Abstract 4138935: Lp(a) and LDL-Cholesterol Interaction Association with Aortic Valve Calcium and Severe Aortic Stenosis

Introduction: Calcific aortic valve disease (CAVD) is the most common valvular disorder with aortic valve calcification (AVC) as a principal underlying mechanism. Low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) [Lp(a)] are risk factors for AVC and aortic stenosis (AS). However, whether an interaction between LDL-C and Lp(a) exists in CAVD is not well studied, which may have implications for trials investigating novel Lp(a) lowering therapies. Methods: Cardiac computed tomography (CT) was used to quantify AVC in participants free of known cardiovascular disease at Multi-Ethnic Study of Atherosclerosis (MESA) Visit 1 and subsequent visits. Incident severe AS was adjudicated through chart review of hospital visits and echocardiogram data. Participants were categorized into four groups based on the cutpoints of LDL-C 160mg/dL and Lp(a) 50mg/dL. We examined the association of the four LDL-C and Lp(a) groups with incident AVC and incident severe AS using multivariable adjusted Cox Hazard models. We also tested for the presence of a multiplicative interaction between LDL-C and Lp(a). Results: In this analysis, 6,603 participants were included. The mean age of participants was 62 years old and 52% were women. Incident AVC occurred among 416 participants and during a median follow-up time of 17 years, 84 participants developed severe AS. At baseline, AVC >0 was present in 11.9% of participants with LDL-C <160mg/dL and Lp(a) <50mg/dL compared to 21.6% participants with LDL-C ≥160mg/dL and Lp(a) ≥50mg/dL (p=<0.01). Compared to participants with LDL-C <160 mg/dL and Lp(a) <50mg/dL, those with LDL-C ≥160 and Lp(a) ≥50 mg/dL had a 2.3-fold higher risk for incident AVC [HR 2.27 (1.34-2.85)] ( Table 1) . There was a statistically significant multiplicative interaction between Lp(a) and LDL-C as continuous variables for both incident AVC (p=0.002) and severe AS (p=0.036). Conclusion: Participants with both an elevated LDL-C and Lp(a) had the highest risk for incident AVC. There was a significant interaction between LDL-C and Lp(a) for both incident AVC and incident AS. Thus, individuals with elevated LDL-C and Lp(a) may be most likely to benefit from novel Lp(a) lowering therapies and/or combined LDL-C and Lp(a) lowering.