BACKGROUND & AIMS: Rupture of atheromatous plaques leading to acute coronary syndromes usually occur in lipid-reach and well-developed coronary lesions. We describe 2 unusual patients with acute coronary syndromes in whom there was angiographic and intravascular ultrasound evidence of an intraluminal thrombus overlying a small, nonocclusive plaque in an enlarged coronary artery.

背景与目标： 导致急性冠状动脉综合征的动脉粥样硬化斑块破裂通常发生在脂质到达和发达的冠状动脉病变中。我们描述了2例不寻常的急性冠状动脉综合征患者，其中有血管造影和血管内超声证据表明腔内血栓覆盖了扩大的冠状动脉中的一个小的非闭塞斑块。

BACKGROUND & AIMS: BACKGROUND:Although the benefit of thrombolytic therapy in reducing mortality in acute myocardial infarction is well established, the types of bleeding and risk factors for bleeding are less well described in large trials.

METHODS AND RESULTS:We analyzed the baseline characteristics, outcomes, and incidence of bleeding by location, severity, and treatment assignment among 41,021 patients in the GUSTO-I trial of thrombolysis for acute myocardial infarction. Of the 40,903 patients for whom there were complete data, 1.2% suffered severe bleeding and 11.4% experienced moderate hemorrhage at a variety of sites. The most common sources of bleeding were procedure related. The thrombolytic regimen was strongly related to the incidence of bleeding; comparatively more bleeding was seen with the therapies of streptokinase plus intravenous heparin and the streptokinase and tissue plasminogen activator plus intravenous heparin combination. In multivariate analysis, the four most powerful independent predictors of hemorrhage were older age, lighter body weight, female sex, and African ancestry; they remained the most important predictors of bleeding when multivariate analysis was performed on patients who did not undergo invasive procedures. The presence of serious hemorrhage was associated with other undesirable outcomes (recurrent events, left ventricular dysfunction, arrhythmia, or stroke).

CONCLUSIONS:Important predictors of bleeding in this population are increased age, lighter weight, female sex, African ancestry, and experiencing invasive procedures. Other nonhemorrhagic adverse clinical outcomes were associated with moderate and severe bleeding, which was in turn associated with increased length of hospital stay and mortality at 30 days.

背景与目标： 背景 : 尽管溶栓治疗在降低急性心肌梗死死亡率方面的益处已得到充分证实，但在大型试验中，出血类型和出血危险因素的描述较少。
方法和结果 : 在GUSTO-I急性心肌梗死溶栓试验中，我们分析了41,021名患者的基线特征，结局和出血发生率，按位置，严重程度和治疗分配。在40,903例有完整数据的患者中，1.2% 例严重出血，11.4% 例在不同部位出现中度出血。最常见的出血来源与手术有关。溶栓方案与出血发生率密切相关; 链激酶加静脉肝素以及链激酶和组织型纤溶酶原激活剂加静脉肝素联合治疗的出血相对较多。在多变量分析中，出血的四个最有效的独立预测因子是年龄较大，体重较轻，女性和非洲血统; 当对未接受侵入性操作的患者进行多变量分析时，它们仍然是出血的最重要预测因子。严重出血的存在与其他不良结果 (复发事件，左心室功能障碍，心律失常或中风) 相关。
结论 : 该人群出血的重要预测因素是年龄增加，体重减轻，女性，非洲血统，经历侵入性手术。其他非出血性不良临床结局与中度和重度出血相关，而中度和重度出血又与30天时的住院时间和死亡率增加相关。

BACKGROUND & AIMS: :Endomyocardial specimens were obtained from 7 patients with acute myocarditis. Immunohistochemical examination of the mononuclear infiltrate showed mainly cytotoxic T lymphocytes and natural killer cells. Perforin (a pore-forming protein found in cytotoxic lymphocytes) was identified in this myocardial lymphocytic infiltrate and electron microscopy showed myocardial cell damage that may have been associated with these perforin containing lymphocytes. The results indicate that in acute idiopathic and viral myocarditis, myocardial damage may be due to the action of perforin-secreting lymphocytes.

