Xiao-Xiong Lin

Early Repolarization Pattern and Risk for Arrhythmia Death: A Meta-Analysis

OBJECTIVES A meta-analysis was performed to determine the risk and incidence rate of arrhythmia death, cardiac death, and all-cause death in the general population with the early repolarization pattern (ERP). BACKGROUND The ERP has recently been associated with vulnerability to ventricular fibrillation in case-control studies. However, the prognostic significance of the ERP in the general population is controversial. METHODS Relevant studies published through July 31, 2012, were searched and identified in the MEDLINE and Embase databases. Studies that reported risk ratio estimates with 95% confidence intervals (CIs) for the associations of interest were included. Data were extracted, and summary estimates of association were obtained using a random-effects model. RESULTS Of the 9 studies included, 3 studies reported on arrhythmia death (31,981 subjects, 1,108 incident cases during 726,741 person-years of follow-up), 6 studies reported on cardiac death (126,583 subjects, 10,010 incident cases during 2,054,674 person-years of follow-up), and 6 studies reported on all-cause death (112,443 subjects, 22,165 incident cases during 2,089,535 person-years of follow-up). The risk ratios of the ERP were 1.70 (95% CI: 1.19 to 2.42; p = 0.003) for arrhythmia death, 0.78 (95% CI: 0.27 to 2.25; p = 0.63) for cardiac death, and 1.06 (95% CI: 0.87 to 1.28; p = 0.57) for all-cause death. The estimated absolute risk differences of subjects with the ERP were 70 cases of arrhythmia death per 100,000 subjects per year. J-point elevation ≥ 0.1 mV in the inferior leads and notching configuration had an increased risk for arrhythmia death in subgroup studies. CONCLUSIONS The ERP was associated with increased risk and a low to intermediate absolute incidence rate of arrhythmia death. Further study is needed to clarify which subgroups of subjects with the ERP are at higher risk for arrhythmia death.

The Role of Macrolide Antibiotics in Increasing Cardiovascular Risk

BACKGROUND Large cohort studies provide conflicting evidence regarding the potential for oral macrolide antibiotics to increase the risk of serious cardiac events. OBJECTIVES This study performed a meta-analysis to examine the link between macrolides and risk of sudden cardiac death (SCD) or ventricular tachyarrhythmias (VTA), cardiovascular death, and death from any cause. METHODS We performed a search of published reports by using MEDLINE (January 1, 1966, to April 30, 2015) and EMBASE (January 1, 1980, to April 30, 2015) with no restrictions. Studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) for the associations of interest were included. RESULTS Thirty-three studies involving 20,779,963 participants were identified. Patients taking macrolides, compared with those who took no macrolides, experienced an increased risk of developing SCD or VTA (RR: 2.42; 95% CI: 1.61 to 3.63), SCD (RR: 2.52; 95% CI: 1.91 to 3.31), and cardiovascular death (RR: 1.31; 95% CI: 1.06 to 1.62). No association was found between macrolides use and all-cause death or any cardiovascular events. The RRs associated with SCD or VTA were 3.40 for azithromycin, 2.16 for clarithromycin, and 3.61 for erythromycin, respectively. RRs for cardiovascular death were 1.54 for azithromycin and 1.48 for clarithromycin. No association was noted between roxithromycin and adverse cardiac outcomes. Treatment with macrolides is associated with an absolute risk increase of 118.1 additional SCDs or VTA, and 38.2 additional cardiovascular deaths per 1 million treatment courses. CONCLUSIONS Administration of macrolide antibiotics is associated with increased risk for SCD or VTA and cardiovascular death but not increased all-cause mortality.

More Favorable Response to Cardiac Resynchronization Therapy in Women Than in Men

Background—Data on sex difference in response to cardiac resynchronization therapy (CRT) remain controversial. We conducted a meta-analysis to summarize all published studies to determine whether sex-based differences in response to CRT exist. Methods and Results—We performed a literature search using MEDLINE (source PubMed; January 1966 to March 2014) and EMBASE (January 1980 to March 2014) with no restrictions. Pooled effect estimates were obtained by using random-effects meta-analysis. Seventy-two studies involving 33 434 patients were identified. Overall, female patients had better outcomes from CRT compared with male patients, with a significant 33% reduction in the risk of death from any cause (hazard ratio, 0.67; 95% confidence interval, 0.61–0.74; P<0.001), 20% reduction in death or hospitalization for heart failure (hazard ratio, 0.80; 95% confidence interval, 0.71–0.90; P<0.001), 41% reduction in cardiac death (hazard ratio, 0.59; 95% confidence interval, 0.42–0.84; P<0.001), and 41% reduction in ventricular arrhythmias or sudden cardiac death (hazard ratio, 0.59; 95% confidence interval, 0.49–0.70; P<0.001). These more favorable responses to CRT in women were consistently associated with greater echocardiographic evidence of reverse cardiac remodeling in women than in men. Conclusions—Women obtained greater reductions in the risk of death from any cause, cardiac cause, death or hospitalization for heart failure, and ventricular arrhythmias or sudden cardiac death with CRT therapy compared with men, with consistently greater echocardiographic evidence of reverse cardiac remodeling in women than in men. Further studies are needed to investigate the exact reasons for these results and determine whether indications for CRT in women should be different from men.

