高密度脂蛋白的代谢相关基因表达产物与动脉粥样硬化

高密度脂蛋白胆固醇水平降低是动脉粥样硬化性心脏病独立和重要的危险因素。血浆高密度脂蛋白胆固醇水平不仅决定于它的生成速率,更重要的是取决于它的代谢水平。一系列的基因及其相关产物参与了高密度脂蛋白参与的胆固醇逆向转运过程,包括与升高血浆高密度脂蛋白胆固醇水平的基因及其产物如三磷酸腺苷结合盒转运A1、磷脂酰胆碱胆固醇酰基转移酶、磷脂转运蛋白和脂蛋白脂酶等,以及降低血浆高密度脂蛋白胆固醇水平的基因和产物如清道夫受体B1、胆固醇酯转运蛋白、肝脂肪酶和内皮细胞脂肪酶等。而高密度脂蛋白代谢与动脉粥样硬化的关系也是多方面的,不能仅由血浆高密度脂蛋白胆固醇水平来明确推断对动脉粥样硬化的影响,降低血浆高密度脂蛋白胆固醇水平与动脉粥样硬化有一定的关联但不是必然的联系。     

高密度脂蛋白与动脉粥样硬化和冠心病

高密度脂蛋白胆固醇水平降低是冠心病独立的预测因子和重要的危险因素.高密度脂蛋白的抗动脉粥样硬化机制有:参与胆固醇逆转运;抗氧化和抗炎;抗血栓、促纤溶;保护内皮功能等.高密度脂蛋白与载脂蛋白和其密度、大小相关的异质性也与动脉粥样硬化有关.升高高密度脂蛋白胆固醇水平能明显减少心血管病事件的发生.冠心病或有冠心病危险因素的患者,应对低高密度脂蛋白胆固醇水平进行治疗,包括生活方式的改变和药物的治疗.     

甲基康派丁——一种用于降胆固醇的HMG-CoA还原酶抑制剂

本文从药理学、药代动力学、临床实验及临床应用等方面介绍了甲基康派丁的作用特点。该药能有效地降低总胆固醇和低密度脂蛋白胆固醇,且还可降低甘油三酯和增加高密度脂蛋白胆固醇,副作用少,是较有希望的降胆固醇新药。     

胆固醇酯转移蛋白抑制剂在动脉粥样硬化性心血管疾病治疗中的研究进展

动脉粥样硬化性心血管疾病与多种因素相关,其中血脂异常占有极其重要的地位。胆固醇酯转移蛋白抑制剂是一种以升高高密度脂蛋白胆固醇为目标的调血脂药,可联合他汀类药物在降低低密度脂蛋白胆固醇的基础上升高高密度脂蛋白胆固醇水平,从而降低高危患者心血管不良事件风险。现将胆固醇酯转移蛋白抑制剂的作用机制、研究现状和未来前景等进行综述。     

肥胖与高密度脂蛋白代谢异常研究进展

肥胖是代谢综合征发生发展的中心环节,其与代谢综合征的各个危险因素密切相关.高密度脂蛋白胆固醇水平降低是代谢综合征的特征性血脂代谢异常之一.有研究表明肥胖可通过多种途径影响体内高密度脂蛋白水平和功能,如高甘油三酯血症,脂肪细胞因子,炎症状态,载脂蛋白M异常等.而高密度脂蛋白胆固醇水平降低及功能异常是动脉粥样硬化进展的独立危险因素.本文就肥胖与高密度脂蛋白异常及其影响因素的研究进展作一综述.     

高密度脂蛋白胆固醇水平与高密度脂蛋白功能:孰是孰非？

早期流行病学研究发现降低的高密度脂蛋白胆固醇(HDLC)水平与增加的冠心病风险密切相关,这促使了高密度脂蛋白抗动脉粥样硬化假说的提出:相对于低密度脂蛋白胆固醇而言,HDLC是"好"的胆固醇,提高血清HDLC水平可能降低心血管事件风险。然而新的研究发现:升高HDLC水平并不能减少临床心血管事件的发生。这使得高密度脂蛋白抗动脉粥样硬化假说遭到质疑。近来,高密度脂蛋白功能而非HDLC水平与动脉粥样硬化的关系被更多地关注。本文就高密度脂蛋白最新相关研究进行综述。     