背景与目标： : 从7例急性心肌炎患者中获得心内膜心肌标本。对单核浸润的免疫组织化学检查显示主要是细胞毒性T淋巴细胞和自然杀伤细胞。在这种心肌淋巴细胞浸润中鉴定出穿孔素 (一种在细胞毒性淋巴细胞中发现的成孔蛋白)，电子显微镜显示心肌细胞损伤可能与这些含有穿孔素的淋巴细胞有关。结果表明，在急性特发性和病毒性心肌炎中，心肌损伤可能是由于穿孔素分泌淋巴细胞的作用所致。

BACKGROUND & AIMS: :Left ventricular (LV) dysfunction and/or heart failure (HF) are frequent complications of hypertension and myocardial infarction (MI), placing affected patients at increased risk of significant morbidity and premature death. Given that the renin-angiotensin-aldosterone system (RAAS) is activated and of pathophysiological importance in such patients, a strong therapeutic rationale exists to target the main effector mechanism (that is, angiotensin II [Ang II]) in order to lessen the associated morbidity and mortality burden. Angiotensin-converting enzyme (ACE) inhibitors have been shown to reduce mortality and LV dysfunction and to slow disease progression in patients with HF, including high-risk, post-MI patients. However, ACE inhibitors (ACE-Is) may not provide optimal long-term RAAS blockade (a finding that is associated with a worse prognosis) and many patients are unable to tolerate such therapy (because of troublesome dry cough, for example). In contrast, Ang II receptor blockers (ARBs) may block the RAAS more completely than ACE-Is and appear to be better tolerated. Several large-scale trials gave evaluated the efficacy of ARBs in patients with LV dysfunction and/or HF (including high-risk, post-MI patients), and have confirmed their utility as an efficacious and well-tolerated alternative to ACE-Is in this setting.

背景与目标： : 左心室 (LV) 功能障碍和/或心力衰竭 (HF) 是高血压和心肌梗塞 (MI) 的常见并发症，使受影响的患者具有显着发病率和过早死亡的风险。鉴于肾素-血管紧张素-醛固酮系统 (RAAS) 在此类患者中被激活并且具有病理生理重要性，因此存在针对主要效应机制 (即血管紧张素II [Ang II]) 的强有力的治疗依据，以减轻相关的发病率和死亡率负担。血管紧张素转换酶 (ACE) 抑制剂已被证明可降低HF患者 (包括高危MI后患者) 的死亡率和LV功能障碍，并可减缓疾病进展。然而，ACE抑制剂 (ACE-Is) 可能无法提供最佳的长期RAAS阻断 (这一发现与更差的预后相关)，并且许多患者无法耐受这种治疗 (例如，由于麻烦的干咳)。相比之下，Ang II受体阻滞剂 (arb) 可能比ACE-Is更完全地阻断RAAS，并且似乎具有更好的耐受性。几项大规模试验评估了ARBs在LV功能障碍和/或HF患者 (包括高危MI后患者) 中的疗效，并已证实其作为ACE-Is的有效且耐受性良好的替代方法在这种情况下。

BACKGROUND & AIMS: :Both animal models of experimental myocardial infarction and clinical studies on reperfusion therapy for acute myocardial infarction have provided evidence of impaired tissue perfusion at the microvascular level after initiation of reperfusion despite adequate restoration of epicardial vessel patency. Characteristics of this "no-reflow" phenomenon found in basic science investigations, such as distinct perfusion defects, progressive decrease of resting myocardial flow with ongoing reperfusion and functional vascular alterations are paralleled by clinical observations demonstrating similar features during the course of reperfusion. In experimental animal investigations of coronary occlusion and reperfusion, this no-reflow phenomenon could be characterized as a fundamental mechanism of myocardial ischemia and reperfusion. Major determinants of the amount of no-reflow are the duration of occlusion, infarct size, but also the length of reperfusion, as rapid expansion of perfusion defects occurs during reperfusion. Moreover, no-reflow appears to persist over a period of at least four weeks, a period when major steps of infarct healing take place. The significant association of the degree of compromised tissue perfusion at four weeks and indices of infarct expansion, found in chronic animal models of reperfused myocardial infarction, might be the pathoanatomic correlate for the prognostic significance observed in the clinical setting.

