OC 37.3 - Increased concentrations of lipoprotein (a) as a factor enhancing hypofibrinolysis in patients with severe aortic stenosis

Background: In severe aortic stenosis (AS) serum level of lipoprotein a [Lp(a)] was a predictor of prolonged clot lysis time (CLT), however the mechanism of this phenomenon has not been elucidated.

Aims: We investigated the impact of increased Lp(a) concentration on the level of proteins involved in fibrinolysis.

Methods: We enrolled 75 patients aged 66±9 years with severe AS defined as mean transvalvular pressure gradient (PGmean)≥40mmHg, peak transvalvular velocity (Vmax)≥4.0m/s and aortic valve area (AVA)≤1cm2 including 50 with Lp(a) concentrations ≥50mg/dL and 25 with Lp(a) < 50mg/dL of similar age and sex. Routine laboratory assays were used to assessed Lp(a), glucose, creatinine, lipid profile, CRP and fibrinogen. Human tissue plasminogen activator (tPA), plasminogen activator inhibitor type 1 (PAI-1) antigen and thrombin activatable fibrinolysis inhibitor (TAFI) levels were assayed using ELISAs. CLT was determined turbidimetrically. The Ethical Committee approved the study and all participants provided written consent.

Results: For AS patients defined as high Lp(a) group the median Lp(a) concentrations was >81mg/dL and >7mg/dL for subjects defined as low Lp(a) group. AS patients with high Lp(a) had 54% higher PAI-1, 14% higher TAFI and 12% prolonged CLT compared to subjects with low Lp(a) (all p< 0.01). There were no intergroup differences regarding other laboratory parameters. Only in high Lp(a) group we observed association between Lp(a) concentrations and PAI-1 (Fig.1A) and TAFI levels (Fig.1B), but not with tPA (p=0.08). Increased Lp(a) was associated with CLT (r=0.62, p< 0.0001). Elevated Lp(a) correlated with AS severity reflected by Vmax (r=0.55, p< 0.0001), PGmax (r=0.56, p< 0.0001) and PGmean (r=0.46, p=0.0007), but not with AVA (p=0.07). Moreover, increased Lp(a) weakly correlated with fibrinogen (r=0.3, p=0.04). There were no associations of Lp(a) with other laboratory parameters in both groups.

Conclusion(s): Elevated Lp(a) concentration is associated with increased levels of fibrinolysis inhibitors leading to hypofibrinolysis.
This work was supported by NCN (UMO-2021/41/N/NZ5/03323).