降低胆固醇及额外作用.ppt

1 降低胆固醇及额外作用 2 LDL-C 在动脉粥样硬化形成中的作用? 3 LDL是含载脂蛋白B的颗粒 Murphy HC et al. Biochemistry. 2000;39(32):97639770. 甘油三酯和胆固醇酯组成 疏水核心 Apo B 表面覆以单层磷脂和游 离胆固醇 4 CV risk increases with increased plasma apo B lipoproteins Blood Apo B lipoprotein particles Modification Macrophage Monocytes bind to adhesion molecules Tabas I et al. Circulation. 2007;116(16):18321844. Williams KJ, Tabas I. Arterioscler Thromb Vasc Biol. 1995;15:551561. Williams KJ, Tabas I. Arterioscler Thromb Vasc Biol. 2005;25:15361540. Hoshiga M et al. Circ Res. 1995;77(6):11291135. Merrilees MJ, Beaumont B. J Vasc Res. 1993;30(5):293302. Nakata A et al. Circulation.1996;94(11):27782786. Steinberg D et al. N Engl J Med. 1989;320(14):915924. Smooth muscle 循环中Apo B 水平越低越不利于脂质沉积 Foam cell Maladaptive inflammatory response 5 大部分急性冠脉综合征的发病原因： 动脉板块破裂导致血栓形成 6 超越降LDL-C的疗效 聚焦降胆固醇的两个作用机制：合成与吸收聚焦降胆固醇的两个作用机制：合成与吸收 其他脂质参数 脂蛋白残粒 植物甾醇 Hs-CRP 7 脂病（Adiposopathy）：流行病学 Figure 1. Distributions of body mass index (BMI) in SHIELD and NHANES Bays HE, Chapman RH, Grandy S. Int J Clin Pract, May 2007, 61, 5, 737747 8 BMI 和 代谢性疾病的相关性 NHANES 1999-2002 18.5-24.9 25-26.927-29.930-34.935-39.940 0 10 20 30 40 50 60 70 Diabetes Mellitus Hypertension Dyslipidemia OVERALL20%) 3.0 Relative Risk for CVE in Healthy American Women 3.0 Hs-CRP, mg/L 63 2005 PPS Ridker PM et al. N Engl J Med. 2005;352:20-28. LDL-C 70 mg/dL, CRP 2 mg/L LDL-C 2 mg/L LDL-C 70 mg/dL, CRP 70 mg/dL, CRP 2 mg/L LDL-C 2 mg/L LDL-C 70 mg/dL, CRP 2 mg/L LDL-C 70 mg/dL, CRP 2 mg/L Recurrent MI or Coronary Death Rate 0.10 0.08 0.06 0.04 0.02 0.00 0.00.51.01.52.02.5 Follow-up (years) PROVE-ITPROVE-I