停用辛伐他汀对健康男性肱动脉内皮功能的影响

目的 观察停用辛伐他汀对Tc水平正常健康男性肱动脉内皮功能的影响.方法 16例健康青年男性服用20mg辛伐他汀4周后停药,分别检测停药前后不同时间点肱动脉内皮依赖性舒张功能(FMD),并测定血管活性物质--NO、血浆内皮素和6-酮-前列腺素F1α(6-keto-PGF1α)以及血脂参数的变化.结果 健康男性服用辛伐他汀4周后,在停药第1天观察到FMD较停药前明显降低,甚至低于未服药时的基线水平(P＜0.05).停药后血清NO水平较停药前和基础值亦明显降低,其变化与FMD的变化一致.停药后血浆内皮素水平升高,6-keto-PGF1α水平降低.血清LDL-C在停药后最初2d内无明显改变,其变化与FMD无明显相关.结论 健康男性服用辛伐他汀后突然停药,不仅使该药对肱动脉内皮功能的改善作用迅速消失,而且还对血管内皮功能造成进一步损害,该不良影响可能与循环中NO水平降低有关,是非TC依赖性的.     

停用辛伐他汀对冠脉病变患者肱动脉内皮及血管功能的影响

目的观察停用辛伐他汀对冠脉病变患者肱动脉内皮及血管功能的影响。方法选择冠脉病变者105例,每晚口服辛伐他汀20 mg,连续服药2周;分别于用药前、用药2周后及停药后1周,采用彩色多普勒超声检测患者静息状态下反应性充血试验及非内皮依赖性舒张功能变化。结果治疗2周后,患者反应性充血实验肱动脉内径较用药前显著增大,停药后1周后较停药前显著减小（P均〈0.05）;伴随冠脉危险因素增多及病变加重,反应性充血实验动脉内径变化率逐渐减小（P〈0.05）。结论停用辛伐他汀可对冠脉病变患者肱动脉内皮依赖性舒张功能造成明显损害,影响动脉血管的功能。     

辛伐他汀对冠心病患者血管内皮功能作用的时效关系

目的探讨辛伐他汀改善冠心病患者血管内皮功能的时效关系。方法共入选30例确诊冠心病患者,每天服用辛伐他汀20mg,进行1年随访。采用超声法检测血流介导的肱动脉内皮依赖性舒张功能(flow mediated dila-tion,FMD),同时观察血脂水平、肝肾功能、血糖以及心肌酶学的变化。结果完成50周随访的25例冠心病患者,辛伐他汀(20mg/d)服后2周、4周、8周、12周及50周可分别使患者血清总胆固醇(TC)降低18.9%、24.3%、29.0%、30.1%、29.4%,低密度脂蛋白胆固醇(LDL-C)降低20.1%、26.8%、34.7%、36.0%、35.2%。辛伐他汀治疗可显著改善冠心病患者的血管内皮功能,FMD较治疗前明显增加,2周:64%,4周:95%,8周:123%,12周:179%,52周:142%(2周、4周P<0.05;8周、12周、52周P<0.01)。FMD的改善与血清TC和LDL-C降低水平无显著相关,而与基础FMD有关。所有患者耐受性好,无明显不良反应。结论辛伐他汀治疗冠心病患者2周时,血管内皮功能即有改善,8~12周达高峰,长期治疗能产生持续的血管内皮功能改善。     

他汀对未合并冠心病的高胆固醇血症患者血管内皮功能的影响

目的探讨辛伐他汀对未合并冠心病的高胆固醇血症患者血管内皮功能及动脉僵硬度的影响。方法 30例高胆固醇血症患者应用辛伐他汀20 mg/d治疗12周,治疗前后分别采集空腹静脉血,通过酶联免疫吸附实验检测血浆一氧化氮（NO）水平;应用动脉硬化测定仪测定肱踝脉搏波传导速度（PWV）,评价动脉硬化程度;应用彩色多普勒超声诊断仪测定肱动脉血流速度积分（VTI）,评价血管舒张功能。结果辛伐他汀治疗后患者总胆固醇（TC）、低密度脂蛋白胆固醇水平明显降低,PWV水平显著降低,血浆NO、肱动脉VTI值显著高于基线水平。结论辛伐他汀可改善无明确冠心病的高脂血症患者血管内皮功能及动脉硬化程度。     

