Superko H R
Berkeley HeartLab and the Cholesterol, Genetics, and Heart Disease Institute, Lawrence Berkeley National Laboratory, University of California, Berkeley 94402, USA.
Am J Cardiol. 1998 Nov 5;82(9A):34Q-46Q. doi: 10.1016/s0002-9149(98)00771-1.
Atherosclerosis/coronary artery disease (CAD) is largely a result of genetically linked dyslipidemias that can often be identified in clinical practice. Expression of these genetic traits is highly individual and can be affected by environmental factors such as diet and exercise. By understanding the heterogeneity of CAD, it becomes clear that all patients cannot be optimally managed with the same therapeutic regimen. Whereas elevated low-density lipoprotein (LDL) cholesterol is strongly correlated with CAD risk, reduction of LDL cholesterol alone is not an adequate strategy in many cases. Patients with the small, dense LDL of the atherogenic lipoprotein profile (pattern B) experience a 3-fold increased risk of CAD, and pattern B is also correlated with the development of type 2 diabetes. Likewise, elevated lipoprotein(a) increases atherosclerotic risk, particularly in the presence of other risk factors, and is predictive of CAD risk in both women and men. Recent data show that the routine lipid profile--total cholesterol, triglycerides, LDL cholesterol, and high-density lipoprotein (HDL) cholesterol--does not detect the most common inherited dyslipidemias. Newer, more sophisticated tests, such as gradient gel electrophoresis, can detect disease-relevant lipidemic details, e.g., LDL subclass pattern, LDL particle diameter, and LDL subregions. Although these testing procedures are more expensive, their cost must be weighed against the potential lifelong cost of sometimes expensive drug treatment that may be avoided based on the results of such tests. Thus, by attending to the implications of family history, the interactions of genetic, metabolic, and environmental factors, and utilizing more targeted testing procedures, physicians can match the patient's disorder with specifically effective therapy while maintaining a cost-effective approach to disease management.
动脉粥样硬化/冠状动脉疾病（CAD）在很大程度上是由基因相关的血脂异常导致的，这些异常在临床实践中常常能够被识别出来。这些遗传特征的表达具有高度个体差异性，并且会受到饮食和运动等环境因素的影响。通过了解CAD的异质性，很明显并非所有患者都能用相同的治疗方案进行最佳管理。虽然低密度脂蛋白（LDL）胆固醇升高与CAD风险密切相关，但仅降低LDL胆固醇在许多情况下并不是一个充分的策略。具有致动脉粥样硬化脂蛋白谱（B型）的小而致密LDL的患者患CAD的风险增加3倍，并且B型也与2型糖尿病的发生相关。同样，脂蛋白（a）升高会增加动脉粥样硬化风险，尤其是在存在其他风险因素的情况下，并且在男性和女性中都是CAD风险的预测指标。最近的数据表明，常规血脂谱——总胆固醇、甘油三酯、LDL胆固醇和高密度脂蛋白（HDL）胆固醇——无法检测出最常见的遗传性血脂异常。更新的、更复杂的检测方法，如梯度凝胶电泳，能够检测与疾病相关的血脂细节，例如LDL亚类模式、LDL颗粒直径和LDL亚区域。尽管这些检测程序更昂贵，但必须将其成本与有时可能基于此类检测结果而避免的昂贵药物治疗的潜在终身成本进行权衡。因此，通过关注家族史的影响、遗传、代谢和环境因素的相互作用，并采用更具针对性的检测程序，医生可以将患者的病症与特效治疗相匹配，同时保持具有成本效益的疾病管理方法。
