From the Department of Clinical Biochemistry (C.M.M., P.R.K., A.L., A.V., B.G.N.), Copenhagen University Hospital, Denmark.
The Copenhagen General Population Study, Herlev and Gentofte Hospital (C.M.M., P.R.K., A.L., A.V., B.G.N.), Copenhagen University Hospital, Denmark.
Arterioscler Thromb Vasc Biol. 2020 Jan;40(1):255-266. doi: 10.1161/ATVBAHA.119.312951. Epub 2019 Oct 3.
High Lp(a) (lipoprotein[a]) cause cardiovascular disease (CVD) in a primary prevention setting; however, it is debated whether high Lp(a) lead to recurrent CVD events. We tested the latter hypothesis and estimated the Lp(a)-lowering needed for 5 years to reduce CVD events in a secondary prevention setting. Approach and Results: From the CGPS (Copenhagen General Population Study; 2003-2015) of 58 527 individuals with measurements of Lp(a), 2527 aged 20 to 79 with a history of CVD were studied. The primary end point was major adverse cardiovascular event (MACE). We also studied 1115 individuals with CVD from the CCHS (Copenhagen City Heart Study; 1991-1994) and the CIHDS (Copenhagen Ischemic Heart Disease Study; 1991-1993). During a median follow-up of 5 years (range, 0-13), 493 individuals (20%) experienced a MACE in the CGPS. MACE incidence rates per 1000 person-years were 29 (95% CI, 25-34) for individuals with Lp(a)<10 mg/dL, 35 (30-41) for 10 to 49 mg/dL, 42 (34-51) for 50 to 99 mg/dL, and 54 (42-70) for ≥100 mg/dL. Compared with individuals with Lp(a)<10 mg/dL (18 nmol/L), the multifactorially adjusted MACE incidence rate ratios were 1.28 (95% CI, 1.03-1.58) for 10 to 49 mg/dL (18-104 nmol/L), 1.44 (1.12-1.85) for 50 to 99 mg/dL (105-213 nmol/L), and 2.14 (1.57-2.92) for ≥100 mg/dL (214 nmol/L). Independent confirmation was obtained in individuals from the CCHS and CIHDS. To achieve 20% and 40% MACE risk reduction in secondary prevention, we estimated that plasma Lp(a) should be lowered by 50 mg/dL (95% CI, 27-138; 105 nmol/L [55-297]) and 99 mg/dL (95% CI, 54-273; 212 nmol/L [114-592]) for 5 years.
High concentrations of Lp(a) are associated with high risk of recurrent CVD in individuals from the general population. This study suggests that Lp(a)-lowering by 50 mg/dL (105 nmol/L) short-term (ie, 5 years) may reduce CVD by 20% in a secondary prevention setting.
高脂蛋白(a)[Lp(a)]可导致心血管疾病（CVD）的一级预防；然而，高 Lp(a) 是否会导致复发性 CVD 事件仍存在争议。我们检验了后者的假设，并估计了在二级预防环境中降低 Lp(a)水平 5 年以减少 CVD 事件所需的幅度。
从 58527 名具有 Lp(a)测量值的 CGPS（哥本哈根一般人群研究；2003-2015 年）中，研究了 2527 名年龄在 20 至 79 岁、有 CVD 病史的个体。主要终点是主要不良心血管事件（MACE）。我们还研究了来自 CCHS（哥本哈根城市心脏研究；1991-1994 年）和 CIHDS（哥本哈根缺血性心脏病研究；1991-1993 年）的 1115 名 CVD 患者。在中位随访 5 年（范围，0-13 年）期间，493 名个体（20%）在 CGPS 中经历了 MACE。每 1000 人年的 MACE 发生率为 Lp(a)<10 mg/dL 的个体为 29（95%CI，25-34），10-49 mg/dL 的个体为 35（30-41），50-99 mg/dL 的个体为 42（34-51），Lp(a)≥100 mg/dL 的个体为 54（42-70）。与 Lp(a)<10 mg/dL（18 nmol/L）的个体相比，多因素调整后的 MACE 发生率比值为 1.28（95%CI，1.03-1.58），Lp(a)为 10-49 mg/dL（18-104 nmol/L），1.44（1.12-1.85）为 50-99 mg/dL（105-213 nmol/L），Lp(a)≥100 mg/dL（214 nmol/L）为 2.14（1.57-2.92）。在 CCHS 和 CIHDS 的个体中获得了独立的证实。为了在二级预防中实现 20%和 40%的 MACE 风险降低，我们估计 Lp(a)应降低 50 mg/dL（95%CI，27-138；105 nmol/L[55-297]）和 99 mg/dL（95%CI，54-273；212 nmol/L[114-592]），持续 5 年。
高浓度的 Lp(a)与一般人群中复发性 CVD 的高风险相关。本研究表明，在二级预防环境中降低 Lp(a)水平 50 mg/dL（105 nmol/L）短期（即 5 年）可能降低 20%的 CVD。
