Intensive statin therapy in acute coronary syndromes: clinical benefits and vascular biology

PURPOSE OF REVIEW: The results of a landmark clinical study comparing intensive statin therapy with conventional statin therapy, in patients with acute coronary syndromes (ACS), are reviewed. The mechanisms behind these results are analysed drawing data from vascular and cell biology. RECENT FINDINGS: The Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction (PROVE IT-TIMI 22) study showed that intensive statin therapy with 80 mg of atorvastatin to achieve a low-density lipoprotein cholesterol of 62 mg/dl resulted in a 3.9% absolute and a 16% relative risk reduction in death or major cardiovascular events up to 2 years, compared to 40 mg of pravastatin, in patients with ACS. The results were especially significant as intensive statin therapy resulted in a very early benefit (<30 days) and occurred against a background of percutaneous coronary intervention (69%) for the index admission and high use of medications for secondary prevention. The PROVE IT and the Myocardial Ischaemia Reduction with Aggressive Cholesterol Lowering (MIRACL) C-reactive protein sub-study also showed that atorvastatin (80 mg) resulted in a significant reduction in markers of inflammation, whilst the Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) study showed that intensive statin therapy was associated with reduced progression of atherosclerosis compared with conventional doses of statins. SUMMARY: Intensive statin therapy results in a significant early reduction in adverse cardiac events in ACS patients which are sustained over 2 years. The early benefits seen are likely to result from modulation of inflammation, endothelial function and coagulation, i.e. the pleiotropic effects, whereas the greater reduction in low-density lipoprotein cholesterol results in reduced long-term events.     

Fluvastatin in the therapy of acute coronary syndrome: Rationale and design of a multicenter, randomized, double-blind, placebo-controlled trial (The FACS Trial)[ISRCTN81331696

BACKGROUND: Activation of inflammatory pathways plays an important contributory role in coronary plaque instability and subsequent rupture, which can lead to the development of acute coronary syndrome (ACS). Elevated levels of serum inflammatory markers such as C-reactive protein (CRP) represent independent risk factors for further cardiovascular events. Recent evidence indicates that in addition to lowering cholesterol levels, statins also decrease levels of inflammatory markers. Previous controlled clinical trials reporting the positive effects of statins in participants with ACS were designed for very early secondary prevention. To our knowledge, no controlled trials have evaluated the potential benefits of statin therapy, beginning immediately at the time of hospital admission. A previous pilot study performed by our group focused on early initiation of cerivastatin therapy. We demonstrated a highly significant reduction in levels of inflammatory markers (CRP and interleukin-6). Based on these preliminary findings, we are conducting a clinical trial to evaluate the efficacy of another statin, fluvastatin, as an early intervention in patients with ACS. METHODS: The FACS-trial (Fluvastatin in the therapy of Acute Coronary Syndrome) is a multicenter, randomized, double-blind, placebo-controlled study evaluating the effects of fluvastatin therapy initiated at the time of hospital admission. The study will enroll 1,000 participants admitted to hospital for ACS (both with and without ST elevation). The primary endpoint for the study is the influence of fluvastatin therapy on levels of inflammatory markers (CRP and interleukin-6) and on pregnancy associated plasma protein A (PAPP-A). A combined secondary endpoint is 30-day and one-year occurrence of death, nonfatal myocardial infarction, recurrent symptomatic ischemia, urgent revascularization, and cardiac arrest. CONCLUSION: The primary objective of the FACS trial is to demonstrate that statin therapy, when started immediately after hospital admission for ACS, results in reduction of inflammation and improvement of prognosis. This study may contribute to new knowledge regarding therapeutic strategies for patients suffering from ACS and may offer additional clinical indications for the use of statins.     

