Association of lipoprotein(a) and MASLD in predicting carotid atherosclerosis in asymptomatic individuals: a large scale cross-sectional and longitudinal study.

BACKGROUND AND AIM: This study investigated the associations of Lipoprotein (a) [Lp(a)] and metabolic dysfunction-associated steatotic liver disease (MASLD) with carotid atherosclerosis (CAS) risk, both independently and in combination. METHODS AND RESULTS: We performed a multicenter cross-sectional study in participants without cardiovascular disease (CVD) (study 1, n = 61,139) and a longitudinal study in participants without CVD and CAS at baseline who underwent at least two health check-up exams with carotid ultrasound (study 2, n = 9720). Hepatic steatosis and liver fibrosis were assessed via abdominal ultrasonography and the fibrosis-4 (FIB-4) index, respectively. In study 1, among participants without MASLD, those with elevated Lp(a) (≥30 mg/dL) had a significantly higher risk of CAS as compared to those with Lp(a) < 30 mg/dL. During a median follow-up of 33 months in Study 2, 2309 (23.76%) of 9720 participants progressed to CAS. Baseline Lp(a) ≥30 mg/dL (adjusted HR = 1.67, 95% CI 1.52-1.83, P < 0.001) and MASLD (adjusted HR = 1.21, 95% CI 1.09-1.33, P < 0.001) were independent risk factors for CAS. In the stratified analysis, a joint effect of Lp(a) ≥30 mg/dL and MASLD on CAS risk was observed. Those with Lp(a) (≥30 mg/dL) and MASLD had a HR (95% CI) of 2.07 (1.76-2.43, P < 0.001) compared to those with Lp(a) < 30 mg/dL without MASLD, but there was no interaction (Pinteraction = 0.453). Meanwhile, the risk of CAS in participants with Lp(a) ≥30 mg/dL and FIB-4 ≥1.3 was 2.62 times higher than Lp(a) < 30 mg/dL and FIB-4<1.3. CONCLUSIONS: The combination of elevated Lp(a) and MASLD conferred a greater risk of CAS than either factor alone, demonstrating a joint cardiovascular risk profile.