Lipoprotein(a) Concentration and Risks of Cardiovascular Disease and Diabetes

作者：Daniel Fannar Gudbjartsson, Guðmundur Þorgeirsson, Patrick Sulem, Anna Helgadóttir, Arnaldur Gylfason, Jona Saemundsdottir, Eyþór Björnsson, Gudmundur Logi Norddahl, Áslaug Jónasdóttir, Aðalbjörg Jónasdóttir, Hannes P. Eggertsson, Sólveig Grétarsdóttir, Guðmar Þorleifsson, Ólafur S. Indridason, Runólfur Pálsson, Friðbert Jónasson, Ingileif Jónsdóttir, Gudmundur Ingi Eyjolfsson, Ólöf Sigurðardóttir, Ísleifur Ólafsson, Ragnar Daníelsen, Stefán E. Matthíasson, Snædís Kristmundsdóttir, Bjarni V. Halldórsson, Ástráður B. Hreiðarsson, Einar Már Valdimarsson, Þórarinn Guðnason, Rafn Benediktsson, Valgerður Steinthórsdóttir, Unnur Arna Thorsteinsdottir, Hilma Hólm, Kāri Stefánsson · 发表于：Journal of the American College of Cardiology · 年份：2019 · DOI：10.1016/j.jacc.2019.10.019 · 被引用次数：229 · 研究领域：Lipoproteins and Cardiovascular Health、Atherosclerosis and Cardiovascular Diseases、HIV-related health complications and treatments

BACKGROUND: Lipoprotein(a) [Lp(a)] is a causal risk factor for cardiovascular diseases that has no established therapy. The attribute of Lp(a) that affects cardiovascular risk is not established. Low levels of Lp(a) have been associated with type 2 diabetes (T2D). OBJECTIVES: This study investigated whether cardiovascular risk is conferred by Lp(a) molar concentration or apolipoprotein(a) [apo(a)] size, and whether the relationship between Lp(a) and T2D risk is causal. METHODS: This was a case-control study of 143,087 Icelanders with genetic information, including 17,715 with coronary artery disease (CAD) and 8,734 with T2D. This study used measured and genetically imputed Lp(a) molar concentration, kringle IV type 2 (KIV-2) repeats (which determine apo(a) size), and a splice variant in LPA associated with small apo(a) but low Lp(a) molar concentration to disentangle the relationship between Lp(a) and cardiovascular risk. Loss-of-function homozygotes and other subjects genetically predicted to have low Lp(a) levels were evaluated to assess the relationship between Lp(a) and T2D. RESULTS: Lp(a) molar concentration was associated dose-dependently with CAD risk, peripheral artery disease, aortic valve stenosis, heart failure, and lifespan. Lp(a) molar concentration fully explained the Lp(a) association with CAD, and there was no residual association with apo(a) size. Homozygous carriers of loss-of-function mutations had little or no Lp(a) and increased the risk of T2D. CONCLUSIO...