Prior statin use is associated with improved outcomes in community-acquired pneumonia

Background

Statins have potent anti-inflammatory effects in laboratory studies of pulmonary inflammation. We investigated whether statin users had improved outcome when admitted with community-acquired pneumonia.

Methods

We carried out a prospective observational study of patients admitted to the hospital with community-acquired pneumonia between January 2005 and November 2007. The use of statins, angiotensin-converting enzyme inhibitors, beta-blockers, and aspirin were recorded. The outcomes of interest were 30-day mortality, need for mechanical ventilation or inotropic support, and the development of complicated pneumonia.

Results

On multivariate logistic regression, statin use was associated with significantly lower 30-day mortality (adjusted odds ratio [AOR] 0.46, 95% confidence interval [CI], 0.25-0.85, P = .01) and development of complicated pneumonia (AOR 0.44, 95% CI, 0.25-0.79, P = .006). There was no effect on requirement of mechanical ventilation or inotropic support (AOR 0.93, 95% CI, 0.49-1.76, P = .8). Patients prescribed statins had more severe pneumonia (median Pneumonia Severity Index 4, interquartile range [IQR] 3-4) compared with patients not prescribed cardiovascular drugs (median Pneumonia Severity Index 3, IQR 2-4, P < .0001). Despite this, C-reactive protein levels on admission were significantly lower in patients prescribed statins (median 119 mg/L, IQR 46-215) compared with patients prescribed no cardiovascular drugs (182 mg/L, IQR 66-326, P < .0001). On multivariate logistic regression, statin use was independently protective against a C-reactive protein that failed to fall by 50% or more at day 4 (AOR 0.50, 95% CI 0.27-0.92, P = .02).

Conclusions

Statin use is associated with reduced markers of systemic inflammation and improved outcomes in patients admitted with community-acquired pneumonia.     

他汀类药物与缺血性脑血管病

除降脂外,他汀类药物还具有广泛的多效性.文章对他汀类药物在缺血性脑血管病防治中的多效性进行了综合和归纳.     

C反应蛋白与冠状动脉粥样硬化性心脏病

冠状动脉粥样硬化性心脏病中炎症扮演了重要的角色,而炎症的重要标记物C反应蛋白与冠心病的关系正逐渐成为研究的热潮。现综述C反应蛋白的来源、特性、代谢等问题,并通过临床试验、药物试验、细胞分子水平实验及动物实验几个方面的论述来认识C反应蛋白与冠心病的关系,试图了解目前的证据能支持C反应蛋白在冠状动脉疾病发生发展中所起的作用。     

高敏C反应蛋白联合低密度脂蛋白胆固醇作为他汀治疗靶目标的临床研究

目的:探讨急性冠状动脉综合征(ACS)介入术后,以高敏C反应蛋白(hs-CRP)联合低密度脂蛋白胆固醇(LDL-C)作为他汀治疗靶目标的可行性。方法:2007-01-2009-01期间,连续纳入ACS患者400例,随机分为A、B组(每组200例),常规行介入手术,术后每组给予阿托伐他汀40mg/d,口服1个月;此后给予阿托伐他汀20mg/d,口服维持。A组治疗靶目标为LDL-C<2.07mmol/L,B组治疗靶目标为LDL-C<2.07mmol/L且hs-CRP<3mg/L,观察2组LDL-C、hs-CRP指标变化,随访6个月、12个月、18个月主要心血管不良事件(MACE:全因性死亡、非致死性心肌梗死、靶血管再次血运重建)。结果:2组患者基线特征差异无统计学意义;2组在18个月时均达到各自治疗靶目标;2组LDL-C水平差异无统计学意义;hs-CRP在12个月和18个月随访时差异有统计学意义,分别为(5.96±3.51)和(3.85±2.23)mg.L-1(P<0.05),(4.68±2.81)和(2.05±0.91)mg.L-1(P<0.05);在18个月随访时,2组靶血管再次血运重建率和MACE发生率差异有统计学意义,分别为8.6%和3.6%(P<0.05),16.8%和9.7%(P<0.05)。A组发生MACE的概率是B组的1.73倍(HR=1.73,95%CI:1.12～5.27,P=0.025)。结论:ACS介入术后,对于血脂已达标但炎症仍较为活跃患者,hs-CRP和LDL-C双重达标可进一步减少MACE发生,降低残余心血管风险。hs-CRP可能是他汀治疗的另一有效靶目标。     