HEART与GRACE危险评分对急性冠脉综合征患者危险分层的对比研究

目的:探讨HEART与GRACE危险评分对急性冠脉综合症(ACS)患者主要心血管不良事件(MACE)发生的预测应用价值。方法:回顾性分析自2015年6月至2018年6月就诊于我院急诊入院的ACS患者591例,分别使用HEART与GRACE危险评分对研究对象进行危险分层(低危组,中危组,高危组),随访患者发病后90天MACE发生情况,分析不同危险分层ACS患者发病后90天MACE发生情况与评分之间的关系,并比较两种评分对ACS患者90天发生MACE事件的预测能力。结果:本研究纳入371例患者,其中男性324例(87.3%),女性47例(12.7%),年龄(58±11.70)岁;167患者(45.1%)在3个月内发生MACE。随着HEART和GRACE危险评分越高,发病90天发生MACE事件的发生率显著增加(P<0.05),HEART评分中高危组预测MACE准确性较GRACE评分高,GRACE评分低危险组预测MACE准确性较HEART评分高。HEART和GRACE评分对ACS患者预测MACE敏感性分别为76.51%,64.73%,特异性分别为96.71%,96.25%。HEART评分具有良好的预测价值,其ROC曲线下面积为0.908(95%CI 0.846~0.974),与GRACE评分ROC曲线下面积的0.801相比,差异有统计学意义(P<0.05)。结论:HEART和GRACE评分都可以应用于ACS患者的危险分层,预后评估和预测MACE发生,但HEART危险评分更可靠。     

急性心肌梗死患者血清外连素、MEG3、HSP-70水平与心肌损伤标志物及心血管不良事件的关系研究

目的:研究急性心肌梗死(AMI)患者血清外连素、母系表达基因3(MEG3)、热休克蛋白70(HSP-70)水平与心肌损伤标志物及心血管不良事件的关系。方法:选取2015年1月-2020年1月期间我院接受治疗的AMI患者200例作为AMI组,另选取同期在我院健康体检的人群100例作为对照组,对比对照组、AMI组心肌型肌酸激酶同工酶(CK-MB)、肌红蛋白(Myo)、心肌肌钙蛋白Ⅰ(cTnI)、外连素、MEG3 RNA、HSP-70。对比心血管不良事件与非心血管不良事件患者的CK-MB、Myo、cTnI、外连素、MEG3 RNA、HSP-70水平。采用Pearson相关性分析AMI患者血清外连素、MEG3 RNA、HSP-70水平与心肌损伤标志物的关系。结果:AMI组CK-MB、Myo、cTnI、外连素、MEG3 RNA、HSP-70均高于对照组(P<0.05)。随访过程中,有59例发生心血管不良事件纳为心血管不良事件组,剩余141例未发生心血管不良事件纳为非心血管不良事件组。心血管不良事件组患者的CK-MB、Myo、cTnI、外连素、MEG3 RNA、HSP-70均高于非心血管不良事件组(P<0.05)。AMI患者外连素、MEG3 RNA、HSP-70水平与CK-MB、Myo、cTnI均呈正相关(P<0.05)。结论:AMI患者中外连素、MEG3 RNA、HSP-70均呈现异常高表达,且与心肌损伤标志物密切相关,可考虑作为AMI患者早期确诊的新型标志物。     

低风险胸痛急性冠状动脉综合征患者心电图特征及其对诊断的价值研究

摘要 目的：分析低风险胸痛急性冠状动脉综合征(acute coronary syndrome,ACS)患者心电图特征及其对诊断的价值。方法：选择我院自2017年1月至2019年8月接诊的194例疑似低风险胸痛ACS患者,均采取心电图检查和冠状动脉造影检查;分析低风险胸痛ACS患者的心电图特征,观察心电图结果与冠状动脉病变支数、狭窄程度的关系,计算心电图诊断低风险胸痛ACS的特异性、敏感性等效能指标,使用受试者工作特征(receiver operating characteristic,ROC)曲线下面积(curve,AUC)定量分析ST段偏移值预测主要不良心血管事件的效能。结果：在194例疑似低风险胸痛ACS患者中,低风险胸痛ACS患者134例,低风险不稳定型心绞痛(UA)患者心电图表现以ST-T缺血性改变为主,发作时改变明显或呈现伪性改善;低风险非ST段抬高的心肌梗死(non-ST-segment elevation myocardial infarction,NSTEMI)患者心电图表现为肢体和胸导联ST段压低,T波低平、倒置,ST-T改变持续存在和呈动态衍变;低风险胸痛ACS患者心电图结果与冠状动脉病变支数无关(P＞0.05),与狭窄程度有关(P＜0.05);心电图诊断低风险胸痛ACS的特异性为71.67 %,敏感性为69.40 %,阳性预测值为84.55 %,阴性预测值为51.19 %,符合率为70.62 %;所有患者均获得随访,经ROC曲线分析,ST段偏移值预测低风险胸痛ACS患者发生主要不良心血管事件的最佳截值为1.85 mm,AUC为0.695,对比全球急性冠状动脉事件注册(GRACE)风险评分的0.675,差异无统计学意义(P＞0.05)。结论：低风险胸痛ACS患者心电图具有多样化,与冠状动脉狭窄程度有关,有助于初步诊断和风险评估,且ST段偏移值预测主要不良心血管事件的效能较好,值得进一步研究应用。     

