BACKGROUND: The fibrinolytic system is part of the defense against thrombotic and cardiovascular events, but so far no study has shown that clinical measurements of fibrinolytic key components such as tissue plasminogen activator (t-PA) or plasminogen activator inhibitor type 1 (PAI-1) have any predictive value beyond 3 years. METHODS AND RESULTS: In 1983 through 1985, 213 consecutive patients with angina pectoris and angiographically verified coronary artery disease were sampled, and the mass concentration of t-PA and the activity of PAI-1 were measured in citrated plasma samples. At a mean follow-up time of 7 years, the all-cause mortality was checked. No patient was lost to follow-up. The data were analyzed by Cox regression, and t-PA mass concentration was found to be the only laboratory risk factor significantly related to mortality in all patients (P < .022) and also in the major subgroup (78% of all patients) subjected to coronary bypass surgery (P < .027). In the latter subgroup, body mass index was also related to mortality. CONCLUSIONS: An increased mass concentration of t-PA is a new risk factor of long-term mortality in patients with angina pectoris and coronary artery stenosis. This paradoxical effect probably reflects increased t-PA levels attributable to enzyme inhibitor complex formation in subjects with increased plasma levels of t-PA inhibitors.
BACKGROUND: The fibrinolytic system is part of the defense against thrombotic and cardiovascular events, but so far no study has shown that clinical measurements of fibrinolytic key components such as tissue plasminogen activator (t-PA) or plasminogen activator inhibitor type 1 (PAI-1) have any predictive value beyond 3 years. METHODS AND RESULTS: In 1983 through 1985, 213 consecutive patients with angina pectoris and angiographically verified coronary artery disease were sampled, and the mass concentration of t-PA and the activity of PAI-1 were measured in citrated plasma samples. At a mean follow-up time of 7 years, the all-cause mortality was checked. No patient was lost to follow-up. The data were analyzed by Cox regression, and t-PA mass concentration was found to be the only laboratory risk factor significantly related to mortality in all patients (P < .022) and also in the major subgroup (78% of all patients) subjected to coronary bypass surgery (P < .027). In the latter subgroup, body mass index was also related to mortality. CONCLUSIONS: An increased mass concentration of t-PA is a new risk factor of long-term mortality in patients with angina pectoris and coronary artery stenosis. This paradoxical effect probably reflects increased t-PA levels attributable to enzyme inhibitor complex formation in subjects with increased plasma levels of t-PA inhibitors.
Authors: J A Schoenhard; F W Asselbergs; K A Poku; S A Stocki; S Gordon; D E Vaughan; N J Brown; J H Moore; Scott M Williams Journal: Hum Genet Date: 2008-10-25 Impact factor: 4.132
Authors: Folkert W Asselbergs; Scott M Williams; Patricia R Hebert; Christopher S Coffey; Hans L Hillege; Harold Snieder; Gerjan Navis; Douglas E Vaughan; Wiek H van Gilst; Jason H Moore Journal: Hum Genet Date: 2007-06-26 Impact factor: 4.132