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

Abstract

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.

Keywords: Lp(a); aortic stenosis; lipids; lipoproteins.

Graphical abstract

Figure 1

Cumulative Incidences of AS Development and Subsequent AVR According to Lp(a) Levels The study compared the cumulative incidences of severe degenerative aortic stenosis (AS) development and subsequent aortic valve replacement (AVR) on the basis of lipoprotein(a) (Lp[a]) levels. As the serum level of Lp(a) increases, there is a corresponding increase in the occurrence of severe AS development and subsequent AVR. Kaplan-Meier curves illustrate the cumulative incidence of (A) severe degenerative AS and (B) AVR.

Figure 2

Adjusted HRs According to Lp(a) Levels These curves depict the adjusted HRs for (A) the development of severe degenerative AS and (B) AVR. Restricted cubic spline regression models were used to adjust for confounding factors, including age, sex, smoking status, body mass index, history of hypertension, history of diabetes, total cholesterol, statin therapy, serum creatinine, and concomitant coronary artery disease. Solid lines indicate HRs, and shaded areas indicate 95% CIs. The risk for severe AS and subsequent AVR increased with increasing serum Lp(a) levels. Abbreviations as in Figure 1.

Figure 3

Incidence Rate Comparisons According to Baseline Severity A high Lp(a) level (>100 mg/dL) was significantly associated with a higher risk for severe degenerative aortic stenosis (AS) development, irrespective of baseline AS severity (P = 0.63 for interaction).

Central Illustration

Association of Lp(a) With Severe Degenerative Aortic Stenosis Development and Aortic Valve Replacement Lipoprotein(a) (Lp[a]) levels >100 mg/dL were significantly associated with risk for severe degenerative aortic stenosis and subsequent aortic valve replacement, even after adjusting for confounding factors, including age, sex, smoking status, body mass index, history of hypertension, history of diabetes, low-density lipoprotein corrected for Lp(a), high-density lipoprotein, statin therapy, serum creatinine, and concomitant coronary artery disease.