超敏C-反应蛋白水平与心脑血管病的关系分析

目的：探讨心脑血管病患者血清超敏C-反应蛋白（hs—CRP）水平及临床意义。方法：选择住院治疗的脑卒中患者176例为脑卒中组,其中脑梗塞133例,脑溢血43例,又根据神经功能缺损评分分为1组（轻度,67例）,2组（中度,67例）,3组（重度,42例）;冠心病患者104例为冠心病组,其中,稳定型心绞痛（SAP,34例）,不稳定型心绞痛（UAP,34例）,急性心肌梗塞（AMI,36例）;正常人64例为正常对照组。采用免疫比浊法检测hs—CRP水平。结果：脑卒中组及冠心病组的血清hs—CRP水平显著高于正常对照组（P均〈0．01）。脑卒中组神经功能缺损越重,血清hs—CRP水平越高,组间比较差异显著（P〈0．05～〈0．01）。冠心病组AMI患者的血清hs—CRP水平较SAP、UAP显著升高（P〈0．01,〈0．05）。绪论：血清hs—CRP参与了心脑血管病后的炎症反应,且与病变严重程度有关。     

A review of high-dose statin therapy: targeting cholesterol and inflammation in atherosclerosis.

Lipid lowering with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors or 'statins' has dramatically reduced morbidity and mortality in patients with established cardiovascular disease. Recently, there have been multiple studies investigating the role of high-dose statin therapy with more aggressive lipid lowering in this setting. Concomitantly, there is increasing evidence implicating a role of inflammation in the pathogenesis of atherosclerosis. These high-dose statin trials and other studies have also provided a wealth of data suggesting that statins have anti-inflammatory and anti-oxidant properties that go beyond their lipid-lowering effects. In this review, we will provide a brief overview of recent, large-scale, randomized, placebo and active controlled trials of high-dose statin therapy in the setting of stable and unstable coronary artery disease and percutaneous coronary intervention. Further, we will discuss the evidence for effects of high-dose statin therapy on inflammation and C-reactive protein.     

高敏C-反应蛋白及颈动脉粥样硬化与急性脑梗死的关系

目的 探讨和分析血清高敏C-反应蛋白(hs-CRP)及颈动脉粥样硬化与急性脑梗死的关系.方法 选取59例急性脑梗死患者为脑梗死组,同期选择健康体检者30例为对照组,测定血清hs-CRP含量,应用颈动脉彩色多普勒超声检查颈动脉粥样硬化斑块及颈动脉内膜-中膜厚度(IMT).同时对急性脑梗死患者血清hs-CRP水平与病情进行相关分析.结果 血清hs-CRP脑梗死组为(5.96±1.52)mg/L高于对照组的(1.78±1.02)mg/L(t=15.383,P＜0.01);颈动脉斑块检出率急性脑梗死组为77.97%,高于对照组的36.67%(x2=12.92,P＜0.01);颈动脉IMT脑梗死组(1.18±0.17)mm高于对照组的(1.02±0.15)mm(t=4.544,P＜0.05);神经功能缺损程度重型组血清hs-CRP水平[(15.68±1.45)mg/L]明显高于轻型组[(1.88±0.34)mg/L]和中型组[(4.16±1.39)mg/L](t值为37.217和25.243,P＜0.01).结论 血清hs-CRP水平升高对急性动脉粥样硬化性脑梗死病变有临床意义,早期测定hs-CRP水平有助于评估急性脑梗死患者的病情及预后.     

C反应蛋白在胰岛素抵抗中的作用及意义

慢性亚临床炎性反应在糖尿病和胰岛素抵抗的发生和发展中起重要的作用.C反应蛋白(CRP)是一个系统的炎性反应标志物.大量的证据表明CRP水平与糖代谢密切相关.在胰岛素抵抗者中,体内CRP水平的高低,可预测其以后并发心血管事件的危险性.     

