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Epidemiology

In MESA, elevated Lp(a) only raises ASCVD risk when waist-to-hip ratio is also high (Prog Cardiovasc Dis 2025)

Original title: Waist to hip ratio modifies the cardiovascular risk of lipoprotein (a): Insights from MESA

Prog Cardiovasc Dis · · 7

Ahmad MI, Chevli PA, Mirzai S, Rikhi R, Bhatia H, Pagidipati N, Blumenthal R, Razavi AC, Ruddiman K, Spitz JA, Nasir K, Shapiro MD

In 4,652 participants from the Multi-Ethnic Study of Atherosclerosis (MESA), isolated elevated Lp(a) (50 mg/dL or above) or isolated high waist-to-hip ratio (WHR, 90th percentile or above) were not significantly associated with atherosclerotic cardiovascular disease (ASCVD) risk on their own (hazard ratio 1.15, 95% CI 0.94-1.39, and hazard ratio 1.14, 95% CI 0.92-1.41, respectively). The combination of elevated Lp(a) and high WHR, however, was strongly associated with ASCVD (hazard ratio 2.34, 95% CI 1.61-3.40). Elevated Lp(a) showed no significant association with ASCVD in the first or second WHR tertile, but became significant in the highest WHR tertile (hazard ratio 1.60, 95% CI 1.23-2.09; interaction p = 0.01). A similar, though non-significant, interaction pattern was seen with BMI. The findings suggest measuring abdominal adiposity alongside Lp(a) could refine cardiovascular risk assessment in people with elevated Lp(a).

Read the paper (DOI)PubMed

Original abstract

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).

epidemiology

Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.