Differential hs-CRP reduction in patients with familial hypercholesterolemia treated with aggressive or conventional statin therapy

BACKGROUND: High sensitivity C-reactive protein (hs-CRP) has emerged as the best studied and most promising marker of inflammation in atherosclerotic vascular disease. MATERIALS AND METHODS: The ASAP (effects of Atorvastatin vs. Simvastatin on Atherosclerosis Progression) study was a 2-year randomised, double-blind trial with 325 familial hypercholesterolemia patients, treated with torvastatin 80 mg or imvastatin 40 mg. Intima media thickness (IMT) of carotid artery segments and hs-CRP levels were determined at baseline, 1 and 2 years. RESULTS: Baseline median hs-CRP values were 2.1 mg/l (interquartile range (IQR) 0.9-5.2) and 2.0 mg/l (IQR 0.8-3.0) and after 2 years these levels decreased to 1.1 mg/l (IQR 0.6-2.4) and 1.5 mg/l (IQR 0.6-3.0) in the atorvastatin 80 mg and simvastatin 40 mg group, respectively. These changes were significant within as well as between the two groups. No correlations were observed between change in hs-CRP after 2 years and change in lipids. A significant correlation was found in univariate analysis between the decrease of hs-CRP and the reduction of IMT. CONCLUSIONS: Our results show that atorvastatin 80 mg reduces hs-CRP levels to a greater extent than simvastatin 40 mg. Furthermore, we show that the extent of hs-CRP reduction is associated with the progression rate of the atherosclerotic process as measured by IMT.     

Effects of simvastatin on C-reactive protein in mixed hyperlipidemic and hypertriglyceridemic patients

This study examined the effects of simvastatin on C-reactive protein (CRP) and other inflammatory markers in study subjects with significant elevations in triglyceride (TG) blood levels. CRP, vascular cellular adhesion molecule (VCAM), serum amyloid A (SAA), and interleukin 6 (IL-6) were measured in archived plasma samples from 2 multicenter, randomized, double-blind, placebo-controlled studies designed to examine the lipid-altering efficacy of simvastatin in study subjects with elevated TGs. In the first study, 130 study subjects with mixed hyperlipidemia (low-density lipoprotein [LDL] cholesterol > or =130 mg/dl; TGs 300 to 700 mg/dl) received placebo or simvastatin 40 or 80 mg once daily for three 6-week periods in a complete-block crossover design. In the second study, 195 study subjects with hypertriglyceridemia (TGs 300 to 900 mg/dl) received daily doses of placebo or simvastatin 20, 40, or 80 mg for 6 weeks. Significant but weak correlations were observed between baseline CRP values and baseline levels of LDL cholesterol and high-density lipoprotein (HDL) cholesterol, but not with TGs. CRP was also correlated with body mass index and fasting levels of glucose and insulin. Treatment with simvastatin 20, 40, and 80 mg led to significant reductions in CRP plasma levels versus placebo (p <0.05). Although CRP change was weakly correlated with changes in LDL cholesterol, TGs, and HDL cholesterol, results of regression analyses showed that only baseline CRP and treatment allocation were significant predictors of CRP response after 6 weeks of study drug administration. Simvastatin had no effect on VCAM, SAA, or IL-6. In summary, simvastatin significantly reduced CRP in patients with mixed hyperlipidemia and hypertriglyceridemia.     

辛伐他汀对急性冠脉综合征患者血清C-反应蛋白的影响

目的观察急性冠脉综合征(ACS)患者早期应用辛伐他汀治疗对血脂和炎症反应标记物的影响及差异,探讨他汀类药物在ACS早期治疗中的作用。方法 ACS住院患者113例,入院后测定血清三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、白介素-6(IL-6)和C反应蛋白 (CRP)水平,然后随机分为辛伐他汀治疗组和对照组。出院时重复测定上述指标。同期测定30例健康者作对照比较。结果治疗组治疗后CRP、IL-6比治疗前明显下降,差异有显著性意义(P<0．05)。结论 ACS患者早期应用辛伐他汀治疗有明显的抗感染作用。     

