Gastroesophageal Reflux Disease and Atrial Fibrillation: A Nationwide Population-Based Study

Objectives

Precise mechanisms of atrial fibrillation (AF) are uncertain, but their association with esophageal disorders has been recently proposed. The association between gastroesophageal reflux disease (GERD), the most common gastroesophageal disorder, and AF remains undetermined. We therefore aimed to investigate the association between GERD and later development of AF.

Methods and Results

Patients with GERD were identified from the 1,000,000-person cohort dataset sampled from the Taiwan National Health Insurance database. The study cohort comprised 29,688 newly diagnosed adult GERD patients; 29,597 randomly selected age-, gender-, comobidity-matched subjects comprised the comparison cohort. Cox proportional hazard regressions were performed as a means of comparing the AF-free survival rate for the two cohorts. During a maximum three years of follow-up, a total of 351 patients experienced AF, including 184 (0.62%) patients in the GERD cohort and 167 (0.56%) in the control group. The log-rank test showed that patients with GERD had significantly higher incidence of AF than those without GERD (p = 0.024). After Cox proportional hazard regression model analysis, GERD was independently associated with the increased risk of AF (hazard ratio, 1.31; 95% confidence interval, 1.06–1.61, p = 0.013).

Conclusion

GERD was independently associated with an increased risk of future AF in a nationwide population-based cohort.     

Vascular Disease and Risk Stratification for Ischemic Stroke and All-Cause Death in Heart Failure Patients without Diagnosed Atrial Fibrillation: A Nationwide Cohort Study

Background

Stroke and mortality risk among heart failure patients previously diagnosed with different manifestations of vascular disease is poorly described. We conducted an observational study to evaluate the stroke and mortality risk among heart failure patients without diagnosed atrial fibrillation and with peripheral artery disease (PAD) or prior myocardial infarction (MI).

Methods

Population-based cohort study of patients diagnosed with incident heart failure during 2000–2012 and without atrial fibrillation, identified by record linkage between nationwide registries in Denmark. Hazard rate ratios of ischemic stroke and all-cause death after 1 year of follow-up were used to compare patients with either: a PAD diagnosis; a prior MI diagnosis; or no vascular disease.

Results

39,357 heart failure patients were included. When compared to heart failure patients with no vascular disease, PAD was associated with a higher 1-year rate of ischemic stroke (adjusted hazard rate ratio [HR]: 1.34, 95% confidence interval [CI]: 1.08–1.65) and all-cause death (adjusted HR: 1.47, 95% CI: 1.35–1.59), whereas prior MI was not (adjusted HR: 1.00, 95% CI: 0.86–1.15 and 0.94, 95% CI: 0.89–1.00, for ischemic stroke and all-cause death, respectively). When comparing patients with PAD to patients with prior MI, PAD was associated with a higher rate of both outcomes.

Conclusions

Among incident heart failure patients without diagnosed atrial fibrillation, a previous diagnosis of PAD was associated with a significantly higher rate of the ischemic stroke and all-cause death compared to patients with no vascular disease or prior MI. Prevention strategies may be particularly relevant among HF patients with PAD.     

Risk of Ischemic Stroke after Intracranial Hemorrhage in Patients with Atrial Fibrillation

Background

We aimed to estimate the risk of ischemic stroke after intracranial hemorrhage in patients with atrial fibrillation.

Materials and Methods

Using discharge data from all nonfederal acute care hospitals and emergency departments in California, Florida, and New York from 2005 to 2012, we identified patients at the time of a first-recorded encounter with a diagnosis of atrial fibrillation. Ischemic stroke and intracranial hemorrhage were identified using validated diagnosis codes. Kaplan-Meier survival statistics and Cox proportional hazard analyses were used to evaluate cumulative rates of ischemic stroke and the relationship between incident intracranial hemorrhage and subsequent stroke.

