In a secondary analysis of the Multi-Ethnic Study of Atherosclerosis (MESA), adults with metabolic dysfunction-associated steatotic liver disease (MASLD) — defined by CT-measured liver-to-spleen attenuation ratios — had paradoxically lower median Lp(a) levels than those without MASLD (11.9 vs 18.1 mg/dL, p<0.001). Despite this, MASLD paired with elevated Lp(a) (>50 mg/dL) was associated with a hazard ratio of 2.07 (95% CI: 1.39–3.09) for hard cardiovascular events. Even patients with MASLD and low Lp(a) faced a 28% higher all-cause mortality risk versus healthy comparators.
The finding that MASLD lowers Lp(a) — likely through hepatic overproduction of apolipoprotein(a) being outcompeted by general liver dysfunction — is biologically provocative and counterintuitive. It means clinicians cannot rely on a normal Lp(a) reading to reassure a MASLD patient of low cardiovascular risk. The study's strength lies in MESA's large, prospective, multi-ethnic design with CT-confirmed hepatic steatosis rather than self-report. Limitations include that this is a secondary observational analysis — causality cannot be established — and Lp(a) was measured at a single baseline timepoint. Practically, this reinforces that MASLD warrants aggressive cardiometabolic risk management regardless of Lp(a) level, and that the rare patient with both conditions may need particularly close cardiovascular surveillance. This finding is confirmatory of MASLD's cardiovascular danger but genuinely novel in quantifying the Lp(a) interaction.