The Association between Triglyceride/High-Density Lipoprotein Cholesterol Ratio and All-Cause Mortality in Acute Coronary Syndrome after Coronary Revascularization

Aims

High triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C) are cardiovascular risk factors. A positive correlation between elevated TG/HDL-C ratio and all-cause mortality and cardiovascular events exists in women. However, utility of TG to HDL-C ratio for prediction is unknown among acute coronary syndrome (ACS).

Methods

Fasting lipid profiles, detailed demographic data, and clinical data were obtained at baseline from 416 patients with ACS after coronary revascularization. Subjects were stratified into three levels of TG/HDL-C. We constructed multivariate Cox-proportional hazard models for all-cause mortality over a median follow-up of 3 years using log TG to HDL-C ratio as a predictor variable and analyzing traditional cardiovascular risk factors. We constructed a logistic regression model for major adverse cardiovascular events (MACEs) to prove that the TG/HDL-C ratio is a risk factor.

Results

The subject’s mean age was 64 ± 11 years; 54.5% were hypertensive, 21.8% diabetic, and 61.0% current or prior smokers. TG/HDL-C ratio ranged from 0.27 to 14.33. During the follow-up period, there were 43 deaths. In multivariate Cox models after adjusting for age, smoking, hypertension, diabetes, and severity of angiographic coronary disease, patients in the highest tertile of ACS had a 5.32-fold increased risk of mortality compared with the lowest tertile. After adjusting for conventional coronary heart disease risk factors by the logistic regression model, the TG/HDL-C ratio was associated with MACEs.

Conclusion

The TG to HDL-C ratio is a powerful independent predictor of all-cause mortality and is a risk factor of cardiovascular events.     

Prevalence and in-hospital outcomes of diabetes among patients with acute coronary syndrome in China: findings from the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome Project

Background

Guidelines have classified patients with acute coronary syndrome (ACS) and diabetes as a special population, with specific sections presented for the management of these patients considering their extremely high risk. However, in China up-to-date information is lacking regarding the burden of diabetes in patients with ACS and the potential impact of diabetes status on the in-hospital outcomes of these patients. This study aims to provide updated estimation for the burden of diabetes in patients with ACS in China and to evaluate whether diabetes is still associated with excess risks of early mortality and major adverse cardiovascular and cerebrovascular events (MACCE) for ACS patients.

Methods

The Improving Care for Cardiovascular Disease in China-ACS Project was a collaborative study of the American Heart Association and the Chinese Society of Cardiology. A total of 63,450 inpatients with a definitive diagnosis of ACS were included. Prevalence of diabetes was evaluated in the overall study population and subgroups. Multivariate logistic regression was performed to examine the association between diabetes and in-hospital outcomes, and a propensity-score-matched analysis was further conducted.

Results

Among these ACS patients, 23,880 (37.6%) had diabetes/possible diabetes. Both STEMI and NSTE-ACS patients had a high prevalence of diabetes/possible diabetes (36.8% versus 39.0%). The prevalence of diabetes/possible diabetes was higher in women (45.0% versus 35.2%, p?<?0.001). Even in patients younger than 45 years, 26.9% had diabetes/possible diabetes. While receiving comparable treatments for ACS, diabetes/possible diabetes was associated with a twofold higher risk of all-cause death (adjusted odds ratio 2.04 [95% confidence interval 1.78–2.33]) and a 1.5-fold higher risk of MACCE (adjusted odds ratio 1.54 [95% confidence interval 1.39–1.72]).

Conclusions

Diabetes was highly prevalent in patients with ACS in China. Considerable excess risks for early mortality and major adverse cardiovascular events were found in these patients.Trial registration NCT02306616. Registered December 3, 2014

     

Intracoronary versus Intravenous Administration of Abciximab in Patients with Acute Coronary Syndrome: A Meta-Analysis

Background

Abciximab is a widely used adjunctive therapy for acute coronary syndrome (ACS). However, the effect of intracoronary (IC) administration of abciximab on cardiovascular events remains unclear when compared with intravenous (IV) therapy.