Results

Among 2,084,735 patients with atrial fibrillation, 50,468 (2.4%) developed intracranial hemorrhage and 89,594 (4.3%) developed ischemic stroke during a mean follow-up period of 3.2 years. The 1-year cumulative rate of stroke was 8.1% (95% CI, 7.5–8.7%) after intracerebral hemorrhage, 3.9% (95% CI, 3.5–4.3%) after subdural hemorrhage, and 2.0% (95% CI, 2.0–2.1%) in those without intracranial hemorrhage. After adjustment for the CHA₂DS₂-VASc score, stroke risk was elevated after both intracerebral hemorrhage (hazard ratio [HR], 2.8; 95% CI, 2.6–2.9) and subdural hemorrhage (HR, 1.6; 95% CI, 1.5–1.7). Cumulative 1-year rates of stroke ranged from 0.9% in those with subdural hemorrhage and a CHA₂DS₂-VASc score of 0, to 33.3% in those with intracerebral hemorrhage and a CHA₂DS₂-VASc score of 9.

Conclusions

In a large, heterogeneous cohort, patients with atrial fibrillation faced a substantially heightened risk of ischemic stroke after intracranial hemorrhage. The risk was most marked in those with intracerebral hemorrhage and high CHA₂DS₂-VASc scores.     

Omentin-1 and Nonfatal Ischemic Heart Disease in Postmenopausal Women: A Population-Based Study

Objective: There is growing evidence that supports the existence of a link between lower levels of circulating omentin-1 and the pathogenesis of coronary atherosclerosis. However, no population-based study has been performed to elucidate the cardioprotective role of this beneficial adipocytokine.Methods: A total of 378 healthy, postmenopausal women were randomly selected from 13 clusters in the port city of Bushehr, Iran. The prevalence of nonfatal ischemic heart disease (IHD) was assessed using the Minnesota code with a 12-lead resting electrocardiogram (EKG). EKG with evidence of IHD (IHD-EKG) was defined as myocardial infarction (codes 1.1 and 1.2) and ischemia (codes 1.3, 4.1 to 4.4, 5.1 to 5.3, and 7.1) occurring together. Serum omentin-1 and adiponectin levels were measured using enzyme-linked immunosorbent assay methods.Results: The prevalence of IHD-EKG among the studied population was 41.8% (159 women). Serum levels of omentin-1 were significantly lower in women with ischemic EKG than in normal subjects (geometric mean ×/multiplicative standard deviation, 10.31 ×/2.35 ng/mL versus 12.44 ×/2.12 ng/mL, respectively; P = .038). Multiple logistic regression analysis indicated that higher serum levels of omentin-1 were significantly associated with a lower prevalence of ischemic EKG after adjusting for potential confounders, including classical cardiovascular risk factors and circulating adiponectin levels (odds ratio, 0.48; confidence interval, 0.24 to 0.95; P = .038).Conclusion: A higher level of circulating omentin-1 is independently associated with a lower prevalence of nonfatal IHD in postmenopausal women. The cardioprotective role of this novel adipocytokine needs to be further elucidated in large-scale longitudinal studies.Abbreviations:BMI = body mass indexEKG = electrocardiogramELISA = enzyme-linked immunosorbent assayHDL = high-density lipoproteinIHD = ischemic heart diseaseLDL = low-density lipoprotein     

Multiscale Entropy of the Heart Rate Variability for the Prediction of an Ischemic Stroke in Patients with Permanent Atrial Fibrillation

Background

Atrial fibrillation (AF) is a significant risk factor for ischemic strokes, and making a robust risk stratification scheme would be important. Few studies have examined whether nonlinear dynamics of the heart rate could predict ischemic strokes in AF. We examined whether a novel complexity measurement of the heart rate variability called multiscale entropy (MSE) was a useful risk stratification measure of ischemic strokes in patients with permanent AF.

