Fibrinogen After Coronary Angioplasty as a Risk Factor for Restenosis

Abstract

Background Fibrinogen is a risk factor for cardiovascular disease and is related to the severity of coronary atherosclerosis. Its role in restenosis after coronary angioplasty remains unknown. Although platelets and thrombosis contribute to the pathogenesis of restenosis, few clinical data are available concerning the relations between restenosis and proteins of the coagulation and fibrinolytic systems. Methods and Results In 107 consecutive patients undergoing coronary angioplasty, we measured plasma levels of tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor–1 (PAI-1), von Willebrand factor, and fibrinogen before and immediately after angioplasty and at a 6-month follow-up. The individual changes of intraluminal diameter were measured by quantitative coronary angiography, and patients were classified according to four definitions of restenosis: (1) a final stenosis >50%, (2) a loss of minimal luminal diameter during the follow-up period greater than the measurement variability in our laboratory (>0.52 mm), (3) a loss of at least 50% of the gain in luminal diameter achieved by angioplasty, and (4) the combination of definitions 1 and 2. The relations between coagulation variables and each definition of restenosis were assessed univariately; then with the clinical variables included, the relations were analyzed multivariately. Angiographic follow-up was obtained in 92% of patients with a primary success of angioplasty. Global restenosis rates were 38%, 43%, 48%, and 30% for definitions 1 through 4, respectively. Plasma levels of t-PA antigen and PAI-1 antigen were not associated with any of the four definitions of restenosis. Multivariate analysis demonstrated that von Willebrand factor measured immediately after angioplasty predicted restenosis according to definitions 2 and 3. Fibrinogen measured within 6 months of follow-up was significantly increased in all restenosis groups of the four definitions. Patients with a fibrinogen concentration >3.5 g/L at follow-up had higher restenosis rates than patients with a concentration <3.5 g/L: 55% versus 22% ( P =.001), 68% versus 31% ( P =.002), 63% versus 37% ( P =.01), and 74% versus 26% ( P =.002) for definitions 1 through 4, respectively. The loss index was lower ( P =.003) and the net gain higher ( P =.03) in patients with a fibrinogen level <3.5 g/L. There was a significant correlation between fibrinogen level and angiographic loss index ( r =.41; P <.0001). Multivariate analysis confirmed that the fibrinogen level predicted restenosis with all definitions. Conclusions An independent relation exists between von Willebrand factor measured immediately after angioplasty and restenosis defined by the degree of intraluminal renarrowing. An elevated fibrinogen level during follow-up is a strong biochemical predictor of restenosis. Therefore, fibrinogen should be considered at least as an independent marker of restenosis and perhaps as a common risk factor for both spontaneous coronary atherosclerosis and postangioplasty restenosis, which is an accelerated form of atherosclerosis.