老年冠心病合并高血压患者血管内皮功能的改变

目的 探讨老年冠心病合并高血压患者血管内皮功能的改变。方法 将90例冠心病患者分组：52例为合并高血压病组，其中老年组（A组）35例及非老年组（B组）17例；38例为非高血压组，其中老年组（C组）25例及非老年组（D组）13例。测定血总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白（HDL）、低密度脂蛋白（LDL）、一氧化氮（NO）、内皮素（ET）等，测肱动脉血压SBP、DBP，采用高分辨超声检测肱动脉基础动脉内径（D0）、内皮依赖性血流介导的舒张功能（FMD）、非内皮依赖性硝酸甘油介导的舒张功能（NID）。结果 A组与B组、C组与D组、A组与C组、B组与D组的FMD、ET、NO有显著性差异（P〈0．01～P〈0．05）。各组D0、NID无显著性差异（P〉0．05）。FMD与NO呈正相关（P〈0．01）；FMD与ET、SBP、DBP、TC、LDL呈负相关（P〈0．01）；SBP、DBP与ET呈正相关（P〈0．01）；SBP、DBP与NO呈负相关（P〈0．01）。结论 老年冠心病患者存在显著的内皮功能障碍，高血压加重冠心病患者的内皮功能障碍，FMD与NO、ET可作为反映冠心病和高血压者血管内皮功能的无创指标。     

普伐他汀对Ⅱ型糖尿病并发冠心病患者肱动脉内皮舒张功能的影响

目的:探讨普伐他汀对Ⅱ型糖尿病并发冠心病患者肱动脉内皮舒张功能的影响。方法:45例Ⅱ型糖尿病并发冠心病患者随机分为常规治疗组和普伐他汀治疗组,治疗4周前后均抽静脉血测定血脂,采用高分辨超声法检测治疗前后肱动脉内皮依赖性舒张功能（FMD）和非内皮依赖性舒张功能（NMD）。结果:普伐他汀治疗4周后肱动脉FMD（6.32±0.35）%较治疗前（2.50±0.21）%显著改善（P<0.05）,而肱动脉NMD无显著性差异（P>0.05）。结论:短期口服普伐他汀（40 mg/d）对Ⅱ型糖尿病并发冠心病患者受损的血管内皮功能有改善作用。     

冠心病合并2型糖尿病患者血管内皮舒张功能检测的价值

目的 探讨冠心病合并2型糖尿病患者内皮依赖性血管舒张功能的变化。方法 选择冠心病患者44例（A组），冠心病合并2型糖尿病患者46例（B组）、健康人群对照组43例（C组）。采用高分辨超声分别测定三组肱动脉的内皮依赖血流介导的扩张反应（FMD），并分别检测血管活性因子内皮素（ET）和一氧化氮（NO）。结果 ①A组、B组分别与C组比较，FMD、NO明显降低，ET明显升高。②B组FMD、NO与A组比较明显降低；ET则明显升高，差异有统计学意义。结论 冠心病患者血管内皮舒张功能损害明显，合并2型糖尿病时损害更为严重。     

冠心病合并2型糖尿病患者的血清AGEs与内皮依赖性血管舒张功能关系探讨

目的　探讨冠心病合并 2型糖尿病 (2 - DM)患者内皮依赖性血管舒张功能与血清糖基化终产物(AGEs)水平变化及二者的关系。方法　选择 6 0例冠心病合并 2 - DM患者为治疗组 ,在冠心病综合治疗的基础上给予胰岛素或其他降糖药物控制血糖 ;另选 6 0例查体健康者为对照组。检测两组血清 AGEs、NO水平 ,采用 Jud-kins法进行选择性冠状动脉造影 ,高分辨超声技术检测肱动脉的血管舒张功能。结果　治疗组治疗前后血清AGEs、NO水平及内皮依赖性血管舒张功能均与对照组有明显差异 (P <0 .0 5 ,<0 .0 1) ,且治疗组治疗前后上述指标亦均有明显差异 (P <0 .0 1)。内皮依赖性血管舒张功能减弱程度与血清 AGEs水平呈负相关 (r =- 0 .39,P <0 .0 1) ,血清 NO水平与血清 AGEs水平呈负相关 (r=- 0 .31,P <0 .0 1)。结论　冠心病合并 2 - DM患者内皮依赖性血管舒张功能明显减弱 ,血清 AGEs水平明显升高 ,可能是 AGEs削弱了其内皮依赖性血管舒张功能。长期良好的血糖控制可降低冠心病合并 2 - DM患者血清 AGEs水平 ,增加血液中 NO水平 ,改善其内皮依赖性血管舒张功能     

