O'Keefe J H, Lavie C J, McCallister B D
Mid America Heart Institute, Kansas City, Missouri.
Mayo Clin Proc. 1995 Jan;70(1):69-79. doi: 10.1016/S0025-6196(11)64669-7.
To present information about risk factor clustering and the oxidation hypothesis of atherosclerosis and attempt to synthesize these facts into a clinically relevant approach to patients with or at risk for coronary artery disease (CAD).
The total cholesterol level is a relatively weak marker for the risk of CAD. The levels of both high-density lipoprotein (HDL) cholesterol and remnants of triglyceride-rich lipoproteins and the inherent susceptibility of the low-density lipoprotein (LDL) particles to oxidative modification may be as important as the total or LDL cholesterol levels. LDL cholesterol must undergo oxidative modification by means of oxygen free radical processes before it becomes atherogenic. Patients with high levels of oxidative stress include those with risk factor clustering or insulin resistance (or both). Such patients are characterized by hypertension, truncal obesity, hypertriglyceridemia, depressed HDL cholesterol levels, and increased insulin levels. They also have increased levels of triglyceride-rich remnant lipoproteins and LDL particles that are characterized by their small dense nature and pronounced predisposition to oxidative modification.
Biologic antioxidants seem to be promising therapy for the prevention of atherogenesis. Although long-term prospective data are not yet available, vitamin E has been shown to be effective in both animal and human models in preventing LDL oxidation, and it may have a role in the prevention of CAD. A healthy diet of fresh fruits, vegetables, and whole grains is beneficial because it improves the lipid levels and provides high levels of natural antioxidants. The atherogenic potential of hydrogenated polyunsaturated fats is approximately equivalent to that of saturated fats. Monounsaturated fat is inherently resistant to oxidation and may be protective against CAD. Niacin may be effective in patients with clustered risk factors. It has been found to convert the easily oxidized small dense LDL pattern to the large buoyant oxidation-resistant particles. Hydroxymethylglutaryl-coenzyme A reductase inhibitors are well tolerated and highly effective in decreasing LDL cholesterol, but they are expensive. Estrogen has multiple potentially beneficial effects relative to cardiovascular disease.
Persons with or at high risk for CAD should be identified early and aggressively treated with a program that involves lifestyle changes, alterations in dietary intake, and pharmacologic therapy.
介绍有关危险因素聚集和动脉粥样硬化氧化假说的信息，并尝试将这些事实综合成一种针对患有冠状动脉疾病（CAD）或有CAD风险患者的临床相关方法。
总胆固醇水平是CAD风险的相对较弱标志物。高密度脂蛋白（HDL）胆固醇水平、富含甘油三酯脂蛋白残粒水平以及低密度脂蛋白（LDL）颗粒对氧化修饰的固有易感性可能与总胆固醇或LDL胆固醇水平同样重要。LDL胆固醇在具有致动脉粥样硬化性之前必须通过氧自由基过程进行氧化修饰。氧化应激水平高的患者包括那些具有危险因素聚集或胰岛素抵抗（或两者兼有）的患者。这类患者的特征是高血压、躯干肥胖、高甘油三酯血症、HDL胆固醇水平降低以及胰岛素水平升高。他们还具有富含甘油三酯的残粒脂蛋白和LDL颗粒水平升高，这些颗粒的特征是小而致密，且极易发生氧化修饰。
生物抗氧化剂似乎是预防动脉粥样硬化的有前景的疗法。尽管尚无长期前瞻性数据，但维生素E已在动物和人体模型中均显示出在预防LDL氧化方面有效，并且它可能在预防CAD中发挥作用。富含新鲜水果、蔬菜和全谷物的健康饮食有益，因为它可改善血脂水平并提供高水平的天然抗氧化剂。氢化多不饱和脂肪的致动脉粥样硬化潜力与饱和脂肪大致相当。单不饱和脂肪固有地抗氧化，可能对CAD有保护作用。烟酸可能对具有聚集危险因素的患者有效。已发现它可将易于氧化的小而致密的LDL模式转变为大的、有浮力的抗氧化颗粒。羟甲基戊二酰辅酶A还原酶抑制剂耐受性良好，在降低LDL胆固醇方面非常有效，但价格昂贵。雌激素相对于心血管疾病具有多种潜在有益作用。
应尽早识别出患有CAD或有高CAD风险的人群，并积极采用包括生活方式改变、饮食摄入调整和药物治疗的方案进行治疗。
