Jinxiu Lin

Is cryoballoon ablation preferable to radiofrequency ablation for treatment of atrial fibrillation by pulmonary vein isolation? A meta-analysis.

Objective Currently radiofrequency and cryoballoon ablations are the two standard ablation systems used for catheter ablation of atrial fibrillation; however, there is no universal consensus on which ablation is the optimal choice. We therefore sought to undertake a meta-analysis with special emphases on comparing the efficacy and safety between cryoballoon and radiofrequency ablations by synthesizing published clinical trials. Methods and Results Articles were identified by searching the MEDLINE and EMBASE databases before September 2013, by reviewing the bibliographies of eligible reports, and by consulting with experts in this field. Data were extracted independently and in duplicate. There were respectively 469 and 635 patients referred for cryoballoon and radiofrequency ablations from 14 qualified clinical trials. Overall analyses indicated that cryoballoon ablation significantly reduced fluoroscopic time and total procedure time by a weighted mean of 14.13 (95% confidence interval [95% CI]: 2.82 to 25.45; P = 0.014) minutes and 29.65 (95% CI: 8.54 to 50.77; P = 0.006) minutes compared with radiofrequency ablation, respectively, whereas ablation time in cryoballoon ablation was nonsignificantly elongated by a weighted mean of 11.66 (95% CI: −10.71 to 34.04; P = 0.307) minutes. Patients referred for cryoballoon ablation had a high yet nonsignificant success rate of catheter ablation compared with cryoballoon ablation (odds ratio; 95% CI; P: 1.34; 0.53 to 3.36; 0.538), and cryoballoon ablation was also found to be associated with the relatively low risk of having recurrent atrial fibrillation (0.75; 0.3 to 1.88; 0.538) and major complications (0.46; 0.11 to 1.83; 0.269). There was strong evidence of heterogeneity and low probability of publication bias. Conclusion Our findings demonstrate greater improvement in fluoroscopic time and total procedure duration for atrial fibrillation patients referred for cryoballoon ablation than those for radiofrequency ablation.

The Association of Four Common Polymorphisms from Four Candidate Genes (COX-1, COX-2, ITGA2B, ITGA2) with Aspirin Insensitivity: A Meta-Analysis

Objective Evidence is mounting suggesting that a strong genetic component underlies aspirin insensitivity. To generate more information, we aimed to evaluate the association of four common polymorphisms (rs3842787, rs20417, rs201184269, rs1126643) from four candidate genes (COX-1, COX-2, ITGA2B, ITGA2) with aspirin insensitivity via a meta-analysis. Methods and Results In total, there were 4 (353/595), 6 (344/698), 10 (588/878) and 7 (209/676) articles (patients/controls) qualified for rs3842787, rs20417, rs20118426 and rs1126643, respectively. The data were extracted in duplicate and analyzed by STATA software (Version 11.2). The risk estimate was expressed as odds ratio (OR) and 95% confidence interval (95% CI). Analyses of the full data set indicated significant associations of rs20417 (OR; 95% CI; P: 1.86; 1.44–2.41; <0.0005) and rs1126643 (2.37; 1.44–3.89; 0.001) with aspirin insensitivity under allelic model. In subgroup analyses, the risk estimate for rs1126643 was greatly potentiated among patients with aspirin semi-resistance relative to those with aspirin resistance, especially under dominant model (aspirin semi-resistance: 5.44; 1.42–20.83; 0.013 versus aspirin resistance: 1.96; 1.07–3.6; 0.03). Further grouping articles by ethnicity observed a stronger prediction of all, but rs20417, examined polymorphisms for aspirin insensitivity in Chinese than in Caucasians. Finally, meta-regression analyses observed that the differences in percentage of coronary artery disease (P = 0.034) and averaged platelet numbers (P = 0.012) between two groups explained a large part of heterogeneity for rs20417 and rs1126643, respectively. Conclusion Our findings provide strong evidence that COX-2 and ITGA2 genetic defects might increase the risk of having aspirin insensitivity, especially for aspirin semi-resistance and in Chinese populations.

The relationship between five widely-evaluated variants in CDKN2A/B and CDKAL1 genes and the risk of type 2 diabetes: a meta-analysis.

