Bryk Agata Hanna, Konieczyńska Małgorzata, Polak Maciej, Plicner Dariusz, Bochenek Maciej, Undas Anetta
Department of Endocrinology, Jagiellonian University Medical College, Krakow, Poland.
John Paul II Hospital, Krakow, Poland.
Cardiovasc Diabetol. 2021 Feb 18;20(1):47. doi: 10.1186/s12933-021-01230-9.
Patients with type 2 diabetes mellitus (T2DM) are at high risk of cardiovascular mortality, but the mechanisms behind this remain unclear. Prothrombotic fibrin clot properties have been shown in T2DM and cardiovascular disease. We hypothesized that formation of denser clots, which are resistant to fibrinolysis, has a negative impact on cardiovascular mortality in T2DM.
We studied 133 T2DM patients aged 43-83 years. Plasma fibrin clot turbidity, permeation, compaction, and efficiency of clot lysis using 3 assays including the determination of maximum concentration (D-D) and rate of increase in D-dimer concentration (D-D) released during tissue plasminogen activator-induced degradation, were evaluated at the time of enrollment, along with thrombin generation and fibrinolytic proteins. During a median follow-up period of 72 months, cardiovascular mortality was recorded.
Cardiovascular deaths (n = 16, 12%) occurred more frequently in patients with increased D-D (> 4.26 mg/l, hazard ratio [HR] 5.43, 95% confidence interval [CI] 1.99-14.79), or decreased D-D (< 0.07 mg/l/min, HR 2.97, 95% CI 1.07-8.23), or increased peak thrombin (> 283.5 nM, HR 5.65, 95% CI 2.07-15.51). These predictors had an even more potent impact on cardiovascular mortality in patients with prior cardiovascular disease (64.7%) and with corresponding risks as follows: HR 6.18, 95% CI 2.02-18.96; HR 8.98, 95% CI 2.99-26.96; and HR 5.35, 95% CI 1.62-17.72, respectively. Other investigated fibrin variables and fibrinolytic proteins did not associate with cardiovascular mortality. In multivariable analysis, cardiovascular mortality was predicted by D-D > 4.26 mg/l, age > 65 years, prior cardiovascular disease, and C-reactive protein > 3 mg/l.
This study is the first to show that formation of denser fibrin clots resistant to fibrinolysis could be a risk factor for long-term cardiovascular mortality in T2DM.
2型糖尿病（T2DM）患者心血管疾病死亡风险较高，但其背后的机制尚不清楚。T2DM和心血管疾病患者已出现促血栓形成的纤维蛋白凝块特性。我们推测，形成更致密且对纤维蛋白溶解有抵抗作用的凝块会对T2DM患者的心血管疾病死亡率产生负面影响。
我们研究了133例年龄在43 - 83岁的T2DM患者。在入组时，使用包括测定组织纤溶酶原激活剂诱导降解过程中释放的最大浓度（D - D）和D - 二聚体浓度增加速率（D - D）在内的3种检测方法，评估血浆纤维蛋白凝块的浊度、渗透性、压实度和凝块溶解效率，同时检测凝血酶生成和纤维蛋白溶解蛋白。在中位随访期72个月期间，记录心血管疾病死亡率。
D - D升高（> 4.26mg/l，风险比[HR] 5.43，95%置信区间[CI] 1.99 - 14.79）、D - D降低（< 0.07mg/l/min，HR 2.97，95% CI 1.07 - 8.23）或凝血酶峰值升高（> 283.5nM，HR 5.65，95% CI 2.07 - 15.51）的患者心血管疾病死亡（n = 16，12%）更为常见。这些预测指标对既往有心血管疾病（64.7%）的患者心血管疾病死亡率的影响更强，相应风险如下：HR 6.18，95% CI 2.02 - 18.96；HR 8.98，95% CI 2.99 - 26.96；以及HR分别为5.35，95% CI 1.62 - 17.72。其他研究的纤维蛋白变量和纤维蛋白溶解蛋白与心血管疾病死亡率无关。在多变量分析中，心血管疾病死亡率由D - D > 4.26mg/l、年龄 > 65岁、既往心血管疾病和C反应蛋白 > 3mg/l预测。
本研究首次表明，形成对纤维蛋白溶解有抵抗作用的更致密纤维蛋白凝块可能是T2DM患者长期心血管疾病死亡的危险因素。
