Independent Relationship of Lipoprotein(a) and Carotid Atherosclerosis With Long-Term Risk of Cardiovascular Disease.

BACKGROUND Lipoprotein(a) (Lp(a)) is considered to be a causal risk factor of atherosclerotic cardiovascular disease (ASCVD), but whether there is an independent or joint association of Lp(a) and atherosclerotic plaque with ASCVD risk remains uncertain. This study aims to assess ASCVD risk independently or jointly conferred by Lp(a) and carotid atherosclerotic plaque. METHODS AND RESULTS A total of 5471 participants with no history of cardiovascular disease at baseline were recruited and followed up for ASCVD events (all fatal and nonfatal acute coronary and ischemic stroke events) over a median of 11.5 years. Independent association of Lp(a), or the joint association of Lp(a) and carotid plaque with ASCVD risk, was explored using Cox proportional hazards models. Overall, 7.6% of the participants (60.0±7.9 years of age; 2649 [48.4%] men) had Lp(a) ≥50 mg/dL, and 539 (8.4/1000 person-years) incident ASCVD events occurred. Lp(a) concentrations were independently associated with long-term risk of total ASCVD events, as well as coronary events and ischemic stroke events. Participants with Lp(a) ≥50 mg/dL had a 62% higher risk of ASCVD incidence (95% CI, 1.19-2.21) than those with Lp(a) <10 mg/dL, and they exhibited a 10-year ASCVD incidence of 11.7%. This association exists even after adjusting for prevalent plaque. Moreover, participants with Lp(a) ≥30 mg/dL and prevalent plaque had a significant 4.18 times higher ASCVD risk than those with Lp(a) <30 mg/dL and no plaque. CONCLUSIONS Higher Lp(a) concentrations are independently associated with long-term ASCVD risk and may exaggerate cardiovascular risk when concomitant with atherosclerotic plaque.

背景 脂蛋白（a）（Lp（a））被认为是动脉粥样硬化性心血管疾病（ASCVD）的一个致病危险因素，但Lp（a）和动脉粥样硬化斑块与ASCVD风险之间是否存在独立或联合关联仍不确定。本研究旨在评估Lp（a）和颈动脉粥样硬化斑块独立或联合赋予的ASCVD风险。 方法与结果 共招募了5471名基线时无心血管疾病病史的参与者，并对其进行了中位时间为11.5年的ASCVD事件（所有致命和非致命的急性冠状动脉和缺血性卒中事件）随访。使用Cox比例风险模型探究了Lp（a）的独立关联，以及Lp（a）和颈动脉斑块与ASCVD风险的联合关联。总体而言，7.6%的参与者（年龄60.0±7.9岁；2649名[48.4%]为男性）Lp（a）≥50mg/dL，发生了539例（8.4/1000人年）ASCVD事件。Lp（a）浓度与总ASCVD事件以及冠状动脉事件和缺血性卒中事件的长期风险独立相关。Lp（a）≥50mg/dL的参与者发生ASCVD的风险比Lp（a）<10mg/dL的参与者高62%（95%置信区间，1.19 - 2.21），并且他们的10年ASCVD发生率为11.7%。即使在对已有的斑块进行调整后，这种关联仍然存在。此外，Lp（a）≥30mg/dL且有斑块的参与者发生ASCVD的风险比Lp（a）<30mg/dL且无斑块的参与者显著高4.18倍。 结论 较高的Lp（a）浓度与长期ASCVD风险独立相关，并且当与动脉粥样硬化斑块同时存在时可能会增加心血管风险。