The genes encoding two cyclin-dependent kinases-inhibitor-2A/B (CDKN2A/B) and 5 regulatory subunit-associated protein-like 1 (CDKAL1) have been investigated extensively in associations with type 2 diabetes; the results, however, are often irreproducible. We therefore sought to evaluate these associations by performing a meta-analysis on five widely-evaluated variants from the two genes. There were 38 studies (patients/controls: 51,940/52,234) for rs10811661, 16 studies (20,029/24,419) for rs564398 in CDKN2A/B gene, and 27 studies (28,383/47,635) for rs7756992, 26 studies (28,816/31,713) for rs7754840, 21 studies (29,260/38,400) for rs10946398 in CDKAL1 gene. Overall risk estimates for type 2 diabetes conferred by rs10811661-T, rs564398-A, rs7754840-C, rs7756992-G, and rs10946398-C alleles were 1.17 (95% CI: 1.10-1.23; P<0.0005; I(2)=83.9%), 1.1 (95% CI: 1.0-1.21; P=0.051; I(2)=88.3%), 1.24 (95% CI: 1.18-1.3; P<0.0005; I(2)=74.3%), 1.2 (95% CI: 1.11-1.3; P<0.0005; I(2)=92.0%), and 1.19 (95% CI: 1.1-1.29; P<0.0005; I(2)=90.8%), respectively. There was evident publication bias for rs564398 and rs7754840. Subgroup analyses by ethnicity showed remarkable divergences in risk estimate for rs564398 between Asians (odds ratio [OR]=1.01; 95% CI: 0.86-1.19; P=0.868) and Caucasians (OR=1.19; 95% CI: 1.03-1.35; P=0.012) (P<0.05). For all variants examined, the results of studies in retrospective design or with population-based controls were comparative with that of overall studies. In meta-regression analyses, age was found to exert a significant influence on the association between rs10811661 and type 2 diabetes (P=0.003), as well as between rs7754840 and gender (P=0.034). Taken together, our findings provide evidence for a significant contribution of CDKN2A/B gene rs10811661 and CDKAL1 gene rs7756992 and rs10946398 to type 2 diabetes.

Preoperative metabolic syndrome and prognosis after radical resection for colorectal cancer: The Fujian prospective investigation of cancer (FIESTA) study.

This prospective study sought to investigate the prediction of preoperative metabolic syndrome and its components for the risk of colorectal cancer (CRC) mortality by analyzing a subset of data from the ongoing Fujian prospective investigation of cancer (FIESTA) study. In total, 1,318 CRC patients who received radical resection were consecutively enrolled between January 2000 and December 2008. The median follow‐up time was 58.6 months, with 412 deaths from CRC. The CRC patients with metabolic syndrome had significantly shorter median survival time (MST) than those without (50.9 vs. 170.3 months, p < 0.001). Among four components of metabolic syndrome, hyperglycemia was the strongest predictor and its presence was associated with shorter MST than its absence (44.4 vs. 170.3 months, p < 0.001). Moreover, the complication of metabolic syndrome in CRC patients was associated with a 2.98‐fold increased risk of CRC mortality (hazard ratio [HR] = 2.98, 95% confidence interval [CI]: 2.40–3.69, p < 0.001) after adjusting for confounding factors. The magnitude of this association was especially potentiated in CRC patients with tumor‐node‐metastasis stage I/II (HR = 3.94, 95% CI: 2.65–5.85, p < 0.001), invasion depth T1/T2 (HR = 5.41, 95% CI: 2.54–11.50, p < 0.001), regional lymph node metastasis N0 (HR = 4.06, 95% CI: 2.85‐5.80, p < 0.001) and negative distant metastasis (HR = 3.23, 95% CI: 2.53–4.12, p < 0.001). Further survival tree analysis reinforced the prognostic capability of fasting blood glucose in CRC survival. Our findings convincingly demonstrated that preoperative metabolic syndrome, especially hyperglycemia, was a robust predictor for CRC mortality, and the protection was more obvious in patients with Stage I/II.

The impact of angiotensin receptor blockers on arterial stiffness: a meta-analysis

Some studies reported a protective role of angiotensin receptor blockers (ARBs) against arterial stiffness. Therefore, we performed a meta-analysis of published clinical trials to systematically assess the impact of ARBs on arterial stiffness as measured by using pulse wave velocity (PWV). Eligible articles were identified by searching PubMed, EMBASE, Cochrane, Wanfang and CNKI databanks before 31 July 2014. The data were extracted independently and in duplicate. Forty articles including 53 clinical trials qualified, including 1650 and 1659 subjects in ARB treatment and control groups, respectively. Overall reductions in carotid-femoral PWV (cfPWV) and brachial-ankle PWV (baPWV) were statistically significant, with an average of −42.52 cm s−1 (95% CI: −81.82 to −3.21; P=0.034) and −107.08 cm s−1 (95% CI: −133.98 to −80.18; P<0.0005), respectively, after receiving ARBs. Subgroup analysis by ARB type revealed that telmisartan (weighted mean difference or WMD=−100.82 cm s−1; P<0.0005) and valsartan (WMD=−104.59 cm s−1; P<0.0005) significantly reduced baPWV, but only valsartan reduced cfPWV (WMD=−65.58; P=0.030). cfPWV was significantly reduced in comparisons of ARBs with placebo (WMD=−79.65 cm s−1; P=0.001), and baPWV was significantly reduced with calcium channel blockers (WMD=−130.74 cm s−1; P<0.0005). There were low probabilities of publication bias. Taken together, our findings support the important role of ARB treatment in improving arterial stiffness.

