强化他汀治疗对ACS患者血清IL-37的影响

目的不同剂量阿托伐他汀对急性冠脉综合征(ACS)患者治疗后血清白介素-37(IL-37)水平的变化,探讨强化他汀治疗对IL-37与冠状动脉粥样硬化斑块的影响。方法将拟行冠脉介入治疗的110例ACS患者随机分为三组,其中常规治疗组30例(阿托伐他汀钙20 mg/晚);强化治疗A组40例(阿托伐他汀40 mg/晚,4周后改为20 mg/晚)、强化治疗B组40例(阿托伐他汀负荷量80 mg顿服1次,随后40 mg/晚,4周后改为20 mg/晚)。ELISA法测定其治疗前后外周静脉血清IL-37水平。结果 1ACS患者血清IL-37在治疗4周过程中呈逐步上升趋势(P0.05);2治疗4周时血清IL-37常规治疗组与强化治疗A组、强化治疗B相比差别有统计学意义(P0.05);3左室功能和校正TIMI计帧数(CTFC)常规治疗组与强化治疗A组、强化治疗B组相比差别有统计学意义(P0.05);4治疗4周时强化治疗A组与强化治疗B组在IL-37水平和临床结果上两组无统计学差别;5三组间的主要心脏不良事件和药物不良反应在4周时无统计学差别。结论 IL-37可作为监测和评估ACS患者的指标;强化他汀治疗可提高抗炎因子IL-37的水平,改善患者CTFC及左室功能;不良反应无增加。     

Simvastatin but not ezetimibe reduces sympathetic activity despite similar reductions in cholesterol levels

The relationship between the sympatholytic effects of statins and their lipid-lowering activity remains unclear. Ezetimibe lowers cholesterol, but its sympatholytic activity is unknown. The purpose of study was to compare the influence of equipotent doses of simvastatin and ezetimibe on sympathetic activity. This randomized double-blinded study was performed in 22 hypertensive patients (age, 45.6 ± 2.2 years; female/male, 2/20) with untreated hypercholesterolemia. The subjects were administered 20 mg/d of simvastatin (n = 11) or 20 mg/d of ezetimibe (n = 11) for 6 weeks. Pre- and post-treatment measurements of muscle sympathetic nerve activity (MSNA), baroreceptor control of heart rate (baroreflex sensitivity), and impedance cardiography were recorded. Simvastatin and ezetimibe produced similar reductions of total (−58.0 ± 23.4 vs. −45.2 ± 17.2 mg/dL; P = .15, respectively) and low-density lipoprotein cholesterol (−52.6 ± 20.9 vs. −37.9 ± 17.6 mg/dL; P = .09, respectively). There was a significant difference in the effect of simvastatin and ezetimibe on muscle sympathetic nerve activity (−8.5 ± 5.1 vs. −0.7 ± 3.5 bursts/min; P = .0005). Simvastatin improved baroreflex sensitivity as compared with ezetimibe (10.0 ± 14.3 vs. −2.8 ± 6.1 ms/mm Hg; P = .01). There was no difference in the effect of both treatments on blood pressure, heart rate, cardiac output, stroke volume, total peripheral resistance, high-density lipoprotein, and triglycerides. Simvastatin reduced sympathetic activity via lipid-independent mechanisms, but ezetimibe exerts no sympatholytic effects.     

Statins and cardiovascular outcomes in elderly and younger patients with coronary artery disease: a post hoc analysis of the GREACE study

Introduction

The effect of cardiovascular disease (CVD) prevention measures aimed at elderly patients requires further evidence. We investigated the effect of statin treatment (targeted to achieve guideline goals) on CVD outcomes in different age groups to determine whether statins are more beneficial in the elderly.

Material and methods

The primary endpoint of this post hoc analysis of the GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) study (n = 1,600 patients with established coronary heart disease (CHD), mean follow-up 3 years) was the absolute and relative CVD event (a composite of death, myocardial infarction, revascularization, unstable angina, heart failure and stroke) risk reduction in age quartiles (each n = 200). Patients on “structured care” with atorvastatin (n = 800) followed up by the university clinic and treated to lipid goal were compared with the corresponding quartiles on “usual care” (n = 800) followed up by specialists or general practitioners of the patient''s choice outside the hospital.