辛伐他汀对CRP诱导变异型心绞痛患者NF-κB合成的影响

目的探讨NF-κB在变异型心绞痛(VA)中的作用和他汀类药物的干预效应。方法采集并培养VA患者(VA组,n=6)和健康对照者(对照组,n=6)的外周血单核细胞,使用C反应蛋白(CRP,终浓度为20 mg/L)刺激24 h;干预组采用辛伐他汀(终浓度10μmol/L)预先孵育单核细胞2 h,继以CRP刺激24 h。采用酶联免疫吸附法测定细胞核中NF-κB的水平,比较两组间的差异。结果基础状态下VA组中NF-κB的水平与对照组相比无差异,给予CRP刺激后,VA组及对照组中NF-κB的水平较其基础状态均升高(P<0.01),VA组较对照组升高幅度显著(P<0.01),辛伐他汀预孵育后可以有效抑制两组CRP刺激后的NF-κB表达(P<0.01)。结论 VA患者受到CRP刺激后外周血单核细胞中NF-κB的水平高于对照组,提示炎症机制可能在VA中发挥一定的作用;辛伐他汀可以有效抑制VA患者体内炎症反应的强度。     

辛伐他汀并非诺贝特治疗急性冠脉综合征的疗效

目的：探讨联合应用辛伐他汀和非诺贝特对急性冠脉综合征（ACS）患者血脂参数及炎症因子的影响。方法：共人选58例ACS患者．随机分为：辛伐他汀组（20mg／d，18例）；非诺贝特组（200mg／d，18例）；联合治疗组（辛伐他汀20rag／d＋非诺贝特200mg／d，22例），疗程均为6个月。观察治疗前、后血清总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、甘油三酯（TG）、高密度脂蛋白胆固醇（HDL—C）、一氧化氮（NO）、内皮素（ET）和C反应蛋白（CRP）含量的变化，以及药物不良反应。结果：各组治疗后血清TC、LDL-C、TG水平显著降低（P均〈0.05），血清HDL—C水平有不同程度增高。其中以联合治疗组最为明显（P均〈0．05）。和辛伐他汀组相比，非诺贝特组TC和LDL-C水平无明显差异（P〉0．05），而TG水平显著降低，HDL—C水平明显增高（P〈0．05），与治疗前相比，各组治疗后血清NO水平增高，CRP和ET水平降低（P〈0．05），联合治疗组较辛伐他汀组、非诺贝特组更显著（P均〈0.05），三组均无不良反应。结论：联合辛伐他汀和非诺贝特治疗可以更全面地改善ACS患者的血脂异常，其改善内皮功能和降低炎症因子的作用较单药治疗更有效。     

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.     

C反应蛋白增强变异型心绞痛患者体内TNF-α和IL-6的表达

目的通过对变异型心绞痛患者及健康对照者外周血的单核细胞给予一定浓度的C反应蛋白（CRP）的刺激,比较两组中肿瘤坏死因子-α（TNF-α）及白细胞介素-6（IL-6）的差异,并观察他汀类药物干预后其水平的变化,探讨炎症相关分子机制在变异型心绞痛中的作用和他汀类药物的干预效应。方法培养变异型心绞痛患者（病例组,n=6）和健康对照者（对照组,n=6）的外周血单核细胞,使用CRP（终浓度为20mg/L）刺激24小时;辛伐他汀干预采用辛伐他汀（终浓度10umol/L）预先孵育单核细胞2小时,继之以CRP刺激24小时。采用酶联免疫吸附法测定培养液上清中的TNF-α和IL-6的水平,比较两组之间的差异。结果基础状态下病例组中TNF-α和IL-6的水平与对照组相比无显著差别,给予CRP刺激后,病例组及对照组中TNF-α和IL-6的水平较其基础状态均有明显升高（p〈0.01）,但病例组中TNF-α和IL-6的升高幅度较对照组更为显著（p〈0.01）,辛伐他汀预孵育后可以有效抑制两组患者CRP刺激后的TNF-α和IL-6表达（p〈0.01）。结论变异型心绞痛患者受到CRP刺激后外周血单核细胞中TNF-α,IL-6的水平明显高于对照组,提示炎症机制可能在变异型心绞痛中起着一定的作用;辛伐他汀可以有效抑制变异型心绞痛患者中炎症反应的强度。     