Left Radial Access Is Preferable to Right Radial Access for the Diagnostic or Interventional Coronary Procedures: A Meta-Analysis Involving 22 Randomized Clinical Trials and 10287 Patients

Objective The transradial approach has been used extensively for both diagnostic and interventional coronary procedures; however, there is no universal consensus hitherto on the optimal choice of radial access from either the left or the right artery. We therefore sought to meta-analyze available randomized clinical trials to compare the left with the right radial access for the diagnostic or interventional coronary procedures. Methods and Results Four electronic databases including the PubMed, EMBASE, Wanfang, and CNKI were searched up to April 2013. In total, there were 22 qualified randomized trials involving 5317 and 4970 patients assigned to the left and the right radial accesses, respectively. Data were extracted independently by two investigators. Analyses of the full data set indicated significant reductions in fluoroscopy time (seconds) (weighted mean difference; 95% confidence interval; P: −36.18; −53.28 to −18.53; <0.0005) and contrast use (mL) (−2.88; −5.41 to −0.34; 0.026) in patients with the left radial access compared to those with the right radial access, and there was strong evidence of heterogeneity but low probability of publication bias. The failure rate of radial access from the left was relatively lower than that from the right (odds ratio: 0.83; 95% confidence interval: 0.68−1.01; P = 0.064). Further in meta-regression analyses, body mass index was found to be a potential source of heterogeneity for both fluoroscopy time (regression coefficient: 35.85; P = 0.025) and catheter number (regression coefficient: 0.35; P = 0.018). Conclusions Our findings demonstrate that left radial access is preferable to right radial access in terms of fluoroscopy time and contrast use for the diagnostic or interventional coronary procedures. The import of this study lies in its great shock to the concept of convenient radial access from the right artery.

Association of Four Genetic Polymorphisms of AGER and Its Circulating Forms with Coronary Artery Disease: A Meta-Analysis

Background Considerable efforts have been devoted to evaluating the association of the receptor for advanced glycation end-products (gene AGER and protein: RAGE) genetic variants to coronary artery disease (CAD); the results, however, are often irreproducible. To generate more information, we sought to explore four common polymorphisms of AGER and its circulating forms associated with the risk of CAD via a meta-analysis. Methodology/Principal Findings Articles were identified by searching PubMed, EMBASE, Wanfang and CNKI databases before March 2013. Qualified articles had case-control designs and investigated AGER four polymorphisms (T-429C, T-374A, Gly82Ser, G1704A) or circulating soluble RAGE (sRAGE) or endogenous secretory RAGE (esRAGE) levels associated with CAD. Twenty-seven articles involving 39 independent groups fulfilled the predefined criteria. Overall, no significance was observed for all examined polymorphisms under allelic and dominant models. When restricting groups to CAD patients with diabetes mellitus or renal disease, deviations of risk estimates from the unity were stronger than overall estimates for all polymorphisms except for G1704A due to limited available studies. For example, under dominant model, having -429C allele increased the odds of developing CAD in diabetic patients by 1.22-fold (95% confidence interval (95% CI) 0.99–1.51; P = 0.06; I 2 = 6.7%) compared with that of overall estimate of 1.15-fold (95% CI: 0.97–1.36; P = 0.111; I 2 = 18.0%). Circulating sRAGE levels were non-significantly lower in CAD patients than in controls, whereas this reduction was totally and significantly reversed in CAD patients with diabetes mellitus (weighted mean difference: 185.71 pg/ml; 95% CI: 106.82 to 264.61 pg/ml). Circulating esRAGE levels were remarkably lower in CAD patients, as well as in subgroups with or without diabetes mellitus and without renal disease. Conclusions Our findings demonstrated that association of AGER genetic polymorphisms with CAD was potentiated in patients with diabetes mellitus or renal disease. Practically, circulating esRAGE might be a powerful negative predictor for the development of CAD.

Impact of renin-angiotensin-aldosterone system-blocking agents on the risk of contrast-induced acute kidney injury: a prospective study and meta-analysis.

