Prognostic value of lipoprotein(a) level in calcific aortic valve stenosis: insight from a prospective Chinese cohort
M Y Lu, Z F Li, Z Yin, X Li, L Bao, W J Zhang, F Luo, H Qiu, J J Li, K F Dou, X Wang, N Q WuAbstract
Background
Lipoprotein(a) [Lp(a)] is a genetic risk factor for the onset of calcific aortic valve stenosis (CAVS). However, whether elevated Lp(a) accelerates hemodynamic progression or independently predicts prognosis in Asian patients with established mild-to-moderate CAVS remains unclear.
Purpose
This study aims to investigate the association between baseline Lp(a) levels and both hemodynamic progression and clinical outcomes in a prospective Chinese cohort.
Methods
We conducted a prospective cohort study of mild-to-moderate CAVS patients defined as a peak aortic valve velocity (Vpeak) of 2.0–4.0 m/s. Patients with prior valve surgery, severe regurgitation, or significant comorbidities were excluded. Patients were stratified by baseline Lp(a) levels (cutoff: 30 mg/dL consistent with risk thresholds in Chinese populations). The primary endpoint was a composite of aortic valve replacement (AVR) or all-cause mortality. The secondary endpoint was hemodynamic progression, calculated as the annualized change in Vpeak [ΔVpeak/year]. Multivariable Cox proportional hazards and linear regression models were used to assess independent effects of Lp(a), adjusting for age, sex, hypertension, diabetes, dyslipidemia, significant valve calcification and baseline Vpeak. Kaplan-Meier curves with log-rank tests compared event-free survival between groups.
Results
A total of 243 participants were included (mean age 67.5 ± 11.2 years, 60% male), 96 patients (39.5%) had elevated Lp(a) (≥ 30 mg/dL). During a mean follow-up of 5.5 years, 117 composite events (AVR or death) occurred. Kaplan-Meier analysis showed significantly lower event-free survival in the high Lp(a) group (Log-rank P < 0.0001). In multivariable Cox regression, Lp(a) ≥ 30 mg/dL remained independently associated with a 2.5-fold increased risk of the primary outcome (adjusted HR 2.51, 95% CI 1.72–3.67, P < 0.001). In patients with long-term follow-up (> 5 years), elevated Lp(a) was identified as a significant independent predictor of an accelerated ΔVpeak/year (adjusted β = 0.059, P < 0.05). This prognostic value was particularly pronounced in patients aged < 65 years (adjusted HR 3.11) and those without significant baseline valve calcification (adjusted HR 2.63).
Conclusion
In this long-term prospective cohort of Chinese patients, elevated Lp(a) is a potent driver of AS progression and a strong independent predictor of adverse clinical events, especially in younger patients and early disease stages. These findings suggest that Lp(a) measurement should be integrated into risk stratification for mild-to-moderate AS and highlight Lp(a) lowering as a potential therapeutic target.The main results.