Association Between Bisphosphonates Therapy and Incident Myocardial Infarction: Meta-analysis and Trial Sequential Analysis.

BACKGROUND: Bisphosphonates have shown potential to inhibit atherosclerosis in animal experiments; however, whether bisphosphonates therapy lowers the risk of incidence of myocardial infarction (MI) is debated. We performed the meta-analysis and trial sequential analysis (TSA) to investigate the relation between bisphosphonates therapy and incident MI. METHODS: Pubmed and Embase databases were systematically searched in April 2015 to identify studies, which compared the incidence of MI in subjects receiving bisphosphonates with that in subjects not receiving the agents. Meta-analysis was conducted using random effects model in consideration of statistical heterogeneity between studies. Reliability of the results from meta-analysis was examined using TSA. RESULTS: Six observational studies (n = 440261) and 3 randomized control trials (RCTs, n = 11,024) met the eligible criteria. In the pooled analysis of observational studies, bisphosphonates therapy was not associated with reduced risk of MI either using unadjusted estimates (relative risk 0.93, 95% confidence interval (CI), 0.75-1.15) or estimates adjusted for confounding factors (hazard ratio 1.01, 95% CI, 0.84-1.21). Furthermore, hazard of incident MI did not differ between alendronate users and nonusers. TSA showed that evidence from observational studies firmly precluded the association between bisphosphonates and incident MI. Pooled analysis of RCTs also suggested no benefits of decrease in incident MI associated with bisphosphonates therapy (relative risk 1.05, 95% CI, 0.53-2.09). However, TSA demonstrated that evidence from RCTs was insufficient to draw a conclusion. CONCLUSIONS: Despite the encouraging findings from animal studies, bisphosphonates therapy is not associated with reduced risk of MI.

Target lesion calcification and risk of adverse outcomes in patients with drug-eluting stents. A meta-analysis.

BACKGROUND: Studies focusing on the relationship between calcified lesions and adverse outcomes in the drug-eluting stent (DES) era have presented inconsistent conclusions. The aim of this study was to assess the association between target lesion calcification and adverse outcomes in patients undergoing DES implantation. METHODS: A systematic search was conducted on Medline (Ovid SP, 1946 to 28 February 2014), Embase (Ovid SP, 1974 to 28 February 2014), and the Chinese Biomedical Literature Database (CBM, 1978 to 28 February 2014). Abstracts from the 2012 and 2013 scientific meetings of the American College of Cardiology and American Heart Association were manually searched. Hazard ratios (HRs) were pooled using a fixed or random effects model in the context of heterogeneity. RESULTS: A total of 13 studies comprising 66,361 patients were included. Target lesion calcification was associated with an increased risk of all-cause mortality (HR = 1.41; 95 % CI = 1.27-1.56), cardiac death (HR = 1.97; 95 % CI = 1.68-2.31), myocardial infarction (HR = 1.33; 95 % CI = 1.13-1.57), target lesion revascularization (TLR; HR 1.47, 95 % CI 1.18-1.83), stent thrombosis (HR 1.63, 95 % CI 1.36-1.96), and major cardiovascular events (HR 1.37, 95 % CI 1.19-1.58). The results proved robust in subgroup analyses for TLR and stent thrombosis. CONCLUSION: Calcified target lesions are risk factors for adverse outcomes in the DES era. Further studies focusing on comprehensive therapy in patients with coronary calcification are urgently needed.

Subclassification of left ventricular hypertrophy based on dilation stratifies coronary artery disease patients with distinct risk.

BACKGROUND: A new 4-tired classification of left ventricular hypertrophy (LVH) based on LV concentricity and dilation has been proposed; however, the association between the new categorization of LV geometry and outcomes in patients with coronary artery disease (CAD) is still unknown. METHODS: All the 2297 patients with CAD included underwent echocardiographic examination prior to discharge. Left ventricular mass (LVM) was calculated, and left ventricular end-diastolic volume (EDV) was indexed by body surface area (BSA). Study cohort was divided into five groups according to LV geometry: (i) eccentric nondilated LVH (normal LVM/EDV((2/3)) and EDV/BSA) (n = 129); (ii) eccentric dilated LVH (normal LVM/EDV((2/3)) with increased EDV/BSA) (n = 222); (iii) concentric nondilated LVH (increased LVM/EDV((2/3)) with normal EDV/BSA) (n = 441); (iv) concentric dilated LVH (increased LVM/EDV((2/3)) and EDV/BSA) (n = 118); and (v) normal LV mass (n = 1387). RESULTS: Dilated LVH was associated with a higher event rates of all-cause death (eccentric 13·1% vs. 3·1%; concentric 13·6% vs. 8·4%) and composite events (eccentric: 17·6% vs. 5·4%; concentric: 18·6% vs. 12·7%) compared with nondilated LVH. While eccentric nondilated LVH had comparable risk for adverse outcomes compared with normal LV mass (all-cause death: relative risk (RR) 0·68, 95% confidential interval (CI) 0·25-1·85; composite events: RR 0·75, 95% CI 0·36-1·58). Cox regression analyses showed that eccentric dilated LVH had the highest propensity to all-cause death (adjusted hazard ratio [aHR] 2·752 [95% CI 1·749-4·328], P < 0·001) and composite events (aHR 2·462 [95% CI 1·688-3·592], P < 0·001). CONCLUSION: In patients with CAD, dilated LVH and nondilated LVH provide distinct prognostic information. Eccentric nondilated LVH does not predict adverse outcomes.