两种不同剂量辛伐他汀对冠心病患者血管内皮功能的影响

目的探讨辛伐他汀10 mg与20 mg不同剂量对冠心病患者血管内皮功能作用的影响。方法共入选66例冠心病患者,随机分为对照组、辛伐他汀10 mg组和辛伐他汀20 mg组,治疗8周。采用超声法检测血流介导的肱动脉内皮依赖性舒张功能,同时观察血脂水平的变化。结果辛伐他汀治疗8周后,10 mg和20 mg辛伐他汀呈剂量依赖性显著降低血总胆固醇和低密度脂蛋白胆固醇水平(总胆固醇分别降低18.3%和29.3%;低密度脂蛋白胆固醇分别降低25.3%和35.4%;P<0.05)。对照组治疗8周后血脂水平无明显变(P>0.05)。10 mg和20 mg辛伐他汀均可显著改善肱动脉内皮依赖性舒张功能(10 mg辛伐他汀组为3.51%±4.03%比7.46%±5.90%;20mg辛伐他汀组为3.89%±3.97%比7.98%±6.16%;P均<0.01)。但两组之间肱动脉内皮依赖性舒张功能的变化值比较差异无显著性(P>0.05),且肱动脉内皮依赖性舒张功能的改善与血总胆固醇和低密度脂蛋白胆固醇水平的降低不相关。对照组肱动脉内皮依赖性舒张功能虽有轻度增加,但无统计学意义。辛伐他汀治疗后肱动脉内径和肱动脉对硝酸甘油的反应均无显著改变。结论10 mg和20 mg辛伐他汀治疗8周后,可显著改善冠心病患者血管内皮功能,但该作用在这2种剂量之间无显著不同,可能独立于调脂作用之外。     

辛伐他汀对冠心病患者血管内皮细胞功能障碍的治疗作用（英文）

目的：研究辛伐他汀对冠心病患者血管内皮细胞功能障碍的干预作用。方法：90例冠心病患者按LDL-C水平分为三组：辛伐他汀20mg组（37例,LDL-C≥2.5mmol/L）,辛伐他汀10mg组（35例,2.5mmol/L〉LDL-C≥1.8mmol/L）,常规治疗组（18例,LDL-C〈1.8mmol/L,未服辛伐他汀）,疗程均为8周。应用彩色多普勒超声诊断仪测量受试者肱动脉血流介导的舒张功能（FMD）。应用硝酸还原酶法检测受试者一氧化氮（NO）的含量。常规检测血清TC、TG、LDL-C及HDL-C的浓度。结果：8周后,与治疗前比较,辛伐他汀20mg,10mg组TC、TG和LDL-C浓度明显下降（P均〈0.05）,而HDL-C明显升高（P均〈0.05）;辛伐他汀20mg组与10mg组间各指标差异无显著性（P〉0.05）;与常规治疗组比较,辛伐他汀20mg、10 mg组FMD[（6.01±0.49）%比（9.01±0.39）%比（9.01±0.47）%]明显改善（P均〈0.01）、血清NO含量[（38.97±8.89）μmol/L比（47.67±10.89）μmol/L比（45.61±9.09）μmol/L]明显升高（P均〈0.05）,辛伐他汀20mg、10 mg组两组间NO和FMD亦无显著差异（P〉0.05）。结论：辛伐他汀可增加冠心病患者一氧化氮含量,改善血管内皮细胞功能,其作用机制与降低血清总胆固醇、甘油三酯和低密度脂蛋白可能有一定关系,但该作用无明显的量效关系,可能独立于降脂作用之外。     

Short-term withdrawal of simvastatin induces endothelial dysfunction in patients with coronary artery disease: a dose-response effect dependent on endothelial nitric oxide synthase

