Low-density lipoprotein (LDL) cholesterol-lowering treatment is beneficial for the secondary or primary prevention of high-risk atherosclerotic cardiovascular disease (ASCVD). However, the prognostic implications of low LDL cholesterol levels in patients without previous ASCVD and without statin use remain elusive. From a nationwide cohort, 2,432,471 participants without previous ASCVD or statin use were included. For myocardial infarction (MI) and ischemic stroke (IS), participants were followed-up from 2009 to 2018. They were stratified according to 10-year ASCVD risk (<5 %, 5 %–<7.5 %, 7.5 %–<20 %, and ≥20 %) and LDL cholesterol level (<70, 70–99, 100–129, 130–159, 160–189, and ≥190 mg/dL). The relationship between LDL cholesterol levels and ASCVD events exhibited a J-shaped curve for both MI and IS. After classification according to the ASCVD risk, this J-shaped relationship was consistently observed for the composite of MI and IS. Participants with an LDL cholesterol level <70 mg/dL showed a higher MI risk than those with a level of 70–99 mg/dL or 100–129 mg/dL in the low-ASCVD risk group. The J-shaped curve between LDL cholesterol levels and MI risk was attenuated across ASCVD risk groups. For IS, participants with an LDL cholesterol level <70 mg/dL demonstrated increased risks compared with those with a level of 70–99 mg/dL, 100–129 mg/dL, or 130–159 mg/dL in the borderline, intermediate, and high ASCVD risk groups, respectively. In contrast, a linear association was observed in participants taking statins. Interestingly, a J-shaped association was observed between LDL cholesterol and high-sensitivity C-reactive protein (hs-CRP) levels; the mean hs-CRP level and the proportion of individuals with increased hs-CRP levels were relatively high among individuals with an LDL cholesterol level <70 mg/dL. Although high LDL cholesterol levels increase the risk of ASCVD, low LDL cholesterol levels do not warrant safety from ASCVD. Therefore, individuals with low LDL cholesterol levels should be carefully monitored.

中文翻译：

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LDL 胆固醇与心血管事件之间的 J 形关联：全国超过 240 万人的纵向一级预防队列

低密度脂蛋白（LDL）降胆固醇治疗有利于高危动脉粥样硬化性心血管疾病（ASCVD）的二级或一级预防。然而，低 LDL 胆固醇水平对既往无 ASCVD 且未使用他汀类药物的患者的预后影响仍然难以捉摸。在全国范围内的队列中，纳入了 2,432,471 名既往没有 ASCVD 或他汀类药物使用史的参与者。对于心肌梗塞 (MI) 和缺血性中风 (IS)，参与者从 2009 年至 2018 年进行了随访。他们根据 10 年 ASCVD 风险进行分层（<5%、5%–<7.5%、7.5%–<20 % 和 ≥20 %）和 LDL 胆固醇水平（<70、70–99、100–129、130–159、160–189 和 ≥190 mg/dL）。 MI 和 IS 的 LDL 胆固醇水平与 ASCVD 事件之间的关系均呈现 J 形曲线。根据 ASCVD 风险进行分类后，对于 MI 和 IS 的组合，一致观察到这种 J 形关系。 LDL 胆固醇水平<70 mg/dL 的参与者比 ASCVD 低风险组中 LDL 胆固醇水平为 70-99 mg/dL 或 100-129 mg/dL 的参与者显示出更高的 MI 风险。 LDL 胆固醇水平与 MI 风险之间的 J 形曲线在 ASCVD 风险组中减弱。对于 IS，LDL 胆固醇水平 <70 mg/dL 的参与者与处于临界、中间水平的 70-99 mg/dL、100-129 mg/dL 或 130-159 mg/dL 水平的参与者相比，风险增加和高 ASCVD 风险人群。相反，在服用他汀类药物的参与者中观察到线性相关性。有趣的是，LDL 胆固醇和高敏 C 反应蛋白 (hs-CRP) 水平之间存在 J 形关联； LDL 胆固醇水平<70 mg/dL 的个体中，平均 hs-CRP 水平和 hs-CRP 水平升高的个体比例相对较高。虽然高 LDL 胆固醇水平会增加 ASCVD 的风险，但低 LDL 胆固醇水平并不能保证避免 ASCVD。因此，应仔细监测低密度脂蛋白胆固醇水平较低的个体。