Methods and Results

We examined 173 consecutive patients (age 69±11 years) with permanent AF who underwent 24-hour Holter electrocardiography from April 2005 to December 2006. We assessed several frequency ranges of the MSE and CHA₂DS₂-VASc score (1 point for congestive heart failure, hypertension, diabetes, vascular disease, an age 65 to 74 years, and a female sex and 2 points for an age≥75 years and a stroke or transient ischemic attack). We found 22 (13%) incident ischemic strokes during a mean follow up of 3.8-years. The average value of the MSE in the very-low frequency subrange (90–300 s, MeanEn_VLF2) was significantly higher in patients who developed ischemic strokes than in those who did not (0.68±0.15 vs. 0.60±0.14, P<0.01). There was no significant difference in the C-statistic between the CHA₂DS₂-VASc score and MeanEn_VLF2 (0.56; 95% confidence interval, 0.43–0.69 vs. 0.66; 95% confidence interval, 0.53–0.79). After an adjustment for the age, CHA₂DS₂-VASc score, and antithrombotic agent, a Cox hazard regression model revealed that the MeanEn_VLF2 was an independent predictor of an ischemic stroke (hazard ratio per 1-SD increment, 1.80; 95% confidence interval, 1.17–2.07, P<0.01).

Conclusion

The MeanEn_VLF2 in 24-hour Holter electrocardiography is a useful risk stratification measure of ischemic strokes during the long-term follow-up in patients with permanent AF.     

Significantly Increased Risk of Cardiovascular Disease among Patients with Gallstone Disease: A Population-Based Cohort Study

Objective

To investigate whether gallstone disease (GD) increases the risk of developing cardiovascular disease (CVD) in a large population-based cohort.

Methods

A study population including 6,981 patients with GD was identified from The Taiwan National Health Insurance Research Database between 2004 and 2005. GD patients were defined as patients with principal discharge diagnoses of cholelithiasis using the ICD-9-CM code 574. 27,924 patients without GD were randomly selected and matched for age and gender. All patients were followed for 6 years or until diagnosis for CVD. Cox proportional hazards regression model was used to assess the risk of developing CVD with adjustment for age, gender and co-morbid conditions.

Results

During the six years follow-up period, 935 patients with GD and 2,758 patients without GD developed CVD. Patients with GD had an elevated risk of CVD (HR, 1.32; 95% CI, 1.22-1.43) when compared with those without GD. Similar relationship was observed when CVD was categorized i.e. stroke (HR, 1.15; 95% CI, 1.01-1.32), coronary heart disease (HR, 1.42; 95% CI, 1.28-1.58) and heart failure (HR, 1.31; 95% CI, 1.00-1.73). When GD was classified according to the level of severity, using patients without GD as reference, the risks of CVD were elevated in patients with non-severe GD (HR, 1.34; 95% CI, 1.24-1.46) as well as those with severe GD (HR, 1.20, 95% CI, 1.02-1.40), after adjusting for age, gender and comorbidities. In age-stratified analysis, patients aged 18-40 years with GD were at higher risk of developing CVD (HR, 1.42; 95% CI, 1.09-1.84) than older GD patients.

Conclusion

This study found an increased risk of CVD in patients diagnosed with GD. The excess risk was particularly high in younger GD patients. Prevention of GD could help reduce the risk of developing CVD, and the better effect could be achieved for the younger age groups.     

老年高血压合并高脂血症并发缺血性心脏病患者的相关危险因素分析

摘要目的：探究老年高血压合并高脂血症并发缺血性心脏病患者的相关危险因素。方法：对我院2008年5月一2011年11月收治的老年高血压患者进行回顾分析,将合并高脂血症及缺血性心脏病患者纳入观察组,其余患者纳入对照组,对年龄、家族史等临床资料进行危险因素回归分析,总结其相关危险因素。结果：单因素分析发现,年龄、家族史、肥胖、糖尿病等9项因素存在统计学差异,将其纳入多因素COX模型分析,发现年龄、吸烟史、高甘油三酯血症、高胆固醇血症、高水平C反应蛋白及高尿酸血症是影响老年高血压合并高脂血症并发缺血性心脏病的独立危险因素。结论：年龄、吸烟史、高甘油三酯血症、高胆固醇血症、高水平C反应蛋白及高尿酸血症是影响老年高血压合并高脂血症并发缺血性心脏病的独立危险因素,对于存在危险因素的患者应及时进行早期干预,防止严重并发疾病的出现。     

Increased Risk of Ischemic Stroke in Young Patients with Ankylosing Spondylitis: A Population-Based Longitudinal Follow-Up Study

Background

Prospective data on the association between ischemic stroke and ankylosing spondylitis (AS) in the young are sparse. The purpose of this population-based, age- and sex-matched longitudinal follow-up study was to investigate the risk of developing ischemic stroke in young patients with AS.