非胰岛素依赖型糖尿病患者血清中甘油三酯浓度与高密度脂蛋白的关系

为探讨高甘油三酯血症时，低高密度脂蛋白胆因醇血症的发生机理，我们以非胰岛素使赖型糖尿病患者高甘油三酯血症组（ｎ＝２４）和正常甘油三酯血症组（ｎ＝６９）为对象，测定了与高密度脂蛋白有关的血清脂质和载脂蛋白的浓度。与正常甘油三脂血症组相比，高甘油三酯血症组高密度脂蛋白胆固醇、高密度脂蛋白２胆固醇、载脂蛋白ＡＩ／载脂蛋白ＡⅡ、高密度脂蛋白胆固醇／载脂蛋白ＡＩ均降低，载脂蛋白ＡⅡ升高。多元回归分析显示：甘油三酯与上述血清脂质、载脂蛋白及其比值之间均存在线性回归关系。以上提示：高甘油三酯血症可能影响载脂蛋白ＡＩ与胆固醇的结合及高密度脂蛋白中胆固醇的酯化速度，从而使高密度脂蛋白胆固醇浓度下降。     

非胰岛素依赖型糖尿病患者血清中甘油三酯浓度与高密度脂蛋白的关系

为探讨高甘油三酯血症时，低高密度脂蛋白胆固醇血症的发生机理，我们以非胰岛素依赖型糖尿病患者高甘油三酯血症组和正常甘不同三酯血症组为对象，测定了与高密度脂蛋白有关的血清脂质和载脂蛋白的浓度，与正常甘油三脂血症组相比，高甘油三酯血症组高密度脂蛋白胆固醇、高密度脂蛋白２胆固醇、载脂蛋白ＡⅠ／载脂蛋白ＡⅡ、高密度脂蛋白胆固醇／载脂蛋白ＡⅠ均降低，载脂蛋白ＡⅡ升高。多元回归分析显示：甘油三酯与上述血清脂质，     

高脂血症危害多

认识危害。高脂血症(也称血脂异常)是指血液里的胆固醇、甘油三酯和低密度脂蛋白胆固醇增高．而高密度脂蛋白胆固醇降低。根据1996年全国血脂异常诊断和治疗专题研讨会规定，血中胆固醇超过5．72毫摩／升、甘油三酯超过1．7毫摩／升、低密度脂蛋白胆固醇超过3．64毫摩／升为升高．同时出现高密度脂蛋白胆固醇降低(低于0．9毫摩／升)，我们就称之为血脂异常。     

他汀类药物治疗冠状动脉粥样硬化性心脏病的研究进展

随着生活水平的提高和饮食结构的改变,动脉粥样硬化性疾病的发病率迅速上升,病变主要累及主动脉、冠状动脉、脑动脉等大动脉,患者多合并脂质代谢紊乱,主要表现为：总胆固醇升高、低密度脂蛋白胆固醇（LDL-C）升高、高密度脂蛋白胆固醇（HDL-C）降低、甘油三酯升高等。     

Low high-density lipoprotein cholesterol and cardiovascular disease: risk reduction with statin therapy

A low level of high-density lipoprotein cholesterol (HDL-C) is a major risk factor for cardiovascular disease; however, patients with low levels of HDL-C without raised low-density lipoprotein cholesterol (LDL-C) levels are not currently eligible for lipid-lowering therapy. Many individuals with low levels of HDL-C have a combination of cardiovascular risk factors that include high LDL particle concentrations. Lowering LDL particle concentration and its surrogate measure, LDL-C, is an important approach to reducing cardiovascular risk. Statins are the most effective agents for lowering levels of LDL and can significantly increase levels of HDL-C. Extending statin therapy to patients with low levels of HDL-C but with LDL-C levels below target may have benefits for cardiovascular disease reduction in these patients.     

HDL: To Treat or Not To Treat?

Several studies have shown an inverse relationship between HDL cholesterol (HDL-C) levels and the risk of cardiovascular disease. Low HDL-C levels are commonly present in subjects with diabetes, metabolic syndrome, or obesity. These observations have suggested that increasing HDL concentrations might help in decreasing the cardiovascular disease risk. However, despite initial positive results, some recent data from clinical trials with HDL-raising therapies failed to confirm this hypothesis; in addition, data from Mendelian randomization analyses showed that nucleotide polymorphisms associated with increased HDL-C levels did not decrease the risk of myocardial infarction, further challenging the concept that higher HDL-C levels will automatically translate into lower cardiovascular disease risk. Differences in the quality and distribution of HDL particles might partly explain these findings, and in agreement with this hypothesis, some observations have suggested that HDL subpopulation levels may be better predictors of cardiovascular disease than simple HDL-C levels. Thus, it is expected that increased HDL-C levels may be beneficial when associated with an improvement in HDL function, suggesting that pharmacological approaches able to correct or increase HDL functions might produce more reliable clinical benefits.     

