Center for Human Genetic Research, Cardiology Division, Massachusetts General Hospital, Boston, MA, USA.
Arterioscler Thromb Vasc Biol. 2009 Nov;29(11):1975-80. doi: 10.1161/ATVBAHA.109.190405. Epub 2009 Sep 3.
Whereas epidemiological studies show that levels of low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) predict incident cardiovascular disease (CVD), there is limited evidence relating lipoprotein subfractions and composite measures of subfractions to risk for CVD in prospective cohort studies.
We tested whether combinations of lipoprotein subfractions independently predict CVD in a prospective cohort of 4594 initially healthy men and women (the Malmö Diet and Cancer Study, mean follow-up 12.2 years, 377 incident cardiovascular events). Plasma lipoproteins and lipoprotein subfractions were measured at baseline with a novel high-resolution ion mobility technique. Principal component analysis (PCA) of subfraction concentrations identified 3 major independent (ie, zero correlation) components of CVD risk, one representing LDL-associated risk, a second representing HDL-associated protection, and the third representing a pattern of decreased large HDL, increased small/medium LDL, and increased triglycerides. The last corresponds to the previously described "atherogenic lipoprotein phenotype." Several genes that may underlie this phenotype-CETP, LIPC, GALNT2, MLXIPL, APOA1/A5, LPL-are suggested by SNPs associated with the combination of small/medium LDL and large HDL.
PCA on lipoprotein subfractions yielded three independent components of CVD risk. Genetic analyses suggest these components represent independent mechanistic pathways for development of CVD.
尽管流行病学研究表明，低密度脂蛋白胆固醇（LDL-C）和高密度脂蛋白胆固醇（HDL-C）水平可预测心血管疾病（CVD）的发生，但在前瞻性队列研究中，有关脂蛋白亚组分和亚组分综合指标与 CVD 风险的证据有限。
我们在一个由 4594 名最初健康的男性和女性组成的前瞻性队列（马尔默饮食与癌症研究，平均随访 12.2 年，发生 377 例心血管事件）中，检验了脂蛋白亚组分的组合是否可以独立预测 CVD。在基线时，使用新型高分辨率离子淌度技术测量血浆脂蛋白和脂蛋白亚组分。亚组分浓度的主成分分析（PCA）确定了 3 个独立的（即零相关）CVD 风险主要成分，一个代表 LDL 相关风险，第二个代表 HDL 相关保护，第三个代表大 HDL 减少、小/中 LDL 增加和甘油三酯增加的模式。最后一个与之前描述的“致动脉粥样硬化脂蛋白表型”相对应。一些可能构成这种表型的基因——CETP、LIPC、GALNT2、MLXIPL、APOA1/A5、LPL——通过与小/中 LDL 和大 HDL 相结合的 SNP 得到提示。
脂蛋白亚组分的 PCA 产生了 CVD 风险的三个独立成分。遗传分析表明，这些成分代表了 CVD 发展的独立机制途径。