Methods

A total of 4562 patients aged 18- to 45-year-old with at least two ambulatory visits in 2001 with a principal diagnosis of AS were enrolled in the AS group. The non-AS group consisted of 22810 age- and sex-matched, randomly sampled subjects without AS. The two-year ischemic stroke-free survival rate for each group were calculated using the Kaplan-Meier method. Cox proportional hazards regression analysis was used to estimate the hazard ratio of ischemic stroke after adjusting for demographic and clinical covariates.

Results

During follow-up, 21 patients in the AS group and 53 in the non-AS group developed ischemic stroke. The ischemic stroke-free survival rate over the 2 year follow-up was lower in the AS group than the non-AS group (p = 0.0021). The crude hazard ratio of ischemic stroke for the AS group was 1.98 (95% CI, 1.20–3.29; p = 0.0079) and the adjusted hazard ratio after controlling for demographic and comorbid medical disorders was 1.93 (95% CI, 1.16–3.20; p = 0.0110).

Conclusion

Our study showed an increased risk of developing ischemic stroke in young patients with AS.     

beta受体阻断药在心力衰竭合并房颤治疗中的再评价

β肾上腺素受体阻断药被认定为心力衰竭治疗领域的里程碑,在心力衰竭指南中,β肾上腺素受体阻断药为IA类推荐。但针对慢性心力衰竭的经典、大型RCT临床试验中,房颤患者所占比率不高。新近对于心力衰竭合并房颤患者应用β肾上腺素受体阻断剂的死亡率和住院率进行Meta-分析示:β肾上腺素受体拮抗剂未见有更多临床获益(即死亡率和住院率减低水平无统计学意义)。本文就心力衰竭定义、心力衰竭时交感神经系统激活、作用于交感神经系统的β肾上腺素受体阻断药药理作用及分类、β肾上腺素受体阻断药在心力衰竭并发房颤治疗中应用地位、心力衰竭并发房颤患者应用β肾上腺素受体阻断药存在的争议及其原因分析进行简要综述。     

Analysis of Bipolar Radiofrequency Ablation in Treatment of Atrial Fibrillation Associated with Rheumatic Heart Disease

Background

Among patients with rheumatic heart disease (RHD), 45% to 60% present with atrial fibrillation (AF), which is associated with increased rates of thromboembolism, heart failure, and even death. The bipolar radiofrequency ablation (BRFA) combining with mitral valve procedure has been adopted in patients of AF associated with RHD, but evaluations about its effectiveness are still limited.

Methods

A total of 87 patients with RHD and long persistent AF who had accepted mitral valve replacement concomitant with BRFA were studied. Clinical data were collected to analyze the midterm results of BRFA and evaluate its efficiency. Univariate and multivariate analyses were used to identify the independent factors associated with late AF recurrence.

Results

Sixty-six (75.9%) patients maintained sinus rhythm after a mean follow-up of 13.4 ± 5.2 months. Late AF recurrence had been detected in 21 (24.1%) patients, 11 (12.6%) patients were confirmed to be AF, 8 (9.2%) patients were atrial flutter and 2 (2.3%) patients were junctional rhythm. In Multivariate logistic regression analysis, body mass index (BMI) (OR = 1.756, 95% CI = 1.289–2.391, p = 0.000) and early AF recurrence (OR = 5.479, 95% CI = 1.189–25.254, p = 0.029) were independent predictors of late AF recurrence. In addition, left ventricular ejection fraction (LVEF) and New York Heart Association class showed a greater improvement in patients who maintained sinus rhythm than those who experienced late AF recurrence.

Conclusion

BRFA is an effective technique for the treatment of long persistent AF associated with RHD during mitral valve replacement. The BMI and early AF recurrence are independent predictors for late AF recurrence. Patients with long-term restoration of sinus rhythm experienced a greater improvement of left ventricular function after BRFA.     

