AIMS: To assess if adiposity measures such as waist-to-hip ratio (WHR) modify the relationship of lipoprotein (a) [Lp(a)] with atherosclerotic cardiovascular disease (ASCVD). METHODS: 4652 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) were grouped as follows: Lp(a) <
50 mg/dl and WHR <
90th percentile(pct) (reference)
Lp(a) <
50 mg/dl and WHR ≥90th pct
Lp(a) ≥ 50 mg/dl and WHR <
90th pct
and Lp(a) ≥50 mg/dl and WHR ≥90th pct. Cox proportional hazard models assessed the relationship of Lp(a) and WHR with time to ASCVD events. RESULTS: Compared to the reference group, isolated elevated Lp(a) ≥ 50 mg/dl or WHR ≥90th pct were not significantly associated with risk of ASCVD (hazard ratio (HR), 1.15, 95 % confidence interval (CI): 0.94-1.39) and (HR, 1.14, 95 % CI: 0.92-1.41), respectively. In contrast, the combination of elevated Lp(a) ≥50 mg/dl and WHR ≥90th pct was associated with ASCVD risk (HR, 2.34, 95 % CI: 1.61-3.40). Lp(a) ≥50 mg/dl was not significantly associated with ASCVD risk in the 1st and 2nd tertile of WHR (HR, 1.06, 95 % CI: 0.72-1.48and HR, 1.08, 95 % CI: 0.79-1.48, respectively). However, Lp(a) ≥50 mg/dl was significantly associated with ASCVD risk in the highest tertile of WHR (HR, 1.60, 95 % CI: 1.23-2.09). (Interaction p = 0.01). Body mass index (BMI) and Lp(a) combinations resulted in similar greater risks of ASCVD in the highest risk category (HR, 1.33, 95 % CI: 1.00-1.77), without a significant interaction (p = 0.99). CONCLUSIONS: In MESA, WHR significantly modifies the risk of ASCVD associated with Lp(a). Measures of abdominal adiposity may further refine the cardiovascular risk in individuals with elevated Lp(a).