Irish A B, Green F R
The Renal Unit, The Churchill Hospital, Headington, Oxford, UK.
Nephrol Dial Transplant. 1998 Mar;13(3):679-84. doi: 10.1093/ndt/13.3.679.
Factor VII coagulant activity (VIIc) is implicated in cardiovascular disease (CVD) risk in the general population. VIIc is correlated with hyperlipidaemia and influenced by a polymorphism of the factor VII gene and could contribute to thrombotic risk in patients with renal disease.
We studied VIIc in 100 patients with chronic renal disease or on maintenance dialysis and examined its relationship with dyslipidaemia, a marker of coagulation activation prothrombin fragment F1+2 (F1+2), the acute-phase reactant and coagulation factor fibrinogen, a mediator of the inflammatory response interleukin-6 (IL6), and the factor VII R353Q polymorphism.
VIIc (186+/-58 vs 140+/-37, % standard, P<0.0001) and F1+2 (0.51 vs 0.30 nM, median, P<0.0001) were increased in the patients with renal disease compared with the control group, consistent with a hypercoagulable state. Patients and controls heterozygous for the factor VII R353Q polymorphism, had 35% lower VIIc than homozygotes for the R353 allele, indicating that the Q353 allele could confer genetic protection from thrombotic risk. There was a significant correlation between VIIc and F1+2 (r=0.26, P<0.05), total and VLDL cholesterol, and triglycerides, but the correlation with lipids did not differ by genotype. VIIc and F1+2 also correlated with increased concentration of IL6 and fibrinogen, and inversely with albumin, suggesting that a persistent inflammatory response could contribute to a hypercoagulable state, possibly via cytokine induced activation of the endothelium, or by induction of monocytes to express tissue factor. Patients with CVD complications or a history of myocardial infarction did not have higher VIIc or F1+2 than those without CVD.
VIIc was significantly increased in renal disease states and strongly influenced by a common polymorphism of the factor VII gene, but the increase in VIIc and its correlation with lipids was not genotype specific. VIIc correlated with evidence of increased coagulation activation and persistence of an inflammatory response. A persistent inflammatory response and the dyslipidaemia of renal disease may contribute to coagulation activation and increased cardiovascular risk. Prospective studies are required to evaluate increased VIIc as a thrombotic risk factor in chronic renal disease.
凝血因子 VII 促凝活性（VIIc）与普通人群的心血管疾病（CVD）风险相关。VIIc 与高脂血症相关，并受凝血因子 VII 基因多态性的影响，可能会增加肾病患者的血栓形成风险。
我们研究了 100 例慢性肾病患者或维持性透析患者的 VIIc，并检测了其与血脂异常、凝血激活标志物凝血酶原片段 F1+2（F1+2）、急性期反应物及凝血因子纤维蛋白原、炎症反应介质白细胞介素 -6（IL6）以及凝血因子 VII R353Q 多态性之间的关系。
与对照组相比，肾病患者的 VIIc（186±58 对 140±37，%标准值，P<0.0001）和 F1+2（0.51 对 0.30 nM，中位数，P<0.0001）升高，这与高凝状态一致。凝血因子 VII R353Q 多态性杂合的患者和对照组，其 VIIc 比 R353 等位基因纯合子低 35%，表明 Q353 等位基因可能赋予对血栓形成风险的遗传保护。VIIc 与 F1+2（r = 0.26，P<0.05）、总胆固醇和极低密度脂蛋白胆固醇以及甘油三酯之间存在显著相关性，但与血脂的相关性在不同基因型之间无差异。VIIc 和 F1+2 还与 IL6 和纤维蛋白原浓度升高相关，与白蛋白呈负相关，这表明持续的炎症反应可能通过细胞因子诱导的内皮激活或通过诱导单核细胞表达组织因子导致高凝状态。有 CVD 并发症或心肌梗死病史的患者，其 VIIc 或 F1+2 并不高于无 CVD 的患者。
VIIc 在肾病状态下显著升高，并受凝血因子 VII 基因常见多态性的强烈影响，但 VIIc 的升高及其与血脂的相关性并非基因型特异性的。VIIc 与凝血激活增加及炎症反应持续的证据相关。持续的炎症反应和肾病患者的血脂异常可能导致凝血激活及心血管风险增加。需要进行前瞻性研究以评估升高的 VIIc 作为慢性肾病血栓形成风险因素的作用。
