Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
J Intern Med. 2014 Sep;276(3):260-8. doi: 10.1111/joim.12187. Epub 2014 Feb 5.
Observational and genetic studies have shown that lipoprotein(a) [Lp(a)] levels and apolipoprotein(a) [apo(a)] isoform size are both associated with coronary heart disease (CHD) risk, but the relative independence of these risk factors remains unclear. Clarification of this uncertainty is relevant to the potential of future Lp(a)-lowering therapies for the prevention of CHD.
Plasma Lp(a) levels and apo(a) isoform size, estimated by the number of kringle IV (KIV) repeats, were measured in 995 patients with CHD and 998 control subjects. The associations between CHD risk and fifths of Lp(a) levels were assessed before and after adjustment for KIV repeats and, conversely, the associations between CHD risk and fifths of KIV repeats were assessed before and after adjustment for Lp(a) levels.
Individuals in the top fifth of Lp(a) levels had more than a twofold higher risk of CHD compared with those in the bottom fifth, and this association was materially unaltered after adjustment for KIV repeats [odds ratio (OR) 2.05, 95% confidence interval (CI) 1.38-3.04, P < 0.001]. Furthermore, almost all of the excess risk was restricted to the two-fifths of the population with the highest Lp(a) levels. Individuals in the bottom fifth of KIV repeats had about a twofold higher risk of CHD compared with those in the top fifth, but this association was no longer significant after adjustment for Lp(a) levels (OR 1.13, 95% CI 0.77-1.66, P = 0.94).
The effect of KIV repeats on CHD risk is mediated through their impact on Lp(a) levels, suggesting that absolute levels of Lp(a), rather than apo(a) isoform size, are the main determinant of CHD risk.
观察性研究和遗传学研究表明，脂蛋白(a)[Lp(a)]水平和载脂蛋白(a)[apo(a)]亚型大小均与冠心病（CHD）风险相关，但这些危险因素的相对独立性尚不清楚。明确这种不确定性与未来降低脂蛋白(a)治疗预防 CHD 的潜力有关。
在 995 例 CHD 患者和 998 例对照中测量了血浆 Lp(a)水平和 apo(a)亚型大小，用 KIV 重复数估计。在调整 KIV 重复数前后，评估了 Lp(a)水平的五分位数与 CHD 风险之间的关系，反之，在调整 Lp(a)水平前后，评估了 KIV 重复数的五分位数与 CHD 风险之间的关系。
与 Lp(a)水平最低五分位数相比，Lp(a)水平最高五分位数的个体发生 CHD 的风险高出两倍以上，而这种关联在调整 KIV 重复数后基本不变[比值比（OR）2.05，95%置信区间（CI）1.38-3.04，P<0.001]。此外，几乎所有的超额风险都局限于 Lp(a)水平最高的人群中的五分之二。与 KIV 重复数最高五分位数相比，KIV 重复数最低五分位数的个体发生 CHD 的风险高出两倍左右，但在调整 Lp(a)水平后，这种关联不再显著（OR 1.13，95%CI 0.77-1.66，P=0.94）。
KIV 重复数对 CHD 风险的影响是通过其对 Lp(a)水平的影响介导的，这表明 Lp(a)的绝对水平，而不是 apo(a)亚型大小，是 CHD 风险的主要决定因素。