Methodology and Principal Findings

We systematically searched the Medline, Embase, and Cochrane Central Register of Controlled Trials databases and reference lists of articles and proceedings of major meetings for obtaining relevant literature. All eligible trials included ACS patients who received either IC administration of abciximab or IV therapy. The primary outcome was major cardiovascular events, and secondary outcomes included total mortality, reinfarction, and any possible adverse events. Of 660 identified studies, we included 9 trials reporting data on 3916 ACS patients. Overall, IC administration of abciximab resulted in 45% reduction in relative risk for major cardiovascular events (RR; 95% confidence interval [CI], 24−60%), 41% reduction in RR for reinfarction (95% CI, 7−63%), and 44% reduction in RR for congestive heart failure relative to IV therapy (95% CI, 8−66%); however, compared to IV therapy, IC administration of abciximab had no effect on total mortality (RR, 0.69; 95% CI, 0.45−1.07). No other significant differences were identified between the effect of IC abciximab administration and IV therapy.

Conclusions/Significance

IC administration of abciximab can reduce the risk of major cardiovascular events, reinfarction, and congestive heart failure when compared with IV therapy.     

替格瑞洛在急性冠脉综合征患者经皮冠状动脉介入治疗术后的应用价值

目的:评价替格瑞洛在急性冠脉综合征(acute coronary syndrome,ACS)患者经皮冠状动脉介入治疗(percutaneous coronary intervention,PCI)术后的应用价值。方法:将我院收治的565例成功行PCI的急性冠脉综合征(acute coronary syndrome,ACS)患者随机分为2组:氯吡格雷组253例,术后口服氯吡格雷75 mg、QD;替格瑞洛组312例,术后口服替格瑞洛首剂180 mg,维持量90mg、BID。两组患者术后常规口服阿司匹林100 mg、QD。研究主要终点为主要不良心血管事件(major adverse cardiovascular events,MACE),包括全因死亡、靶血管血运重建和脑梗塞;次要终点为TIMI主要出血(定义为血红蛋白下降50 g/L或颅内出血有关的临床显著出血事件)。结果:565例患者平均随访12个月,替格瑞洛组MACE发生率低于氯吡格雷组(3.8%vs.8.7%,P0.05),两组TIMI主要出血事件发生率比较,差异无统计学意义(2.9%vs.3.2%,P0.05)。结论:替格瑞洛能明显减少PCI术后主要不良心血管事件,并不增加主要出血。     

Elevated homocysteine level and prognosis in patients with acute coronary syndrome: a meta-analysis

Objective: Controversial results exist with respect to the association between elevated homocysteine level and adverse prognosis in acute coronary syndrome (ACS) patients. We performed a meta-analysis to evaluate the prognostic value of homocysteine level on ACS patients.

Materials and methods: A comprehensive literature search of PubMed and Embase databases was conducted prior to August 2018. Prospective observational studies reporting the association of baseline homocysteine level with major adverse cardiovascular events (MACE), cardiovascular or all-cause mortality in ACS patients were selected. Pooled risk ratio (RR) and corresponding 95% confidence intervals (CI) were calculated for the highest versus the lowest homocysteine level.

Results: Ten studies including 4120 ACS patients were identified. ACS patients with the highest homocysteine level had an increased risk of MACE (RR 2.01; 95% CI 1.53–2.64) and all-cause mortality (RR 2.05; 95% CI 1.50–2.79) after controlling confounding factors. However, the association between elevated homocysteine level and cardiovascular mortality (RR 1.08; 95% CI 0.83–1.39) was not statistically significant.

Conclusions: Elevated homocysteine level was associated with an increased risk of MACE and all-cause mortality among ACS patients. However, the association of elevated homocysteine level with cardiovascular mortality in ACS patients should be further confirmed in future studies.     