Changes in the incidence and prevalence of ischemic stroke and associations with natural disasters: an ecological study in 193 countries.

Epidemiological studies have indicated that natural disasters have important impacts on ischemic stroke. This study determined the associations between natural disasters and the incidence and prevalence of ischemic stroke at the global level. A 28-year ecological trend study was performed to estimate worldwide changes in the incidence and prevalence of ischemic stroke and their associations with natural disasters by analyzing data from 193 countries. Quantum geographic information system-based visualization and multivariable linear regression were used. Changes in the incidence and prevalence of ischemic stroke, as well as disaster occurrence, varied among the different regions over the past 28 years (p < 0.001). Multiple linear regression revealed an independent and positive association between disaster occurrence and the incidence of ischemic stroke in males, females and both sexes combined (standardized coefficients = 0.515, 0.470 and 0.483, p < 0.001); similar associations were found for the prevalence of ischemic stroke (standardized coefficients = 0.471, 0.417 and 0.438, p < 0.001). The incidence and prevalence of ischemic stroke changed significantly at the global level and were independently associated with natural disasters. Both males and females show common but different vulnerabilities to natural disasters. This evidence supports policy making and resource allocation for disaster response and disease burden reduction.

Changes in ischemic heart disease mortality at the global level and their associations with natural disasters: A 28-year ecological trend study in 193 countries.

BACKGROUND: Natural disasters are believed to be associated with cardiovascular disease. This study aimed to explore the changes in mortality due to ischemic heart disease (IHD) and their associations with natural disasters at the global level. METHODS: Country-specific data on the impact of natural disasters, rates of mortality due to IHD and years of life lost (YLL) and socioeconomic variables were obtained for 193 countries for the period from 1990 to 2017. An ecological trend study was conducted to estimate the changes in the IHD mortality and YLL rates and their associations with natural disasters (occurrence, casualties and total damage). Correlation analyses and multivariate linear regression were used. RESULTS: Significant changes were found in the IHD mortality and YLL rates and the occurrence of disasters between the two equal periods (1990 to 2003 and 2004 to 2017) (p<0.001). The bivariate Pearson correlation test revealed that the trend in the occurrence of natural disasters was positively correlated with trends in the IHD mortality and YLL rates among females and all individuals (p<0.05) and was marginally correlated among males. Multiple linear regression revealed an independent association between the occurrence of natural disasters and the IHD mortality rate among males, females and all individuals (standardized coefficients = 0.163, 0.357 and 0.241, p<0.05), and similar associations were found for the YLL rate (standardized coefficients = 0.194, 0.233 and 0.189, p<0.05). CONCLUSIONS: Our study demonstrated significant changes in the IHD mortality and YLL rates at the global level and their independent associations with natural disasters. Both males and females were vulnerable to natural disasters. These results provide evidence that can be used to support policy making and resource allocation when responding to disasters and developing strategies to reduce the burden of IHD.

Disability-Adjusted Life Years (DALYs) Due to Ischemic Heart Disease (IHD) Associated with Natural Disasters: A Worldwide Population-Based Ecological Study.

Background: Recent studies have reported an association between natural disasters of various kinds and ischemic heart disease (IHD). We investigated the association between Disability-adjusted life years (DALYs) due to IHD and natural disasters and aimed to assess DALYs as a quantification of the burden of IHD related to natural disasters at the global level. Methods: Country-specific data of natural disaster impacts DALYs due to IHD and socioeconomic variables were obtained from open sources over the period of 1990-2013 and 2014-2017. A population-based trend ecological design was conducted to estimate the association between trends in DALYs and natural disasters (occurrence, casualties and total damage), adjusting for socioeconomic variables. Results: Most countries have experienced increases in natural disaster occurrences and decreases in DALYs during this study period. The unadjusted correlation analysis demonstrated a positive and significant correlation between DALYs and natural disasters for females and for both sexes (R = 0.163 and 0.146, p = 0.024 and 0.043), and a marginally significant correlation for males (R = 0.128, p = 0.076). After adjusting for socioeconomic variables, multiple linear regression demonstrated independent associations between the occurrence and DALYs due to IHD for males, females and both sexes (standardized coefficients = 0.192, 0.23 and 0.187, p = 0.016, 0.004 and 0.022). Conclusions: A weak but significantly positive association between natural disaster and IHD was confirmed and quantified at the global level by this DALY metric analysis. Adaptation strategies for natural disaster responses and IHD disease burden reduction need to be developed.

Rapamycin enhances platelet aggregation induced by adenosine diphosphate in vitro.