背景与目标： : 实验性心肌梗死的动物模型和急性心肌梗死再灌注治疗的临床研究都提供了尽管心外膜血管通畅性得到充分恢复，但再灌注开始后微血管水平组织灌注受损的证据。在基础科学研究中发现的这种 “无复流” 现象的特征，例如明显的灌注缺陷，静息心肌血流的进行性减少和持续的再灌注以及功能性血管改变，与临床观察结果平行，证明了在再灌注过程中的相似特征。在冠状动脉闭塞和再灌注的实验动物研究中，这种无复流现象可以表征为心肌缺血和再灌注的基本机制。无回流量的主要决定因素是闭塞的持续时间，梗塞面积以及再灌注的长度，因为在再灌注过程中会发生灌注缺陷的快速扩展。此外，无复流似乎持续了至少四个星期，这是发生梗塞愈合的主要步骤。在再灌注心肌梗塞的慢性动物模型中发现，在四周时组织灌注受损程度与梗塞扩展指数之间的显着关联，可能是在临床环境中观察到的预后意义的病理解剖相关。

BACKGROUND & AIMS: :In this study, several electrocardiogram (ECG)-derived indices corresponding to both ventricular depolarization and repolarization were evaluated during acute myocardial ischemia in an experimental model of myocardial infarction produced by 40 min coronary balloon inflation in 13 pigs. Significant changes were rapidly observed from minute 4 after the start of coronary occlusion, achieving their maximum values between 11 and 22 min for depolarization and between 9 and 12 min for repolarization indices, respectively. Subsequently, these maximum changes started to decrease during the latter part of the occlusion. Depolarization changes associated with the second half of the QRS complex showed a significant but inverse correlation with the myocardium at risk (MaR) estimated by scintigraphic images. The correlation between MaR and changes of the downward slope of the QRS complex, [Formula: see text], evaluated at the two more relevant peaks observed during the occlusion, was r = -0.75, p < 0.01 and r = -0.79, p < 0.01 for the positive and negative deflections observed in [Formula: see text], temporal evolution, respectively. Repolarization changes, analyzed by evaluation of ST segment elevation at the main observed positive peak, also showed negative, however non-significant correlation with MaR: r = -0.34, p = 0.28. Our results suggest that changes evaluated in the latter part of the depolarization, such as those described by [Formula: see text], which are influenced by R-wave amplitude, QRS width and ST level variations simultaneously, correlate better with the amount of ischemia than other indices evaluated in the earlier part of depolarization or during the ST segment.

背景与目标： : 在这项研究中，在13头猪的40分钟冠状动脉球囊充气产生的心肌梗死实验模型中，评估了急性心肌缺血期间对应于心室去极化和复极化的几种心电图 (ECG) 衍生指标。从冠状动脉闭塞开始后的第4分钟开始迅速观察到显着变化，分别在去极化11至22分钟和复极化指数9至12分钟之间达到最大值。随后，在闭塞的后期，这些最大变化开始减少。与QRS复合物的后半部分相关的去极化变化与闪烁显像估计的危险心肌 (MaR) 呈显着但呈负相关。在闭塞期间观察到的两个更相关的峰处评估的MaR与QRS复合体向下斜率的变化之间的相关性为r = -0.75，p <0.01和r = -0.79，对于在 [公式: 参见文本] 中观察到的正偏转和负偏转，分别为p <0.01。通过评估主要观察到的正峰处的ST段抬高来分析复极化变化，也显示出负的，但与MaR无关: r = -0.34，p = 0.28。我们的结果表明，在去极化的后半部分评估的变化，例如 [公式: 参见文本] 所描述的变化，同时受到R波振幅，QRS宽度和ST电平变化的影响，与在去极化早期或ST段期间评估的其他指标相比，与缺血量的相关性更好。