Chemokines CCL3/MIP1α, CCL5/RANTES and CCL18/PARC are Independent Risk Predictors of Short-Term Mortality in Patients with Acute Coronary Syndromes

Cytokines play an important role in ischemic injury and repair. However, little is known about their prognostic value in cardiovascular disease. The aim of this study was to investigate the prognostic importance of chemokines CCL3/MIP-1α, CCL5/RANTES and CCL18/PARC for the risk of future cardiovascular events in patients with acute coronary syndromes (ACS). Baseline levels of CCL3/MIP-1α, CCL5/RANTES and CCL18/PARC were determined in ACS patients from the Bad Nauheim ACS II registry (n = 609). During the following 200 days, patients were monitored for the occurrence of fatal and non-fatal cardiovascular events. Patients with CCL3/MIP1α, CCL5/RANTES and CCL18/PARC concentrations in the highest tertile were associated with an increased risk of a fatal event during follow-up (HR: 2.19, 95%CI: 1.04–4.61 for CCL3/MIP1α, HR: 3.45, 95%CI: 1.54–7.72 for CCL5/RANTES and HR: 3.14, 95%CI: 1.33–7.46 for CCL18/PARC). This risk was highest for patients with all three biomarkers concentrations in the upper tertile (HR: 2.52, 95%CI: 1.11–5.65). Together with known risk predictors of cardiovascular events, CCL3/MIP-1α, CCL5/RANTES and CCL18/PARC combined improved the c-statistics from 0.74 to 0.81 (p = 0.007). In conclusion, CCL3/MIP-1α, CCL5/RANTES and CCL18/PARC are independently associated with the risk of short-term mortality in ACS patients. Combining all three biomarkers further increased their prognostic value.     

Pre-hospital point-of-care troponin measurement: a clinical example of its additional value

In the majority of patients with chest pain, an acute coronary syndrome (ACS) can be ruled out. However, early recognition of an ACS is required in order to start treatment as soon as possible and reduce risks associated with myocardial ischaemia. Because of the lack of pre-hospital protocols to rule out an ACS, patients with a suspected ACS are transported to the emergency department, where the HEART score can be used to estimate the risk of major adverse cardiac events (MACE). Patients with a low HEART score have a low risk of MACE. A point-of-care (POC) troponin measurement enables ambulance paramedics to calculate the HEART score in the pre-hospital setting. POC troponin measurement and HEART score assessment have several potential advantages, including early recognition of an ACS and identification of high-risk patients before hospital arrival. Moreover, pre-hospital rule-out of an ACS could prevent unnecessary emergency department visits. The safety and cost-effectiveness of referring low-risk patients with a normal POC troponin value to the general practitioner are currently being investigated in the ARTICA randomised trial. This point-of-view article demonstrates one of the potential advantages of early detection of an ACS.

     

Total knee replacement surgery is followed by transitory endothelial dysfunction

Acute coronary syndrome (ACS) presents today the leading group of post-operative cardiovascular complications, while endothelial dysfunction (ED) is one of the key elements in its development. The chronic ED represents thus the basis for the gradual development of atherosclerotic changes, while its sudden aggravation leads to ACS. The persistent ED occurs due to the effects of chronic cardiovascular risk factors, while according to the available studies it can also develop or aggravate under the impact of different acute events. We have directed this study to the investigation of the dynamic of endothelial function before and after a major orthopaedic surgical intervention. This randomised prospective study included 19 patients that underwent the intervention of total knee replacement and 20 healthy examinees of the adequate age and gender High-resolution ultrasound test based on the flow mediated dilatation of the brachial artery is what at we carried out at the beginning of the research, respectively 12, 24, 48 and 72 hours, as well as 7 days after the surgical intervention. The starting values of the FMD test were within the normal range in both groups, although the ability of dilatation upon stimulus was significantly lower in the investigated group. The FMD percentage change in the total sample was negatively connected with the body weight, not having shown additional connections with other cardiovascular risk factors. During the early post-operative period, a significant transitory lowering of the FMD percentage change was recorded, having reached the lowest value 24 hours after the surgery. During the seven-day prospective surveillance, no significant cardiovascular complications were recorded. Further research is necessary in order to confirm these results as well as the testing of the possible connection of the described post-operative transitory endothelial dysfunction with the development of cardiovascular complications and the adverse event.     

Use of CHADS2 and CHA2DS2-VASc Scores to Predict Subsequent Myocardial Infarction,Stroke, and Death in Patients with Acute Coronary Syndrome: Data from Taiwan Acute Coronary Syndrome Full Spectrum Registry

Background

Acute coronary syndrome (ACS) patients have a wide spectrum of risks for subsequent cardiovascular events and death. However, there is no simple, convenience scoring system to identify risk of adverse outcomes. We investigated whether CHADS₂ and CHA₂DS₂-VASc scores were useful tools to assess the risk for adverse events among ACS patients.

