德国汉堡大学心脏和血管中心Stefan Blankenberg小组宣布，他们的最新研究分析了非高密度脂蛋白胆固醇在以人群为基础的心血管风险分层中的应用。该研究2019年12月3日发表于国际一流学术期刊《柳叶刀》。

据悉，血脂浓度与心血管疾病长期发病率的相关性以及降脂治疗对心血管疾病预后的相关性尚不清楚。因此，研究组调查了与血液非高密度脂蛋白（HDL）胆固醇浓度全谱相关的心血管疾病风险。

在这项风险评估与风险模型研究中，研究组使用了来自欧洲、澳大利亚和北美19个国家的跨国心血管风险联盟的数据，选择了38个队列中的398846人的资料，其中衍生队列199415人，验证队列199431人，所有参与者在基线时均无心血管疾病。

中位随访13.5年后，共有54542名参与者发生心血管事件，即冠心病事件或缺血性卒中。对发病曲线进行分析，当非HDL胆固醇浓度<2.6 mmol/L时，女性和男性的30年心血管疾病的发病率分别为7.7%和12.7%，而当非HDL胆固醇≥5.7 mmol/L时，则分别升至33.7%和43.6%。

以非HDL胆固醇<2.6 mmol/L为参考的多变量校正Cox模型显示，非HDL胆固醇浓度与男女心血管疾病呈正相关。非HDL胆固醇浓度降低50%可显著降低75岁时心血管疾病的风险，且越早越好。

总之，血液中非HDL胆固醇浓度与动脉粥样硬化性心血管疾病的长期风险密切相关，研究组为评估个体长期风险和早期降脂干预的潜在益处提供了一个简单的工具。

附：英文原文

Title: Application of non-HDL cholesterol for population-based cardiovascular risk stratification: results from the Multinational Cardiovascular Risk Consortium

Author: Fabian J Brunner, Christoph Waldeyer, Francisco Ojeda, Veikko Salomaa, Frank Kee, Susana Sans, Barbara Thorand, Simona Giampaoli, Paolo Brambilla, Hugh Tunstall-Pedoe, Marie Moitry, Licia Iacoviello, Giovanni Veronesi, Guido Grassi, Ellisiv B Mathiesen, Stefan Sderberg, Allan Linneberg, Hermann Brenner, Philippe Amouyel, Jean Ferrières, Abdonas Tamosiunas, Yuriy P Nikitin, Wojciech Drygas, Olle Melander, Karl-Heinz Jckel, David M Leistner, Jonathan E Shaw, Demosthenes B Panagiotakos, Leon A Simons, Maryam Kavousi, Ramachandran S Vasan, Robin P F Dullaart, S Goya Wannamethee, Ulf Risérus, Steven Shea, James A de Lemos, Torbjrn Omland, Kari Kuulasmaa, Ulf Landmesser, Stefan Blankenberg, Tanja Zeller, Jukka Kontto, Satu Mnnist, Andres Metspalu, Karl Lackner, Philipp Wild, Annette Peters, Christa Meisinger, Chiara Donfrancesco, Stefano G. Signorini, Maris Alver, Mark Woodward, Francesco Gianfagna, Simona Costanzo, Tom Wilsgaard, Mats Eliasson, Torben Jrgensen, Henry Vlzke, Marcus Drr, Matthias Nauck, Ben Schttker, Thiess Lorenz, Nataliya Makarova, Raphael Twerenbold, Jean Dallongeville, Annette Dobson, Sofia Malyutina, Andrzej Pajak, Gunnar Engstrm, Martin Bobak, Brge Schmidt, Tuija Jskelinen, Teemu Niiranen, Pekka Jousilahti, Graham Giles, Allison Hodge, Jens Klotsche, Dianna J. Magliano, Magnus N. Lyngbakken, Kristian Hveem, Christos Pitsavos, Emelia J. Benjamin, Stephan J.L. Bakker, Peter Whincup, M. Kamran Ikram, Martin Ingelsson, Wolfgang Koenig

Issue&Volume: December 03, 2019

Abstract:

Background

The relevance of blood lipid concentrations to long-term incidence of cardiovascular disease and the relevance of lipid-lowering therapy for cardiovascular disease outcomes is unclear. We investigated the cardiovascular disease risk associated with the full spectrum of bloodstream non-HDL cholesterol concentrations. We also created an easy-to-use tool to estimate the long-term probabilities for a cardiovascular disease event associated with non-HDL cholesterol and modelled its risk reduction by lipid-lowering treatment.

Methods

In this risk-evaluation and risk-modelling study, we used Multinational Cardiovascular Risk Consortium data from 19 countries across Europe, Australia, and North America. Individuals without prevalent cardiovascular disease at baseline and with robust available data on cardiovascular disease outcomes were included. The primary composite endpoint of atherosclerotic cardiovascular disease was defined as the occurrence of the coronary heart disease event or ischaemic stroke. Sex-specific multivariable analyses were computed using non-HDL cholesterol categories according to the European guideline thresholds, adjusted for age, sex, cohort, and classical modifiable cardiovascular risk factors. In a derivation and validation design, we created a tool to estimate the probabilities of a cardiovascular disease event by the age of 75 years, dependent on age, sex, and risk factors, and the associated modelled risk reduction, assuming a 50% reduction of non-HDL cholesterol.

Findings

Of the 524?444 individuals in the 44 cohorts in the Consortium database, we identified 398?846 individuals belonging to 38 cohorts (184?055 [48·7%] women; median age 51·0 years [IQR 40·7–59·7]). 199?415 individuals were included in the derivation cohort (91?786 [48·4%] women) and 199?431 (92?269 [49·1%] women) in the validation cohort. During a maximum follow-up of 43·6 years (median 13·5 years, IQR 7·0–20·1), 54?542 cardiovascular endpoints occurred. Incidence curve analyses showed progressively higher 30-year cardiovascular disease event-rates for increasing non-HDL cholesterol categories (from 7·7% for non-HDL cholesterol <2·6 mmol/L to 33·7% for ≥5·7 mmol/L in women and from 12·8% to 43·6% in men; p<0·0001). Multivariable adjusted Cox models with non-HDL cholesterol lower than 2·6 mmol/L as reference showed an increase in the association between non-HDL cholesterol concentration and cardiovascular disease for both sexes (from hazard ratio 1·1, 95% CI 1·0–1·3 for non-HDL cholesterol 2·6 to <3·7 mmol/L to 1·9, 1·6–2·2 for ≥5·7 mmol/L in women and from 1·1, 1·0–1·3 to 2·3, 2·0–2·5 in men). The derived tool allowed the estimation of cardiovascular disease event probabilities specific for non-HDL cholesterol with high comparability between the derivation and validation cohorts as reflected by smooth calibration curves analyses and a root mean square error lower than 1% for the estimated probabilities of cardiovascular disease. A 50% reduction of non-HDL cholesterol concentrations was associated with reduced risk of a cardiovascular disease event by the age of 75 years, and this risk reduction was greater the earlier cholesterol concentrations were reduced.

Interpretation

Non-HDL cholesterol concentrations in blood are strongly associated with long-term risk of atherosclerotic cardiovascular disease. We provide a simple tool for individual long-term risk assessment and the potential benefit of early lipid-lowering intervention. These data could be useful for physician–patient communication about primary prevention strategies.

DOI: 10.1016/S0140-6736(19)32519-X

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)32519-X/fulltext