BACKGROUND & AIMS: BACKGROUND:The complement system is an important mediator of inflammation, which plays a pivotal role in atherosclerosis and acute myocardial infarction (AMI). Animal studies suggest that activation of the complement cascade resulting in the formation of soluble membrane attack complex (sMAC), contributes to both atherosclerosis and plaque rupture and may be the direct cause of tissue damage related to ischemia/reperfusion injury. However clinical data of sMAC during an AMI is sparse. Accordingly the aim was to investigate the prognostic role of sMAC in patients with ST-segment elevation myocardial infarction (STEMI). METHODS:We included 725 STEMI-patients admitted to a single, high-volume invasive heart centre, treated with primary percutaneous coronary intervention (PCI), from September 2006 to December 2008. Blood samples were drawn immediately before PCI. Plasma sMAC was measured using an in-house immunoassay. Endpoints were all-cause mortality (n = 62) and the combined endpoint (n = 122) of major cardiovascular events (MACE) defined as cardiovascular mortality and admission due recurrent AMI or heart failure. Follow-up time was 12 months. RESULTS:During 12 months of follow-up 62 patients died from all causes and 122 patients reached the combined end-point of MACE. Patients with high sMAC (>75th percentile) had increased risk of both all-cause mortality and MACE. Even after adjustment for confounding risk factors by Cox-regression analyses, high levels of sMAC remained an independent predictor of all-cause mortality (hazard ratio 1.81 [95% CI 1.06-3.06; P = .029]) and MACE (hazard ratio 1.70 [95% CI 1.16-2.48; P = .006]). CONCLUSIONS:High plasma sMAC independently predicts all-cause mortality and MACE in STEMI-patients treated with PCI.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:Circulating microRNAs (miRs) have emerged as potential diagnostic markers in patients with myocardial infarction. Previous studies, however, were based on limited patient numbers and could not assess the relation of miRs to myocardial damage. Moreover, the prognostic value of miRs in ST-elevation myocardial infarction (STEMI) is unknown. The aims of this study were (1) to assess the relation between miR-133a and myocardial damage assessed by cardiovascular magnetic resonance (CMR) imaging and (2) to evaluate the prognostic value of miR-133a in reperfused STEMI. METHODS:MicroRNA-133a concentrations were determined in 216 consecutive patients with STEMI undergoing primary angioplasty less than 12 hours after symptom onset. Patients were categorized into 2 groups defined by the median miR-133a value on admission. Cardiovascular magnetic resonance was performed for assessment of infarct size, myocardial salvage, and microvascular obstruction. The primary clinical end point was the occurrence of major adverse cardiovascular events defined as a composite of death, reinfarction, and new congestive heart failure within 6 months after infarction. RESULTS:All prognostic relevant CMR markers (infarct size, microvascular obstruction, myocardial salvage index) showed significant correlations with circulating miR-133a concentrations (P < .001 for all).The strongest predictors of miR-133a concentrations were the time from symptom onset to reperfusion and the amount of the salvaged area at risk. Major adverse cardiovascular events occurred significantly more often in the miR-133a ≥ median group (9% vs 20%, P = .025). However, miR-133a concentrations were unable to independently predict clinical events. CONCLUSIONS:Elevated levels of circulating miR-133a in patients with STEMI are associated with decreased myocardial salvage, larger infarcts, and more pronounced reperfusion injury. Consequently, miR-133a concentrations can provide prognostic information but do not add independent prognostic information to traditional and CMR markers of clinical prognosis in a high-risk STEMI population.

背景与目标：

BACKGROUND & AIMS: :Myocardial extracellular volume fraction (ECV) reflecting diffuse myocardial fibrosis can be measured with T1 mapping cardiovascular magnetic resonance (CMR) before and after the application of a gadolinium-based extracellular contrast agent. The equilibrium between blood and myocardium contrast concentration required for ECV measurements can be obtained with a primed contrast infusion (equilibrium contrast-CMR). We hypothesized that equilibrium can also be achieved with a single contrast bolus to accurately measure diffuse myocardial fibrosis in patients with congenital heart disease (CHD). Healthy controls (n = 17; median age 24.0 years) and patients with CHD (n = 19; 25.0 years) were prospectively enrolled. Using modified Look-Locker inversion recovery T1 mapping before, 15 min after bolus injection, and during constant infusion of gadolinium-DOTA, T1 values were obtained for blood pool and myocardium of the left ventricle (LV), the interventricular septum (IVS), and the right ventricle (RV) in a single midventricular plane in short axis or in transverse orientation. ECV of LV, IVS and RV by bolus-only and bolus-infusion correlated significantly in CHD patients (r = 0.94, 0.95, and 0.74; p < 0.01, respectively) and healthy controls (r = 0.96, 0.89, and 0.64; p < 0.05, respectively). Bland-Altman plots revealed no significant bias between the techniques for any of the analyzed regions. ECV of LV and RV myocardium measured by bolus-only T1 mapping agrees well with bolus-infusion measurements in patients with CHD. The use of a bolus-only approach facilitates the integration of ECV measurements into existing CMR imaging protocols, allowing for assessment of diffuse myocardial fibrosis in CHD in clinical routine.