Raised serum levels of soluble CD40 ligand in patients with familial hypercholesterolemia: downregulatory effect of statin therapy

OBJECTIVES: In the present study, we investigated the effects of statins on serum levels of soluble CD40 ligand (sCD40L) in patients with familial hypercholesterolemia (FH). BACKGROUND: Atherosclerotic disease seems to involve inflammatory and immunologic mechanisms, and sCD40L has recently been identified as one of the key players in the atherosclerotic process. HMG-Co A reductase inhibitors, statins, have been recognized as immunomodulators and reduce cardiovascular events and mortality, but the effects of statins on sCD40L has not been clarified. METHODS: In a randomized, double-blind, clinical trial, as part of the Atorvastatin versus Simvastatin on Atherosclerosis Progression (ASAP) trial, 110 patients with FH were given atorvastatin 80 mg/daily (n = 57) or simvastatin 40 mg/daily (n = 53) for two years. RESULTS: Our main findings were: 1) at baseline patients with FH had significantly higher (approximately 27-fold) serum levels of sCD40L than healthy controls; 2) statin therapy markedly decreased serum levels of sCD40L (approximately 40% reduction); 3) this decrease in sCD40L was found during both "aggressive" (i.e., atorvastatin) and "conventional" (i.e., simvastatin) statin therapy and was not correlated with the degree of reduction in cholesterol levels. CONCLUSIONS: Our findings may suggest enhanced CD40L-CD40 interaction in FH and that this inflammatory response may be downregulated by statins.     

他汀类药物对血清甘油三酯的作用

为观察他汀类药物对血清甘油三酯的作用及治疗前基础血清甘油三酯水平对其治疗作用的影响,本文分析了１９９４－１９９８年期间进行的辛伐他汀和洛伐他汀两项中心临床药物试验。治疗前血清总胆固醇≥５．９８ｍｍｏｌ／Ｌ,甘油三酯≤４．５２ｍｍｏｌ／Ｌ,按治疗前基础血清甘油三酯水平分组：辛伐他汀试验者１６６例,口服辛伐他汀１０ｍｇ／ｄ;洛伐他汀试验者１４６例,口服洛伐他汀２０ｍｇ／ｄ疗程均为８周。     

国产辛伐他汀对不稳定型心绞痛患者血浆C反应蛋白的影响

目的　研究京必舒新对不稳定型心绞痛患者血浆C反应蛋白 (CRP)的水平的影响。方法　 60例不稳定型心绞痛 (unstableanginaUA)病人随机分为治疗组与对照组 ,治疗组除用UA常规治疗外加用京必舒新 2 0mg每晚口服 ,对照组仅给予UA常规治疗。比较两组病人治前及经治后 2周、4周、8周的血浆CRP。结果　治疗组自 2周始CRP水平即开始下降 ,4周及 8周的CRP水平较治疗前出现显著差异 (P <0 .0 1) ;对照组治疗前、后的CRP水平未见明显变化(P >0 .0 5 )。结论　京必舒新可显著降低UA病人的血浆CRP浓度。     

Baseline lipid values partly determine the response to high-dose simvastatin in patients with familial hypercholesterolemia. The examination of probands and relatives in Statin studies with familial hypercholesterolemia (ExPRESS FH)