Results

In the elderly (mean age 69 ±4 and 70 ±3 years in the “structured” and “usual care”, respectively) the absolute CVD event reduction between “structured” and “usual care” was 16.5% (p < 0.0001), while in the younger patients (mean age 51 ±3 years and 52 ±3 years in the “structured” and “usual care”, respectively) this was 8.5% (p = 0.016); relative risk reduction (RRR) 60% (p < 0.0001) vs. 42% respectively (p = 0.001). The elderly had higher rates of chronic kidney disease and higher uric acid levels, plus an increased prevalence of diabetes, metabolic syndrome and non-alcoholic fatty liver disease. These factors might contribute to the increased CVD risk in older patients.

Conclusions

All age groups benefited from statin treatment, but the elderly on “structured care” had a greater absolute and relative CVD risk reduction than the younger patients when compared with the corresponding patients assigned to “usual care”. These findings suggest that we should not deprive older patients of CVD prevention treatment and lipid target achievement.     

他汀类药物的安全性风险评价

他汀类药物是最广泛的可用药物治疗降低胆固醇水平,并控制其发展的处方药。所有的他汀类药物,如阿托伐他汀、氟伐他汀、洛伐他汀、匹伐他汀、普伐他汀、瑞舒伐他汀和辛伐他汀可用于心血管疾病事件的预防。众所周知,在治疗过程中一些服用他汀类药物的患者出现不良反应,如肝损害、癌症的风险和骨骼肌损害。因此,认识他汀类药物的安全性风险是很重要的。根据发表的他汀类药物的临床研究文献数据,分析和认识这类药物的安全性、不良反应及毒性的风险,并简要介绍了由美国心脏协会和美国心脏病学院基于4年评述而制定的2013年他汀类降胆固醇药物新使用指南。     

Uremic Toxins Enhance Statin-Induced Cytotoxicity in Differentiated Human Rhabdomyosarcoma Cells

The risk of myopathy and rhabdomyolysis is considerably increased in statin users with end-stage renal failure (ESRF). Uremic toxins, which accumulate in patients with ESRF, exert cytotoxic effects that are mediated by various mechanisms. Therefore, accumulation of uremic toxins might increase statin-induced cytotoxicity. The purpose of this study was to determine the effect of four uremic toxins—hippuric acid, 3-carboxy-4-methyl-5-propyl-2-furanpropionate, indole-3-acetic acid, and 3-indoxyl sulfate—on statin-induced myopathy. Differentiated rhabdomyosarcoma cells were pre-treated with the uremic toxins for seven days, and then the cells were treated with pravastatin or simvastatin. Cell viability and apoptosis were assessed by viability assays and flow cytometry. Pre-treatment with uremic toxins increased statin- but not cisplatin-induced cytotoxicity (p < 0.05 vs. untreated). In addition, the pre-treatment increased statin-induced apoptosis, which is one of the cytotoxic factors (p < 0.05 vs. untreated). However, mevalonate, farnesol, and geranylgeraniol reversed the effects of uremic toxins and lowered statin-induced cytotoxicity (p < 0.05 vs. untreated). These results demonstrate that uremic toxins enhance statin-induced apoptosis and cytotoxicity. The mechanism underlying this effect might be associated with small G-protein geranylgeranylation. In conclusion, the increased severity of statin-induced rhabdomyolysis in patients with ESRF is likely due to the accumulation of uremic toxins.     

Strategy for treating elderly Japanese with hypercholesterolemia*

Background: It has been widely accepted that control of serum cholesterol levels is effective for prevention of cardiovascular events. Recent data have suggested that this is also the case in the elderly. Methods: A research group (chaired by T. Kita) was organized as part of the Comprehensive Research on Aging and Health conducted by the Japanese Ministry for Health, Labour, and Welfare in 1999–2002 to determine the best strategy for control of cholesterol levels in elderly Japanese with hypercholesterolemia. In order to do this a review of the literature was conducted. Conclusion: The research group concluded: (i) Japanese patients aged 65–74 years with hypercholesterolemia should be treated by following the Guideline for Diagnosis and Treatment of Atherosclerotic Cardiovascular Diseases by the Japan Atherosclerosis Society (2002), as cholesterol‐lowering therapy would bring a similar, or even larger, preventive effect to the elderly, whose absolute risk of cardiovascular events is higher than that in the younger population; (ii) target cholesterol levels in elderly Japanese aged ≥ 75 years with hypercholesterolemia should be determined individually according to their physical activities. It is noted that the elderly are more susceptible to drug‐related adverse effects than the younger since renal and liver functions, required for metabolizing drugs, in the elderly are relatively weaker.     