高密度脂蛋白与冠心病的关系

应用他汀类将低密度脂蛋白胆固醇（LDL—C）降低至正常水平后,临床心血管事件的发生风险可减少30％～40％,但是,仍有大约30％患者会发生心血管事件。流行病学调查发现,高密度脂蛋白胆固醇（HDL—C）水平降低是心血管病的一个独立风险因子,本文综述HDL—C与冠心病的关系。     

What is the most effective strategy for managing diabetic dyslipidaemia?

The dyslipidaemic profile of diabetes greatly contributes to the increased cardiovascular risk associated with the disorder, and evidence from many intervention trials using statins, fibrates, nicotinic acid or a nicotinic acid-statin combination, indicates the substantial cardiovascular risk reduction to be gained from lipid modification. Several large statin trials have demonstrated the efficacy of cholesterol-lowering in individuals with coronary heart disease and raised low-density lipoprotein-cholesterol (LDL-C) (>or=130 mg/dL; >or=3.4 mmol/L), but for the 40% of patients whose LDL-C is within recommended limits, many of whom have low high-density lipoprotein-cholesterol (HDL-C), an alternative strategy is necessary if excess risk is to be minimized. The veterans affairs high-density lipoprotein cholesterol intervention trial (VA-HIT) proved the efficacy of the fibric acid derivative, gemfibrozil, to elevate HDL-C and reduce triglycerides, with a resulting 22% relative risk reduction for cardiovascular death or non-fatal myocardial infarction, and even greater reductions in individuals with insulin resistance and diabetes. Increased HDL-C was independently predictive of reduction in coronary heart disease. In the Coronary Drug Project, individuals with diabetes or insulin resistance derived as much as 70% cardiovascular risk reduction from the HDL-C elevations achieved with nicotinic acid therapy. The effects of lowering LDL-C and raising HDL-C are additive and predictive of total cardiovascular event reduction, and by using statin-nicotinic acid combination therapy, cardiovascular risk reductions as great as 90% are possible. Such combination strategies offer patients the greatest opportunity for improved cardiovascular health and are likely to become the treatment strategy of the future.     

A prospective study of serum high density lipoprotein cholesterol, cardiovascular and cerebrovascular risk in a Chinese muti-provinces cohort

OBJECTIVE:To evaluate the association between serum HDL-C and the risk of cardiovascular diseases (CHD) in subjects aged 35-64 years. METHODS: A prospective study was carried out in 11 provinces from 1992 to 2002. The association of baseline HDL-C level and cardiovascular disease occurrence was analyzed in 30384 subjects aged 35-64 years using Cox multivariate proportional hazards regression. RESULTS: (1) Compared with the group of HDL-C > or = 1.56 mmol/L, multivariate-adjusted relative risk of ischemic cardiovascular disease (ICVD), including CHD and ischemic stroke increased continuously with decreased HDL-C level. (2) HDL-C level had different impact on different types of CVD. Positive association was observed between HDL-C level and the risk of ischemic stroke, but the relationship between HDL-C level and the risk of hemorrhagic stroke was indefinite. Compared with the group with HDL-C > or = 1.56 mmol/L, the risk of CHD of the group with HDL-C < or =1.03 mmol/L increased by 45% (RR = 1.45, P<0.05) and that of ischemic stroke increased by 53% (RR = 1.53, P <0.01). (3) 6.4% of ICVD, 7.2% of the acute CHD and 7.3% of the acute stroke was attributable to low serum high density lipoprotein cholesterol. CONCLUSIONS: Starting from HDL-C > or = 1.56 mmol/L, the risk of ICVD increases continuously with decreased HDL-C level. Comprehensive intervention for multiple risk factor clustering should be strengthened to reduce theoverall risk of CVD.     

CETP Inhibition: Does the Future Look Promising?

Based on epidemiologic studies conducted throughout the world, it is established that there is an inverse relationship between high-density lipoprotein cholesterol (HDL-C) and risk for coronary artery disease (CAD). The incidence of low HDL-C is high and increasing throughout the world. A variety of pharmacologic approaches are being developed to therapeutically modulate serum levels of HDL-C. One controversial approach to this is the use of molecules that inhibit the activity of cholesteryl ester transfer protein (CETP), an enzyme involved in neutral lipid transfer between lipoproteins. The inhibition of CETP can lead to substantial elevations in HDL-C. Based on a number of considerations, including the complex relationship between loss of function mutations in CETP and risk for CAD and the clinical experience with torcetrapib, it is difficult to predict if CETP inhibition will be associated with reductions in rates of atherosclerosis disease progression and risk for cardiovascular events.     

