Primary and Secondary Prevention of Ischemic Stroke and Cerebral Hemorrhage: JACC Focus Seminar

Stroke is a leading cause of permanent disability. Therefore, primary prevention of first stroke and secondary prevention of recurrent stroke are a high priority. Primary prevention of ischemic stroke includes lifestyle modification and diet, treatment of risk factors including hypertension, diabetes mellitus and lipid disorders, antiplatelet therapy for high vascular risk patients, and anticoagulation in atrial fibrillation. Secondary prevention of ischemic stroke includes additional carotid surgery or stenting in selected symptomatic patients, closure of patent foramen ovale after cryptogenic stroke, treatment of insulin resistance, and best medical treatment of intracranial stenosis. The most important preventive strategies in the primary and secondary prevention of cerebral hemorrhage include the treatment of hypertension, reduction in alcohol intake, and occlusion of the left atrial appendage in patients with atrial fibrillation and permanent contraindications for oral anticoagulation.     

Worldwide Prevalence of Familial Hypercholesterolemia: Meta-Analyses of 11 Million Subjects

BackgroundDespite the greater prevalence of familial hypercholesterolemia (FH) in subjects with ischemic heart disease (IHD), premature IHD, and severe hypercholesterolemia (low-density lipoprotein ≥190 mg/dl), overall prevalence estimates are not available.ObjectivesThe aim of this study was to provide worldwide estimates of FH prevalence in subjects with IHD, premature IHD, and severe hypercholesterolemia compared with those in the general population.MethodsIn this systematic review and meta-analyses, Embase, PubMed, and the Web of Science were searched until June 3, 2019, for peer-reviewed papers and conference abstracts reporting heterozygous FH prevalence in nonfounder populations, revealing 104 studies eligible for inclusion.ResultsEstimates of FH prevalence were pooled using random-effects meta-analyses and were 0.32% (95% confidence interval [CI]: 0.26% to 0.39% [corresponding to 1:313]) among 10,921,310 unique subjects in the general population (33,036 patients with FH) on the basis of 44 studies, 3.2% (95% CI: 2.2% to 4.3% [1:31]) among 84,479 unique subjects with IHD (2,103 patients with FH) on the basis of 28 studies, 6.7% (95% CI: 4.9% to 8.7% [1:15]) among 31,316 unique subjects with premature IHD (1,471 patients with FH) on the basis of 32 studies, and 7.2% (95% CI: 4.6% to 10.8% [1:14]) among 17,728 unique subjects with severe hypercholesterolemia (920 patients with FH) on the basis of 7 studies. FH prevalence in the general population was similar using genetic versus clinical diagnoses. Seventeen of 195 countries (9%) in the world have reported FH prevalence for the general population, leaving 178 (91%) countries in the world with unknown prevalence.ConclusionsCompared with 1:313 among subjects in the general population, FH prevalence is 10-fold higher among those with IHD, 20-fold higher among those with premature IHD, and 23-fold higher among those with severe hypercholesterolemia. The prevalence of FH is unknown in 90% of countries in the world.     

Melatonin-stimulated exosomes enhance the regenerative potential of chronic kidney disease-derived mesenchymal stem/stromal cells via cellular prion proteins

Chronic kidney disease (CKD) is caused by dysfunctional kidneys, which result in complications like cardiovascular diseases. Chronic kidney disease-induced pathophysiological conditions decrease efficacy of autologous mesenchymal stem/stromal cell (MSC)-based therapy by reducing MSC functionality. To enhance therapeutic potential in patients with CKD, we isolated exosomes derived from melatonin-treated healthy MSCs (MT exosomes) and assessed the biological functions of MT exosome–treated MSCs isolated from patients with CKD (CKD-MSCs). Treatment with melatonin increased the expression of cellular prion protein (PrP^C) in exosomes isolated from MSCs through the upregulation of miR-4516. Treatment with MT exosomes protected mitochondrial function, cellular senescence, and proliferative potential of CKD-MSCs. MT exosomes significantly increased the level of angiogenesis-associated proteins in CKD-MSCs. In a murine hindlimb ischemia model with CKD, MT exosome–treated CKD-MSCs improved functional recovery and vessel repair. These findings elucidate the regenerative potential of MT exosome–treated CKD-MSCs via the miR-4516-PrP^C signaling axis. This study suggests that the treatment of CKD-MSCs with MT exosomes might be a powerful strategy for developing autologous MSC-based therapeutics for patients with CKD. Furthermore, miR-4516 and PrP^C could be key molecules for enhancing the regenerative potential of MSCs in ischemic diseases.     

Supporting families in their child's journey with neonatal encephalopathy and therapeutic hypothermia

Neonates and families face challenges in hypothermic therapy, including trauma to parents, extreme emotions, and unfamiliarity with the medical system. Communication is an essential element to supporting parents while their children are in the NICU, and beyond, building the foundation for the ongoing relationship the family has with the medical system. Significant consideration needs to be given to the critical element of integrating the family into the care of a baby being treated with therapeutic hypothermia. Clinicians can promote healing of accumulated traumas of parents through ensuring parent's emotional safety, facilitating a trusting relationship, and promoting parent empowerment. Connecting parents with resources, especially peer support, is an essential part of a hospital stay. In this chapter, we explore best practices to support families during and after hypothermic therapy.     

