目前尚不清楚脂蛋白(a)升高是否与低度炎症具有因果相关性。丹麦一项研究表明，脂蛋白(a)水平升高与通过C反应蛋白测定的低度炎症无因果相关性，但其与主动脉瓣狭窄和心肌梗死风险升高具有因果相关性。论文5月4日在线发表于《临床内分泌与代谢杂志》(J Clin Endocrinol Metab)。

此项研究共纳入100578例受试者。测定受试者脂蛋白和C反应蛋白血浆水平和/或可对其产生影响的基因型，并通过登记系统确定主动脉瓣狭窄和心肌梗死诊断信息。利用多向孟德尔随机方法评估脂蛋白升高与低度炎症的观察和因果相关性，以及与主动脉瓣狭窄和心肌梗死的相关性。

结果显示，脂蛋白(a)每升高50 mg/dL，C反应蛋白升高29%。然而，两种LPA单核苷酸多态性(SNP)和kringle IV type 2(KIV-2)基因型与脂蛋白(a)水平分别升高98 mg/dL、95 mg/dL和68 mg/dL具有相关性，但与C反应蛋白升高无因果相关性。

对于主动脉瓣狭窄，脂蛋白(a)水平没升高1标准差与多因素校正危险比1.23具有观察相关性;基于LPA SNP和LPA KIV-2基因型时影响的因果相对危险度分别为1.38和1.21。对于心肌梗死，相应的观察性值为1.20，因果性值分别为1.18和1.31。对C反应蛋白水平进行进一步校正之后，主动脉瓣狭窄和心梗的观察性危险比相似。

参考文献：Anne Langsted,et al. J Clin Endocrinol Metab .Published Online: May 04, 2015 .DOI: http://dx.doi.org/10.1210/jc.2015-1096

Elevated lipoprotein(a) does not cause low-grade inflammation, despite causal association with aortic valve stenosis and myocardial infarction: a study of 100,578 individuals from the general population
Anne LangstedMD1,2,4, Anette VarboMD, PhD1,2,4, Pia R KamstrupMD, PhD1,2,4, and Børge G NordestgaardMD, DMSc.1,2,3,4

Address all correspondence and requests for reprints to: Address for correspondence: B∅rge G. Nordestgaard, professor, chief physician, MD, DMSc.,
Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev Ringvej 75, DK-2730 Herlev, Denmark
, Phone: +45 3868 3297; Fax: +45 3868 3311, E-mail: Boerge.Nordestgaard@regionh.dk.
DOI: http://dx.doi.org/10.1210/jc.2015-1096
Received: January 12, 2015
Accepted: April 24, 2015
Published Online: May 04, 2015
Abstract
Context
Whether elevated lipoprotein(a) is causally associated with low-grade inflammation is unknown.
Objective
We tested the hypothesis that elevated lipoprotein(a) observationally and causally is associated with low-grade inflammation together with aortic valve stenosis and myocardial infarction.
Design and setting
Using a multidirectional Mendelian randomization approach, we studied 100,578 individuals from the Danish general population with plasma levels of and/or genotypes known to affect levels of lipoprotein(a) and C-reactive protein, and using information regarding diagnosis of aortic valve stenosis and of myocardial infarction from registries.
Results
Observationally, C-reactive protein increased by 29% (95%CI:23;34) per 50 mg/dL increase in lipoprotein(a). However, two LPA single nucleotide polymorphisms (SNPs) and the kringle IV type 2 (KIV-2) genotype that were associated with 98 mg/dL, 95 mg/dL and 68 mg/dL higher lipoprotein(a) levels, were not causally associated with increased C-reactive protein levels. For aortic valve stenosis, a one standard deviation increase in lipoprotein(a) levels was associated observationally with a multifactorially adjusted hazard ratio of 1.23(95%CI:1.06;1.41), with corresponding causal risk ratios of 1.38(1.23;1.55) based onLPA SNPs and of 1.21(1.06;1.40) based on LPA KIV-2 genotype. For myocardial infarction, corresponding values were 1.20(1.10;1.31) observationally, and 1.18(1.11;1.26) and 1.31(1.22;1.42) causally, respectively. Observational hazard ratios for aortic valve stenosis and myocardial infarction were similar after further adjustment for C-reactive protein levels.
Conclusions
Elevated levels of lipoprotein(a) were not causally associated with increased low-grade inflammation as measured through C-reactive protein, despite a causal association with increased risk of aortic valve stenosis and myocardial infarction.