Studies have demonstrated the important role of platelets in the formation of stent thrombosis associated with drug-eluting stents, but little is known about the effects of drugs eluted from stents on platelet function. The extent of platelet aggregation in platelet-rich plasma induced by adenosine diphosphate (ADP) was measured at various doses of rapamycin, and the ability of aspirin to inhibit platelet aggregation was determined at the same concentrations of rapamycin. Compared with lower concentrations, rapamycin at higher doses (>10 ng/mL) enhanced platelet aggregation induced by ADP, and the enhancement was significant at 50 ng/mL and 100 ng/mL (P = 0.005 and P = 0.04). The ability of aspirin to inhibit platelet aggregation was reduced at higher concentrations of rapamycin. These data suggest that higher concentrations of rapamycin can enhance platelet aggregation in response to ADP, and reduce the ability of aspirin to inhibit platelet aggregation.

What is the Optimal Age for Students to Receive Cardiopulmonary Resuscitation Training?

OBJECTIVES: Training students has been proven to be the optimal way to deliver cardiopulmonary resuscitation (CPR) skills. However, it is somehow unknown whether or not the current recommendations appropriate for Caucasian students are also suitable for East Asian students. The purpose of this study is to explore the best age for East Asian students to receive CPR training. METHODS: Students were recruited from six schools. Students participated in a standard CPR training program provided by tutors. Each student attended a 60-minute training session with a manikin. After being trained, within one hour, the student's compression quality was assessed. RESULTS: A total of 360 students who constituted 12 continuous grades were recruited for this study. Adequate compression depth and satisfactory compression rate with correct hand position could be achieved since the age of 12. However, successful compression rate and complete release could be achieved since the younger age of six. CONCLUSIONS: Current recommendations for Caucasian students to cultivate a full-capacity CPR rescuer at the age of 12 are also appropriate for East Asian students. However, the optimal age for students to receive CPR training should be decided based on evidence and importance assessment of CPR.He D, Huang K, Yang Y, Jiang W, Yang N, Yang H. What is the optimal age for students to receive cardiopulmonary resuscitation training? Prehosp Disaster Med. 2018;33(4):394-398.

Heparin is Not Inferior to Bivalirudin in Percutaneous Coronary Intervention-Focusing on the Effect of Glycoprotein IIb/IIIa Inhibitor Use: A Meta-Analysis.

Our aim was to compare the efficacy and safety of bivalirudin (Biv) versus heparin (Hep) with or without similar usage rate of glycoprotein IIb/IIIa inhibitors (GPIs) during percutaneous coronary intervention (PCI). The PubMed and EMbase were searched. Randomized trials comparing Biv versus Hep were eligible for inclusion. With imbalanced GPI use, Biv had significantly lower major bleeding (pooled risk ratio [RR], 0.67; 95% confidence interval [CI], 0.54-0.83) without difference in mortality (pooled RR, 0.95; 95% CI, 0.80-1.14). With comparable GPI use, no significant difference was observed in major bleeding (pooled RR, 0.95; 95% CI, 0.82-1.10) and mortality (pooled RR, 1.13; 95% CI, 0.85-1.50). With no GPI use, Biv was associated with numerically higher mortality (pooled RR, 1.17; 95% CI, 0.83-1.65) without significant difference in major bleeding (pooled RR, 0.81; 95% CI, 0.64-1.02). In conclusion, when comparing different anticoagulants during PCI, the effect of GPIs should not be underestimated. Heparin as such was found noninferior to Biv.

Inappropriate left ventricular mass and poor outcomes in patients with angina pectoris and normal ejection fraction.

OBJECTIVES: Although inappropriate left ventricular mass has been associated with clustered cardiac geometric and functional abnormalities, its predictive value in patients with coronary artery disease is still unknown. This study examined the association of inappropriate left ventricular mass with clinical outcomes in patients with angina pectoris and normal ejection fraction. PARTICIPANTS AND METHODS: Consecutive patients diagnosed with angina pectoris whose ejection fraction was normal were recruited from 2008 to 2012. Inappropriate left ventricular mass was determined when the ratio of actual left ventricular mass to the predicted one exceeded 150%. The primary endpoint was a composite of all-cause death, nonfatal myocardial infarction, and nonfatal stroke. Clinical outcomes between the inappropriate and appropriate left ventricular mass group were compared before and after propensity matching. RESULTS: Of the total of 1515 participants, 18.3% had inappropriate left ventricular mass. Patients with inappropriate left ventricular mass had a higher composite event rate compared with those with appropriate left ventricular mass (11.2 vs. 6.6%, P=0.010). Multivariate Cox regression analyses showed that inappropriate left ventricular mass was an independent risk factor for adverse events (adjusted hazard ratio, 1.59; 95% confidence interval, 1.03-2.45; P=0.035). The worse outcome in patients with inappropriate left ventricular mass was further validated in a propensity matching cohort and patients with the traditional definition of left ventricular hypertrophy. CONCLUSION: Inappropriate left ventricular mass was associated with an increased risk of adverse events in patients with angina pectoris and normal ejection fraction.