A Population-Based Cohort Study on Peripheral Arterial Disease in Patients with Schizophrenia

Purpose

Peripheral arterial disease (PAD) is considered the leading cause of atherosclerotic cardiovascular morbidity. Several risk factors of PAD have been observed in patients with schizophrenia. Therefore, we hypothesize that the incidence of PAD is higher in the schizophrenia population than in the general population.

Methods

The patients in this population-based cohort study were selected from the Taiwanese National Health Insurance Research Database on the basis of the claims data from 2000 to 2011. We compared the incidence of PAD between schizophrenia and nonschizophrenia cohorts. Cox proportional hazard regression models were employed for analyzing the risk of PAD after adjustment for sex, age, and comorbidities.

Results

The adjusted hazard ratio (HR) for PAD in the schizophrenia cohort was 1.26-fold higher than that in the nonschizophrenia cohort. Furthermore, patients with schizophrenia using atypical antipsychotics exhibited a high adjusted HR for PAD.

Conclusion

Compared with the general population, the risk of PAD is higher among patients with schizophrenia. Early diagnosis and intervention can mitigate complications resulting from cardiovascular diseases and lower mortality.     

Protein Analysis of Atrial Fibrosis via Label-Free Proteomics in Chronic Atrial Fibrillation Patients with Mitral Valve Disease

Background

Atrial fibrosis, as a hallmark of atrial structure remodeling, plays an important role in maintenance of chronic atrial fibrillation, but interrelationship of atrial fibrosis and atrial fibrillation is uncertain. Label-free proteomics can implement high throughput screening for finding and analyzing pivotal proteins related to the disease.. Therefore, we used label-free proteomics to explore and analyze differentially proteins in chronic atrial fibrillation patients with mitral valve disease.

Methods

Left and right atrial appendages obtained from patients with mitral valve disease were both in chronic atrial fibrillation (CAF, AF≥6 months, n = 6) and in sinus rhythm (SR, n = 6). One part of the sample was used for histological analysis and fibrosis quantification; other part were analyzed by label-free proteomic combining liquid chromatography with mass spectrometry (LC-MS), we utilized bioinformatics analysis to identify differential proteins.

Results

Degree of atrial fibrosis was higher in CAF patients than that of SR patients. 223 differential proteins were detected between two groups. These proteins mainly had vital functions such as cell proliferation, stress response, focal adhesion apoptosis. We evaluated that serine/threonine protein kinase N2 (PKN2), dermatopontin(DP), S100 calcium binding protein B(S100B), protein tyrosine kinase 2(PTK2) and discoidin domain receptor tyrosine kinase 2(DDR2) played important roles in fibrotic process related to atrial fibrillation.

Conclusion

The study presented differential proteins responsible for atrial fibrosis in chronic atrial fibrillation patients through label-free proteomic analysis. We assessed some vital proteins including their characters and roles. These findings may open up new realm for mechanism research of atrial fibrillation.     

Lifestyle Factors,Medication Use and Risk for Ischaemic Heart Disease Hospitalisation: A Longitudinal Population-Based Study

Background

Lifestyle factors have been implicated in ischaemic heart disease (IHD) development however a limited number of longitudinal studies report results stratified by cardio-protective medication use.

Purpose

This study investigated the influence of self-reported lifestyle factors on hospitalisation for IHD, stratified by blood pressure and/or lipid-lowering therapy.

Methods

A population-based cohort of 14,890 participants aged 45+ years and IHD-free was identified from the Western Australian Health and wellbeing Surveillance System (2004 to 2010 inclusive), and linked with hospital administrative data. Adjusted hazard ratios for future IHD-hospitalisation were estimated using Cox regression.

Results

Current smokers remained at higher risk for IHD-hospitalisation (adjusted HR=1.57; 95% CI: 1.22-2.03) after adjustment for medication use, as did those considered overweight (BMI=25-29 kg/m²; adjusted HR=1.28; 95% CI: 1.04-1.57) or obese (BMI of ≥30kg/m²; adjusted HR=1.31; 95% CI: 1.03-1.66). Weekly leisure-time physical activity (LTPA) of 150 minutes or more and daily intake of 3 or more fruit/vegetable servings reduced risk by 21% (95% CI: 0.64-0.97) and 26% (95% CI: 0.58-0.96) respectively. Benefits of LTPA appeared greatest in those on blood pressure lowering medication (adjusted HR=0.50; 95% CI: 0.31-0.82 [for LTPA<150 mins], adjusted HR=0.64; 95% CI: 0.42-0.96 [for LTPA>=150 mins]). IHD risk in smokers was most pronounced in those taking neither medication (adjusted HR=2.00; 95% CI: 1.41-2.83).

