Yun-Jiu Cheng

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.

Adiponectin is associated with increased mortality in patients with already established cardiovascular disease: A systematic review and meta-analysis

BACKGROUND The overall quantitative estimate on the possible association of adiponectin concentrations with mortality in patients with cardiovascular diseases (CVD) has not been reported. METHODS We performed a systematic review and meta-analysis of prospective studies to evaluate the overall quantitative estimates on the adiponectin levels for risk of mortality in patients with CVD. MEDLINE, EMBASE, CINAHL, and the Cochrane Library (up to Mar 22, 2014) were used to search for studies evaluating the effect of adiponectin levels on mortality in patients with CVD. Random-effect models were selected to estimate overall effect estimates. RESULTS Data from 14063 CVD patients enrolled in 15 prospective cohort and 1 nested case control studies were collated. The meta-analyses showed strong positive association of adiponectin with all-cause (n=14 studies, overall pooled effect estimate=1.45 [95% CI, 1.17-1.79]) and cardiovascular (n=11 studies, overall pooled effect estimate=1.69 [1.35-2.10]) mortality, for the highest tertile of adiponectin levels versus the lowest tertile. Subgroup analyses show study characteristics (including effect estimate, mean age, study location, sample sizes, gender, durations of follow-up, types of primary event, and acute or chronic CVD) did not substantially influence these positive associations. CONCLUSIONS Our results showed that increased baseline plasma adiponectin levels are significantly associated with elevated risk of all-cause and cardiovascular mortality in subjects with CVD. These positive associations may have been amplified by adjustment for potential intermediates or residual confounding, and their basis requires further investigation.

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.

Risk of Thromboembolic Events in Atrial Fibrillation With Chronic Kidney Disease

Background and Purpose— Chronic kidney disease may increase the risk for ischemic stroke or systemic embolism in patients with nonvalular atrial fibrillation (AF). We conducted a meta-analysis to summarize all published studies to investigate the link between chronic kidney disease and risk of thromboembolic events in AF. Methods— We performed a literature search using MEDLINE (source PubMed, 1966 to July, 2014) and EMBASE (1980 to July 2014) with no restrictions. Pooled effect estimates were obtained by using random-effects meta-analysis. Results— Eighteen studies involving 538 479 patients and 41 719 incident thromboembolic events were identified. From the pooled analysis, AF patients with estimated glomerular filtration rate <60 mL/min compared with those with estimated glomerular filtration rate ≥60 mL/min experienced a significantly increased risk for developing thromboembolic events (relative risk, 1.62 [95% confidence interval, 1.40–1.87; P<0.001]). The annual rate of thromboembolic events increased by 0.41% (95% confidence interval, 0.17%–0.65%) for a 10 mL/min decrease in renal function. Addition of renal impairment to CHADS2 slightly improved the stroke risk stratification. Conclusions— Impaired renal function is an independent predictor of stroke or systemic embolism in patients with nonvalvular AF. Consideration of renal function may improve stroke risk stratification in patients with AF.

Association between Adiponectin Concentrations and Cardiovascular Disease in Diabetic Patients: A Systematic Review and Meta-Analysis

Background This systematic review and meta-analysis of prospective studies evaluates the association between adiponectin concentrations and risk of cardiovascular disease (CVD) in individuals with diabetes mellitus (DM). Methods PubMed and Embase were searched for prospective studies on the association of adiponectin concentrations and risk of CVD up to June 2013. Random-effect model was selected to pool the relative risk (RR) and 95% CI. Results Five prospective cohort studies and one nested case-control studies met the included criterion. The estimated summary RR and 95% CI of five prospective cohort studies for type 2 diabetes comparing top vs low tertile of adiponectin concentrations was 0.99 (95% CI: 0.67–1.45), with significant heterogeneity between studies (p = 0.037, I 2 = 60.9%). This heterogeneity was explained by one study conducted in Korean. Conclusions This study represents the first meta-analysis between adiponectin levels and CVD in diabetic patients and indicated no association was found. This result should be verified further by large sample size, long duration of follow-up, and well-designed prospective clinical trials.

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.