C反应蛋白与动脉粥样硬化

C反应蛋白(CRP)作为炎症介质被认为是心血管事件最强有力的预测因子之一.慢性炎症是动脉粥样硬化发生发展的重要机制.作为急性时相反应蛋白的CRP从其结构、生物特性来看与炎症反应关系密切,成为动脉粥样硬化的介导和标志物.本文就CRP与AS的关系作一综述.     

Systematic, immediate in-hospital initiation of lipid-lowering drugs during acute coronary events improves lipid control

Background: Patients who have had a coronary heart attack often go completely untreated for hypercholesterolemia. We investigated whether immediate initiation of lipid-lowering drugs during hospitalization for acute coronary events increases the proportion of correctly treated patients compared to referred treatment as recommended by current guidelines. Methods: This prospective, multicenter study randomized 57 hypercholesterolemic patients hospitalized for acute coronary events to immediate in-hospital initiation or to referred initiation of lipid-lowering drugs by primary care physicians 3 months after unsuccessful nutritional intervention. Results: After 6 months, 53 patients were available for follow-up. More patients in the immediate initiation group (26/30 patients, 87%) were treated with lipid-lowering drugs than in the referred initiation-group (13/23 patients, 57%, P=0.03). Twenty-seven patients (87%) in the immediate initiation group versus 17 patients (65%) in the referred initiation group had a 10% or greater decrease in total cholesterol or a 15% or greater decrease in LDL-cholesterol (P=0.18). Although statistically not significant, there was a trend to improved lipid values in the immediate initiation group compared to the referred initiation group (TC, −21.1 vs. −13.8% (P=0.08); LDL-C, −28.2 vs. −18.9% (P=0.13); HDL-C, +10.8 vs. +5% (P=0.44); TC/HDL-C ratio, −24.7 vs. −15.1% (P=0.22)), and the LDL-C/HDL-C ratio was −34.1 vs. −19.1% (P=0.04, P=NS after Bonferroni correction). Conclusion: The immediate initiation of lipid-lowering drugs in hypercholesterolemic patients hospitalized for acute coronary events increases the rate of correctly treated patients and has the potential to improve lipid control.     

The predictive role of C-reactive protein in patients with hypertension and subclinical atherosclerosis

Background: Recent guidelines published by the joint European Society of Hypertension/European Society of Cardiology have suggested the inclusion of C-reactive protein (CRP) in the standard assessment of cardiovascular risk in hypertensive patients, but few data are available on the role of CRP in patients with carotid lesions.
Methods: We studied 472 patients, 236 with and 236 without hypertension, sex- and age-matched, with and without early stages of atherosclerosis (e.g. those with an asymptomatic intima–media thickness of >0.9 mm), the influence of all the other traditional cardiovascular risk factors (e.g. older age, male sex, obesity, diabetes, smoking habit, family history of coronary artery disease, dyslipidaemia) and of high-sensitivity CRP levels on cerebrovascular and cardiovascular events in a 5-year follow up.
Results: At the end of follow up, patients with hypertension had more events than those without (25% vs 17%, P < 0.05). Proportional hazard analysis revealed in the group of patients without hypertension the presence of baseline carotid lesions ( P = 0.02) as predictor of events. In patients with hypertension, the presence of baseline carotid lesions ( P = 0.04) and elevated CRP levels ( P = 0.02) predicted clinical events. Patients with hypertension also showed a significant relationship between clinical events and quintiles of CRP levels ( P < 0.01).
Conclusion: Beyond the utility of high-sensitivity CRP levels in the prediction of early and late stages of atherosclerosis and subsequently on its association with clinical events, the therapeutic implications of these results remain to be evaluated by further studies.     

C反应蛋白与动脉粥样硬化的新进展

动脉粥样硬化是一种由于血管内皮功能紊乱或受损而引发的慢性炎症性疾病.目前认为,Ross[1]的"炎症假说"是动脉粥样硬化(atherosclerosis,AS)的主要发病机制,临床上可表现为脂质沉积、炎症细胞浸润、泡沫细胞形成、斑块的纤维化及钙化等[2].     