Methods

This observational prospective study was conducted at 39 hospitals. Totally 3,183 patients with ACS were enrolled, and CHADS₂ and CHA₂DS₂-VASc scores were calculated. The primary endpoint was occurrence of adverse event, including subsequent myocardial infarction, stroke, or death, within 1 year of discharge.

Results

CHADS₂ and CHA₂DS₂-VASc scores were significant predictors of adverse events in separate multivariate regression analyses. A Kaplan-Meier analysis of CHADS₂ and CHA₂DS₂-VASc scores of ≥2 showed a higher rate of adverse events as compared with scores of <2 (P<0.001;log-rank test). CHA₂DS₂-VASc score was better than CHADS₂ score in predicting subsequent adverse events; the area under the receiver operating characteristic curve increased from 0.66 to 0.70 (p<0.001). Patients with CHADS₂ scores of 0 or 1 were further classified according to CHA₂DS₂-VASc score, using a cutoff value of 2. The rate of adverse events significantly differed between those with a score of <2 and those with a score of ≥2 (4.1% vs.10.7%, P<0.001).

Conclusions

CHADS₂ and CHA₂DS₂-VASc scores were useful predictors of subsequent adverse events in ACS patients.     

坐式八段锦联合运动康复治疗对急性冠脉综合征PCI术后患者运动耐力、血清心肌损伤标志物和生活质量的影响

摘要 目的：探讨坐式八段锦联合运动康复治疗对急性冠脉综合征（ACS）经皮冠状动脉介入治疗术（PCI）后患者运动耐力、血清心肌损伤标志物和生活质量的影响。方法：根据随机数字表法,将我院2020年4月~2021年5月期间收治的ACS行PCI术的患者（n=120）分为对照组（运动康复治疗,n=60）和研究组（坐式八段锦联合运动康复治疗,n=60）。对比两组心功能指标[左心室舒张末期内径（LVEDD）、左心室射血分数（LVEF）、氨基末端B型脑利钠肽前体（NT-proBNP）、左心室舒张末期容积（LVEDV）]、心肌损伤标志物[肌酸激酶同工酶（CK-MB）、心肌肌钙蛋白I（cTnI）]、运动耐力指标[无氧阈（AT）、最大摄氧量（VO_2max ）、运动持续时间（ED）]和生活质量[西雅图心绞痛量表（SAQ）评分：躯体活动受限程度（PL）、心绞痛稳定情况（AS）、疾病认知程度（DS）、心绞痛发作状况（AF）和治疗满意程度（TS）],并纪录两组不良心血管事件发生情况。结果：研究组的心血管不良事件发生率低于对照组（P<0.05）。研究组治疗3个月后LVEF高于对照组,LVEDD、LVEDV、NT-proBNP低于对照组（P<0.05）。研究组治疗3个月后CK-MB、cTnI低于对照组（P<0.05）。研究组治疗3个月后AT、VO_2max 、ED高于对照组（P<0.05）。研究组治疗3个月后PL、AS、DS、AF、TS评分高于对照组（P<0.05）。结论：坐式八段锦联合运动康复治疗可促进ACS患者PCI术后心功能改善,减轻心肌损伤,进而提高运动耐力和生活质量。     

Use of low‐dose quetiapine increases the risk of major adverse cardiovascular events: results from a nationwide active comparator‐controlled cohort study