背景与目标： : 反映弥漫性心肌纤维化的心肌细胞外体积分数 (ECV) 可以在施用基于g的细胞外造影剂之前和之后用T1映射心血管磁共振 (CMR) 测量。ECV测量所需的血液和心肌对比浓度之间的平衡可以通过灌注对比输注 (平衡对比-CMR) 获得。我们假设，通过单次对比推注也可以实现平衡，以准确测量先天性心脏病 (CHD) 患者的弥漫性心肌纤维化。前瞻性地纳入健康对照 (n   =   17; 中位年龄24.0岁) 和CHD患者 (n   =   19; 25.0岁)。在推注前，推注后15分钟以及在不断输注g-DOTA期间，使用改良的Look-Locker反转恢复T1映射，获得左心室 (LV)，室间隔 (IVS) 的血池和心肌的T1值，和右心室 (RV) 在单个心室中平面中的短轴或横向方向。在CHD患者 (分别为r   =   0.94、0.95和0.74; P  <  0.01) 和健康对照组 (分别为r   =   0.96、0.89和0.64; P  <  0.05) 中，仅推注和推注LV、IVS和RV的ECV显著相关。Bland-Altman图显示，任何分析区域的技术之间都没有明显的偏差。通过仅推注T1映射测量的LV和RV心肌的ECV与冠心病患者的推注测量非常吻合。仅推注方法的使用有助于将ECV测量结果集成到现有的CMR成像协议中，从而可以在临床常规中评估CHD中的弥漫性心肌纤维化。

BACKGROUND & AIMS: BACKGROUND AND OBJECTIVE:Shared decision making and advance planning in end-of-life decisions have become increasingly important aspects of the management of seriously ill patients. Here, we describe the use and timing of do-not-resuscitate (DNR) orders in patients hospitalized with acute myocardial infarction (AMI). STUDY DESIGN AND SETTING:The nonconcurrent prospective study population consisted of 4182 patients hospitalized with AMI in central Massachusetts in four annual periods between 2001 and 2007. RESULTS:One-quarter (25%) of patients had a DNR order written either prior to or during hospitalization. The frequency of DNR orders remained constant (24% in 2001; 26% in 2007). Among patients with DNR orders, there was a significant increase in orders written prior to hospitalization (2001: 9%; 2007: 55%). Older patients and those with a medical history of heart failure or myocardial infarction were more likely to have prior DNR orders than respective comparison groups. Patients with prior DNR orders were less likely to die 1 month after hospitalization than patients whose DNRs were written during hospitalization. CONCLUSION:Although the use of DNR orders in patients hospitalized with AMI was stable during the period under study, in more recent years, patients are increasingly being hospitalized with DNR orders already in place.

背景与目标：

BACKGROUND & AIMS: :Purpose. To evaluate whether 3T clinical MRI with a small-animal coil and gradient-echo (GE) sequence could be used to characterize long-term left ventricular remodelling (LVR) following nonreperfused myocardial infarction (MI) using semi-automatic segmentation software (SASS) in a rat model. Materials and Methods. 5 healthy rats were used to validate left ventricular mass (LVM) measured by MRI with postmortem values. 5 sham and 7 infarcted rats were scanned at 2 and 4 weeks after surgery to allow for functional and structural analysis of the heart. Measurements included ejection fraction (EF), end-diastolic volume (EDV), end-systolic volume (ESV), and LVM. Changes in different regions of the heart were quantified using wall thickness analyses. Results. LVM validation in healthy rats demonstrated high correlation between MR and postmortem values. Functional assessment at 4 weeks after MI revealed considerable reduction in EF, increases in ESV, EDV, and LVM, and contractile dysfunction in infarcted and noninfarcted regions. Conclusion. Clinical 3T MRI with a small animal coil and GE sequence generated images in a rat heart with adequate signal-to-noise ratio (SNR) for successful semiautomatic segmentation to accurately and rapidly evaluate long-term LVR after MI.