Statins decrease low-density lipoprotein cholesterol (LDL-C), and additionally, reduce triglycerides (TG) and raise high-density lipoprotein cholesterol (HDL-C) levels. This study evaluated the frequency of abnormal TG and HDL-C levels in patients with classical familial hypercholesterolemia (FH) and assessed therapeutic response at different baseline levels of these lipoproteins after 1 year of statin therapy. A total of 508 FH patients were included and mean LDL-C levels (8.37+/-2.12 mmol l(-1)) were severely elevated. After a washout period of 6 weeks, all patients started monotherapy with 80 mg simvastatin. Remarkably, LDL-C reduction was dependent on baseline LDL-C levels ranging from 51.1 to 45.5% in the top versus the bottom third of the LDL-C distribution. Unexpected in FH, elevated baseline TG levels were seen in 30% and low HDL-C levels in 15% of all patients. Also, changes in these lipoproteins were dependent on baseline levels; TG reduction was 40.7 versus 22.2% in patients with elevated versus normal levels, while HDL-C increase was 29.1 versus 11.4% in patients with low versus normal HDL-C levels. In conclusion, FH patients with the worst lipoprotein profile showed the greatest benefit from high-dose simvastatin treatment, since changes in these parameters were partly determined by baseline lipid levels.     

The reduction of inflammatory biomarkers by statin, fibrate, and combination therapy among diabetic patients with mixed dyslipidemia: the DIACOR (Diabetes and Combined Lipid Therapy Regimen) study.

OBJECTIVES: The primary objective was to determine the effect of statin-fibrate combination therapy on inflammatory biomarkers in patients with diabetes. BACKGROUND: Atherosclerosis is a long-term, chronic inflammatory disease that is exacerbated in patients with diabetes. METHODS: Patients (n = 300) with type II diabetes, mixed dyslipidemia (2 or more of low-density lipoprotein > or =100 mg/dl, triglycerides > or =200 mg/dl, or high-density lipoprotein <40 mg/dl), and no history of coronary heart disease were randomly assigned to receive simvastatin 20 mg, fenofibrate 160 mg, or a combination of simvastatin 20 mg and fenofibrate 160 mg daily. At 12 weeks after randomization, we measured levels of high-sensitivity C-reactive protein (hsCRP) and lipoprotein-associated phospholipase A2 (Lp-PLA(2)). RESULTS: At 12 weeks, median hsCRP was significantly reduced (-14.6%, p = 0.004) from baseline, but the effect did not differ between treatments. The effect was greatest among patients with baseline hsCRP levels >2.0 mg/l (fenofibrate = -18.9%, p = 0.002 vs. baseline; simvastatin = -24.8%, p < 0.0001; combination = -27.3%, p = 0.002). Likewise, median Lp-PLA(2) levels in the overall study population were significantly reduced (-16.8%, p < 0.0001), and the effect did not differ among treatments. This effect also was greatest among patients with increased baseline levels of Lp-PLA(2) greater than the median of 320.9 ng/ml (fenofibrate = -41.3%, p < 0.0001; simvastatin = -47.5%, p < 0.0001; combination = -46.8%, p < 0.0001). CONCLUSIONS: Simvastatin, fenofibrate, and combination therapy each lowered hsCRP and Lp-PLA(2). These anti-inflammatory effects were most pronounced among patients with increased baseline levels. Combination therapy was no more effective than either form of monotherapy. (The DIACOR Study; http://www.clinicaltrials.gov/ct/show/NCT00309712?order=1).     

Inflammatory predictors of mortality in the Scandinavian Simvastatin Survival Study

BACKGROUND AND HYPOTHESIS: The predictive value of specific markers of infection and autoimmunity for coronary events, such as the effects of statins on inflammation, is still controversial. METHODS: A case-control design was used to compare C-reactive protein (CRP) levels, seropositivity for Chlamydia pneumoniae and Helicobacter pylori, and anti-oxidized low-density lipoprotein (oxLDL) antibody levels in prerandomization blood samples from 129 participants in the Scandinavian Simvastatin Survival Study who died (cases), and from 129 matched participants who were alive during 5-year follow-up (controls). RESULTS: Patients with CRP levels in the highest quartile had an increased risk of death compared with those in the first through third quartile (odds ratio [OR] = 2.51, 95% confidence interval [CI] 1.3-4.8). Seropositivity for Chlamydia pneumoniae or Helicobacter pylori and anti-oxLDL antibody levels were similar in cases and controls (p = NS). At a 4-month control, simvastatin reduced CRP levels (p = 0.009) while placebo did not (p = NS). However, the risk of death associated with high baseline CRP levels was similar in patients randomized to placebo (OR = 2.36, 95% CI 1.06-5.26) or simvastatin (OR = 3.13, 95% CI 1.06-9.21). CONCLUSIONS: Elevated CRP levels, but not seropositivity for Chlamydia pneumoniae or Helicobacter pylori, nor levels of anti-oxLDL antibodies, predict the risk of death in patients with stable ischemic heart disease. Simvastatin treatment reduces CRP levels, but without affecting the increased risk conferred by higher CRP levels at baseline.     

