社区人群他汀干预策略预防心血管病效果的马尔可夫模型评价

目的: 在中国鄞州电子健康档案研究(Chinese electronic health records research in Yinzhou, CHERRY)的队列人群中,评价西方发达国家指南普遍推荐的基于风险评估的他汀干预策略对我国发达地区人群心血管病一级预防的效果。方法: 采用马尔可夫模型比较基于风险评估的他汀干预的不同策略,具体包括：(1)不采取基于风险评估的他汀干预的常规策略,作为本研究的对照(策略0);(2)采用2019年世界卫生组织(World Health Organization, WHO)心血管病风险评估简易模型(无实验室指标)进行风险分层,并对高危人群(风险20%及以上)进行他汀干预(策略1);(3)采用WHO心血管病风险评估复杂模型(含实验室指标)进行风险分层,并对高危人群(风险20%及以上)进行他汀干预(策略2);(4)采用中国动脉粥样硬化性心血管病风险预测研究(prediction for atherosclerotic cardiovascular disease risk in China, China-PAR)风险评估模型进行风险分层,并对高危人群(风险10%及以上)进行他汀干预(策略3)。在上述策略的情境下,依据指南对中危人群采取生活方式干预,高危人群采取生活方式加他汀药物干预,研究期限设为10年,马尔可夫模型的循环周期设为1年,模拟10个周期并计算心血管病事件发生数和死亡数等结局事件数,以及每预防一例心血管病事件或死亡的需干预人数(number need to treat, NNT)等效果评价指标。马尔可夫模型的参数主要来源于CHERRY队列人群、公开发表的中国人群研究数据、meta分析及系统综述。采用单因素敏感性分析探讨一般人群心血管病发病率的不确定性对结果的影响,采用概率敏感性分析探讨干预措施效应风险比参数的不确定性。结果: 纳入的225 811名基线未患心血管病的40~79岁的研究人群中,与不采取基于风险评估的他汀干预的常规策略相比,采用WHO简易模型的策略1可预防的心血管病事件为3 482例[95%不确定性区间(uncertainty interval, UI): 2 110~4 661],采用WHO复杂模型的策略2为3 685例(95%UI: 2 255~4 912),采用China-PAR模型的策略3为3 895例(95%UI: 2 396~5 181)。每预防一例心血管病事件使用他汀的NNT在策略1、2和3分别为22人(95%UI: 14~54)、21人(95%UI: 14~52)和27人(95%UI: 17~67)。策略3能够预防更多的心血管病事件,而策略1和2每预防一例心血管病事件使用他汀的需干预人数更少。单因素敏感性分析及概率敏感性分析的结果与主分析一致。结论: 在我国发达地区人群中采用西方国家心血管病一级预防指南普遍推荐的基于风险评估的他汀干预策略能够取得更好的健康效果;在风险评估工具的选择上,采用China-PAR模型可以获得更多的健康收益,而采用预测变量更少的WHO模型则更有效率。     

Lipoprotein-associated phospholipase A₂ activity is increased in patients with definite familial hypercholesterolemia compared with other forms of hypercholesterolemia

Background and Aim

Lipoprotein-associated phospholipase A₂ (Lp-PLA₂) plays a key role in atherosclerosis development. It is considered a marker of increased risk of cardiovascular disease (CVD) and plaque vulnerability. Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated plasma levels of low-density lipoprotein cholesterol and a higher prevalence of early CVD.Our aim was to evaluate the differences in Lp-PLA₂ activity in a population of hypercholesterolemic patients with and without definite FH.

Lipids and CVD management: towards a global consensus.