C-reactive protein,platelets, and patent ductus arteriosus

The association between inflammation, platelets, and patent ductus arteriosus (PDA) has not been studied so far. The purpose of this study was to evaluate whether C-reactive protein (CRP) is related to low platelet count and PDA. This was a retrospective study of 88 infants with a birth weight ≤1500 g and a gestational age ≤30 weeks. Platelet count, CRP, and an echocardiogram were assessed in all infants. The subjects were matched by sex, gestational age, and birth weight. Differences were compared using the χ², t-test, or Mann–Whitney U-test, as appropriate. Significant variables were entered into a logistic regression model. The association between CRP and platelets was evaluated by correlation and regression analysis. Platelet count (167 000 vs. 213 000 µl^?1, p = 0.015) was lower and the CRP (0.45 vs. 0.20 mg/dl, p = 0.002) was higher, and the platelet count correlated inversely with CRP (r = ?0.145, p = 0.049) in the infants with vs. without PDA. Only CRP was independently associated with PDA in a logistic regression model (OR 64.1, 95% confidence interval 1.4–2941, p = 0.033).     

Central obesity and smoking are key modifiable risk factors for elevated C-reactive protein in Asian individuals who are not eligible for statin therapy

Objective:

Statin therapy reduces coronary heart disease (CHD) and mortality in individuals with elevated C-reactive protein (CRP) but low-density lipoprotein cholesterol below the threshold at which statin therapy is recommended. We determined the proportion of individuals with elevated CRP in whom statin therapy was not indicated, and examined predictors for elevated CRP in a multi-ethnic Asian population.

Design:

We studied 3404 participants (Chinese, Malays and Asian-Indians) without a history of hypercholesterolemia living in Singapore (mean age±s.d.: 48.9±11.2 years). Eligibility for statin therapy was determined based on the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III (ATPIII)) guideline. CRP was measured by high-sensitivity enzyme-linked immunosorbent assay method. CRP level greater than 2 mg l⁻¹ was considered as elevated.

Results:

Elevated CRP was found in 29.3% participants who were not eligible for statin therapy (n=2974). Elevated CRP was more common in females and amongst those of Malay or Asian-Indian ethnicity. Compared with participants with low CRP, those with elevated CRP were shown to have higher levels of obesity, blood pressure, triglyceride and insulin resistance (IR), but lower high-density lipoprotein cholesterol levels (all Ps<0.001). After multivariate analysis, gender (odds ratio (OR) 3.34 for females), ethnicity (Malay OR 1.57, 95% confidence interval (CI) 1.25–1.96; Asian-Indian OR 1.97, 95% CI 1.55–2.50), waist circumference (OR 1.06, 95% CI 1.05–1.07), smoking (OR 1.49, 95% CI 1.08–2.05) and IR (OR 1.14, 95% CI 1.07–1.22) were significant predictors of CRP (all Ps--values<0.05).

Conclusion:

Routine measurement of CRP identifies a substantial number of Asian individuals at risk of CHD in whom statin therapy is not currently indicated, particularly in women and certain ethnic groups (Malays and Asian Indians). Weight loss and smoking cessation are important measures to reduce the proportion of individuals with elevated CRP.     

Longitudinal trends and predictors of statin use among patients with diabetes

Aim

Statins reduce morbidity and mortality among patients with diabetes, but their use remains suboptimal. Understanding trends in statin use may inform strategies for improvement.

高敏C反应蛋白对新发脑出血风险的预测价值

目的 探讨基线血清高敏C反应蛋白(hs-CRP)水平对新发脑出血风险的预测价值.方法 采用回顾性巢式病例对照研究方法,选择观察队列中新发脑出血患者323例,对照组646例.比较两组组间基线hs-CRP水平,分析不同基线hs-CRP水平对新发脑出血的风险.结果 新发脑出血患者基线hs-CRP水平(1.10 mg/L)高于对照组(0.66 mg/L,P<0.01);hs-CRP四分位数水平较高者(>2.12 mg/L)新发脑出血的风险是较低者(≤0.30 mg/L)的2.58倍(95%CI 1.77～3.76,P<0.01);对hs-CRP以3 mg/L及以第八十百分位点为临界值分组后进行统计分析,hs-CRP与新发脑出血风险的相关性依然存在,OR值分别为2.26(95%CI 1.60～3.20,P<0.01)和2.24(95%CI 1.60～3.13,P<0.01).结论 基线hs-CRP水平对新发脑出血有预测价值,基线hs-CRP水平较高者新发脑出血风险增加.     