C-reactive protein as a marker for active coronary artery disease in patients with chest pain in the emergency room

BACKGROUND: Markers of inflammation, such as C-reactive protein (CRP), were found to be related to risk for cardiovascular disease (CVD) events in patients with angina pectoris. In addition, recent studies have shown that, in the case of atherosclerosis, increased CRP concentration reflects the inflammatory condition of the vascular wall. HYPOTHESIS: The study was undertaken to determine whether CRP levels in individuals with chest pain attending the emergency room (ER) may be used as a marker of active CVD. METHODS: Serum CRP level was measured in 226 of 326 consecutive patients (128 men, 98 women; mean age 61.3 +/- 5.9 years; range 19-87 years) referred to the ER with chest pain. The decision whether to admit orrelease the subjects was determined without taking the CRP level into account. Follow-up was then performed for 1 year. RESULTS: Eighty-four patients were admitted to the hospital. Of these, 9 with acute coronary syndrome (ACS) had very high levels of CRP (25-40 mg/l), 35 had had an acute coronary event within the preceding 3 months, with levels of CRP 14-20 mg/l. Only eight patients with nonsignificant CVD had elevated CRP levels. Twenty-eight subjects who were released from the ER had elevated CRP levels (7-14 mg/l); 8 of these, in addition to 4 subjects with normal CRP levels, had a late coronary event. CONCLUSION: This study indicates that in patients referred to the ER with chest pain and no other indication for hospitalization, a normal level of CRP suggests safe release. Most hospitalized patients with normal CRP will not have acute coronary syndrome. Patients who will develop early coronary events have very high CRP levels. High serum CRP level, after excluding other inflammatory sources, was proven to be a sensitive diagnostic and prognostic marker for significant coronary disease.     

Comparison of the efficacy and tolerability of simvastatin and atorvastatin in the treatment of hypercholesterolemia

BACKGROUND: Simvastatin and atorvastatin are effective statins for treating hypercholesterolemia. HYPOTHESIS: The study was undertaken to compare the efficacy and tolerability of simvastatin 20 and 40 mg/day and atorvastatin 10 and 20 mg/day. METHODS: In this multinational, open-label, crossover study, 258 patients with primary hypercholesterolemia were randomized after 4 weeks of diet plus placebo to once-daily administration of a starting dose sequence of simvastatin (20 mg) or atorvastatin (10 mg), or a higher dose sequence of simvastatin (40 mg) or atorvastatin (20 mg) for 6 weeks. Patients were then switched after a 1-week washout to the corresponding starting or higher dose of the alternate drug for a second 6-week period. The primary endpoint was the mean percent change from baseline to Week 6 in low-density lipoprotein (LDL) cholesterol; percent changes from baseline in total cholesterol, high-density lipoprotein cholesterol, triglycerides, and apolipoprotein B were also compared. Safety was assessed through adverse experiences and laboratory measurements. RESULTS: Both statins produced statistically significant improvements in all measured plasma lipids and lipoproteins. The main treatment comparison showed no statistically significant difference in changes in LDL cholesterol and triglycerides, whereby the overall effects were comparable when doses of 20 mg and 40 mg of simvastatin were compared with atorvastatin 10 mg and 20 mg. The mean percent reductions for LDL cholesterol from baseline to Week 6 ranged from 35-42% for the entire study cohort. An LDL cholesterol level < or = 130 mg/dl (3.4 mmol/l) was achieved in approximately 70% of patients treated with both drugs in this study. Simvastatin and atorvastatin were well tolerated at the doses studied. CONCLUSION: In patients with hypercholesterolemia, the most commonly used doses of simvastatin and atorvastatin produced similar changes in LDL cholesterol and achieved an LDL cholesterol level < or = 130 mg/dl (3.4 mmol/l) in a similar number of patients. Both statins were well tolerated.     