Long‐Term Cardiovascular Risk After Radiotherapy in Women With Breast Cancer

Background Radiotherapy for breast cancer often involves some incidental exposure of the heart to ionizing radiation. The effect of this exposure on the subsequent risk of heart disease is uncertain. We performed a meta‐analysis to investigate the link between radiotherapy and long‐term cardiovascular morbidity and mortality in patients with breast cancer. Methods and Results We performed a literature search using MEDLINE (January 1966 to January 2015) and EMBASE (January 1980 to January 2015) with no restrictions. Studies that reported relative risk (RR) estimates with 95%CIs for the associations of interest were included. Pooled effect estimates were obtained by using random‐effects meta‐analysis. Thirty‐nine studies involving 1 191 371 participants were identified. Patients who received left‐sided radiotherapy, as compared with those receiving right‐sided radiotherapy, experienced increased risks of developing coronary heart disease (RR 1.29, 95%CI 1.13‐1.48), cardiac death (RR 1.22, 95%CI 1.08‐1.37) and death from any cause (RR 1.05, 95%CI 1.01‐1.10). In a comparison of patients with radiotherapy and without radiotherapy, the RRs were 1.30 (95%CI 1.13‐1.49) for coronary heart disease and 1.38 (95%CI 1.18‐1.62) for cardiac mortality. Radiotherapy for breast cancer was associated with an absolute risk increase of 76.4 (95%CI 36.8‐130.5) cases of coronary heart disease and 125.5 (95%CI 98.8‐157.9) cases of cardiac death per 100 000 person‐years. The risk started to increase within the first decade for coronary heart disease and from the second decade for cardiac mortality. Conclusions Exposure of the heart to ionizing radiation during radiotherapy for breast cancer increases the subsequent risk of coronary heart disease and cardiac mortality.

Role of Early Repolarization Pattern in Increasing Risk of Death

Background An early repolarization pattern (ERP) has been hypothesized to be arrhythmogenic in experimental studies, but the prognostic significance of the ERP in the general population is controversial. We performed a meta‐analysis to examine the link between ERP and the risk of sudden cardiac arrest (SCA), cardiac death, and death from any cause. Methods and Results We performed a literature search using MEDLINE (January 1, 1966 to July 31, 2015) and EMBASE (January 1, 1980 to July 31, 2015) with no restrictions. Studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) for the associations of interest were included. Sixteen studies involving 334 524 subjects were identified. Compared with those without ERP, subjects with ERP experienced significantly increased risk for developing SCA (RR 2.18; 95% CI 1.29–3.68), cardiac death (RR 1.48; 95% CI 1.06–2.07), and death from any cause (RR 1.21; 95% CI 1.02–1.42), respectively. The increased risk was present predominantly in Asians and whites but not in African Americans. ERP with J‐point elevation in inferior leads, notching configuration, and horizontal or descending ST segment connote higher risk. ERP was associated with an absolute risk increase of 139.6 (95% CI 130.3–149.3) additional SCAs per 100 000 person‐years and responsible for 7.3% (95% CI 1.9–15.2) of SCA in the general population. Conclusions ERP is associated with significant increased risk for SCA, cardiac death, and death from any cause. Future studies should focus on understanding the exact mechanisms for the arrhythmia risk and developing reliable tools for risk stratification.

Astragalus Polysaccharides Lowers Plasma Cholesterol through Mechanisms Distinct from Statins

To determine the efficacy and underlying mechanism of Astragalus polysaccharides (APS) on plasma lipids in hypercholesterolemia hamsters. The effect of APS (0.25g/kg/d) on plasma and liver lipids, fecal bile acids and neutral sterol, cholesterol absorption and synthesis, HMG-CoA reductase activity, and gene and protein expressions in the liver and small intestine was investigated in twenty-four hypercholesterolemia hamsters. Treatment periods lasted for three months. APS significantly lowered plasma total cholesterol by 45.8%, triglycerides by 30%, and low-density lipoprotein-cholesterol by 47.4%, comparable to simvastatin. Further examinations revealed that APS reduced total cholesterol and triglycerides in the liver, increased fecal bile acid and neutral sterol excretion, inhibited cholesterol absorption, and by contrast, increased hepatic cholesterol synthesis and HMG-CoA reductase activity. Plasma total cholesterol or low-density lipoprotein-cholesterol levels were significantly correlated with cholesterol absorption rates. APS up-regulated cholesterol-7α-hydroxylase and LDL-receptor gene expressions. These new findings identify APS as a potential natural cholesterol lowering agent, working through mechanisms distinct from statins.

