Simon T, Steg PG, Becquemont L, et al. Effect of paraoxonase-1 polymorphism on clinical outcomes in patients treated with clopidogrel after an acute myocardial infarction. Clin Pharmacol Ther 2011;90(4):561–7. [6] Sibbing D, Koch W, Massberg S, et al. No association of paraoxonase-1 Q192R genotypes with platelet response to clopidogrel and risk of stent thrombosis after coronary stenting. Eur Heart J 2011 Jul;32(13):1605–13. [7] Lewis JP, Fisch AS, Ryan K, et al. Paraoxonase 1 (PON1) gene variants are not associated with clopidogrel response. Clin Pharmacol Ther 2011;90(4):568–74. [8] Bliden KP, DiChiara J, Tantry US, et al. Increased risk in patients with high platelet aggregation receiving chronic clopidogrel therapy undergoing percutaneous coronary intervention: is the current antiplatelet therapy adequate? J Am Coll Cardiol 2007;49(6):657–66.

INCREASED MONOCYTIC EXPRESSION OF UROKINASE RECEPTOR IN ACUTE CORONARY SYNDROME: A POTENTIAL MARKER OF CLINICAL INSTABILITY

Objectives Urokinase receptor (uPAR) is highly expressed in atheromatous plaques and plays a crucial role in inflammation by modulating cell migration and matrix degradation. We hypothesise that uPAR is also increased in the circulating monocytes of patients with acute coronary syndrome (ACS) compared to patients with chronic stable angina (CSA) and may be a marker of clinical instability. Methods Consecutive angina patients were prospectively assessed including 195 with ACS [80 ST elevation myocardial infarction (STEMI), 66 with non-ST elevation myocardial infarction (NSTEMI), 49 with unstable angina (UA)] and 37 with CSA. The percentage of uPAR expressing monocytes (PUEM) and the mean fluorescence intensity (MFI) index of uPAR were measured using a flow cytometer. Results The PUEM (median and IQR) on admission was significantly higher in patients with ACS (49.53%, 22.69%–88.30%) than in patients with CSA (10.00%, 2.30%–19.47%, p<0.001). Within ACS subgroups, the PUEM was elevated to 40.27% (20.68%–58.30%) and 46.39% (14.25%–84.07%) in patients with UA and NSTEMI, respectively, and peaked at 64.32% (26.78%–93.18%) in patients with STEMI. PUEM was positively correlated with left main stem disease (p=0.04) and hs-CRP (p=0.003) in the whole patient group and was the only significant predictor of ACS (OR 8.11, 95% CI 2.81 to 23.43, p<0.001) together with hs-CRP (OR 3.55, 95% CI 1.35 to 9.38, p=0.01). Conclusions Increased uPAR in circulating monocytes has an independent significant association with ACS. These findings suggest that an increase of monocytic uPAR may be a marker of atheromatous plaque vulnerability.