Cardiovascular disease (CVD) is currently the leading cause of morbidity and mortality worldwide and its incidence is likely to increase. Multiple risk factors contribute to CVD. Elevated LDL-cholesterol (LDL-C) and triglyceride levels, low HDL-cholesterol levels, hypertension, type 2 diabetes, and smoking are key modifiable risk factors. Such risk factors are present in 80-90% of coronary heart disease (CHD) patients. For many factors, modification can significantly reduce CVD incidence. For example, statin-induced LDL-C reductions reduce cardiovascular events by 24-37% and smoking cessation reduces CHD mortality by 36%. The need to identify and treat these risk factors has led many national and local groups to develop clinical practice guidelines for management of CVD. Although the aim of such guidelines is to provide practitioners with a framework to identify, prioritize, and manage patients, the plethora of guidelines can cause confusion. In addition, research indicates that guidelines are not being optimally implemented. This review considers these practical issues, highlights the common goals shared by many guidelines, and focuses on how these can be best achieved. It also highlights areas where the guidelines differ and discusses points to consider when selecting the most appropriate recommendation.     

阿托伐他汀对不同血脂水平的高血压病患者血管内皮功能的影响

目的研究阿托伐他汀对正常血脂和高血脂的高血压病(EH)患者血管内皮功能的影响。方法采用双盲、随机、对照方法，将正常血脂(NC组)和高血脂(HC组)高血压病患者分为他汀治疗组(阿托伐他汀20mg／d，共8周，NC组，n=22；HC组，n=24)和未用药对照组(NC组n=21；HC组，n=24)；运用无创超声检查技术，观察用药前后颈动脉内-中膜厚度(IMT)及肱动脉内皮依赖性舒张功能(FMD)的变化，同时检测血清一氧化氮(NO)及内皮素-1(ET-1)的浓度水平。结果治疗前NC、HC各组IMT值和血清ET-1水平较健康对照组(n=40)明显升高(P＜0．01)，FMD值和NO水平却显著下降(P＜O．01)，IMT、FMD、NO与LDI-C存在着显著的相关性。治疗8周后，NC、HC各组IMT值和ET-1水平明显降低，FMD和NO水平显著上升。与对照组比较，他汀治疗组的IMT、ET-1降低更明显(P＜O．05)，FMD和NO升高更为显著(P＜O．05)。两他汀治疗组的血脂水平较治疗前均明显下降(P＜O．05，P＜O．01)。结论阿托伐他汀治疗正常血脂和高血脂的高血压病患者，可在有效调脂的同时，发挥其非调脂作用，逆转或延迟颈动脉IMT的进程，改善血管内皮功能。     

High-Dose Simvastatin Is Effective in Preventing Cerebral Vasospasm after Aneurysmal Subarachnoid Hemorrhage: A Prospective Cohort Study in Korean Patients

ObjectiveThe goal of this study was to assess the effect of high-dose simvastatin on cerebral vasospasm and its clinical outcome after aneurysmal subarachnoid hemorrhage (SAH) in Korean patients.MethodsThis study was designed as a prospective observational cohort study. Its subjects were aneurysmal SAH patients who had undergone aneurysm clipping or coiling. They were assigned to 1 of 3 groups : the 20 mg, 40 mg, and 80 mg simvastatin groups. The primary end-point was the occurrence of symptomatic vasospasm. The clinical outcome was assessed with the modified Rankin Scale (mRS) score after 1 month and 3 months. The risk factors of the development of vasospasm were assessed by logistic regression analysis.ResultsNinety nine patients with aneurysmal SAH were treated and screened. They were sequentially assigned to the 20 mg (n=22), 40 mg (n=34), and 80 mg (n=31) simvastatin groups. Symptomatic vasospasm occurred in 36.4% of the 20 mg group, 8.8% of the 40 mg group, and 3.2% of the 80 mg group (p=0.003). The multiple logistic regression analysis showed that poor Hunt-Hess grades (OR=5.4 and 95% CI=1.09-26.62) and high-dose (80 mg) simvastatin (OR=0.09 and 95% CI=0.1-0.85) were independent factors of symptomatic vasospasm. The clinical outcomes did not show a significant difference among the three groups.ConclusionThis study demonstrated that 80 mg simvastatin treatment was effective in preventing cerebral vasospasm after aneurysmal SAH, but did not improve the clinical outcome in Korean patients.     