BACKGROUND: Patients with coronary artery disease (CAD) have impaired endothelial function. Simvastatin therapy has been demonstrated to significantly improve endothelial function in these patients. Although withdrawal of statins is a frequent problem in clinical practice, the effects after discontinuation of statins treatment on endothelial function in patients with CAD are largely unknown. OBJECTIVE: This study investigated the effects after withdrawal of simvastatin on brachial artery endothelial function in patients with CAD and the underlying mechanisms. METHODS: We recruited 30 patients with established CAD. They were treated with 20 mg simvastatin for 4 weeks. Endothelial dependent flow-mediated vasodilation (FMD) was assessed in the brachial artery using high-resolution ultrasound at baseline, 4 weeks during simvastatin treatment, and 1 week after termination of therapy. 20 healthy subjects were also studied as a control group. Furthermore, we investigated underlying mechanisms on human umbilical vein endothelial cells (HUVECs) confluent monolayers at passages 2-3. HUVECs were exposed to simvastatin. After 24 h cells were repeatedly washed to remove the drugs, and the conditioned mediums were collected at the indicated time points. The nitric oxide (NO) production and levels of eNOS mRNA after 24 h of withdrawal of statins were examined. RESULTS: (1) Abrupt discontinuation of simvastatin treatment leads to a rebound of serum total cholesterol (21.3%) and LDL cholesterol (18.2%) in patients within 1 week, but they were still lower than the baseline values (P<0.05 for each parameter). (2) A significant decreased of FMD (-59.3%) was observed in patients after discontinuation of simvastatin in 1 week, and furthermore, the FMD was even lower than the baseline levels (4.6% vs. 5.6%, P<0.05). The reduction of FMD was not correlated with the change of LDL cholesterol (r=-0.343, P=0.081). In contrast to the unchanged LDL cholesterol level, abrupt discontinuation of therapy caused a rapid and significant decrease in FMD from 10.6% to 5.2% in healthy subjects at day 1, but it returned to baseline levels within 1 week. (3) In HUVECs, a maximum decrease of nitrite levels (-80%) was observed at 6 h after stopping simvastatin treatment, which was below the control levels. 24 h after stopping 10(-5) mmol/L and 10(-6) mmol/L simvastatin treatment, eNOS mRNA expression decreased to -71% and -42% (P<0.05), respectively. CONCLUSIONS: Abrupt withdrawal of simvastatin treatment not only acutely and completely abrogates its beneficial effects on endothelial function in patients with CAD, but also induced further vascular injury compared with pretreatment status, independent of cholesterol levels. The underlying mechanism of these negative effects may be related to the suppression of endothelial NO production, which are dose-dependent.     

Early statin therapy restores endothelial function in children with familial hypercholesterolemia

OBJECTIVES: This study was designed to determine whether simvastatin improves endothelial function in children with familial hypercholesterolemia (FH). BACKGROUND: Endothelial function measured by flow-mediated dilation of the brachial artery (FMD) is used as a surrogate marker of cardiovascular disease (CVD). Adult studies have shown that statins reverse endothelial dysfunction and therefore reduce the risk for future CVD. METHODS: The study included 50 children with FH (9 to 18 years) and 19 healthy, non-FH controls. Children with FH were randomized to receive simvastatin or placebo for 28 weeks. The FMD was performed at baseline and at 28 weeks of treatment. RESULTS: At baseline, FMD was impaired in children with FH versus non-FH controls (p < 0.024). In the simvastatin FH group, FMD improved significantly, whereas the FMD remained unaltered in the placebo FH group throughout the study period (absolute increase 3.9% +/- 4.3% vs. 1.2% +/- 3.9%, p < 0.05). In the simvastatin FH group, FMD increased to a level similar to the non-FH controls (15.6% +/- 6.8% vs. 15.5% +/- 5.4%, p = 0.958). Upon treatment, the simvastatin FH group showed significant absolute reductions of total cholesterol (TC) (-2.16 +/- 1.04 mmol/l, 30.1%) and low-density lipoprotein cholesterol (LDL-C) (-2.13 +/- 0.99 mmol/l, 39.8%). The absolute change of FMD after 28 weeks of therapy was inversely correlated to changes of TC (r = -0.31, p < 0.05) and LDL-C (r = -0.31, p < 0.05). CONCLUSIONS: Our data show significant improvement of endothelial dysfunction towards normal levels after short-term simvastatin therapy in children with FH. These results emphasize the relevance of statin therapy in patients with FH at an early stage, when the atherosclerotic process is still reversible.     