辛伐他汀对急性冠状动脉综合征患者高敏C-反应蛋白的影响

目的探讨调脂对急性冠状动脉综合征(ACS)患者冠脉病变炎症的影响。方法采用随机、单盲、对照方法将125例ACS患者分为辛伐他汀治疗组(n=63)非辛伐他汀治疗组(n=62),另选健康对照组(n=60),测定治疗前、治疗后8周血浆高敏C-反应蛋白(hs-CRP)水平的变化。结果ACS患者的hs-CRP水平明显增高,经辛伐他汀治疗8周后其血浆hs-CRP水平明显下降,非他汀治疗组各项指标无明显变化。结论他汀调脂可阻滞ACS患者冠脉病变的炎症反应。     

Anti-inflammatory effects of pioglitazone and/or simvastatin in high cardiovascular risk patients with elevated high sensitivity C-reactive protein: the PIOSTAT Study.

OBJECTIVES: The purpose of this study was to test the safety and efficacy of pioglitazone and simvastatin in combination versus each drug individually in non-diabetic subjects with cardiovascular disease (CVD) and elevated high-sensitivity C-reactive protein (hs-CRP) levels. BACKGROUND: Low-grade inflammation is a pathogenic factor for atherosclerosis. High-sensitivity CRP, matrix metalloproteinase (MMP)-9, and plasminogen activator inhibitor (PAI)-1 are markers of inflammation. Statins and peroxisome proliferator-activated receptor (PPAR)-gamma agonists lower inflammatory markers and reduce CVD in type 2 diabetes. METHODS: In a 12-week, prospective, double-blind trial, 125 subjects were randomized to simvastatin or pioglitazone plus placebo or a simvastatin/pioglitazone combination. We tested changes in hs-CRP by analysis of covariance. A subgroup analysis was performed in patients with and without the metabolic syndrome (MetS). The correlation between changes in hs-CRP and homeostasis model assessment (HOMA; a measure of insulin resistance) was calculated with the Spearman's rank test. RESULTS: At baseline, there were no significant between-group differences. At 12 weeks, pioglitazone and simvastatin monotherapies significantly reduced hs-CRP (3.64 +/- 2.42 mg/l to 2.48 +/- 1.77 mg/l and 3.26 +/- 2.02 mg/l to 2.81 +/- 2.11 mg/l) and the combination regimen had an additive effect (from 3.49 +/- 1.97 mg/l to 2.06 +/- 1.42 mg/l, p < 0.001). For subgroups, the difference between monotherapy and combination therapy was only significant for simvastatin versus simvastatin plus pioglitazone in patients without MetS. Homeostasis model assessment decreased in those receiving pioglitazone, and the correlation between changes in HOMA and hs-CRP was significant (r = 0.43; p < 0.05). The PAI-1 decreased significantly in the pioglitazone groups only, and MMP-9 was also significantly lowered in the pioglitazone groups. No treatment-related serious adverse events occurred in any group. CONCLUSIONS: Pioglitazone, probably by reducing insulin resistance, has additive anti-inflammatory effects to simvastatin in non-diabetic subjects with CVD and high hs-CRP.     

