Austin M A, Hokanson J E
Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle.
Med Clin North Am. 1994 Jan;78(1):99-115. doi: 10.1016/s0025-7125(16)30178-x.
In addition to LDL cholesterol, triglyceride; small, dense LDL (LDL subclass phenotype B); and lipoprotein(a) are emerging as important risk factors for CHD. Elevated plasma levels of each of these risk factors have consistently been associated with increased risk of CHD in case-control studies of white patients. In prospective studies, however, the association between triglycerides and CHD is generally not independent of HDL cholesterol in multivariate statistical analyses. Although the data are scarce, studies in women show that triglycerides are a stronger risk factor for CHD in women than in men. Although no prospective studies of LDL subclass phenotype B have been reported, a number of potential atherogenic mechanisms may be responsible for the association with CHD seen in the case-control studies. Similarly, few prospective studies of lipoprotein(a) have been published, all in Scandinavian men. The observational studies generally show an association between elevated lipoprotein(a) and CHD in whites but not in blacks. Each of these risk factors also has a genetic component. Of the two familial forms of hypertriglyceridemia, FCH has been associated with familial CHD in two cross-sectional studies. LDL subclass phenotype B is inherited consistent with a single major gene effect, and candidate gene linkage studies are in progress to map the chromosomal location of this proposed gene. Finally, lipoprotein(a) levels are largely attributable to variation at the apo(a) locus on chromosome 6. Whether other genetic variations explain the lack of reported associations between lipoprotein(a) and CHD in black populations remains to be determined. Understanding of these "non-LDL" lipoprotein-related risk factors will provide important information for the development of new, effective intervention strategies for the prevention of CHD.
除低密度脂蛋白胆固醇外，甘油三酯、小而密的低密度脂蛋白（低密度脂蛋白亚类表型B）以及脂蛋白(a)正逐渐成为冠心病的重要危险因素。在白人患者的病例对照研究中，这些危险因素中每一种的血浆水平升高都一直与冠心病风险增加相关。然而，在前瞻性研究中，在多变量统计分析中，甘油三酯与冠心病之间的关联通常并非独立于高密度脂蛋白胆固醇。尽管数据稀少，但针对女性的研究表明，甘油三酯对女性冠心病而言是比男性更强的危险因素。虽然尚未有关于低密度脂蛋白亚类表型B的前瞻性研究报告，但一些潜在的致动脉粥样硬化机制可能是病例对照研究中所见的与冠心病关联的原因。同样，关于脂蛋白(a)的前瞻性研究很少发表，且均针对斯堪的纳维亚男性。观察性研究一般显示，白人中脂蛋白(a)升高与冠心病有关联，而黑人中则不然。这些危险因素中的每一种也都有遗传成分。在两种家族性高甘油三酯血症中，家族性混合型高脂血症在两项横断面研究中与家族性冠心病相关。低密度脂蛋白亚类表型B的遗传符合单一主要基因效应，目前正在进行候选基因连锁研究以确定该假定基因的染色体定位。最后，脂蛋白(a)水平很大程度上归因于6号染色体上载脂蛋白(a)基因座的变异。其他遗传变异是否能解释黑人人群中脂蛋白(a)与冠心病之间缺乏报告的关联仍有待确定。对这些“非低密度脂蛋白”脂蛋白相关危险因素的了解将为制定预防冠心病的新的有效干预策略提供重要信息。
