BACKGROUND Soluble proprotein convertase subtilisin/kexin type 9 (PCSK9) has been shown to be predictive of cardiovascular events (CVEs) in patients who are at high cardiovascular risk. No data on the effect of PCSK9 levels in patients with atrial fibrillation (AF) are available. OBJECTIVES This study investigated the association between PCSK9 and CVEs in AF as well as the relationship between PCSK9 and urinary 11-dehydro-thromboxane B2 (11-dh-TxB2), a marker of platelet activation. METHODS We conducted a prospective, single-center cohort study, including 907 patients with AF treated with vitamin K antagonists (3,865 patient-years), to assess CVEs, including fatal and nonfatal myocardial infarction, ischemic stroke, and cardiovascular death. At admission, plasma PCSK9 and urinary 11-dh-TxB2 (n = 852) were measured. The population was divided into tertiles of PCSK9 for the analysis. RESULTS The mean age of patients was 73.5 ± 8.2 years, and 43.0% were women. At follow-up, 179 CVEs (4.6%/year) occurred: 43 (15.3%), 49 (15.5%), and 87 (28.0%) in the first, second, and third tertiles of PCSK9, respectively (log-rank test p = 0.009). Patients with CVEs had higher median PCSK9 compared with those without (1,500 pg/ml [IQR: 1,000 to 2,300 pg/ml] vs. 1,200 pg/ml [IQR: 827 to 1,807 pg/ml], respectively; p < 0.001). Multivariable Cox regression analysis showed that the third versus the first tertile of PCSK9 (hazard ratio: 1.640; 95% confidence interval: 1.117 to 2.407; p = 0.012), female sex, age, diabetes, smoking, heart failure, previous cerebrovascular and cardiac events, digoxin use, and total cholesterol to high-density lipoprotein cholesterol ratio were associated with CVEs. In 682 patients not treated with antiplatelet therapy, circulating PCSK9 and 11-dh-TxB2 were significantly correlated (Spearman's rho: 0.665; p < 0.001). CONCLUSIONS Plasma PCSK9 levels are associated with an increased risk of CVEs in patients with AF. The direct correlation between PCSK9 and 11-dh-TxB2 suggests PCSK9 as a mechanism potentially implicated in platelet activation.

中文翻译：

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房颤患者PCSK9和尿血栓素排泄与心血管事件的关系

背景 可溶性前蛋白转化酶枯草杆菌蛋白酶/kexin 9 型 (PCSK9) 已被证明可预测心血管风险高的患者的心血管事件 (CVE)。没有关于 PCSK9 水平对心房颤动 (AF) 患者影响的数据。目的 本研究调查了 AF 中 PCSK9 与 CVE 之间的关联，以及 PCSK9 与尿 11-脱氢-血栓烷 B2 (11-dh-TxB2)（血小板活化标志物）之间的关系。方法 我们进行了一项前瞻性、单中心队列研究，包括 907 名接受维生素 K 拮抗剂治疗的 AF 患者（3,865 患者年），以评估 CVE，包括致命和非致命性心肌梗死、缺血性卒中和心血管死亡。入院时，测量血浆 PCSK9 和尿 11-dh-TxB2（n = 852）。将群体分成 PCSK9 的三分位数进行分析。结果 患者的平均年龄为 73.5 ± 8.2 岁，43.0% 为女性。随访时，发生了 179 个 CVE（4.6%/年）：分别在 PCSK9 的第一、第二和第三三分位数（log-rank检验 p = 0.009）。与没有 CVE 的患者相比，患有 CVE 的患者具有更高的中位 PCSK9（分别为 1,500 pg/ml [IQR：1,000 至 2,300 pg/ml] 与 1,200 pg/ml [IQR：827 至 1,807 pg/ml]；p < 0.001）。多变量 Cox 回归分析显示 PCSK9 的第三个与第一个三分位数（风险比：1.640；95% 置信区间：1.117 至 2.407；p = 0.012）、女性、年龄、糖尿病、吸烟、心力衰竭、既往脑血管和心脏事件，地高辛使用，总胆固醇与高密度脂蛋白胆固醇的比率与 CVE 相关。在 682 名未接受抗血小板治疗的患者中，循环 PCSK9 和 11-dh-TxB2 显着相关（Spearman's rho：0.665；p < 0.001）。结论血浆 PCSK9 水平与 AF 患者发生 CVE 的风险增加有关。PCSK9 和 11-dh-TxB2 之间的直接相关性表明 PCSK9 是一种可能与血小板活化有关的机制。