他汀类药物治疗脓毒血症的进展

他汀类药物是临床上常用的一种降血脂药物,此外,它还具有抗炎、改善内皮细胞的功能、调节免疫功能,近年来研究发现,他汀类药物对脓毒血症有着重要的影响,它可以抑制炎症因子的释放,抑制炎症细胞的黏附,降低脓毒血症的发生率和病死率,本文对这一领域的最新进展作一综述.     

Changes of Lipid Proffie and C-Reactive Protein after Withdrawal of Xuezhikang, an Extract of Cholestin, in Patients With Stable Angina Pectoris

Objectives In addition to its lipid-lowering properties, statin decreases the level of C-reactive protein （CRP） resulting in reduction of cardiovascular events. However, information about discontinuation of statin therapy in stable cardiac patients is limited. This was a prospective cohort study to explore whether withdrawal of statin treatment could result in rebound of inflammation in patients with stable angina pectofis in a short-term course. Methods and Results 75 patients with stable angina pectoris were randomly divided into three groups： ① Pretreatment with Xuezhikang （XZK, an extract of cholestin） for 6 weeks and then replaced by placebo; ②Treatment with XZK throughout the study; ③ Placebo. Lipid levels, highly sensitive CRP （hs-CRP） and serum cardiac troponin T （cTnT） were assessed before receiving the XZK therapy, 1 day before discontinuation of XZK, and on day 1, 2, 3, 7 and 14 after discontinuation of XZK, respectively. At day 14 after discontinuation of XZK therapy, total cholesterol, LDL-C and triglyceride significantly increased, whereas HDL-C level significantly decreased. The median level of hs-CRP increased significantly from the second day after withdrawal of XZK therapy. There was a prominent rebound of hs-CRP concentration 3 days after discontinuation of XZK therapy. 7 to 14 days after discontinuation of XZK therapy, the hs-CRP concentration declined to a similar level as in the placebo group. Elevated eTnT level did not occur throughout the study course in either guroup Conclusios Short-term discontinuation of statin therapy could induce a rapid rebound phenomenon of inflammatory response independently of changes of lipid parameters. However, it was not enough to induce myocardial injury in this cohort of patients with stable angina peetoris.     

Carotid intima-media thickness and coronary atherosclerosis: weak or strong relations?

AIMS: Measurement of change in carotid intima-media thickness (CIMT) has been proposed as an alternative for the occurrence of cardiovascular (CV) events in the assessment of therapeutic interventions. Nevertheless, criticism has been voiced based on observations indicating a weak relation between CIMT and coronary atherosclerosis as well as on the virtual absence of data showing that progression of CIMT indeed predicts coronary artery disease (CAD) and stroke. METHODS AND RESULTS: We set out to review the evidence on these issues by performing a literature search on these topics. Of the 34 studies on the relation of CIMT with coronary atherosclerosis, as assessed by angiography (n=33) or intravascular ultrasound (n=1), 30 showed a modest positive relationship; the magnitude of which was similar to that found in autopsy studies. Of all studies on CIMT and future CV events (n=18), 17 showed graded positive relationships. At present, only one study has provided evidence on the relation of change in CIMT and future CV events, showing an increased risk with CIMT progression. The paucity of data on progression and future CV risk is partly attributable to time windows required to complete these studies. CONCLUSION: The modest relation between CIMT and coronary atherosclerosis most likely reflects variability in atherosclerosis development between the vascular beds rather than limitations of CIMT measurements. Additional data on the relation between change in CIMT and future CV events is required and currently is in progress.     

Effects of pravastatin on coronary events in 2073 patients with low levels of both low-density lipoprotein cholesterol and high-density lipoprotein cholesterol: results from the LIPID study.