辛伐他汀对冠心病患者血管内皮功能作用的量效关系

目的探讨不同剂量(5mg,10mg,20mg)的辛伐他汀对冠心病患者血管内皮功能的作用及其量效关系。方法共入选80例冠心病患者,随机分为4组:对照组(不服用辛伐他汀),辛伐他汀5 mg组、辛伐他汀10 mg组、辛伐他汀20 mg组、每组20例,治疗8周。采用超声法检测血流介导的肱动脉内皮依赖性舒张功能(FMD),同时观察血脂水平的变化。结果辛伐他汀治疗8周后,5 mg、10 mg、20 mg呈剂量依赖性显著降低血总胆固醇(分别降低9%,18%,29%)和低密度脂蛋白胆固醇水平(分别降低12%、24%、35%),不同剂量组间P<0.05。对照组治疗8周后血脂水平无明显变化(P>0.05)。5 mg、10 mg、20 mg的辛伐他汀均可显著改善FMD[5mg:(3.41±2.99)%VS(7.46±5.11)%;10mg:(3.76±3.01)%比(7.98±4.92)%;20mg:(3.59±3.47)%比(8.09±6.10)%;P均<0.01]。但三组之间FMD的变化值比较无显著差异(P>0.05),且FMD的改善与血TC、LDL-C水平的降低不相关。对照组FMD虽有轻度增加,但无统计学意义。辛伐他汀治疗后肱动脉内径、肱动脉对硝酸甘油的反应均无显著改变。结论辛伐他汀5 mg、10 mg、20 mg治疗8周后,可显著改善冠心病患者血管内皮功能,但该作用无明显的量效关系,可能独立于调脂作用之外。     

不同剂量辛伐他汀对冠状动脉粥样硬化症患者血管内皮细胞功能的影响

目的观察不同剂量辛伐他汀对冠状动脉粥样硬化症患者血管内皮细胞功能的影响。方法纳入133例冠状动脉粥样硬化症患者,依据低密度脂蛋白胆固醇(LDL-C)水平将入组患者分为4组:LDL-C≥4.16 mmol/L患者30例,给予辛伐他汀40 mg/d干预治疗(40 mg组);3.64 mmol/L≤LDL-C4.16mmol/L患者35例,给予辛伐他汀20 mg/d干预治疗(20 mg组);2.6 mmol/L≤LDL-C3.64 mmol/L患者37例,给予辛伐他汀10 mg/d干预治疗(10 mg组),LDL-C2.6 mmol/L患者31例,不给予辛伐他汀治疗(对照组)。应用彩色多普勒超声诊断仪测量受试者肱动脉血流介导的舒张功能(FMD)及硝酸甘油介导的舒张功能(NMD),应用硝酸酶还原法检测受试者血清一氧化氮的含量。常规检测血清总胆固醇、甘油三酯、低密度脂蛋白及高密度脂蛋白的水平。结果治疗前,辛伐他汀干预组(10 mg组、20 mg组、40 mg组)患者血清NO水平与对照组比较无统计学差异(P0.05)。治疗8周后,辛伐他汀干预组(10mg组、20 mg组、40 mg组)患者NO水平显著升高,与治疗前比较,有明显统计学差异(P0.05);与对照组比较有统计学差异(P0.05)。对照组患者治疗前后NO水平无明显变化(P0.05)。治疗前,辛伐他汀干预组(10 mg组、20 mg组、40 mg组)患者肱动脉内径基础值、FMD及NMD水平与对照组比较均无统计学差异(P0.05)。治疗8周后,辛伐他汀干预组(10 mg组、20 mg组、40 mg组)患者肱动脉内径基础值、NMD水平与治疗前比较,无统计学差异(P0.05);FMD水平较治疗前显著增加,与对照组比较也呈明显增加趋势,差异有统计学意义(P0.05);NMD水平与与照组比较,差异无统计学意义(P0.05)。结论辛伐他汀可增加冠状动脉粥样硬化症患者血清一氧化氮水平,改善血管内皮细胞功能,其作用机制与改善血脂水平无明显的量效关系。     

Protective effect of high density lipoprotein on endothelium-dependent vasodilatation