Conclusion

This study confirms the contribution of previously reported lifestyle factors towards IHD hospitalisation, even after adjustment for antihypertensive and lipid-lowering medication use. Medication stratified results suggest that IHD risks related to LTPA and smoking may differ according to medication use.     

Young Male Patients with Atrial Fibrillation and CHA2DS2-VASc Score of 1 May Not Need Anticoagulants: A Nationwide Population-Based Study

Background

It is unclear whether oral anticoagulants are beneficial for atrial fibrillation (AF) patients with low CHA₂DS₂-VASc score. Age could be important in determining the risk of thromboembolism in low risk AF patients (CHA₂DS₂-VASc score of 1 for male or 2 for female).

Methods

The Taiwan National Health Insurance Research Database (NHIRD) was used and 27,521 AF patients with CHA₂DS₂-VASc score of 1 (male) or 2 (female) not receiving anticoagulants were acquired as the study cohort, which were classified into three age groups: 20–49, 50–64, and 65–74 years. The clinical endpoint was the occurrence of ischemic thromboembolism within one year of follow up.

Results

During the follow-up of 0.94 ± 0.19 years, 385 (2.19%) male patients experienced ischemic thromboembolism, with annual rate of 2.32%. The annual risk ranged from 1.29%, 2.43% to 2.77% for male patients aged 20–49, 50–64 and 65–74 years respectively. Of the female patients, 218 (2.20%) experienced clinical event with annual rate of 2.32%. The annual risk increased from 1.87%, 2.28% to 2.64% for female patients aged 20–49, 50–64 and 65–74 years respectively. There was no difference in risk between the male patients aged 20–49 years with CHA₂DS₂-VASc score of 1 and overall male patients with CHA₂DS₂-VASc score of 0. (P = 0.631) The female patients aged 20–49 years with CHA₂DS₂-VASc score of 2 was associated with a higher risk of thromboembolic events than overall female patients with CHA₂DS₂-VASc score of 1 (HR = 1.93; P = 0.008).

Conclusions

Age is important in determining the risk of thromboembolism in AF patients with single risk factor. In male patients <50 years old with CHA₂DS₂-VASc score of 1, the risk of ischemic thromboembolism was low. Considering the benefits and the risk of bleeding, oral anticoagulation therapy may not be favorable in these patients.     

Increased Risk of Acute Coronary Syndrome among Patients with Urinary Stone Disease: A Nationwide Population-Based Cohort Study

Background/Objectives

Urinary stones (US) are associated with systemic metabolic and endocrine disorders that share risk factors typically associated with acute coronary syndrome (ACS).

Methods

For this investigation, 30 142 patients with US were set as the research group, and 121 768 randomly selected patients were set as the comparison group through frequency matching by age, sex, and index year. Each patient was individually tracked to identify those who developed ACS during the follow-up period. Cox proportional hazards regression and the Kaplan-Meier method were adopted to calculate the hazard ratios of ACS risk and plot the survival curve.

Results

Overall, 275 (13.4 per 10 000 person-y) and 736 events (9.1 per 10 000 person-y) were observed among patients in the research and comparison cohorts, respectively. The patients with US had a substantially lower ACS-free survival rate compared with that of the patients in the comparison cohort (P<.001). After adjusting for potential risk factors, the patients with US were observed to have a 1.22-fold higher risk of ACS compared with patients in the comparison cohort (95% confidence interval = 1.05–1.40, P<.001), particularly among younger patients.

Conclusions

The results indicate that US is associated with increased risk of developing ACS, particularly among young (≤49 years) and male adults. Future studies should examine the possible mechanisms of US-related ACS morbidity by conducting multicenter recruitment and measurements of laboratory data.     