AIMS: Fibrates or nicotinic acid are usually recommended for secondary prevention of coronary heart disease in patients with low plasma levels of both low-density lipoprotein cholesterol (LDL-C) < or =140 mg/dL (< or =3.6 mmol/L) and high-density lipoprotein cholesterol (HDL-C) < or =40 mg/dL (< or =1.03 mmol/L). The LIPID trial, a randomised, placebo-controlled trial in 9014 patients at 87 centres in Australia and New Zealand, provided an opportunity to investigate the effects of an HMG-CoA reductase inhibitor in patients with low LDL-C and low HDL-C. METHODS AND RESULTS: Participants in this post hoc substudy were 2073 patients aged 31-75 years with baseline LDL-C < or =140 mg/dL (< or =3.6 mmol/L), HDL-C < or =40 mg/dL (< or =1.03 mmol/L), and triglyceride < or =300 mg/dL (< or =3.4 mmol/L). The relative risk reduction with pravastatin treatment was 27% for major coronary events (95% CI 8-42%), 27% for coronary heart disease mortality (95% CI 0-47%), 21% for all-cause mortality (95% CI 0-38%), and 51% for stroke (95% CI 24-69%). The number needed to treat to prevent a major coronary event over 6 years was 22. CONCLUSIONS: Treatment with pravastatin in patients with both low LDL-C and low HDL-C significantly reduced major coronary events, stroke, and all-cause mortality. The level of HDL-C is crucial to the risk of recurrent CHD events and, consequently, the benefit of lowering LDL-C.     

Protective effect of atorvastatin on acute systemic inflammation-induced endothelial dysfunction in hypercholesterolaemic subjects.

AIMS: Recent studies suggest an association between acute inflammation and deterioration of arterial function. The effect of acute inflammation on endothelial function and the role of treatment with statins have not been investigated in subjects with dyslipidaemia. METHODS AND RESULTS: In this randomized, placebo-controlled, double-blind study, we generated a transient systemic inflammation by Salmonella typhi vaccination in 50 volunteers with mild hypercholesterolaemia after 4 days of treatment with atorvastatin 40 mg or placebo once daily. Endothelium-dependent flow-mediated dilation (FMD) of the brachial artery and circulating levels of endothelial and inflammatory markers were measured before and 8 h after the vaccine. Vaccination produced a decline on FMD at 8 h (absolute decrease of 2.55%, P = 0.001), indicating an unfavourable effect on endothelial function. In contrast, in atorvastatin-treated subjects, FMD was preserved after vaccination (decrease of 0.15%, P = 0.005 vs. placebo). The vaccination-induced decline in plasma level of nitric oxide metabolites (by 6.0 micromol/L, P = 0.007) and antioxidant capacity (by 20.6 micromol/L, P = 0.001) in the placebo group were completely abolished by atorvastatin (P = 0.038 and P = 0.005, respectively, vs. placebo). In contrast, atorvastatin had no significant effect on cytokine levels. CONCLUSION: Acute inflammation is aetiologically associated with the deterioration of vasomotor and systemic endothelial function in hypercholesterolaemic patients. Atorvastatin effectively abrogates these deleterious effects.     

他汀类药物预处理对不稳定性心绞痛斑块破裂发生的影响

目的观察冠心病患者在使用他汀类药物后对斑块破裂及不稳定性心绞痛(UAP)发生的影响。方法采用回顾性病例对照研究方法,分析62例冠心病患者的血脂异常率、他汀类药物治疗率以及治疗后低密度脂蛋白胆固醇(LDL-C)达标率;比较各组冠心病他汀类药物治疗患者的UAP发生率;应用血管内超声(IVUS)测量、分析责任血管狭窄病变处、近端参考血管、远端参考血管外弹力膜截面积、斑块破裂、钙化斑块比例及冠状动脉重构情况。结果非他汀组患者LDL-C未达标率为96.4%(27/28),应获得而未得到他汀类药物治疗率为46.4%(13/28);他汀组患者LDL-C达标率为26.5%(9/34)。他汀组UAP发生率显著低于非他汀组(χ~2=34.491,P=0.001),他汀组LDL-C达标者与未达标者UAP发生率比较差异无统计学意义(χ~2=0.002,P=0.968)。他汀组LDL-C显著低于非他汀组(2.457±0.802 vs 3.218±1.130,Z=-9.760,P=0.001);他汀组未达标患者LDL-C水平显著低于非他汀组未达标患者(2.816±0.640 vs 3.370±0.963,F=-3.613,P=0.001)。他汀组斑块破裂的发生率低于非他汀组(38.2%vs 60.7%,χ~2=3.107,P=0.1500.05),正性重构率亦明显低于非他汀组(29.4%vs 46.4%,χ~2=1.905,P=0.090.05)。结论他汀类药物治疗冠心病患者UAP发生率显著降低。使用他汀治疗可使斑块破裂减少,其独立于冠脉重构之外。他汀类药物治疗的最主要效果在于预防动脉粥样硬化斑块的破裂。     

LIPID‐LOWERING THERAPY IN CHRONIC KIDNEY DISEASE: IS THERE A ROLE FOR EZETIMIBE?

