载脂蛋白 A-II 影响高密度脂蛋白胆固醇和 C 反应蛋白水平较高的女性中载脂蛋白 E 相关心血管疾病的风险。

Apolipoprotein A-II influences apolipoprotein E-linked cardiovascular disease risk in women with high levels of HDL cholesterol and C-reactive protein.

机构信息

Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.

出版信息

PLoS One. 2012;7(6):e39110. doi: 10.1371/journal.pone.0039110. Epub 2012 Jun 18.

BACKGROUND

In a previous report by our group, high levels of apolipoprotein E (apoE) were demonstrated to be associated with risk of incident cardiovascular disease in women with high levels of C-reactive protein (CRP) in the setting of both low (designated as HR1 subjects) and high (designated as HR2 subjects) levels of high-density lipoprotein cholesterol (HDL-C). To assess whether apolipoprotein A-II (apoA-II) plays a role in apoE-associated risk in the two female groups.

METHODOLOGY/PRINCIPAL: Outcome event mapping, a graphical data exploratory tool; Cox proportional hazards multivariable regression; and curve-fitting modeling were used to examine apoA-II influence on apoE-associated risk focusing on HDL particles with apolipoprotein A-I (apoA-I) without apoA-II (LpA-I) and HDL particles with both apoA-I and apoA-II (LpA-I:A-II). Results of outcome mappings as a function of apoE levels and the ratio of apoA-II to apoA-I revealed within each of the two populations, a high-risk subgroup characterized in each situation by high levels of apoE and additionally: in HR1, by a low value of the apoA-II/apoA-I ratio; and in HR2, by a moderate value of the apoA-II/apoA-I ratio. Furthermore, derived estimates of LpA-I and LpA-I:A-II levels revealed for high-risk versus remaining subjects: in HR1, higher levels of LpA-I and lower levels of LpA-I:A-II; and in HR2 the reverse, lower levels of LpA-I and higher levels of LpA-I:A-II. Results of multivariable risk modeling as a function of LpA-I and LpA-I:A-II (dichotomized as highest quartile versus combined three lower quartiles) revealed association of risk only for high levels of LpA-I:A-II in the HR2 subgroup (hazard ratio 5.31, 95% CI 1.12-25.17, p = 0.036). Furthermore, high LpA-I:A-II levels interacted with high apoE levels in establishing subgroup risk.

CONCLUSIONS/SIGNIFICANCE: We conclude that apoA-II plays a significant role in apoE-associated risk of incident CVD in women with high levels of HDL-C and CRP.

背景

在我们小组之前的一份报告中，载脂蛋白 E（apoE）水平较高与 CRP 水平较高的女性发生心血管疾病的风险相关，这些女性的高密度脂蛋白胆固醇（HDL-C）水平较低（指定为 HR1 组）或较高（指定为 HR2 组）。为了评估载脂蛋白 A-II（apoA-II）在这两组女性的 apoE 相关风险中是否发挥作用。

方法/原理：采用结局事件映射（一种图形数据探索工具）、Cox 比例风险多变量回归和曲线拟合模型，研究 apoA-II 对 apoE 相关风险的影响，重点关注不含 apoA-II（LpA-I）的载脂蛋白 A-I（apoA-I）高密度脂蛋白颗粒和含有 apoA-I 和 apoA-II（LpA-I:A-II）的 HDL 颗粒。apoE 水平和 apoA-II/apoA-I 比值作为函数的结局映射结果揭示了每个亚组的高风险亚组的特征，在每种情况下，高风险亚组的特征是 apoE 水平较高，并且：在 HR1 中，apoA-II/apoA-I 比值较低；在 HR2 中，apoA-II/apoA-I 比值中等。此外，高风险与其余受试者的衍生 LpA-I 和 LpA-I:A-II 水平估计值表明：在 HR1 中，LpA-I 水平较高，LpA-I:A-II 水平较低；在 HR2 中，LpA-I 水平较低，LpA-I:A-II 水平较高。作为 LpA-I 和 LpA-I:A-II 函数的多变量风险建模结果（二分法为最高四分位数与三个较低四分位数的组合）仅揭示了 HR2 亚组中 LpA-I:A-II 水平较高与风险相关（风险比 5.31，95%CI 1.12-25.17，p = 0.036）。此外，高 LpA-I:A-II 水平与高 apoE 水平相互作用，确定了亚组风险。

结论/意义：我们的结论是，apoA-II 在 CRP 水平较高的女性发生 CVD 的 apoE 相关风险中起着重要作用，这些女性的 HDL-C 水平较高。