血脂领域热点荟萃

近年来动脉粥样硬化性心血管疾病(ASCVD)的概念得到统一,包括冠心病(CHD)、缺血性卒中和外周动脉粥样硬化性疾病等。新近各国血脂异常防治指南共同提出了管理胆固醇防治ASCVD的核心理念。胆固醇在动脉粥样硬化发病中的核心地位得到认同。本文综述了近年血脂领域在遗传学、循证医学及药物研发中的重要进展,并进一步阐述了科学管理胆固醇的策略。他汀类药物仍是管理胆固醇的基石,但非他汀类药物已取得突破性进展,联合降脂治疗是未来全面管理胆固醇、降低ASCVD风险的重要手段。     

载脂蛋白B水平在动脉粥样硬化性心脏病的评估研究进展

动脉粥样硬化性心血管疾病（ASCVD）患病人数逐年上升,低密度脂蛋白胆固醇（LDL-C）是作为其风险评估及降脂疗效的指标,可有效减少患病率。但部分患者LDL-C不高或降脂有效仍然发生心血管事件。目前多项研究表明载脂蛋白B(apoB)在ASCVD风险预测及评估较LDL-C或者非高密度脂蛋白胆固醇（非HDL-C）具优越性,多部指南及共识重视推荐apoB在临床上应用。此文主要讨论apoB的生理特点、参与ASCVD的过程,重点阐述国内外对apoB心血管事件风险预测研究。     

LDL-C、HDL-C和IMT与动脉粥样硬化的关系

目的探讨低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）和颈动脉内中膜厚度（IMT）与动脉粥样硬化（AS）的关系。方法选取本院2008年6月至2011年6月住院健康体检者120例,其中男78例,女42例,年龄在20岁85之间,平均（50.6±11.5）岁。采用日立7020型全自动生化仪检测患者LDL-C、HDL-C含量;采用日本东芝SSA-520A超声诊断仪测量颈动脉内中膜厚度（IMT）;采用SPSS16.0统计学软件对结果进行分析。结果动脉粥样硬化患者的LDL-C、HDL-C和IMT与健康对照组相比均差异有统计学意义（P〈0.05）,LDL-C与AS呈负相关、HDL-C、IMT与AS呈正相关。结论 LDL-C、HDL-C和IMT的是预防动脉粥样硬化疾病的有效指标。     

PCSK9抑制剂在动脉粥样硬化性心血管疾病中的临床研究进展

动脉粥样硬化性心血管疾病(ASCVD)现已成为危害人类健康的主要疾病之一。降低胆固醇治疗尤其是低密度脂蛋白-胆固醇(LDL-C),是ASCVD防治的基石,目前指南推荐控制LDL-C水平首选他汀类药物。但在临床实践中,经过他汀治疗的ASCVD患者仍存在较高剩留风险,另仍有部分患者不能耐受他汀类药物或在他汀类药物最大耐受剂量的情况下血脂仍不能达标。人前蛋白转化酶枯草溶菌素9(PCSK9)与LDL-C代谢密切相关,近年来大量基础和临床研究均证实PCSK9抑制剂能够显著降低血LDL-C水平,且耐受性和安全性良好。目前国外已批准PCSK9抑制剂用于临床。本文将系统综述有关PCSK9基因与血脂代谢的关系、PCSK9抑制剂的研发过程,总结其在基础和临床研究的最新进展。     

莽草酸对动脉粥样硬化大鼠血脂及血液流变学影响的实验研究

目的：探讨莽草酸对动脉粥样硬化（AS）大鼠血脂、血液流变学的影响。方法：采用高脂饲料复制动脉粥样硬化模型,观察莽草酸对动脉粥样硬化大鼠血脂、血液流变学指标的影响。结果：莽草酸可显著降低动脉粥样硬化大鼠血清总胆固醇（TC）、三酰甘油（TG）、低密度脂蛋白（LDL）水平,升高高密度脂蛋白（HDL）水平（P〈0．05）,并能显著降低动脉粥样硬化大鼠全血黏度（高、中、低切）、血浆黏度和红细胞压积（P〈0．05）。结论：莽草酸可改善AS大鼠血脂水平和血液流变学指标,对AS具有一定的防治作用。     

安阳市职业女性血脂及脂蛋白水平与年龄关系分析调查

目的分析安阳市职业女性血脂及脂蛋白水平与年龄关系。方法对女性的总胆固醇(TC)、甘油三脂(TG)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C)等4项指标进行检测,按照我国2007年制定的《中国成人血脂异常防治指南》和参考美国ATPⅢ指南,对血脂及脂蛋白检测结果进行分析。结果女性40岁以后,血脂及脂蛋白呈增龄性升高趋势,大多数调查对象有不同类型的血脂及脂蛋白异常。结论女性血脂及脂蛋白呈增龄性升高趋势表明动脉粥样硬化(AS)、心脑血管疾病的风险明显增高。提示女性40岁后应定期做血脂及脂蛋白测定,做好预防保健及健康教育工作,对妇女健康和心脑血管疾病预防意义重大。     

