Abdalrhim Ahmed D, Marroush Tariq S, Austin Erin E, Gersh Bernard J, Solak Nusret, Rizvi Syed A, Bailey Kent R, Kullo Iftikhar J
Department of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, United States of America.
Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, United States of America.
PLoS One. 2016 Jun 10;11(6):e0156965. doi: 10.1371/journal.pone.0156965. eCollection 2016.
Osteopontin (OPN) is a secreted glycophosphoprotein that has a role in inflammation, immune response and calcification. We hypothesized that plasma OPN levels are associated with adverse cardiovascular outcomes in patients with stable coronary artery disease (CAD) and preserved ejection fraction (EF) enrolled in the PEACE trial. We measured plasma OPN levels at baseline in 3567 CAD patients (mean age 64.5 ± 8.1 years, 81% men) by a sandwich chemiluminescent assay (coefficient of variation = 4.1%). OPN levels were natural log (Ln) transformed prior to analyses. We assessed whether Ln OPN levels were associated with the composite primary endpoint of cardiovascular death, non-fatal myocardial infarction and hospitalization for heart failure using multiple event multivariable Cox proportional hazards regression. Adjustment was performed for: (a) age and sex; (b) additional potential confounders; and (c) a parsimonious set of statistically significant 10 variates. During a median follow-up of 4.8 years, 416 adverse cardiovascular outcomes occurred in 366 patients. Ln OPN was significantly associated with the primary endpoint; HR (95% CI) = 1.56 (1.27, 1.92); P <0.001, and remained significant after adjustment for age and sex [1.31 (1.06, 1.61); P = 0.01] and after adjustment for relevant covariates [1.24 (1.01, 1.52); P = 0.04]. In a secondary analysis of the individual event types, Ln OPN was significantly associated with incident hospitalization for heart failure: HR (95% CI) = 2.04 (1.44, 2.89); P <0.001, even after adjustment for age, sex and additional relevant covariates. In conclusion, in patients with stable CAD and preserved EF on optimal medical therapy, plasma OPN levels were independently associated with the composite incident endpoint of adverse cardiovascular outcomes as well as incident hospitalization for heart failure.
骨桥蛋白（OPN）是一种分泌型糖磷蛋白，在炎症、免疫反应和钙化过程中发挥作用。我们推测，在参加PEACE试验的稳定型冠状动脉疾病（CAD）且射血分数（EF）保留的患者中，血浆OPN水平与不良心血管结局相关。我们通过夹心化学发光法（变异系数 = 4.1%）测量了3567例CAD患者（平均年龄64.5 ± 8.1岁，81%为男性）基线时的血浆OPN水平。在分析前对OPN水平进行了自然对数（Ln）转换。我们使用多事件多变量Cox比例风险回归评估Ln OPN水平是否与心血管死亡、非致命性心肌梗死和因心力衰竭住院的复合主要终点相关。进行了以下调整：（a）年龄和性别；（b）其他潜在混杂因素；（c）一组简约的10个具有统计学意义的变量。在中位随访4.8年期间，366例患者发生了416例不良心血管结局。Ln OPN与主要终点显著相关；风险比（95%置信区间）= 1.56（1.27，1.92）；P <0.001，在调整年龄和性别后仍具有显著性[1.31（1.06，1.61）；P = 0.01]，在调整相关协变量后也具有显著性[1.24（1.01，1.52）；P = 0.04]。在对个体事件类型的二次分析中，Ln OPN与因心力衰竭住院显著相关：风险比（95%置信区间）= 2.04（1.44，2.89）；P <0.001，即使在调整年龄、性别和其他相关协变量后也是如此。总之，在接受最佳药物治疗的稳定型CAD且EF保留的患者中，血浆OPN水平与不良心血管结局的复合发生终点以及因心力衰竭住院独立相关。