Low concentrations of high-density lipoprotein cholesterol (HDL-C) have been associated with increased risk of coronary heart disease (CHD) even when the total cholesterol (TC) and triglyceride (TG) levels are not elevated. The mechanism by which HDL confers protection against atherosclerosis remains speculative. Using high-resolution ultrasound, we measured the dilatation changes of brachial arteries during reactive hyperemia and after sublingual glyceryl trinitrate (GTN) in 63 patients with established (CHD) and 45 controls, in which the serum TC level was normal. The results showed that both flow-mediated dilatation (FMD) and GTN-induced dilatation of brachial arteries in patients with CHD were much reduced compared with control group (2.31+/-2.46% vs. 7.43+/-4.10% and 16.41+/-6.15% vs. 22.44+/-8.63%, respectively, P<0.001 for all). Univariate analysis indicated that FMD of brachial arteries was inversely related to age (r=-0.226, P<0.05), hypertension (r=-0.229, P<0.05), baseline diameter (r=-0.299, P<0.01) and LDL-C (r=-0.237, P<0.05) and positively related to HDL-C (r=0.491, P<0.01). GTN induced vasodilatation was inversely related to age (r=-0.216, P<0. 05) and baseline diameter (-0.476, P<0.01). Multiple stepwise regression analyses in two groups taken together showed that HDL-C and age were the independent predictors of the FMD of brachial arteries (beta=0.466, P=0.000 and beta=-0.184, P=0.020, respectively). Baseline diameter was significant predictor of GTN-induced vasodilatation (beta=-0.390, P=0.000). The analysis in the group of CHD patients showed that only HDL-C was significantly relate to the FMD of brachial arteries (beta=0.295, P=0.018 ) and in controls that hypertension and HDL-C were significantly relate to the FMD of brachial arteries (beta=-0.395, P=0.004 and beta=0.344, P=0.011, respectively). These finding suggest that endothelium-dependent and endothelium-independent vasodilatation are impaired in the patients with CHD. HDL exerts a protective effect on endothelium-dependent vasodilatation in TC being relatively normal population.     

Efficacy of fenofibrate and simvastatin on endothelial function and inflammatory markers in patients with combined hyperlipidemia: relations with baseline lipid profiles

Given that combination therapy with statin plus fibrate confers a risk of myopathy, it is worthwhile to determine whether statin or fibrate monotherapy is associated with greater clinical benefit in individuals with combined hyperlipidemia. In this randomized double-blind study, we compared the efficacy of simvastatin and fenofibrate on indexes of endothelial function (flow-mediated dilation (FMD) of the brachial artery) and inflammatory markers (plasma high-sensitivity C-reactive protein (CRP), interleukin-1β (IL-1β), soluble CD40, and soluble CD40 ligand (sCD40L) levels), as surrogate indicators of future coronary heart disease (CHD), in patients with combined hyperlipidemia. A total of 70 patients with plasma triglyceride levels between 200 and 500 mg/dl and total cholesterol levels of >200 mg/dl were randomly assigned to receive either simvastatin (20 mg/day) (n=35) or micronized fenofibrate (200 mg/day) (n=35) for 8 weeks. Treatment with simvastatin was associated with significantly greater reduction of total cholesterol and low-density lipoprotein cholesterol (LDL-C), while the decrease in triglycerides was significantly greater in patients receiving fenofibrate. Both fenofibrate and simvastatin markedly reduced plasma levels of high-sensitivity CRP, IL-1β, and sCD40L, and improved endothelium-dependent FMD without mutual differences. The changes in plasma inflammatory markers did not correlate with baseline clinical characteristics in both groups. However, the improvement in FMD with fenofibrate treatment correlated inversely with baseline high-density lipoprotein cholesterol (HDL-C) levels, whereas the improvement in FMD with simvastatin treatment was positively related to HDL-C levels. Accordingly, in the subgroup with a baseline HDL-C of ≤40 mg/dl, only fenofibrate significantly improved the endothelium-dependent FMD. On the other hand, in the subgroup with HDL-C >40 mg/dl, only treatment with simvastatin achieved significant improvement in FMD. The data here indicate that in patients with combined hyperlipidemia, both fenofibrate and simvastatin have comparative beneficial effects on various inflammatory markers and differential beneficial effects on endothelial function according to baseline HDL-C levels. These findings should be validated by additional prospective studies, in which patients are stratified by baseline HDL-C prior to randomization.