《中国血脂管理指南(2023年)》药物更新透视

血脂管理对于动脉粥样硬化性心血管疾病(ASCVD)的防治与预后改善十分重要。为更好地指导临床实践，《中国血脂管理指南(2023年)》在《中国成人血脂异常防治指南(2016年修订版)》基础上，结合国内外新的循证医学证据和中国国情，对从儿童到老年全生命周期的血脂管理，包括血脂检测项目、筛查频率、ASCVD风险评估及特定人群降脂目标、治疗原则、药物治疗方案等多个方面的内容进行了调整、扩增和完善。该文就治疗药物部分的更新进行综述。     

有关他汀类调脂药抗动脉粥样硬化新指南的争议

2013年底至2014年初美国和欧洲相继对高血压领域及血脂领域发布了数个指南,其中影响最大的是《2014年美国成人高血压治疗指南（JNC8）》和美国心脏学会（AHA）/美国心脏病学会（ACC）《降低动脉粥样硬化性心血管疾病（ASCVD）风险指南》（以下简称《美国血脂新指南》）两部,尤其是后者在中国遭遇了水土不服。     

天津市老年女性干部群体血脂状况分析

摘要： 目的 了解天津市区老年女性干部人群的血脂状况及年龄变化趋势, 探讨老年女性心血管疾病的防治策略。 方法 分析 1 837 例女性干部体检数据, 其中老年女性 847 例（≥60 岁）, 分析该群体的血脂水平、异常状况及随年龄变化规律。 结果 老年女性总胆固醇（TC）、三酰甘油（TG）、低密度脂蛋白胆固醇（LDL-C）及体质指数（BMI）均高于非老年女性（P < 0.01）。 TC、TG、LDL-C、LDL-C/HDL-C、TG/HDL-C 及非高密度脂蛋白胆固醇（non-HDL-C）随 年龄增加呈先升后降的趋势, 至 60～ 69 岁达峰值; HDL-C 存在随年龄增加呈先降后升的趋势, 至 60～ 69 岁达谷底。 结论血脂水平随增龄出现规律性的变化, 老年女性人群心血管疾病发病风险随年龄增加而增高。     

血脂水平波动的危险因素及其与ASCVD的关系研究进展

血脂水平波动受多种危险因素的影响，除了受年龄和性别、妊娠和遗传、气象因素等不可干预的危险因素影响外，还与吸烟和饮酒、超重和肥胖、体重指数、饮食和运动、药物因素、高血压、糖尿病、高尿酸血症等可干预的危险因素密切相关，血脂异常增加了动脉粥样硬化性心血管疾病(ASCVD)的发生风险，定期健康体检监测血脂水平的动态变化、早期发现血脂异常，采取综合的管理措施以降低或延缓ASCVD的进程。     

从传统他汀及其联合治疗看调脂治疗的临床获益

摘要： 动脉粥样硬化性心血管疾病 （ASCVD） 是全球范围内主要的疾病负担, 亦是患者死亡的主要原因。既往大量关于他汀类药物调脂治疗的临床试验证实, 他汀类药物可有效降低 ASCVD 患者低密度脂蛋白胆固醇 （LDL-C） 水平、 全因死亡率和心血管病死亡率, 无 ASCVD 的患者亦可获益。然而, 目前无论是 ASCVD 高危患者还是无 ASCVD 的人群, 并未广泛应用降脂治疗。因此, 本文阐述了他汀类及其联合用药所带来的临床获益, 旨在增大受益人群, 改善预后。     