At standard doses used for schizophrenia or bipolar disorder, quetiapine has been associated with weight gain and increased levels of triglycerides, to­tal cholesterol and low‐density lipoprotein (LDL) cholesterol, which are risk factors for cardiovascular morbidity and mortality. However, this drug is also commonly used off‐label at low doses for anxiolytic or hypnotic purposes, and its cardiovascular safety at these doses is unknown. We aimed to assess the risk of major adverse cardiovascular events with use of low‐dose quetiapine compared to use of Z‐drug hypnotics in a nationwide, active comparator‐controlled cohort study. The cohort included new users of either drugs in Denmark from 2003 to 2017, aged 18‐85 years, without history of ischemic stroke, myocardial infarction, cancer, and severe mental illness. The main outcome was the occurrence of major adverse cardiovascular events, defined as non‐fatal myocardial infarction or ischemic stroke, or death from cardiovascular causes. Selective serotonin reuptake inhibitors (SSRIs) were used as an alternative comparator in sensitivity analyses. Altogether, we compared 60,566 low‐dose quetiapine users with 454,567 Z‐drug users, followed for 890,198 person‐years in intent‐to‐treat analysis, and 330,334 person‐years in as‐treated analysis. In intention‐to‐treat analysis, low‐dose quetiapine was associated with an increased risk of major adverse cardiovascular events (adjusted hazard ratio, aHR=1.13, 95% CI: 1.02‐1.24, p=0.014) and cardiovascular death (aHR=1.26, 95% CI: 1.11‐1.43, p<0.001). In as‐treated analysis, continuous low‐dose quetiapine use was associated with increased risk of major adverse cardiovascular events (aHR=1.52, 95% CI: 1.35‐1.70, p<0.001), non‐fatal ischemic stroke (aHR=1.37, 95% CI: 1.13‐1.68, p=0.002) and cardiovascular death (aHR=1.90, 95% CI: 1.64‐2.19, p<0.001). The risk of major adverse cardiovascular events was greater in women (aHR=1.28, p=0.02) and those aged ≥65 years at initiation (aHR=1.24, p<0.001). Compared to SSRIs, low‐dose quetiapine use was associated with an increased risk of major adverse cardiovascular events (aHR=1.42, p<0.001), non‐fatal ischemic stroke (aHR=1.27, p=0.0028) and cardiovascular death (aHR=1.72, p<0.001). So, we conclude that the use of low‐dose quetiapine is associated with an increased risk of major adverse cardiovascular events, especially in women and the elderly. On the basis of these findings, we suggest that use of off‐label low‐dose quetiapine for sedative or hypnotic purposes should be discouraged.     

Soluble urokinase plasminogen activator receptor as a long-term prognostic biomarker in acute coronary syndromes

Abstract

Purpose: The aim of our study was to analyse the long-term prognostic value of soluble urokinase plasminogen activator receptor (suPAR) in the setting of an acute coronary syndrome (ACS).

Methods: We included 340 patients with an ACS who underwent coronary angiography and plasma suPAR concentration was measured. Patients were classified into low suPAR concentrations (<2.6?ng/mL) and high suPAR concentrations (≥2.6?ng/mL) and long-term events were evaluated. suPAR prognostic value was assessed beyond a clinical model that included age, GRACE score, estimated glomerular filtration rate, cardiac troponin-I peak and left ventricular ejection fraction <40%.

Results: Higher suPAR concentrations were associated with an increased prevalence of cardiovascular risk factors. After multivariate adjustment, suPAR ≥2.6?ng/mL were independently associated with an increased risk of all-cause death (HR 2.3; 95%CI 1.2–4.4; p?=?.017), major adverse cardiovascular events (MACE) (HR 1.7; 95%CI 1.1–2.5; p?=?.020) and heart failure (HR 4.1; 95%CI 1.3–12.6; p?=?.015), but not with myocardial infarction. For long-term all-cause death significant improvement of reclassification and discrimination were seen after addition of suPAR to a clinical model.

Conclusions: In the setting of an ACS, suPAR is associated with long-term all-cause death, heart failure and MACE, and provides incremental prognostic value beyond traditional risks factors.     

Circulating Biomarkers for Predicting Cardiovascular Disease Risk; a Systematic Review and Comprehensive Overview of Meta-Analyses

Background

Cardiovascular disease is one of the major causes of death worldwide.Assessing the risk for cardiovascular disease is an important aspect in clinical decision making and setting a therapeutic strategy, and the use of serological biomarkers may improve this. Despite an overwhelming number of studies and meta-analyses on biomarkers and cardiovascular disease, there are no comprehensive studies comparing the relevance of each biomarker. We performed a systematic review of meta-analyses on levels of serological biomarkers for atherothrombosis to compare the relevance of the most commonly studied biomarkers.

Methods and Findings

Medline and Embase were screened on search terms that were related to “arterial ischemic events” and “meta-analyses”. The meta-analyses were sorted by patient groups without pre-existing cardiovascular disease, with cardiovascular disease and heterogeneous groups concerning general populations, groups with and without cardiovascular disease, or miscellaneous. These were subsequently sorted by end-point for cardiovascular disease or stroke and summarized in tables. We have identified 85 relevant full text articles, with 214 meta-analyses. Markers for primary cardiovascular events include, from high to low result: C-reactive protein, fibrinogen, cholesterol, apolipoprotein B, the apolipoprotein A/apolipoprotein B ratio, high density lipoprotein, and vitamin D. Markers for secondary cardiovascular events include, from high to low result: cardiac troponins I and T, C-reactive protein, serum creatinine, and cystatin C. For primary stroke, fibrinogen and serum uric acid are strong risk markers. Limitations reside in that there is no acknowledged search strategy for prognostic studies or meta-analyses.