B-Type Natriuretic Peptide and Prognosis of End-Stage Renal Disease: A Meta-Analysis

Background The prognostic importance of B-type natriuretic peptide (BNP) or N-terminal pro BNP (NT-proBNP) in patients with end-stage renal disease (ESRD) remains controversial. Methodology/Principal Findings We conducted an unrestricted search from the MEDLINE and EMBASE in all languages that were published between 1966 and Augest2013. Twenty-seven long-term prospective studies met our inclusion criterias. From the pooled analysis, elevated BNP/NT-proBNP was significantly associated with increased all cause mortality [odds ratio (OR), 3.85; 95% CI, 3.11 to 4.75], cardiovascular mortality (OR, 4.05; 95% CI, 2.53 to 6.84), and cardiovascular events (OR, 7.02; 95% CI, 2.21 to 22.33). The funnel plot showed no evidence of publication bias. The corresponding pooled positive and negative likelihood ratio for prediction of all cause mortality were 1.86 (95% CI, 1.66 to 2.08) and 0.48 (95% CI, 0.42 to 0.55), respectively. Conclusions/Significance BNP/NT-proBNP is a promising prognostic tool to risk-stratify the patients with ESRD. Further investigations are warranted to elucidate the specific pathogenic mechanisms and the impact of other potential prognostic factors.

Early diagnostic and prognostic utility of high‐sensitive troponin assays in acute myocardial infarction: a meta‐analysis

To determine the diagnostic and prognostic utility of high‐sensitive troponin assays in the very early phase of acute myocardial infarction (AMI) (less than 3 h since symptoms onset) by performing a meta‐analysis of prospective studies.

Effects of Nardostachys chinensis on spontaneous ventricular arrhythmias in rats with acute myocardial infarction.

Objectives: To investigate the effects and mechanisms of Nardostachys chinensis (NC) on spontaneous ventricular arrhythmias in rats with hyper-acute myocardial infarction (AMI). Methods: Seventy-two rats were randomly divided into the control group (n = 24), metoprolol group (n = 24), and the NC group (n = 24). Premature ventricular contractions (PVCs), ventricular tachycardias (VTs), ventricular fibrillations (VFs), and blood pressure were monitored for 4 hours after coronary artery ligation. The connexin 43 (Cx43) expression in ventricular myocardium was measured by immunohistochemistry, Western blot, and real-time RT-PCR. Results: Compared with the control, metoprolol and NC decreased the VF incidence (50% vs. 4.2%, P < 0.001, and 50% vs. 12.5%, P = 0.005, respectively). There was a steady decrease in the cumulative number of PVCs and VTs within 4 hours from ligating in 3 groups. Compared with the control, metoprolol and NC reduced the cumulative number of VTs and PVCs. Compared with control, metoprolol and NC decreased the infarct size of the left ventricular tissue (55.98% ± 6.20% vs. 39.13% ± 4.53%, P < 0.001, and 55.98% ± 6.20% vs. 42.39% ± 3.44%, P < 0.001, respectively). The results from immunohistochemistry, Western blot, and real-time RT-PCR showed that the protein expression of Cx43 in the control group was significantly lower than that in the metoprolol and NC groups in the infarcted zone. Conclusions: NC decreased the incidence of spontaneous ventricular arrhythmias (especially VF), reduced Cx43 degradation, and improved Cx43 redistribution in myocardial infarcted zone in rats with hyper-AMI. The data of the present study indicated that NC may be a promising drug in the future to prevent patients with AMI from lethal ventricular arrhythmias in prehospital setting.

Cardiac troponin and C-reactive protein for predicting all-cause and cardiovascular mortality in patients with chronic kidney disease: A meta-analysis

Elevated serum levels of cardiac troponin and C-reactive protein are associated with all-cause and cardiovascular mortality in patients with end-stage renal disease. However, the relationship between these two biomarker levels and mortality in patients with chronic kidney disease remains unclear. We conducted a meta-analysis to quantify the association of cardiac troponin and C-reactive protein levels with all-cause and cardiovascular mortality in patients with chronic kidney disease. Relevant studies were identified by searching the MEDLINE database through November 2013. Studies were included in the meta-analysis if they reported the long-term all-cause or cardiovascular mortality of chronic kidney disease patients with abnormally elevated serum levels of cardiac troponin or C-reactive protein. Summary estimates of association were obtained using a random-effects model. Thirty-two studies met our inclusion criteria. From the pooled analysis, cardiac troponin and C-reactive protein were significantly associated with all-cause (HR 2.93, 95% CI 1.97-4.33 and HR 1.21, 95% CI 1.14-1.29, respectively) and cardiovascular (HR 3.27, 95% CI 1.67-6.41 and HR 1.19, 95% CI 1.10-1.28, respectively) mortality. In the subgroup analysis of cardiac troponin and C-reactive protein, significant heterogeneities were found among the subgroups of population for renal replacement therapy and for the proportion of smokers and the C-reactive protein analysis method. Elevated serum levels of cardiac troponin and C-reactive protein are significant associated with higher risks of all-cause and cardiovascular mortality in patients with chronic kidney disease. Further studies are warranted to explore the risk stratification in chronic kidney disease patients.