Lp(a) May Be an Unreliable Cardiovascular Risk Estimator in NASH

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Advanced non-alcoholic steatohepatitis may be linked to low serum lipoprotein(a) levels

According to the results of new study published in Atherosclerosis, advanced non-alcoholic steatohepatitis (NASH) appears to be associated with low serum lipoprotein(a) [Lp(a)] levels. They conclude that Lp(a) levels may not be useful when evaluating cardiovascular risk in individuals with NASH.

While Lp(a) is typically serves as a risk factor for cardiovascular disease, the relationship between serum Lp(a) and advanced NASH, which is associated with increased risk of cardiovascular disease, is unknown.

To address this knowledge gap, Konishi and colleagues examined the relationship between serum Lp(a) levels and biopsy-proven non-alcoholic fatty liver disease (NAFLD). They enrolled patients at the Ehime University Hospital in Japan between February 2011 and January 2019. All participants underwent comprehensive blood chemistry tests and liver biopsy for histological examination according to the NAFLD Activity Score (NAS).

In total, 170 patients with NAFLD (male/female N, 80/90) and a median age of 59 (IQR, 44.3–68) were included in the study. The median serum Lp(a) level was 8.2 mg/dL (range, 1.7-123.8 mg/dL).

Additional measures (median) included: serum levels of total cholesterol (TC, 4.9 mmol/L; range, 2.6-8.7 mmol/L), high-density lipoprotein cholesterol (HDL-C, 1.1 mmol/L; range, 0.6-3.6 mmol/L), low-density lipoprotein cholesterol (LDL-C, 3 mmol/L; range, 0.9-6.4 mmol/L), and triglycerides (TG, 1.4 mmol/L; range, 0.4-6.3 mmol/L).

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Patients with advanced (stage 3-4) fibrosis had lower levels of serum Lp(a) than patients with non-advanced (stage 0-2) fibrosis (P <.05). After adjusting for covariates (age, sex, body mass index, and blood chemistry components), the investigators found a significant inverse association between advanced fibrosis and serum Lp(a) levels (P <.01).

While the level of Lp(a) was inversely associated with NAS of 5-8, which indicates NASH, no significant association was found between Lp(a) levels and NAS adjusted for covariates and the use of lipid-lowering agents (adjusted odds ratio, 0.849; 95% CI:0.511-1.396; P = .552).

Limitations of the study include limited generalizability (only Japanese participants at a single center), variability in Lp(a) measures (depending on the assay of choice), and a lack of data on diet and exercise.

“Therefore, in advanced NASH, it is difficult to evaluate the risk of cardiovascular disease using only lipid markers, and it is necessary to consider other risk factors such as age, BMI, and HbA1c level, as well as the use of imaging examination,” wrote the authors.

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Konishi K, Miyake T, Furukawa S, et al. Advanced fibrosis of non-alcoholic steatohepatitis affects the significance of lipoprotein(a) as a cardiovascular risk factor. Atherosclerosis. 2020;299:32-37. doi:10.1016/j.atherosclerosis.2020.02.026