老年心功能不全患者mink S38G多态性与房颤的相关性

探讨老年慢性心功能不全患者中,心肌细胞Iks通道β亚单位基因mink-S38G多态性与心房颤动（atrial fibrillation, AF）发生的相关性.收集慢性心功能不全患者共127例,其中房颤组63例,窦律组64例.采用聚合酶链反应限制性片段长度多态性（restriction fragment length polymorphism, PCR—RFLP）检测房颤组和窦律组的mink基因S38G多态性位点的基因型.房颤组与窦律组之间minkS38G的3种基因型频率为SS(9.52% vs 23.44%),SG(41.27% vs 50.00%),GG(49.21% vs 26.56%).在房颤组中,GG基因型的频率明显高于窦律组,两组间基因型存在明显差异, P=0.013;多因素Logistic回归提示,minkS38G多态性与房颤的发生有明显相关（P=0.010）.因此,在老年慢性心功能不全患者中,mink基因S38G多态性与房颤的发生有关,具有GG基因型的患者其发生房颤的风险较高     

Angiogenesis Inhibitor Bevacizumab Increases the Risk of Ischemic Heart Disease Associated with Chemotherapy: A Meta-Analysis

Concerns have arisen regarding the risk of ischemic heart disease with the novel antiangiogenic agent bevacizumab, a recombinant humanised monoclonal antibody to the vascular endothelial growth factor that is widely used in cancer treatment. Currently, the role of bevacizumab in ischemic heart disease is controversial. This meta-analysis was therefore performed to assess the overall risk of ischemic heart disease associated with the use of bevacizumab. The databases of PubMed, EMBASE and Web of Science were searched for English language studies of randomised controlled trials comparing bevacizumab with control therapy published through October 25, 2012. Summary incidence rates, relative risks (RRs) and 95% confidence intervals (CIs) were calculated using random-effects or fixed-effects models based on the heterogeneity of the included studies. A total of 4,617 patients from 7 randomised controlled trials were identified and included for analysis. Among those patients receiving bevacizumab, the summary incidence of ischemic heart disease was 1.0% (95% CI, 0.6%–1.4%). Patients treated with bevacizumab had a significantly increased risk of ischemic heart disease with an RR of 2.49 (95% CI, 1.37–4.52) compared with controls. In addition, both high doses and low doses of bevacizumab increased the risk of cardiac ischemia (low dose at 2.5 mg/kg per week: RR, 2.14 [95% CI, 1.09–4.19]; high dose at 5 mg/kg per week: RR, 4.81 [95% CI, 1.03–22.42]). Bevacizumab was also found to significantly increase the risk of cardiac ischemia in patients with colorectal cancer (RR, 2.13; 95% CI, 1.11–4.06) compared with controls. This meta-analysis shows the use of bevacizumab was associated with an increased risk of developing ischemic heart disease in colorectal cancer patients receiving this drug. Our conclusions are limited by the available data. Further evaluations of high-quality RCTs are needed.     

Physiological Evaluation of the Results of Myocardial Revascularization in Patients with Ischemic Heart Disease

Intraoperative assessment of the myocardial blood flow was performed in different heart areas in 94 patients with ischemic heart disease prior to and after myocardial revascularization. An ALF-21 laser–Doppler flowmeter (Transonic Systems Inc.) was used to measure the myocardial blood flow near the anterior and posterior surfaces of the left ventricle (LV_asand LV_ps, respectively) and the anterior surface of the right ventricle (RV_as). According to the results of revascularization, the patients were divided into four groups: group I with increased myocardial blood flow in all areas tested, group II and group III with blood flow redistributed along LV and RV, and group IV with moderately decreased myocardial blood flow in all test areas. All groups showed a postoperative decrease in blood flow differences between different myocardium areas and the leveling of blood flow in the whole myocardium. The efficiency of revascularization depended on a number of factors, including the initial level of myocardial blood flow, completeness of revascularization of ischemic areas, the number and quality of bypass grafts, and the patients' age. The most pronounced positive results were observed in patients under the age of 60 years.