The use of lipid-lowering therapy (LLT) in chronic kidney disease (CKD) results in a reduction in atherosclerotic cardiovascular events but not mortality. The risk reduction for patients on dialysis appears to be less than in pre-dialysis CKD. These findings may be due to the higher rate of non-atherosclerotic cardiovascular disease found in end-stage disease. Because of this, the role of LLT is less clear in CKD than in the general population. This review outlines the results of recent trials of LLT, particularly Ezetimibe, and implications for patients with CKD. The evidence in favour of lipid lowering in CKD comes largely from the SHARP study. This study used combined simvastatin and Ezetimibe to reduce cholesterol. Though the benefits of statins are well proven, there is no evidence that Ezetimibe independently reduces cardiovascular events in any population. Data which support the use of Ezetimibe show only that it effectively reduces cholesterol. Surrogate end-point data are contentious. Some studies suggest benefit whilst others suggest off-target effects that question the validity of Ezetimibe in the absence of quality cardiovascular outcome data.     

Do statins influence the prognostic impact of non-sustained ventricular tachycardia after ST-elevation myocardial infarction?

AIMS: The study evaluates the effect of statin therapy on the prognostic impact of non-sustained ventricular tachycardia (NSVT) occurring after acute ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS: From the German Acute Coronary Syndrome Registry (ACOS), 3137 patients with STEMI and in-hospital Holter monitoring were analysed. Three hundred and forty-six (11.0%) patients had NSVT. When compared with patients with no documented NSVT, patients with NSVT were older, more often had myocardial infarction in their history, diabetes mellitus, and an ejection fraction <40%. Regarding frequency of drug application, medication at discharge did not (beta-blockers, ACE-inhibitors, amiodarone) or only slightly (acetylsalicylic acid, statins, and sotalol) differ between both groups. Multivariable analysis of 1 year mortality, adjusted for age, gender, diabetes, reperfusion therapy, ejection fraction <40%, and beta-blocker therapy showed the following results: In patients without statin treatment and no NSVT, 1 year mortality after STEMI was 9.2%, but increased to 25.0% [odds ratio (OR) 3.02; 95% confidence interval (CI) 1.47-6.20], if NSVT were present. In patients on statin treatment and no NSVT, 1 year mortality was only 3.2%, and in the presence of NSVT 1 year mortality was not significantly increased anymore (5.3%; OR 1.03; 95% CI 0.55-1.92). CONCLUSION: After STEMI, only in patients not on statin treatment, the occurrence of NSVT is associated with a significant and marked increase in 1 year mortality.     

Improvement of arterial stiffness by the antioxidant and anti-inflammatory effects of short-term statin therapy in patients with hypercholesterolemia

The preventive effect of statins on coronary events is not only associated with the cholesterol-lowering effect of these drugs, but also various direct effects on the vascular wall, which include improvement of endothelial function, antioxidant activity, and anti-inflammatory activity. We investigated whether short-term statin therapy could improve arterial stiffness and assessed its mechanism of action in patients with hypercholesterolemia. We assessed arterial stiffness in 10 patients (mean age: 62.9 ± 9.0 years) with hypercholesterolemia (total cholesterol 220mg/dl). The patients were treated with cerivastatin (0.15mg/day) for 4 weeks. Before and after 4 weeks of treatment, we determined arterial stiffness from brachial-ankle pulse wave velocity and the ankle-brachial blood pressure index (ABI) using a FORM apparatus (Colin, Komaki, Japan). We also measured the blood levels of high-sensitivity C-reactive protein (hsCRP) and malondialdehyde low-density lipoprotein (MDA-LDL) as markers of inflammation and oxidation, respectively. After statin therapy, both the right and left abPWV were significantly decreased from 1544.6 ± 157.1 to 1349.0 ± 223.9cm/s and from 1592.1 ± 164.8 to 1424.8 ± 245.2cm/s, respectively (P < 0.05). However, the ABI was unchanged after 4 weeks of cerivastatin therapy. MDA-LDL decreased significantly (from 161.2 ± 42.4 to 119.4 ± 33.5U/l, P < 0.05) and hsCRP also decreased. Total cholesterol and LDL-cholesterol decreased, while triglycerides and high-density lipoprotein-cholesterol were unchanged. Blood pressure was not significantly altered from the baseline value by statin therapy. These results suggest that the preventive effect of statins on coronary events is partly associated with the various actions of these drugs on the vascular wall, and that statins are not only cholesterol-lowering agents but also antiatherosclerotic agents.