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. FUNDING EU Framework Programme, UK Medical Research Council, and German Centre for Cardiovascular Research.

中文翻译：

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非高密度脂蛋白胆固醇在基于人群的心血管风险分层中的应用：多国心血管风险联盟的结果。

背景 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与心血管疾病结局的相关性尚不清楚。我们调查了与全谱血流非高密度脂蛋白胆固醇浓度相关的心血管疾病风险。我们还创建了一个易于使用的工具来估计与非 HDL 胆固醇相关的心血管疾病事件的长期概率，并通过降脂治疗对其风险降低进行建模。方法 在这项风险评估和风险建模研究中，我们使用了来自欧洲、澳大利亚和北美 19 个国家/地区的跨国心血管风险联盟数据。包括在基线时没有普遍心血管疾病并且具有关于心血管疾病结果的可靠可用数据的个体。动脉粥样硬化性心血管疾病的主要复合终点定义为冠心病事件或缺血性卒中的发生。根据欧洲指南阈值使用非 HDL 胆固醇类别计算性别特异性多变量分析，并根据年龄、性别、队列和经典的可修改心血管危险因素进行调整。在推导和验证设计中，我们创建了一个工具来估计 75 岁时心血管疾病事件的概率，这取决于年龄、性别和风险因素，以及相关的建模风险降低，假设降低 50%非高密度脂蛋白胆固醇。在 Consortium 数据库的 44 个队列中的 524 444 名个体中，我们确定了属于 38 个队列的 398 846 名个体（184 055 [48·7%] 名女性；中位年龄 51·0 岁 [IQR 40·7-59·7 ]). 推导队列中包括 199 415 人（91 786 [48·4%] 女性）和验证队列中的 199 431 人（92 269 [49·1%] 女性）。在最长 43·6 年的随访期间（中位数 13·5 年，IQR 7·0-20·1），发生了 54542 例心血管终点事件。发病率曲线分析显示，随着非 HDL 胆固醇类别的增加，30 年心血管疾病事件发生率逐渐升高（从非 HDL 胆固醇 <2·6 mmol/L 的 7·7% 到≥5·7 mmol/L 的 33·7% /L 在女性中，在男性中从 12·8% 到 43·6%；p<0·0001)。以非 HDL 胆固醇低于 2·6 mmol/L 作为参考的多变量调整 Cox 模型显示，对于两性，非 HDL 胆固醇浓度与心血管疾病之间的关联增加（来自风险比 1·1，95% CI 1· 0-1·3 非高密度脂蛋白胆固醇 2·6 至 <3·7 mmol/L 至 1·9, 1·6-2·2 女性≥5·7 mmol/L 和 1·1, 1 ·0-1·3 至 2·3，男性为 2·0-2·5）。派生工具允许估计特定于非 HDL 胆固醇的心血管疾病事件概率，派生队列和验证队列之间具有很高的可比性，如平滑校准曲线分析所反映的，以及心血管疾病估计概率的均方根误差低于 1% . 非高密度脂蛋白胆固醇浓度降低 50% 与 75 岁时心血管疾病事件风险降低相关，并且这种风险降低幅度越大，胆固醇浓度越早降低。解释 血液中的非高密度脂蛋白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。我们为个人长期风险评估和早期降脂干预的潜在益处提供了一个简单的工具。这些数据可能有助于医患就初级预防策略进行交流。资助欧盟框架计划、英国医学研究委员会和德国心血管研究中心。解释 血液中的非高密度脂蛋白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。我们为个人长期风险评估和早期降脂干预的潜在益处提供了一个简单的工具。这些数据可能有助于医患就初级预防策略进行交流。资助欧盟框架计划、英国医学研究委员会和德国心血管研究中心。解释 血液中的非高密度脂蛋白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。我们为个人长期风险评估和早期降脂干预的潜在益处提供了一个简单的工具。这些数据可能有助于医患就初级预防策略进行交流。资助欧盟框架计划、英国医学研究委员会和德国心血管研究中心。