Focusing on high-density lipoprotein for coronary heart disease risk reduction

A low level of high-density lipoprotein (HDL) is an acknowledged risk factor for coronary heart disease (CHD). HDL cholesterol (HDL-C) exerts its primary cardioprotective effect through a reverse cholesterol transport process, and suppression of this process has been the focus of the development of novel therapeutic agents for increasing HDL-C levels. Several strategies can be used to increase HDL-C levels to target cardiovascular risk reduction. This article presents a review of the biologic actions of HDL that can serve as a potential basis for antiatherosclerotic activity and discusses strategies for targeting HDL for CHD risk reduction.     

Identification of Cardiometabolic Risk: Visceral Adiposity Index Versus Triglyceride/HDL Cholesterol Ratio

Background

The plasma concentration ratio of triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C) can identify cardiometabolic risk and cardiovascular disease. The visceral adiposity index is a sex-specific index, in which measurements of body mass index and waist circumference are combined with TG and HDL-C concentrations. The current analysis was initiated to see if the visceral adiposity index would improve the ability of the TG/HDL-C to identify increased cardiometabolic risk and outcome.

Methods

Cardiometabolic data were obtained in 2003 from 926 apparently healthy individuals, 796 of whom were evaluated in 2012 for evidence of incident cardiovascular disease. The relationship between TG/HDL-C and values for visceral adiposity index was evaluated by Pearson's correlation coefficient. The relative risks for first cardiovascular event between individuals above and below the TG/HDL-C sex-specific cut points, and in the top quartile of visceral adiposity index versus the remaining 3 quartiles, were estimated using Cox proportional hazard models.

Results

TG/HDL-C concentration and visceral adiposity index were highly correlated (r = 0.99) in both men and women. Although more men (133 vs121) and women (73 vs 59) were identified as being at “high risk” by an elevated TG/HDL-C ratio, the individual cardiometabolic risk factors were essentially identical with either index used. However, the hazard ratio of developing cardiovascular disease was significantly increased in individuals with an elevated TG/HDL-C, whereas it was not the case when the visceral adiposity index was used to define “high risk.”

Conclusion

The visceral adiposity index does not identify individuals with an adverse cardiometabolic profile any better than the TG/HDL-C.     

Increasing HDL cholesterol with extended-release nicotinic acid: from promise to practice

BACKGROUND: The inverse relation between high-density lipoprotein cholesterol (HDL-C) and cardiovascular (CV) disease underscores the need for clinical evaluation of the effect of HDL-C increasing drugs on the prevalence of CV disease. METHODS: We review the efficacy of Niaspan on serum lipids and the occurrence of side effects either alone or in combination with statins, in randomised controlled trials (RCT) and comparative cohort trials (CCT). RESULTS: In four RCTs, low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and lipoprotein(a) (Lp(a)) were decreased by 13, 26, and 17%, respectively, whereas HDL-C increased by 18%. In four CCTs a combination of Niaspan and statins showed an additional 22% reduction in LDL-C, 8% in TG and 6% in Lp(a) levels, compared with Niaspan monotherapy. Statin therapy had a minor additional effect of 1% on a total of 25% HDL-C increase during Niaspan treatment. Flushes occurred in 69% of the patients without any additional toxicity during combination therapy. CONCLUSION: Niaspan effectively raises HDL-C with concomitant beneficial effects on TG and LDL-C. Niaspan can be combined safely with statins and is also effective in patients with combined dyslipidaemia and type 2 diabetes mellitus. Trials on CV endpoints evaluating the effect of statins with Niaspan are urgently needed to settle whether this combination can confirm the high expectations for cardiovascular outcome.     

Raising HDL-C can be achieved by both lifestyle changes and pharmacological means. Introduction

Lowering low-density lipoprotein-cholesterol (LDL-C) levels using statins can significantly reduce cardiovascular (CV) risk in patients with dyslipidemia. However, the risk of major vascular events in those attaining the maximum levels of LDL-C-reduction is only reduced by around one third, which leaves a substantial residual risk. The Emerging Risk Factors Collaboration has shown that low levels of high-density lipoprotein-C (HDL-C) are independent risk factors for CV disease. It is therefore important that treatment strategies for dyslipidemia should target HDL-C in addition to LDL-C. Raising HDL-C can be achieved by both lifestyle changes and pharmacological means. Therapeutic strategies include niacin, fibrates, thiazolidinediones, apolipoprotein A1 mimetics, cholesteryl ester transfer protein inhibitors, statins and combinations thereof. In general, statins produce inconsistent increases in HDL-C. However, pitavastatin, a new member of the statin family that was launched in 2003, and rosuvastatin consistently elicit marked increases in HDL-C that are sustained over time. This supplement will discuss the contribution of HDL-C as a possible predictor and modifiable risk factor for CV disease and will examine the potential role for pitavastatin in reducing residual CV risk.