Acute reduction of lipoprotein(a) by tissue-type plasminogen activator.

BACKGROUND: Lipoprotein(a) Lp(a) is a low density lipoprotein-like particle whose apolipoprotein B (apo B) moiety is disulfide-linked to apo(a), a plasminogen-like inhibitor of fibrinolysis in vitro. We hypothesized that plasma concentrations of Lp(a) are acutely affected by intravenous tissue-type plasminogen activator (t-PA). METHODS AND RESULTS: Patients with unstable angina were randomized to receive either intravenous t-PA (n = 15) or placebo (n = 11). Two-way ANOVA using repeated measures revealed a significant effect of t-PA on concentrations of Lp(a) (p = 0.026). There was a 48% fall in Lp(a) from baseline concentrations in the t-PA group at 12 hours (p = 0.031) but not at 72 hours. Lp(a) in the placebo group was unchanged. CONCLUSIONS: We conclude that t-PA produces a sharp and substantial but reversible reduction in plasma Lp(a). These data suggest that Lp(a) concentration is not as static in vivo as had been believed and might be acutely modifiable through some mechanism that induces its removal from the freely circulating state.