不同剂量辛伐他汀对不稳定型心绞痛患者血脂及血清淀粉样蛋白A的影响

目的观察不同剂量辛伐他汀早期干预对不稳定型心绞痛（UAP）患者血清淀粉样蛋白A（SAA）水平的影响及调脂作用与安全性。方法选择人院具有缺血性胸痛、冠状动脉造影异常临床诊断UAP患者41例，随机分组：①常规治疗加辛伐他汀20mg治疗组20例；②常规治疗加辛伐他汀40mg治疗组21例。另选18名健康体检者为对照组。分别测定UAP患者治疗前、辛伐他汀20mg和40mg治疗2周后及对照组外周血SAA和血脂水平。SAA用ELISA法检测，同时观察用药安全性。结果UAP应用不同剂量辛伐他汀治疗后，40mg组TC、LDL-C的水平较20mg组低[（4．73±0．44）mmol／L和（5．05±0．34）mmol／L，（2．96＋0．27）mmol／L和（3．16±0．29）mmol／L，P均〈0．05]；40mg组血清SAA水平下降更为显著[（1600±257）ng／ml和（2479±365）ng／ml，P〈0．05]。单因素相关分析显示，血清SAA浓度与患者较高的TC、LDL—C、HDL—C和TG的基线值无相关性（r=0．133，P=0．329；r=0．196，P=0．148；r=0．154，P=0．257；r=-0．168，P=0．216，P〉0．05）。结论①UAP患者血清SAA水平明显升高；②应用辛伐他汀治疗可明显降低SAA水平，且与TC、LDL—C降低水平无相关性。SAA降低程度可能与辛伐他汀剂量有关。     

Vascular effects of simvastatin combined with ramipril in hypercholesterolemic patients with coronary artery disease, compared with simvastatin alone: a randomized, double-blind, placebo-controlled, crossover study

Because the mechanisms of the biological effects of statin and angiotensin converting enzyme inhibitor therapies differ, we studied the vascular responses to these therapies in hypercholesterolemic patients with coronary artery disease. We administered simvastatin 20 mg and placebo or ramipril 10 mg daily during 2 months with washout 2 months to 32 hypercholesterolemic patients with coronary artery disease. This study was randomized, double-blind, placebo-controlled, crossover in design. Simvastatin alone or combined with ramipril significantly changed lipoproteins, and improved the percent flow-mediated dilator response to hyperemia relative to baseline measurements by 33 +/- 6% and by 50 +/- 14%, respectively (both P <0.001) and reduced plasma levels of nitrate relative to baseline measurements (P=0.413 and 0.037, respectively), the plasma MDA levels relative to baseline measurements by 8 +/- 8% and by 18 +/- 9% (P=0.039 and P <0.001, respectively) and MCP-1 relative to baseline measurements by 7 +/- 4% and by 13 +/- 3%, respectively (P=0.019 and P <0.001, respectively), and CRP from 0.22 to 0.14 mg/dl and from 0.22 to 0.15 mg/dl, respectively (P=0.124 and 0.002, respectively), and PAI-1 antigen relative to baseline measurements (P=0.690 and 0.018, respectively). However, simvastatin combined with ramipril changed to greater but statistically insignificant extent the percent flow-mediated dilator response to hyperemia and plasma levels of nitrate, MDA, MCP-1, and PAI-1 antigen than simvastatin alone. Simvastatin alone or combined with ramipril showed significant beneficial effects on endothelial function in hypercholesterolemic patients with coronary artery disease. However, simvastatin combined with ramipril did not significantly change, compared with simvastatin alone.     

Anti-inflammatory effects of simvastatin in subjects with hypercholesterolemia

AIMS: Beneficial effects of statins in preventing cardiovascular events may depend, at least in part, on their anti-inflammatory action. The aim of the study was to assess the influence of simvastatin and aspirin on serum levels of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in hypercholesterolemic subjects. METHODS AND RESULTS: In 33 asymptomatic men with total cholesterol (TC) >6.5 mmol l(-1) and in 25 men with coronary heart disease and borderline-high cholesterol levels (between 5.2 and 6.5 mmol l(-1)) chronically treated with low-dose aspirin (75 mg/d), serum levels of CRP, TNF-alpha, IL-6, and IL-8 were determined before and after a 3-month simvastatin therapy (20-40 mg daily). In the former group, these markers of inflammation were also measured before and after a 2-week treatment with aspirin (300 mg/d), implemented prior to and in combination with simvastatin. A distinct reduction of CRP and TNF-alpha was found in both groups; IL-6 levels were decreased only in subjects with marked hypercholesterolemia. Aspirin had no effect on the anti-inflammatory action of simvastatin. CONCLUSIONS: In men with hypercholesterolemia simvastatin treatment lowers serum levels of CRP and proinflammatory cytokines. Low-dose aspirin does not add to the anti-inflammatory action of simvastatin.