Association of Lipoprotein(a) With Severe Degenerative Aortic Valve Stenosis

Background: Lipoprotein(a) (Lp[a]) is associated with the development of aortic valve calcification.

Objectives: The aim of this study was to evaluate the association between the serum level of Lp(a) and the development of severe degenerative aortic stenosis (AS) and subsequent aortic valve replacement (AVR).

Methods: A total of 44,742 patients with Lp(a) measurements and echocardiography at baseline evaluation between 2000 and 2020 were included from a single tertiary heart center. The primary outcome was the development of severe degenerative AS, defined as a transaortic maximal velocity of ≥4.0 m/s.

Results: During a median follow-up period of 6.8 years (Q1-Q3: 2.3-12.4 years), severe degenerative AS was diagnosed in 472 patients (1.1%), and subsequent AVR was performed in 387 patients (0.9%). Lp(a) levels were associated with risk for severe degenerative AS, with levels of 30 to 50, 50 to 100, and >100 mg/dL demonstrating adjusted HRs of 1.02 (95% CI: 0.78-1.34; P = 0.88), 1.18 (95% CI: 0.91-1.53; P = 0.22), and 1.96 (95% CI: 1.31-2.94; P = 0.001) compared to <30 mg/dL. Similarly, the risk for AVR due to severe degenerative AS was significantly associated with higher levels of Lp(a) (>100 mg/dL) (adjusted HR: 2.05; 95% CI: 1.31-3.19; P = 0.002). Such associations were not observed in the development of severe bicuspid (P = 0.63) or rheumatic (P = 0.96) AS.

Conclusions: Lp(a) levels >100 mg/dL were significantly associated with risk for severe degenerative AS and subsequent AVR, regardless of the baseline severity of AS. Such associations were not observed in other etiologies of severe AS.