Objective: We sought to assess the impact of the pretreatment with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) for coronary intervention on the risk of contrast-induced acute kidney injury (CI-AKI) after 72-hour postcontrast administration, together with a comprehensive meta-analysis in this aspect. Methods and Results: In this prospective study, 401 patients referred for percutaneous coronary intervention were enrolled with 134 patients in non–renin-angiotensin-aldosterone system group, 204 patients in ACEIs group and 63 patients in ARBs group. For further meta-analysis, articles were identified through PubMed, EMBASE, Wanfang, and VIP. Data extraction and study quality were assessed in duplicate. Altogether, 14 qualified trials (including this prospective study) with 1960 patients taking ACEIs or ARBs and 1457 patients receiving no renin-angiotensin-aldosterone system blockers were analyzed. There was an overall 1.28-fold increased risk for CI-AKI in patients taking ACEIs or ARBs (odds ratio [OR] = 1.28; 95% confidence interval [CI], 0.79–2.09; P = 0.315). Overall changes in serum creatinine, estimated GFR, and blood urea nitrogen were also nonsignificant. Subgroup analyses identified a significantly increased risk for CI-AKI in patients taking ARBs (OR = 3.31; 95% CI, 1.89–5.78; P < 0.0005), and no significance was observed for patients taking ACEIs (OR = 0.86; 95% CI, 043–1.72; P = 0.664). Also, patients taking ARBs had serum creatinine markedly increased by 0.05 mg/dL (95% CI, 0.02–0.09; P = 0.005). Conclusions: The findings of this meta-analysis provide clear evidence for a deleterious impact of ARBs on the development of CI-AKI.

Preoperative Metabolic Syndrome Is Predictive of Significant Gastric Cancer Mortality after Gastrectomy: The Fujian Prospective Investigation of Cancer (FIESTA) Study

Metabolic syndrome (MetS) has been shown to be associated with an increased risk of gastric cancer. However, the impact of MetS on gastric cancer mortality remains largely unknown. Here, we prospectively examined the prediction of preoperative MetS for gastric cancer mortality by analyzing a subset of data from the ongoing Fujian prospective investigation of cancer (FIESTA) study. This study was conducted among 3012 patients with gastric cancer who received radical gastrectomy between 2000 and 2010. The latest follow-up was completed in 2015. Blood/tissue specimens, demographic and clinicopathologic characteristics were collected at baseline. During 15-year follow-up, 1331 of 3012 patients died of gastric cancer. The median survival time (MST) of patients with MetS was 31.3 months, which was significantly shorter than that of MetS-free patients (157.1 months). The coexistence of MetS before surgery was associated with a 2.3-fold increased risk for gastric cancer mortality (P < 0.001). The multivariate-adjusted hazard ratios (HRs) were increased with invasion depth T1/T2 (HR = 2.78, P < 0.001), regional lymph node metastasis N0 (HR = 2.65, P < 0.001), positive distant metastasis (HR = 2.53, P < 0.001), TNM stage I/II (HR = 3.00, P < 0.001), intestinal type (HR = 2.96, P < 0.001), negative tumor embolus (HR = 2.34, P < 0.001), and tumor size ≤ 4.5 cm (HR = 2.49, P < 0.001). Further survival tree analysis confirmed the top splitting role of TNM stage, followed by MetS or hyperglycemia with remarkable discrimination ability. In this large cohort study, preoperative MetS, especially hyperglycemia, was predictive of significant gastric cancer mortality in patients with radical gastrectomy, especially for early stage of gastric cancer.

The elevated preoperative fasting blood glucose predicts a poor prognosis in patients with esophageal squamous cell carcinoma: The Fujian prospective investigation of cancer (FIESTA) study

Diabetes as a latent risk factor for cancer has been extensively investigated, while its postoperative prognosis for esophageal cancer is rarely reported. We therefore sought to assess whether the elevated fasting blood glucose before surgery was associated with poor survival in esophageal cancer patients by eliciting a subset of data from the ongoing Fujian prospective investigation of cancer (FIESTA) study. Over 15-year follow-up, 2535 patients receiving three-field lymphadenectomy were assessable. Only patients with esophageal squamous cell carcinoma (ESCC) (n=2396) were analyzed due to the lower prevalence of the other histological types. In ESCC patients, the follow-up duration ranged from 0.5 to 180 months (median 38.2 months). The median survival time (MST) was remarkably shorter in males than in females (80.7 vs. 180+ months, Log-rank test: P<0.001). In males, the survival was worse in patients with diabetes than those without (MST: 27.9 vs. 111.1 months, Log-rank test: P<0.001). In females, the survivor was improved in patients with diabetes (MST: 71.5 months), but was still worse than patients without diabetes (MST: 180+ months, Log-rank test: P<0.001). The overall multivariate hazard ratio for per unit increment in fasting blood glucose was 1.11 (95% confidence interval or CI: 1.09-1.14, P<0.001) and 1.08 (95% CI: 1.03-1.13, P=0.002) in males and females, respectively. Further survival tree analysis consolidated the discrimination ability of fasting blood glucose for the survival of ESCC patients. Taken together, our findings convincingly demonstrated that the elevated preoperative fasting blood glucose can predict poor survival of ESCC patients, especially in males.