Service of Laboratory Medicine, Department of Genetics and Laboratory Medicine, Geneva University Hospitals, Geneva 14, Switzerland.
Eur Heart J. 2010 Apr;31(7):815-23. doi: 10.1093/eurheartj/ehq055. Epub 2010 Feb 22.
To assess the prognostic value of anti-apolipoprotein A-1 (anti-apoA-1) IgG after myocardial infarction (MI) and its association with major cardiovascular events (MACEs) at 12 months and to determine their association with resting heart rate (RHR), a well-established prognostic feature after MI. Anti-apoA-1 IgG have been reported in MI without autoimmune disease, but their clinical significance remains undetermined.
A total of 221 consecutive patients with MI were prospectively included, and all completed a 12-month follow-up. Major cardiovascular events consisted in death, MI, stroke, or hospitalization either for an acute coronary syndrome or heart failure. Resting heart rate was obtained on Holter the day before discharge under the same medical treatment. Neonate rat ventricular cardiomyocytes (NRVC) were used in vitro to assess the direct anti-apoA-1 IgG effect on RHR. During follow-up, 13% of patients presented a MACE. Anti-apoA-1 IgG positivity was 9% and was associated with a higher RHR (P = 0.0005) and higher MACE rate (adjusted OR, 4.3; 95% CI, 1.46-12.6; P = 0.007). Survival models confirmed the significant nature of this association. Patients with MACE had higher median anti-apoA-1 IgG values at admission than patients without (P = 0.007). On NRVC, plasma from MI patients and monoclonal anti-apoA-1 IgG induced an aldosterone and dose-dependent positive chronotropic effect, abrogated by apoA-1 and therapeutic immunoglobulin (IVIG) pre-incubation.
In MI patients, anti-apoA-1 IgG is independently associated with MACE at 1-year, interfering with a currently unknown aldosterone-dependent RHR determinant. Knowing whether anti-apoA-1 IgG assessment could be of interest to identify an MI patient subset susceptible to benefit from apoA-1/IVIG therapy remains to be demonstrated.
评估心肌梗死后抗载脂蛋白 A-1（anti-apoA-1）IgG 的预后价值及其与 12 个月时主要心血管事件（MACE）的关系，并确定其与静息心率（RHR）的关系，RHR 是 MI 后的一个既定预后特征。已有报道称在没有自身免疫性疾病的情况下，MI 患者体内存在 anti-apoA-1 IgG，但它们的临床意义仍未确定。
共前瞻性纳入 221 例连续 MI 患者，所有患者均完成 12 个月随访。主要心血管事件包括死亡、MI、卒中和因急性冠状动脉综合征或心力衰竭住院。在相同的药物治疗下，在出院前一天通过动态心电图获取静息心率。体外使用新生大鼠心室心肌细胞（NRVC）评估 RHR 对直接抗 apoA-1 IgG 的影响。随访期间，13%的患者发生 MACE。anti-apoA-1 IgG 阳性率为 9%，与更高的 RHR（P=0.0005）和更高的 MACE 发生率（调整后的 OR，4.3；95%CI，1.46-12.6；P=0.007）相关。生存模型证实了这种相关性的重要性。与无 MACE 的患者相比，发生 MACE 的患者入院时的平均 anti-apoA-1 IgG 值更高（P=0.007）。在 NRVC 上，MI 患者的血浆和单克隆抗 apoA-1 IgG 诱导了一种醛固酮依赖性和剂量依赖性的正性变时作用，该作用可被 apoA-1 和治疗性免疫球蛋白（IVIG）预孵育所阻断。
在 MI 患者中，anti-apoA-1 IgG 与 1 年后的 MACE 独立相关，干扰了一个目前未知的醛固酮依赖性 RHR 决定因素。确定抗 apoA-1 IgG 评估是否有助于确定易受益于 apoA-1/IVIG 治疗的 MI 患者亚组，这一点仍有待证明。
