载脂蛋白 B、载脂蛋白 A-1 和载脂蛋白 B/载脂蛋白 A-1 比值与主要心血管事件长期风险的关系：来自瑞典 AMORIS 队列的经验：一项队列研究。

BACKGROUND: Elevated apolipoprotein B (apoB) and elevated apoB/apoA-1 ratio increase the risk of myocardial infarction (MI) and stroke, whereas high apoA-1 is protective. We study how these apolipoproteins are associated with major adverse cardiovascular events (MACEs), whether apoA-1 contributes to this association, and whether abnormal values occur decades before such events develop. METHODS AND FINDINGS: In the Swedish AMORIS (Apolipoprotein-related MOrtality RISk) cohort study, 137,100 men and women aged 25-84 years were followed an average 17.8 years. ApoB, apoA-1, and the apoB/apoA-1 ratio were analysed in relation to MACEs (non-fatal MI, stroke, and cardiovascular [CV] mortality), yielding 22,473 events. Hazard ratios (HRs) were estimated using Cox regression. Kaplan-Meier estimates were used to investigate the relationship of MACEs with increasing quintiles of the apoB/apoA-1 ratio in all age groups for both sexes. In nested case-control analyses, cases were randomly matched to age- and sex-matched controls, yielding population trajectories for apolipoproteins. Increased level of apoB and increased apoB/apoA-1 ratio were associated with risk of MACE and all clinical sub-components in both men and women across all ages (10th versus first decile in both sexes combined: HR 1.7 for MACE and 2.7 for non-fatal MI). Decreased values of apoA-1 potentiated the impact of apoB at all levels of apoB (on average across apoB range: 40% increase in HR for MACE and 72% increase in HR for non-fatal MI), indicating that the apoB/apoA-1 ratio covers a broader range of persons with dyslipidaemia at risk than apoB alone. In both men and women, MACEs occurred earlier on average for each increasing quintile of the apoB/apoA-1 ratio. Individuals with the highest levels of apoB/apoA-1 ratio experienced CV events on average several years earlier than those with lower ratios. Higher apoB/apoA-1 ratio in cases of MACE versus controls was seen already about 20 years before the event. A limitation of this study was that adjustment for tobacco smoking and hypertension was only possible in a small validation study. CONCLUSIONS: An imbalance between apoB and apoA-1 resulting in an increased apoB/apoA-1 ratio is strongly associated with the outcome MACE and its sub-components, in both men and women of all ages. An increased apoB/apoA-1 ratio already 2 decades before events calls for early recognition and primary prevention. Simple evidence-based cut values should be considered in future cardiovascular guidelines.

背景：载脂蛋白 B（apoB）升高和 apoB/apoA-1 比值升高会增加心肌梗死（MI）和中风的风险，而高 apoA-1 则具有保护作用。我们研究了这些载脂蛋白与主要不良心血管事件（MACE）的关系，apoA-1 是否有助于这种关系，以及异常值是否在这些事件发生前几十年就出现。

方法和发现：在瑞典 AMORIS（载脂蛋白相关死亡率风险）队列研究中，对 137100 名年龄在 25-84 岁的男性和女性进行了平均 17.8 年的随访。apoB、apoA-1 和 apoB/apoA-1 比值与 MACE（非致命性 MI、中风和心血管[CV]死亡率）相关，共发生 22473 例事件。使用 Cox 回归估计风险比（HR）。Kaplan-Meier 估计用于调查所有年龄组男女中 MACE 与 apoB/apoA-1 比值递增五分位数的关系。在嵌套病例对照分析中，病例随机匹配年龄和性别匹配的对照，为载脂蛋白生成人群轨迹。apoB 水平升高和 apoB/apoA-1 比值升高与男性和女性各年龄段的 MACE 和所有临床亚组的风险相关（两性联合的第 10 个五分位数与第 1 个十分位数相比：MACE 的 HR 为 1.7，非致命性 MI 的 HR 为 2.7）。apoA-1 值降低会增强 apoB 在 apoB 所有水平上的影响（apoB 范围内平均：MACE 的 HR 增加 40%，非致命性 MI 的 HR 增加 72%），表明 apoB/apoA-1 比值比单独的 apoB 涵盖了更广泛的具有血脂异常风险的人群。在男性和女性中，MACE 平均每增加一个 apoB/apoA-1 比值五分位数就会更早发生。apoB/apoA-1 比值最高的个体发生 CV 事件的平均时间比比值较低的个体早几年。与对照组相比，MACE 病例中的 apoB/apoA-1 比值在事件发生前约 20 年就已经升高。本研究的一个局限性是，只能在一项小型验证研究中对吸烟和高血压进行调整。

结论：apoB 和 apoA-1 之间的不平衡导致 apoB/apoA-1 比值升高，与男性和女性各年龄段的 MACE 及其亚组密切相关。apoB/apoA-1 比值在事件发生前 20 年就已经升高，这呼吁早期识别和初级预防。未来心血管指南应考虑使用简单的基于证据的临界值。