背景与目标： : 目的。评估是否可以使用半自动分割软件 (SASS) 在大鼠模型中使用带有小动物线圈和梯度回波 (GE) 序列的3t临床MRI来表征非再灌注心肌梗死 (MI) 后的长期左心室重塑 (LVR)。材料和方法。5只健康大鼠用于验证MRI测量的左心室质量 (LVM) 和死后值。在手术后2周和4周对5只假手术大鼠和7只梗死大鼠进行扫描，以进行心脏的功能和结构分析。测量包括射血分数 (EF)，舒张末期容积 (EDV)，收缩末期容积 (ESV) 和LVM。使用壁厚分析来量化心脏不同区域的变化。结果。健康大鼠的LVM验证表明MR与死后值之间存在高度相关性。MI后4周的功能评估显示EF显着降低，ESV，EDV和LVM增加以及梗塞和非梗塞区域的收缩功能障碍。结论。具有小动物线圈和GE序列的临床3T MRI在大鼠心脏中生成的图像具有足够的信噪比 (SNR)，可成功进行半自动分割，以准确，快速地评估MI后的长期LVR。

BACKGROUND & AIMS: BACKGROUND:Reductions in admissions for myocardial infarction (MI) have been reported in locales where smoke-free workplace laws have been implemented, but no study has assessed sudden cardiac death in that setting. In 2002, a smoke-free restaurant ordinance was implemented in Olmsted County, Minnesota, and in 2007, all workplaces, including bars, became smoke free. METHODS:To evaluate the population impact of smoke-free laws, we measured, through the Rochester Epidemiology Project, the incidence of MI and sudden cardiac death in Olmsted County during the 18-month period before and after implementation of each smoke-free ordinance. All MIs were continuously abstracted and validated, using rigorous standardized criteria relying on biomarkers, cardiac pain, and Minnesota coding of the electrocardiogram. Sudden cardiac death was defined as out-of-hospital deaths associated with coronary disease. RESULTS:Comparing the 18 months before implementation of the smoke-free restaurant ordinance with the 18 months after implementation of the smoke-free workplace law, the incidence of MI declined by 33% (P < .001), from 150.8 to 100.7 per 100,000 population, and the incidence of sudden cardiac death declined by 17% (P = .13), from 109.1 to 92.0 per 100,000 population. During the same period, the prevalence of smoking declined and that of hypertension, diabetes mellitus, hypercholesterolemia, and obesity either remained constant or increased. CONCLUSIONS:A substantial decline in the incidence of MI was observed after smoke-free laws were implemented, the magnitude of which is not explained by community cointerventions or changes in cardiovascular risk factors with the exception of smoking prevalence. As trends in other risk factors do not appear explanatory, smoke-free workplace laws seem to be ecologically related to these favorable trends. Secondhand smoke exposure should be considered a modifiable risk factor for MI. All people should avoid secondhand smoke to the extent possible, and people with coronary heart disease should have no exposure to secondhand smoke.

背景与目标：

BACKGROUND & AIMS: AIMS:We sought to evaluate bleeding complications and periprocedural outcomes of the radial approach (RA) as compared to the femoral approach (FA) during percutaneous coronary intervention (PCI) in "real-world" patients with ST-segment elevation myocardial infarction (STEMI). METHODS AND RESULTS:The study group consisted of 22,812 consecutive patients with STEMI treated with PCI and stent implantation between January 2014 and June 2015 in 151 tertiary invasive cardiology centres in Poland (the ORPKI Polish National Registry). Patients treated using the RA and FA were compared using a propensity score analysis to avoid possible selection bias. The analysis was carried out in an "as-treated" manner. The FA was used in 9,334 (40.9%) and the RA in 13,478 (59.1%) patients. After propensity score matching, a higher total amount of contrast (191.8±8.0 vs. 174.8±68.8 ml; p=0.001) and lower radiation doses (1,279.5±1,346.3 vs. 1,182.6±887 mGy; p=0.02) were reported in FA. More access-site-related bleeding complications after both angiography (0.17% vs. 0.02%; p=0.004) and PCI (0.23% vs. 0.09%; p=0.049) were reported in the FA group. Periprocedural death (1.94% vs. 0.93%; p=0.001) was more common after PCI performed with the FA. CONCLUSIONS:The radial approach was associated with a lower incidence of periprocedural death in STEMI patients as well as a significant reduction of bleeding complications at the access site.