Conclusions

For primary cardiovascular events, markers with strong predictive potential are mainly associated with lipids. For secondary cardiovascular events, markers are more associated with ischemia. Fibrinogen is a strong predictor for primary stroke.     

Serum tryptase detected during acute coronary syndrome is significantly related to the development of major adverse cardiovascular events after 2?years

Background

One of the greatest challenges in cardiovascular medicine is to define the best tools for performing an accurate risk stratification for the recurrence of ischemic events in acute coronary syndrome (ACS) patients.

Methods

We followed 65 ACS patients enrolled in a previous pilot study for 2 years after being discharged, focusing on the occurrence of major adverse cardiovascular events (MACE).The relationship between serum tryptase levels on admission, SYNergy between percutaneous coronary intervention with the TAXUS drug-eluting stent and the cardiac surgery score (SX-score), cardiovascular complexity and MACE at 2 years follow-up were analyzed.

Results

The ACS population was divided in two groups: patients with MACE (n = 23) and patients without MACE (n = 42).The tryptase measurement at admission (T0) and at discharge (T3) and SX-score were higher in patients who experienced MACE than in those without (p = 0.0001, p < 0.0001 and p = 0.006, respectively). Conversely, we found no significant association between MACE and C-reactive protein (CRP), and between MACE and maximum level of high-sensitivity troponin (hs-Tn) values.Among all patients with MACE, 96% belonged to the group that presented with cardiovascular complexity at the beginning of ACS index admission (p < 0.0001).The predictive accuracy of serum tryptase for MACE at follow up set at the cut-off point of 4.95 ng/ml at T0 and of 5.2 ng/ml at T3. Interestingly, patients with both the above cut-off tryptase values at T0 and at T3 presented a 1320% increase in the odds of developing MACE (p < 0.0001).

Conclusion

In ACS patients, serum tryptase measured during index admission is significantly correlated to the development of MACE up to 2 years, demonstrating a possible long-term prognostic role of this biomarker.

Electronic supplementary material

The online version of this article (doi:10.1186/s12948-015-0013-0) contains supplementary material, which is available to authorized users.     

Cardiovascular and gastrointestinal effects of COX-2 inhibitors and NSAIDs: achieving a balance

Conventional 'nonselective' nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for the treatment of pain and inflammation; however, the potential gastrointestinal risks associated with their use can be a cause for concern. In response to the adverse effects that can accompany nonselective NSAID use, selective cyclo-oxygenase (COX)-2 inhibitors were developed to target the COX-2 isoenzyme, thus providing anti-inflammatory and analgesic benefits while theoretically sparing the gastroprotective activity of the COX-1 isoenzyme. Data from large-scale clinical trials have confirmed that the COX-2 inhibitors are associated with substantial reductions in gastrointestinal risk in the majority of patients who do not receive aspirin. However, some or all of the gastrointestinal benefit of COX-2 inhibitors may be lost in patients who receive low, cardioprotective doses of aspirin, and recent evidence suggests that some of these agents, at some doses, may be associated with an increased risk for cardiovascular adverse events compared with no therapy. The risks and benefits of conventional NSAIDs and of COX-2 inhibitors must be weighed carefully; in clinical practice many patients who might benefit from NSAID or COX-2 therapy are likely to be elderly and at relatively high risk for gastrointestinal and cardiovascular adverse events. These patients are also more likely to be taking low-dose aspirin for cardiovascular prophylaxis and over-the-counter NSAIDs for pain. Identifying therapies that provide relief from arthritis related symptoms, confer optimum cardioprotection, and preserve the gastrointestinal mucosa is complex. Factors to consider include the interference of certain NSAIDs with the antiplatelet effects of aspirin, differences in the adverse gastrointestinal event rates among nonselective NSAIDs and selective COX-2 inhibitors, emerging data regarding the relative risks for cardiovascular events associated with these drugs, and the feasibility and cost of co-therapy with proton pump inhibitors.