他汀类药物对高龄冠心病患者多种作用影响的临床研究

目的探讨70岁以上高龄冠状动脉粥样硬化性心脏病(冠心病)患者经氟伐他汀(来适可80 mg)及瑞舒伐他汀(可定10 mg)治疗后,其血脂、炎症指标及肾功能的变化。方法选择行经皮冠状动脉介入治疗的冠心病患者共120例,随机(抽签方式)分为两组(A组和B组),每组60例;A组服用氟伐他汀,B组服用瑞舒伐他汀。比较两组介入治疗后72 h及随访4周后血清低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDLC)、同型半胱氨酸(homocysteine,Hcy)、肌酐(creatinine,Cr)、肌酸激酶(creatine kinase,CK)浓度及估算肾小球滤过率(estimated glomerular filtration rate,e GFR)。结果 A组与B组术后72 h与治疗前的LDL-C、Hcy、Cr、e GFR检测结果比较,差异有统计学意义(P<0.05);经过4周的氟伐他汀及瑞舒伐他汀治疗后,冠心病各组患者的LDL-C、Hcy浓度较治疗前均有所下降,差异有统计学意义(P<0.05);且治疗后两组间LDL-C及Hcy浓度比较,差异有统计学意义(P<0.05);但两组治疗后Cr、e GFR及CK浓度比较,差异无统计学意义(P>0.05)。结论氟伐他汀及瑞舒伐他汀可有效降低血脂,同时具有抗炎作用,且安全性相当;但瑞舒伐他汀的降脂效果要强于氟伐他汀。     

Lipid-lowering therapy in patients with type 2 diabetes: the case for early intervention

Chronic complications of type 2 diabetes, in particular, macrovascular complications, confer substantial morbidity and mortality and adversely affect a patient's quality of life. Early intensive intervention to control cardiovascular risk factors is essential in clinical management. Atherogenic dyslipidaemia characterized by elevated triglycerides, a low level of high-density lipoprotein cholesterol (HDL-C), and an increase in the preponderance of small, dense low-density lipoprotein (LDL) particles, is a key modifiable risk factor for macrovascular diabetic complications. Lowering low-density lipoprotein cholesterol (LDL-C) with a statin (or the combination of statin and ezetimibe) is the main focus for reducing cardiovascular risk in patients with diabetes. However, statins fail to address the residual cardiovascular risk associated with low HDL-C. Fibrates are effective against all components of the atherogenic dyslipidaemia associated with type 2 diabetes. Secondary analyses of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study suggest a role for early treatment with fenofibrate in improving cardiovascular risk reduction in type 2 diabetes and provide safety data supporting the use of fenofibrate in combination with a statin. Data from the FIELD study suggest that fenofibrate may also have potential to impact on microvascular diabetic complications associated with type 2 diabetes. Data are awaited from the ongoing Action to Control Cardiovascular Risk in Diabetes (ACCORD) study to evaluate the outcome benefits of combining fenofibrate with a statin in patients with type 2 diabetes. Finally, in view of divergent study results and outstanding data, assessment of the risk of the individual with type 2 diabetes is mandatory to assist clinical decision-making when initiating lipid therapy.     

Combination niacin and statin therapy in primary and secondary prevention of cardiovascular disease

Statin monotherapy may not be sufficient to reach serum lipid goals in many patients, especially in those with combined lipid abnormalities. Statins cause only a modest increase in high-density lipoprotein cholesterol (HDL)--an established independent protective factor for coronary heart disease (CHD)--and a modest decrease in triglycerides (TG). Niacin is an effective pharmacologic agent for increasing HDL, as well as lowering TG. Used in combination with a statin, niacin provides an option to help patients attain their low-density lipoprotein cholesterol (LDL-C) goals, non-HDL goals, and HDL goals. Based on the National Health and Nutrition Examination Survey, 1999 to 2000, only 12% of the surveyed adult population were under treatment for diagnosed hypercholesterolemia. Furthermore, only 5.4% of the surveyed population had attained goal total cholesterol levels of < 5.2 mmol/I (< 200 mg/dl). Combination therapy offers a means to get more people to goal. This paper reviews the impact of lipid-modifying combination therapy with niacin plus a statin on lipid profile outcomes.