背景与目标：

BACKGROUND & AIMS: :Although low-dose acetylsalicylic acid (ASA) is recommended for prevention of cardiovascular events in at-risk patients, its long-term use can be associated with the risk of peptic ulcer and upper gastrointestinal (GI) symptoms that may impact treatment compliance. This prespecified secondary analysis of the OBERON study (NCT00441727) determined the efficacy of esomeprazole for prevention/resolution of low-dose ASA-associated upper GI symptoms. A post hoc analysis of predictors of symptom prevention/resolution was also conducted. Helicobacter pylori-negative patients taking low-dose ASA (75-325 mg) for cardiovascular protection who had ≥1 upper GI risk factor were eligible. The patients were randomized to once-daily esomeprazole 40 mg, 20 mg, or placebo, for 26 weeks; 2303 patients (mean age 67.6 years; 36% aged >70 years) were evaluable for upper GI symptoms. The proportion of patients with dyspeptic or reflux symptoms (self-reported Reflux Disease Questionnaire) was significantly lower (P < 0.0001) in those treated with esomeprazole versus in those treated with placebo. Treatment with esomeprazole (P < 0.0001), age >70 years (P < 0.01), and the absence of upper GI symptoms at baseline (P < 0.0001) were all factors associated with prevention/resolution of upper GI symptoms. Together, these analyses demonstrate that esomeprazole is effective in preventing and resolving patient-reported upper GI symptoms in low-dose ASA users at increased GI risk.

背景与目标： : 尽管低剂量乙酰水杨酸 (ASA) 被推荐用于预防高危患者的心血管事件，但长期使用可能与消化性溃疡和上消化道 (GI) 症状的风险有关，这可能会影响治疗依从性。这项预先设定的OBERON研究 (NCT00441727) 的二次分析确定了埃索美拉唑预防/缓解低剂量ASA相关上消化道症状的疗效。还对症状预防/解决的预测因素进行了事后分析。幽门螺杆菌阴性患者服用低剂量ASA (75-325 mg) 进行心血管保护，且上消化道危险因素 ≥ 1。患者被随机分配至每日一次埃索美拉唑40 mg、20 mg或安慰剂，持续26周; 2303患者 (平均年龄67.6岁; 36% 年龄> 70岁) 可评估上消化道症状。与安慰剂组相比，使用埃索美拉唑治疗的患者有消化不良或反流症状 (自我报告的反流疾病问卷) 的比例显著降低 (P <0.0001)。埃索美拉唑治疗 (P < 0.0001) 、年龄> 70岁 (P < 0.01) 和基线时没有上消化道症状 (P < 0.0001) 都是与预防/缓解上消化道症状相关的因素。总之，这些分析表明，埃索美拉唑可有效预防和解决患者报告的上消化道症状，在胃肠道风险增加的低剂量ASA使用者中。

BACKGROUND & AIMS: OBJECTIVE:Statins reduce inflammation and risk of myocardial infarction (MI). Because the myeloid IgA Fc receptor encoded by FCAR mediates inflammation, we hypothesized that the FCAR Asp92Asn polymorphism is associated with risk of MI and that this risk would be modified by pravastatin. METHODS AND RESULTS:In the placebo arm of the Cholesterol and Recurrent Events (CARE) study, male carriers of the 92Asn allele had an adjusted hazard ratio for incident MI of 1.68 (95% CI 1.10 to 2.57); relative risk reduction by pravastatin was 69% in carriers and 12% in noncarriers (P(interaction)=0.007). In the placebo arm of the all-male West of Scotland Coronary Prevention Study (WOSCOPS), carriers had an adjusted odds ratio for incident coronary heart disease (CHD) of 1.46 (90% CI 1.05 to 2.03); for pravastatin compared with placebo treatment, the adjusted odds ratios were 0.55 (95% CI 0.32 to 0.93) in carriers and 0.65 (95% CI 0.51 to 0.83) in noncarriers (P(interaction)=0.55). CONCLUSIONS:Carriers of 92Asn had increased risk of MI in CARE and increased odds of CHD in WOSCOPS. Pravastatin significantly reduced risk in carriers in both CARE and WOSCOPS. A genotype by treatment interaction was observed in CARE but not in WOSCOPS.

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