Metabolic syndrome: therapeutic considerations

The metabolic syndrome is a constellation of metabolic risk factors for atherosclerotic cardiovascular disease (ASCVD) occurring in one individual. There are five cardiovascular risk factors that accompany the metabolic syndrome: atherogenic dyslipidemia [elevated apolipoprotein B (apo B), elevated triglyceride, small low-density lipoprotein (LDL) particles, and low high-density lipoprotein (HDL)cholesterol], elevated blood pressure, elevated glucose, a prothrombotic state, and a proinflammatory state. The likelihood of an individual developing metabolic syndrome is enhance by underlying risk factors, notably, obesity, insulin resistance, lack of physical activity, advancing age, and hormonal factors (e.g., androgens and corticosteroids). Besides being at higher risk for ASCVD, persons with the metabolic syndrome are at increased risk for type 2 diabetes. Persons with the metabolic syndrome deserve management in the clinical setting to reduce the risk for both ASCVD and type 2 diabetes. The two major therapeutic strategies for treatment of affected persons are modification of the underlying risk factors and separate drug treatment of the particular metabolic risk factors when appropriate. First-line therapy for underlying risk factors is therapeutic lifestyle changes, i.e., weight loss in obese persons, increased physical activity, and anti-atherogenic diet. These changes will improve all of the metabolic risk factors. Whether use of drugs to reduce insulin resistance is effective, safe, and cost-effective before the onset of diabetes awaits the results of more clinical research. Turning to individual risk components, for atherogenic dyslipidemia, drug therapies that promote lowering of apo B and raise HDL cholesterol will be needed for higher risk patients. Treatment of categorical hypertension with drugs has become standard practice. When hyperglycemia reaches the diabetic level, glucose-lowering agents will become necessary when dietary control is no longer effective, and reduction of a prothrombotic state with low-dose aspirin may be indicated in higher-risk patients.     

新型降脂药人前蛋白转化酶枯草溶菌素9抑制剂与动脉粥样硬化性心血管疾病、静脉血栓栓塞疾病关系的研究进展

随着生活方式的改变,心脑血管疾病逐渐成为全人类死亡的“头号杀手”,高于恶性肿瘤、糖尿病等。血脂的升高尤其是低密度脂蛋白胆固醇(LDL-C)的升高与动脉粥样硬化性心血管疾病(ASCVD)的发生、发展息息相关。现有的专家共识、指南提出他汀类药物是降低LDL-C的一线用药,但仍可能会发生复发性缺血事件。人前蛋白转化酶枯草溶菌素9(PCSK9)抑制剂作为一类新型降脂药,有显著降低血LDL-C水平,同时又可降低脂蛋白(a)的水平,又与ASCVD与静脉血栓栓塞疾病(VTE)的发病可能相关。本文将系统地阐述新型降脂药PCSK9抑制剂与ASCVD、VTE的关系研究进展。     

Dynamic changes of the composition of plasma HDL particles in patients with cardiac disease: Spotlight on sphingosine‐1‐phosphate/serum amyloid A ratio

Several epidemiological studies reported an inverse relationship between plasma high‐density lipoprotein (HDL) cholesterol levels and atherosclerotic cardiovascular disease (ASCVD). However, therapeutic interventions targeted at raising HDL‐cholesterol failed to improve cardiovascular outcomes, suggesting that HDL components distinct from cholesterol may account for the anti‐atherothrombotic effects attributed to this lipoprotein. Sphingosine‐1‐phosphate (S1P) and the acute phase protein serum amyloid A (SAA) have been identified as integral constituents of HDL particles. Evidence suggests that S1P and SAA levels within HDL particles may be affected by inflammation and oxidative stress, which are coexisting processes underlying ASCVD. Because SAA, an inflammation‐related marker, and S1P, an anti‐atherothrombotic marker, have relatively clear opposite characteristics among the HDL‐associated proteins, the approach of assessing the two markers simultaneously may provide new insights in clinical practice (S1P/SAA Index). This review focuses on evidence in support of the concept that the S1P/SAA Index may affect the HDL atheroprotective properties and may, therefore represent a potential target for therapeutic interventions.     

Spotlight from the American Society for Preventive Cardiology on Key Features of the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guidelines on the Management of Blood Cholesterol

The 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol retains focus on recommendations for statin treatment in the original four statin-eligible groups [those with atherosclerotic cardiovascular disease (ASCVD), diabetes, low-density lipoprotein cholesterol (LDL-C) ≥ 190 mg/dL, and higher risk primary prevention] without the use of treatment initiation or target LDL-C levels from the earlier 2013 American College of Cardiology/American Heart Association (ACC/AHA) guideline, but has several new features. First, patients with primary prevention are divided into those who are at low (< 5%), borderline (5% to < 7.5%), intermediate (7.5% to < 20%), and high (≥ 20%) risk based on the ASCVD risk estimator. Moreover, the new guideline goes further to consider a wider range of factors [now called “risk enhancers”—premature family history of ASCVD, persistently high LDL-C, chronic kidney disease (CKD), metabolic syndrome, conditions specific to women, inflammatory diseases, and high-risk ethnicities] that can be used to better inform the treatment decision. Moreover, more detailed recommendations on how the results of coronary calcium scanning can be used to inform the treatment decision are provided, including how it may be used to “de-risk” certain patients for delaying or avoiding the use of statin therapy. There are also specific sections for cholesterol management in other patient subgroups including women, children, certain ethnic groups, those with CKD, chronic inflammatory disorders and HIV, as well as discussion on the management of hypertriglyceridemia. Importantly, for persons with known ASCVD, a distinction is made for those who are at “very high risk” based on having had two major ASCVD events or one major event and two or more other high risk conditions, such as diabetes or other major risk factors, or bypass surgery or percutaneous intervention. Finally, the concept of a threshold LDL-C for initiating a non-statin therapy (after considering highest tolerated statin dosage) is provided, with ezetimibe recommended as the key non-statin to be added if the LDL-C still remains ≥ 70 mg/dL for all ASCVD patients, and in those who are at “very high risk”, further consideration for using a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor. While the new guideline does have greater detail (and arguably, complexity), the refinements provide a strategy for guiding the clinician to target both statin and non-statin therapy to those most likely to derive benefit.     

