State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital and National Center for Cardiovascular Diseases, China.
Heart Institute (InCor), University of Sao Paulo Medical School Hospital, Brazil.
Eur J Prev Cardiol. 2021 Apr 23;28(3):272-279. doi: 10.1177/2047487319880985. Epub 2019 Oct 11.
AIMS: Familial hypercholesterolemia patients are characterized by early onset of coronary artery calcification and atherosclerosis, and high incidence of cardiovascular events. Plasma proprotein convertase subtilisin/kexin type 9 was reported to be a predictor for cardiovascular risk in the general population. However, its prognostic value for predicting recurrent cardiovascular events in familial hypercholesterolemia patients remains undetermined. METHODS: A total of 249 patients with molecularly and/or clinically (Dutch Lipid Clinic Network score > 6) defined familial hypercholesterolemia who had experienced a first cardiovascular event were consecutively included and plasma proprotein convertase subtilisin/kexin type 9 concentrations were measured by enzyme-linked immunosorbent assay. Coronary artery calcification was measured using Agatston method and coronary severity was assessed by Gensini score, respectively. All patients received standard lipid-lowering therapy and were followed-up for recurrent cardiovascular events. Univariate and multivariate regression and Cox analyses was used to calculate hazard ratios with 95% confidence interval. RESULTS: Circulating proprotein convertase subtilisin/kexin type 9 concentrations were positively associated with coronary artery calcification scores and Gensini score by both univariate and multivariate analyses. During a mean follow-up of 43 ± 19 months, 29 (11.51%) recurrent cardiovascular events occurred. Kaplan-Meier analysis showed that patients with the highest proprotein convertase subtilisin/kexin type 9 levels had the lowest event-free survival time. Multivariable Cox regression analysis revealed that proprotein convertase subtilisin/kexin type 9 was independently associated with recurrent cardiovascular events (hazard ratio: 1.45, 95% confidence interval: 1.11-1.88). The combination of proprotein convertase subtilisin/kexin type 9 to Cox prediction model led to an enhanced predictive value for recurrent cardiovascular events. CONCLUSIONS: Increased level of proprotein convertase subtilisin/kexin type 9 was a significant risk factor of atherosclerosis and independently predicted future recurrent cardiovascular events in familial hypercholesterolemia patients receiving standard lipid-lowering treatment.
目的：家族性高胆固醇血症患者的冠状动脉钙化和动脉粥样硬化发病较早，心血管事件发生率较高。有报道称，血浆脯氨酰肽链内切酶/羧肽酶 9 可作为普通人群心血管风险的预测因子。然而，其在预测家族性高胆固醇血症患者复发性心血管事件中的预后价值仍不确定。
方法：共纳入 249 例经分子和/或临床（荷兰血脂临床网络评分>6）确诊的家族性高胆固醇血症患者，这些患者均经历过首次心血管事件。通过酶联免疫吸附试验检测血浆脯氨酰肽链内切酶/羧肽酶 9 浓度。采用 Agatston 法测量冠状动脉钙化程度，采用 Gensini 评分评估冠状动脉狭窄程度。所有患者均接受标准降脂治疗，并随访复发性心血管事件。采用单因素和多因素回归及 Cox 分析计算风险比及其 95%置信区间。
结果：单因素和多因素分析均显示，循环脯氨酰肽链内切酶/羧肽酶 9 浓度与冠状动脉钙化评分和 Gensini 评分呈正相关。在平均 43±19 个月的随访期间，29 例（11.51%）患者发生复发性心血管事件。Kaplan-Meier 分析显示，脯氨酰肽链内切酶/羧肽酶 9 水平最高的患者无事件生存时间最短。多变量 Cox 回归分析显示，脯氨酰肽链内切酶/羧肽酶 9 与复发性心血管事件独立相关（风险比：1.45，95%置信区间：1.11-1.88）。将脯氨酰肽链内切酶/羧肽酶 9 纳入 Cox 预测模型可提高复发性心血管事件的预测价值。
结论：升高的脯氨酰肽链内切酶/羧肽酶 9 水平是动脉粥样硬化的一个重要危险因素，可独立预测接受标准降脂治疗的家族性高胆固醇血症患者未来发生复发性心血管事件的风险。
J Transl Med. 2019-11-11
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