Factor VII coagulant activity (VIIc) and hypercoagulability in chronic renal disease and dialysis: relationship with dyslipidaemia, inflammation, and factor VII genotype

被引:34
作者
Irish, AB
Green, FR [1 ]
机构
[1] John Radcliffe Hosp, Nuffield Dept Surg, Oxford OX3 9DU, England
[2] Churchill Hosp, Renal Unit, Oxford OX3 7LJ, England
关键词
chronic renal disease; dyslipidaemia; factor VII genotype; factor VII coagulant activity (VIIc); interleukin; 6; prothrombin fragment F1+2;
D O I
10.1093/ndt/13.3.679
中图分类号
R3 [基础医学]; R4 [临床医学];
学科分类号
1001 ; 1002 ; 100602 ;
摘要
Background. 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. Methods. 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. Results. 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. Conclusions. 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.
引用
收藏
页码:679 / 684
页数:6
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