Dobreanu Minodora, Gălăţeanu Catrinel, Simionescu Agneta, Deac R
Department of Clinical Biochemistry, U.M.P. Tîrgu Mureş, Gh. Marinescu 38, 4300 Tîrgu Mureş.
Rom J Intern Med. 2002;40(1-4):61-73.
Recent publications have reanimated the point of view that there exist links between atherosclerosis--inflammation and hypercholesterolemia. The aim of our study was to investigate the possible influence of statins on some inflammatory parameters in persons with severe primary hypercholesterolemia (PHC). The effects of the HMG CoA reductase inhibitor--Atorvastatin--on serum lipids, apoproteins, C reactive protein (CRP), soluble Intercellular Adhesion Molecule (sICAM), lipid peroxides, antibodies to oxidized LDL (Ab oxLDL) and homocystein were evaluated in 21 persons (52.9 +/- 8.38 years old) with severe PHC, 12 of these having significant coronary-artery stenosis (diameter stenosis > or = 70%), in at least one major coronary artery branch. Ab oxLDL, sICAM, TBARS, CRP and homocystein were significantly increased (p < 0.05) in patients with coronary-artery stenosis. Following a 4 weeks hypolipemiant free baseline period, all persons were treated with Atorvastatin 40 mg once daily for 8 weeks. Atorvastatin 40 mg resulted in a reduction of LDL-C with 57.8% (baseline 259.6 +/- 71.39 mg%) p < 0.001, total Cholesterol with 44.08% (baseline 343.1 +/- 71.72 mg%) p < 0.001, Apo B with 50.6% (baseline 194.7 +/- 48.71 mg%) p < 0.001, TG with 12.02% (baseline 177.4 +/- 83.63 mg%) and HDL-C was increased with 6.84% (baseline 48.0 +/- 7.86 mg%). In coronary heart disease patients, Atorvastatin reduced homocystein concentrations with 19.41% (baseline 17.7 +/- 11.16 microM/l) (p < 0.01), and CRP with 21.9% (baseline 4.8 +/- 4.19 mg/l) p < 0.01 and TBARS with 52% (baseline 0.87 +/- 0.89 nM/ml) p < 0.001, but did not influence sICAM and Ab oxLDL. Thus atherogenic concentrations of LDL-C have to be closely modulated by minimal changes in LDL oxidative state. The effects of Atorvastatin on inflammatory parameters may crucially contribute to the clinical benefit of statins, independent of cholesterol lowering. Plaque stabilization may be a paradigm for antiinflammatory mechanism of action by this class of drugs.
近期发表的文献重新唤起了一种观点，即动脉粥样硬化、炎症和高胆固醇血症之间存在联系。我们研究的目的是调查他汀类药物对重度原发性高胆固醇血症（PHC）患者某些炎症参数的可能影响。在21例（年龄52.9±8.38岁）重度PHC患者中评估了HMG CoA还原酶抑制剂阿托伐他汀对血脂、载脂蛋白、C反应蛋白（CRP）、可溶性细胞间黏附分子（sICAM）、脂质过氧化物、氧化型低密度脂蛋白抗体（Ab oxLDL）和同型半胱氨酸的影响，其中12例患者至少有一支主要冠状动脉分支存在显著冠状动脉狭窄（直径狭窄≥70%）。冠状动脉狭窄患者的Ab oxLDL、sICAM、硫代巴比妥酸反应物（TBARS）、CRP和同型半胱氨酸显著升高（p<0.05）。在为期4周的无降脂药基线期后，所有患者每天服用一次40mg阿托伐他汀，持续8周。40mg阿托伐他汀使低密度脂蛋白胆固醇（LDL-C）降低57.8%（基线值259.6±71.39mg%），p<0.001；总胆固醇降低44.08%（基线值343.1±71.72mg%），p<0.001；载脂蛋白B降低50.6%（基线值194.7±48.71mg%），p<0.001；甘油三酯（TG）降低12.02%（基线值177.4±83.63mg%），高密度脂蛋白胆固醇（HDL-C）升高6.84%（基线值48.0±7.86mg%）。在冠心病患者中，阿托伐他汀使同型半胱氨酸浓度降低19.41%（基线值17.7±11.16μmol/L）（p<0.01），CRP降低21.9%（基线值4.8±4.19mg/L），p<0.01，TBARS降低52%（基线值0.87±0.89nM/ml），p<0.001，但对sICAM和Ab oxLDL无影响。因此，必须通过LDL氧化状态的微小变化来密切调节致动脉粥样硬化的LDL-C浓度。阿托伐他汀对炎症参数的影响可能对他汀类药物的临床益处起关键作用，与降低胆固醇无关。斑块稳定可能是这类药物抗炎作用机制的一个范例。