Endothel,Inflammation und Statine

Zusammenfassung Der hohe Stellenwert der Statine in der Risikoreduktion von Patienten mit Herz-Kreislauf-Erkrankungen oder hohem kardiovaskulärem Risiko ist unbestritten. Dabei wurde in den letzten Jahren immer klarer, dass die Cholesterinsenkung nur einen von vielen Effekten darstellt und zelluläre Effekte (pleiotrope Wirkungen) hinzukommen. Diese beruhen auf Veränderungen der Geranylierung und Farnesylierung von Signalproteinen in verschiedenen Zellen, einschließlich kardiovaskulärer Zellen. So üben Statine bis zu 100 verschiedene bekannte, lipidunabhängige Wirkungen auf Entzündungszellen (Makrophagen), Interleukinbildung, Extrazellulärmatrixproteine, die freie Radikalbildung, aber auch das Endothel aus. Diese Wirkungen zusammen mit der LDL-Cholesterin-Senkung tragen zur Plaquestabilisierung und damit Senkung von kardiovaskulären Ereignissen bei. Die direkten Endothelwirkungen der Statine konnten als vasodilatierende Effekte in zahlreichen Studien belegt werden. Gerade Hochrisikopatienten, wie Diabetiker, profitieren hiervon; konsistente Endpunktstudien, einschließlich der ausschließlich an Diabetikern durchgeführten CARDS, belegen dies eindrucksvoll. Leider besteht eine gravierende Unterversorgung, sodass nur ein kleiner Teil der möglichen Risikoreduktion auch realisiert wird.     

强化他汀治疗对经皮冠状动脉介入治疗后患者肾损伤的保护作用

目的研究强化他汀治疗对经皮冠状动脉介入治疗(PCI)后肾功能的保护作用和预防对比剂肾病(CIN)的效果,探讨其可能机制。方法 228例接受择期PCI的急性冠脉综合征(ACS)患者,随机分为标准他汀治疗组(SSG,n=115)和强化他汀治疗组(ISG,n=113)。于PCI术前7d开始,SSG组患者口服20mg/d辛伐他汀,ISG组患者则口服80mg/d辛伐他汀。于PCI术前、术后24、48h分别测定血清肌酐水平,按Cochcroft-Gault公式计算肌酐清除率。于PCI术前、术后24h分别测定血清高敏C反应蛋白(hs-CRP)、P选择素和细胞间黏附分子1(ICAM-1)水平。结果 PCI后血肌酐水平显著升高,并于术后24h达高峰,然后逐渐下降,术后48hISG组血肌酐水平显著回降(与术后24h比较P0.001)至术前水平(P=0.94),而SSG组血肌酐水平未显著回降(与术后24h比,P=0.11)。PCI术后24、48h,ISG组的血肌酐水平均显著低于SSG组(术后24h,P0.05;术后48hP0.001)。PCI术后,两组肌酐清除率均显著降低,最低值出现在术后24h,然后逐渐回升。术后48h,SSG组肌酐清除率显著回升(与术后24h相比,P=0.03),但仍低于术前水平(P0.001),而ISG组术后48h显著回升(与术后24h相比,P0.001)并恢复到术前水平(P=0.87),在术后24、48h,ISG组肌酐清除率的回升程度均显著高于SSG组(均P0.001)。虽然PCI术后血清hs-CRP、P选择素和ICAM-1水平均显著升高(均P0.001),但ISG组低于SSG组(均P0.001)。结论与标准剂量他汀治疗相比,PCI前使用强化剂量他汀治疗可进一步保护PCI术后肾脏功能,降低CIN的发生率。这种益处伴随有血清hs-CRP、P选择素和ICAM-1水平的显著降低。