AMP-活化蛋白激酶与缺血性脑血管病

作为细胞内的能量感受器,AMP-活化蛋白激酶(AMP-activated protein kinase,AMPK)在维持细胞和机体能量平衡中发挥着重要作用。最初,AMPK在糖尿病、肥胖等代谢性疾病的病理生理学过程中的作用研究较多;近年来,AMPK在脑组织中的分布以及酸中毒、氧化应激损伤和细胞凋亡等病理生理学过程中的作用日益受到重视。同时发现,卒中后人为调节AMPK活性可改变神经细胞结局。因此,AMPK有望成为治疗缺血性脑血管病的新靶点。     

急诊经皮冠状动脉介入治疗前强化阿托伐他汀对急性心肌梗死患者的中期疗效观察

目的探讨急性ST段抬高心肌梗死(STEMI)患者术前强化阿托伐他汀治疗的中期临床疗效。方法对拟行急诊PCI治疗的102例STEMI患者随机分为A组32例,B组32例,C组38例。观察术后90 min内ST段回落、术后24、72 h高敏C反应蛋白(hs-CRP)、术后肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)峰值及术后6个月主要不良心血管事件。结果 3组患者入院和术后24 h hs-CRP比较,差异无统计学意义(P>0.05)。与A组比较,B组、C组术后72 h hs CRP明显升高(P<0.05)。术前3组CK与CK-MB比较,差异无统计学意义(P>0.05)。与A纽比较,B组、C组术后CK、CK-MB明显升高,ST段回落均值及发生率明显降低(P<0.05)。A组、B组、C组术后6个月主要心血管不良事件发生率分别为9.4%、9.4%和10.5%,差异无统计学意义(P>0.05)。结论急诊PCI术前强化阿托伐他汀治疗可抑制STEMI患者炎性反应,减轻心肌梗死范围。     

Relationship between C-reactive protein concentrations during glucocorticoid therapy and recurrent atrial fibrillation.

BACKGROUND: Little direct information is available on the effect of C-Reactive Protein (CRP) lowering on the reduction of recurrent atrial fibrillation (AF). METHODS AND RESULTS: We compared low-dose glucocorticoid therapy (16 mg methylprednisolone for 4 weeks tapered to 4 mg for 4 months) and placebo in 104 patients who had experienced persistent AF with a median concentration of CRP 1.14 mg/dL (min=0.01, max=2.58). Methylprednisolone reduced recurrent AF (primary end-point) from 50% in the placebo group to 9.6% in the glucocorticoid group and permanent AF (expanded end-point) from 29% in the placebo group to 2% in the glucocorticoid group. Survival distributions for methylprednisolone were significantly different (for both primary and expanded end-point, P < 0.001). In multivariate Cox analysis, average CRP concentrations during follow-up were significant predictors of the primary end-point, with a relative risk 6.72 (P = 0.006) and the expanded end-point, with a relative risk of 11.67 (P = 0.0006). CONCLUSIONS: CRP concentration is a risk factor for recurrent and permanent AF. Methylprednisolone successfully prevents recurrent and permanent AF.     

血清高敏C反应蛋白浓度与高血压病关系探讨

目的：探讨高敏 C 反应蛋白(hsCRP)与高血压之间的关系。方法：选择56例高血压1,2,3级患者和52例正常时照者,测定并比较其血清 hsCRP 浓度。结果：高血压病患者血清 hsCRP 浓度明显高于对照组(P＜0.05),高血压3级患者的血清 hsCRP 浓度显著高于高血压1.2级患者(P＜0.05)。结论：高血压病患者血清 hsCRP 浓度显著增加,且 hsCRP 浓度可反映其血压水平,炎症反应可能参与了高血压病的发生。