The Impact of Socioeconomic Factors,Coverage and Access to Health on Heart Ischemic Disease Mortality in a Brazilian Southern State: A Geospatial Analysis

Background:No other disease has killed more than ischemic heart disease (IHD) for the past few years globally. Despite the advances in cardiology, the response time for starting treatment still leads patients to death because of the lack of healthcare coverage and access to referral centers.Objectives:To analyze the spatial disparities related to IHD mortality in the Parana state, Brazil.Methods:An ecological study using secondary data from Brazilian Health Informatics Department between 2013–2017 was performed to verify the IHD mortality. An spatial analysis was performed using the Global Moran and Local Indicators of Spatial Association (LISA) to verify the spatial dependency of IHD mortality. Lastly, multivariate spatial regression models were also developed using Ordinary Least Squares and Geographically Weighted Regression (GWR) to identify socioeconomic indicators (aging, income, and illiteracy rates), exam coverage (catheterization, angioplasty, and revascularization rates), and access to health (access index to cardiologists and chemical reperfusion centers) significantly correlated with IHD mortality. The chosen model was based on p < 0.05, highest adjusted R² and lowest Akaike Information Criterion.Results:A total of 22,920 individuals died from IHD between 2013–2017. The spatial analysis confirmed a positive spatial autocorrelation global between IDH mortality rates (Moran’s I: 0.633, p < 0.01). The LISA analysis identified six high-high pattern clusters composed by 66 municipalities (16.5%). GWR presented the best model (Adjusted R²: 0.72) showing that accessibility to cardiologists and chemical reperfusion centers, and revascularization and angioplasty rates differentially affect the IHD mortality rates geographically. Aging and illiteracy rate presented positive correlation with IHD mortality rate, while income ratio presented negative correlation (p < 0.05).Conclusion:Regions of vulnerability were unveiled by the spatial analysis where sociodemographic, exam coverage and accessibility to health variables impacted differently the IHD mortality rates in Paraná state, Brazil.Highlights

• The increase in ischemic heart disease mortality rates is related to geographical disparities.
• The IHD mortality is differentially associated to socioeconomic factors, exam coverage, and access to health.
• Higher accessibility to chemical reperfusion centers did not necessarily improve patient outcomes in some regions of the state.
• Clusters of high mortality rate are placed in regions with low amount of cardiologists, income and schooling.

     

功能性心肌血流指数评价缺血性冠心病可行性分析

目的:运用功能性心肌血流指数(MBFI)评价缺血性冠心病(ICAD)可行性分析。方法:回顾性分析冠心病疑似患者行冠状动脉CT血管成像(CCTA)检查,同期接受有创冠状动脉造影(ICA)及导管法心肌血流储备分数(FFR)检查共81例患者,其中男性43例,女性38例,年龄(59.27±9.09)岁;计算MBFI;以FFR≤0.80为金标准,分别以四格表诊断试验确定MBFI与ICA的最佳切点值来判断ICAD;评价MBFI、ICA的ROC曲线特征及诊断准确度。结果:81例患者,CCTA扫描平均剂量为(3.06±1.22)mSv。MBFI、ICA最佳切点值分别为0.074、70%,25例患者FFR≤0.80。MBFI、ICA两者ROC曲线下面积分别为0.825、0.699(Z=2.024,P=0.0429),其敏感度、特异度、阳性预测值、阴性预测值分别为88.00%、80.35%、66.67%、93.75%和76.00%、51.79%、41.30%、82.86%,诊断准确度分别为82.72%、59.26%(χ2=10.753,P<0.01)。33例患者(40.74%,33/81)ICA狭窄程度为65%或70%,其中27例患者(81.82%,27/33)心肌不缺血,运用MBFI值大于0.074可明确23例患者心肌并不缺血(69.70%,23/33)。结论:MBFI属于功能性指标,可用于排查缺血性冠心病。     

Antiplatelet therapy and outcomes following endovascular therapy for acute ischemic stroke: A systemic review and meta-analysis

ObjectiveThe outcomes of antiplatelet therapy (APT) in patients with acute ischemic stroke (AIS) receiving endovascular therapy (EVT) remains controversial. Thus, we sought to make a systematic review and meta-analysis of recent clinical trials to confirm the safety and efficacy of APT.MethodsAll of clinical trails were systematically retrieved from PubMed, Embase and Cochrane. The endpoints or main outcome measures included symptomatic intracranial hemorrhage (sICH), 3-month mortality, successful recanalisation (SR) and 3-month functional independence (FI). Odd ratios (ORs) with their 95% confidence intervals (CIs) were calculated to synthesize effect size by using random-effects models. Sensitivity analysis was performed via calculation of rest data owiting one by one.Results23 articles were included after screening. APT as an adjunct to EVT was associated with a higher likelihood of pooled successful recanalisation (OR 1.46, 95% CI 1.07–2.00) and 3-month FI (OR 1.24, 95% CI 1.01–1.51), no associated with sICH and 3-month mortality. However, Sensitivity analysis indicated that the association between APT and SR and 3-month FI were unstable. For patients with prior use of APT or receiving intravenous thrombolysis before EVT, no associated were found between APT and all of endpoints above.ConclusionAlthough adjuvant APT appears to increase the number of SR and 3-month FI, the results were unstable. Randomised controlled trials are needed to confirm the efficacy.