Department of Internal Medicine, (CARIM), Maastricht University Medical Center, The Netherlands.
CTH, University Medical Center of the Johannes Gutenberg-University Mainz, Germany.
Haematologica. 2020 Sep 1;105(9):2327-2334. doi: 10.3324/haematol.2019.221655.
Thrombin generation may be a potential tool to improve risk stratification for cardiovascular diseases. This study aims to explore the relation between thrombin generation and cardiovascular risk factors, cardiovascular diseases, and total mortality. For this study, N=5000 subjects from the population-based Gutenberg Health Study were analysed in a highly standardized setting. Thrombin generation was assessed by the Calibrated Automated Thrombogram method at 1 and 5 pM tissue factors trigger in platelet poor plasma. Lag time, endogenous thrombin potential, and peak height were derived from the thrombin generation curve. Sex-specific multivariable linear regression analysis adjusted for age, cardiovascular risk factors, cardiovascular diseases and therapy, was used to assess clinical determinants of thrombin generation. Cox regression models adjusted for age, sex, cardiovascular risk factors and vitamin K antagonists investigated the association between thrombin generation parameters and total mortality. Lag time was positively associated with obesity and dyslipidaemia for both sexes (p<0.0001). Obesity was also positively associated with endogenous thrombin potential in both sexes (p<0.0001) and peak height in males (1 pM tissue factor, p=0.0048) and females (p<0.0001). Cox regression models showed an increased mortality in individuals with lag time (1 pM tissue factor, hazard ratio=1.46, [95% CI: 1.07; 2.00], p=0.018) and endogenous thrombin potential (5 pM tissue factor, hazard ratio = 1.50, [1.06; 2.13], p=0.023) above the 95th percentile of the reference group, independent of the cardiovascular risk profile. This large-scale study demonstrates traditional cardiovascular risk factors, particularly obesity, as relevant determinants of thrombin generation. Lag time and endogenous thrombin potential were found as potentially relevant predictors of increased total mortality, which deserves further investigation.
凝血酶生成可能是改善心血管疾病风险分层的潜在工具。本研究旨在探讨凝血酶生成与心血管危险因素、心血管疾病和总死亡率之间的关系。在这项研究中，我们在高度标准化的环境中分析了来自人群为基础的古滕贝格健康研究的 5000 名受试者。使用 Calibrated Automated Thrombogram 方法在血小板缺乏血浆中 1 和 5 pM 组织因子触发时评估凝血酶生成。从凝血酶生成曲线中得出滞后时间、内源性凝血酶潜能和峰值高度。使用多变量线性回归分析调整年龄、心血管危险因素、心血管疾病和治疗，评估凝血酶生成的临床决定因素。使用 Cox 回归模型调整年龄、性别、心血管危险因素和维生素 K 拮抗剂，研究凝血酶生成参数与总死亡率之间的关系。滞后时间与肥胖和血脂异常呈正相关（p<0.0001）。肥胖也与两性的内源性凝血酶潜能呈正相关（p<0.0001），与男性（1 pM 组织因子，p=0.0048）和女性（p<0.0001）的峰值高度呈正相关。Cox 回归模型显示，滞后时间（1 pM 组织因子，危险比=1.46，[95%CI：1.07；2.00]，p=0.018）和内源性凝血酶潜能（5 pM 组织因子，危险比=1.50，[1.06；2.13]，p=0.023）超过参考组第 95 百分位数的个体的死亡率增加，独立于心血管风险状况。这项大规模研究表明，传统的心血管危险因素，特别是肥胖，是凝血酶生成的相关决定因素。滞后时间和内源性凝血酶潜能被认为是总死亡率增加的潜在相关预测因素，值得进一步研究。
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