The association of MASLD, lipoprotein(a) and long-term outcomes: Results from the multi-ethnic study of atherosclerosis.

Background

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Aims

Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with an increased risk of cardiovascular events and frequently coexists with other atherosclerosis risk factors, including obesity, metabolic syndrome, sleep apnea, and insulin resistance. Lipoprotein(a) [Lp(a)] is a low-density lipoprotein-like particle bound to apolipoprotein(a), that has been studied to have pro-thrombotic and pro-inflammatory properties and is an established independent risk factor for atherosclerotic disease. However, the association between MASLD and Lp(a) and their impact on long-term clinical outcomes have not been evaluated previously.

Methods

We performed a secondary analysis of the prospectively collected data from the Multi-Ethnic Study of Atherosclerosis (MESA). Baseline MASLD was defined as either a liver-to-spleen (L:S) attenuation ratio less than 1.0 or liver attenuation <40 HU on computed tomography (CT) imaging, excluding individuals with excess alcohol consumption (>15 drinks/week for men and > 10 drinks/week for women) and the presence of at least one cardiometabolic risk factor, including elevated BMI or waist circumference, type 2 diabetes mellitus, hypertension, hypertriglyceridemia, or reduced HDLC. Baseline Lp(a) levels were measured using a latex-enhanced turbidimetric immunoassay (Denka Seiken, Tokyo, Japan).

Results

Median Lp(a) levels were significantly lower in those with baseline MASLD compared to those without MASLD (11.9 vs 18.1 mg/dL, p-value <0.001). Individuals with MASLD and low Lp(a) levels (≤ 50 mg/dL) had a significantly higher risk of all-cause mortality compared to those without MASLD and with low Lp(a) (HR 1.28; 95% CI: 1.025-1.56), independent of traditional cardiovascular risk factors. Additionally, individuals with baseline MASLD and elevated Lp(a) were independently associated with an increased risk of hard cardiovascular disease (HR 2.07, 95% CI: 1.39-3.09), compared to individuals without MASLD and with Lp(a) ≤ 50 mg/dL.

Conclusions

MASLD is independently associated with lower levels of Lp(a). Patients with baseline MASLD and elevated levels of Lp(a) exhibit nearly twice the risk of cardiovascular diseases as compared to the cohort with no MASLD and lower Lp(a) levels. Importantly, even in the absence of elevated Lp(a), MASLD is associated with increased all-cause mortality. These findings suggest that while Lp(a) is a strong contributor to cardiovascular risk, MASLD itself is an independent determinant of long-term mortality.