Raising high-density lipoprotein cholesterol with reduction of cardiovascular risk: the role of nicotinic acid – a position paper developed by the European Consensus Panel on HDL-C*

SUMMARY

Reduction of low-density lipoprotein cholesterol (LDL-C) is presently the primary focus of lipid-lowering therapy for prevention and treatment of coronary heart disease (CHD). However, the high level of residual risk among statin-treated patients in recent coronary prevention studies indicates the need for modification of other major components of the atherogenic lipid profile. There is overwhelming evidence that a low plasma level of high-density lipoprotein cholesterol (HDL-C) is an important independent risk factor for CHD. Moreover, a substantial proportion of patients with or at risk of developing premature CHD typically exhibit distinct lipid abnormalities, including low HDL-C levels. Thus, therapeutic intervention aimed at raising HDL-C, within the context of reducing global cardiovascular risk, would benefit such patients, a viewpoint increasingly adopted by international treatment guidelines.     

Treatment of dyslipidaemia in HIV-infected persons

Accumulating evidence suggests that HIV-infected individuals have an increased risk of cardiovascular events. This risk seems to be at least partially mediated by dyslipidaemia, which is related to the use of highly active antiretroviral therapy (HAART). As HIV-infected individuals live longer due to HAART, their cardiovascular risk will invariably increase. Because HAART is likely to be used indefinitely, HAART-related dyslipidaemia has emerged as a major cardiovascular concern. This article summarises the evaluation of dyslipidaemia and cardiovascular risk in HIV-infected individuals, the potential pathophysiological and genetic mechanisms involved in HAART-related dyslipidaemia and the current treatment approaches. In general, dyslipidaemia is evaluated and treated as in HIV-negative persons. The first step is cardiovascular risk assessment and the determination of target lipid levels. A healthier lifestyle and, in particular, smoking cessation should be promoted. Lowering levels of low-density lipoprotein cholesterol (or, in the setting of significant hypertriglyceridaemia, non-high-density lipoprotein cholesterol) is the primary target of intervention. Switching HAART to a more lipid-favourable regimen should be considered if this does not jeopardise virological control. Many patients will need lipid-lowering drug therapy. Appropriate low-density lipoprotein cholesterol target levels may be more difficult to reach than in the HIV-negative population, and the potential for drug interactions when using lipid-lowering agents together with HAART needs to be considered. The identification of HAART strategies with no or minimal metabolic toxicity, and the identification of the safest and most efficacious lipid-lowering therapies for HIV-infected individuals with dyslipidaemia are important research goals.     

Treatment of dyslipidaemia in HIV-infected persons

Accumulating evidence suggests that HIV-infected individuals have an increased risk of cardiovascular events. This risk seems to be at least partially mediated by dyslipidaemia, which is related to the use of highly active antiretroviral therapy (HAART). As HIV-infected individuals live longer due to HAART, their cardiovascular risk will invariably increase. Because HAART is likely to be used indefinitely, HAART-related dyslipidaemia has emerged as a major cardiovascular concern. This article summarises the evaluation of dyslipidaemia and cardiovascular risk in HIV-infected individuals, the potential pathophysiological and genetic mechanisms involved in HAART-related dyslipidaemia and the current treatment approaches. In general, dyslipidaemia is evaluated and treated as in HIV-negative persons. The first step is cardiovascular risk assessment and the determination of target lipid levels. A healthier lifestyle and, in particular, smoking cessation should be promoted. Lowering levels of low-density lipoprotein cholesterol (or, in the setting of significant hypertriglyceridaemia, non-high-density lipoprotein cholesterol) is the primary target of intervention. Switching HAART to a more lipid-favourable regimen should be considered if this does not jeopardise virological control. Many patients will need lipid-lowering drug therapy. Appropriate low-density lipoprotein cholesterol target levels may be more difficult to reach than in the HIV-negative population, and the potential for drug interactions when using lipid-lowering agents together with HAART needs to be considered. The identification of HAART strategies with no or minimal metabolic toxicity, and the identification of the safest and most efficacious lipid-lowering therapies for HIV-infected individuals with dyslipidaemia are important research goals.