All the authors would like to dedicate this paper to Professor George Miller, who died on 14 August 2006. We are grateful for the major contribution he made to this article, and would like to pay tribute to his commitment and contribution to the field of cardiovascular medicine. It was a great privilege to work with him.
The plasma kallikrein–kinin system and risk of cardiovascular disease in men
Article first published online: 5 JUL 2007
© 2007 International Society on Thrombosis and Haemostasis
Journal of Thrombosis and Haemostasis
Volume 5, Issue 9, pages 1896–1903, September 2007
How to Cite
GOVERS-RIEMSLAG, J. W. P., SMID, M., COOPER, J. A., BAUER, K. A., ROSENBERG, R. D., HACK, C. E., HAMULYAK, K., SPRONK, H. M. H., MILLER, G. J. and TEN CATE, H. (2007), The plasma kallikrein–kinin system and risk of cardiovascular disease in men. Journal of Thrombosis and Haemostasis, 5: 1896–1903. doi: 10.1111/j.1538-7836.2007.02687.x
- Issue published online: 5 JUL 2007
- Article first published online: 5 JUL 2007
- Received 9 March 2007, accepted 26 June 2007
- coronary heart disease;
- factor XII;
- plasma kallikrein–kinin system;
- risk factors
Summary. Background: The plasma kallikrein–kinin system (PKKS) has been implicated in cardiovascular disease, but activation of the PKKS has not been directly probed in individuals at risk of coronary heart disease (CHD) or stroke. Objective: To determine the involvement of the PKKS, including factor XI, in cardiovascular disease occurring in a nested case–control study from the Second Northwick Park Heart Study (NPHS-II). Methods and results: After a median follow-up of 10.7 years, 287 cases of CHD and stroke had been recorded and 542 age-matched controls were selected. When FXIIa–C1 esterase inhibitor (C1-inhibitor) concentrations were divided into tertiles (lowest tertile as reference), the odds ratios (ORs) at 95% CIs for CHD were 0.52 (0.34–0.80) in the middle tertile and 0.73 (0.49–1.09) in the highest tertile (P = 0.01 for the overall difference; P = 0.01 for CHD and stroke combined). For kallikrein–C1-inhibitor complexes, the ORs for stroke were 0.29 (0.12–0.72) and 0.67 (0.30–1.52) in the middle and high tertiles, respectively (P = 0.02). FXIIa–C1-inhibitor and kallikrein–C1-inhibitor complexes were negatively related to smoking and fibrinogen (P < 0.005). FXIa–inhibitor complexes correlated strongly with FXIIa–inhibitor complexes. Conclusions: Lower levels of inhibitory complexes of the PKKS enzymes and particularly of FXIIa contribute to the risk of CHD and stroke in middle-aged men. This observation supports the involvement of the PKKS in atherothrombosis.