Photo Credit: Mohammed Haneefa Nizamudeen

Liver fibrosis in MASH is linked with elevated risk for cardiovascular events, according to an analysis of NHANES study data.

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Metabolic dysfunction-associated steatohepatitis with liver fibrosis is associated with an elevated risk for cardiovascular events, according to a recent analysis of 2017–2020 NHANES data that was published in PLOS One.

“MASH is an increasingly significant public health concern in the US. Current estimates of MASH in US adults suggest a prevalence of 5% to 6%, but it has been observed to range from approximately 1% to 12%,” Jonathan J. Woolley, MS, and colleagues wrote.

According to the researchers, the prevalence of MASH has increased in recent years and is likely to continue. MASH can result in cirrhosis, liver failure, and liver cancer.

“Estimation of excess cardiovascular-event risk associated with MASH, as well as addressing potential confounding of type 2 diabetes, may help inform clinical understanding of the relationship between MASH and cardiovascular disease,” Woolley and colleagues wrote. “Accordingly, this analysis sought to estimate the association of MASH with risk of a primary cardiovascular event, independent of diabetes status.”

The researchers performed a cross-sectional analysis of pre-COVID pandemic data from NHANES between 2017 and March 2020. Because of the pandemic, the 2019-2020 survey cycle was not conducted; however, Woolley and colleagues noted that the National Center for Health Statistics combined data from early 2020 with data from the prior cycle, 2017-2018, to develop an estimate.

Woolley and colleagues matched 125 patients with MASH to 2,585 controls according to age, sex, race or ethnicity, and diabetes status. The investigators used weighted logistic regression analysis, with elevated predicted cardiovascular risk as the dependent variable and indicators of MASH or fibrosis progression as independent variables.

Link Between MASH Fibrosis and CVD Risk

Patients with MASH were more likely to have obesity compared to controls (85% vs 42%), the researchers reported. They were also more likely to have hypertension (65% vs 42%), as well as low HDL cholesterol (57% vs 31%). Patients with MASH were less likely than controls to be current smokers (7% vs 18%, P<0.01 for all). According to the researchers, Three-fourths of the patients with MASH had significant fibrosis, compared with 10% of the controls (P<0.01).

The researchers reported that people with MASH with significant fibrosis had an elevated 10-year cardiovascular disease risk compared to controls. However, they noted that this association was only significant for the Pooled Cohort Equations analysis (odds ratio [OR]=2.34; 95% CI, 1.25-4.36) and not for the Framingham Risk Score (OR=1.55; 95% CI, 0.68-3.56).

According to Woolley and colleagues, MASH with any stage of fibrosis trended toward significance in its association with cardiovascular events in both the PCE (OR=1.66, 95% CI: 0.96-2.86) and FRS analyses (OR=1.23, 95% CI: 0.58-2.58).

The researchers added that when they restricted their analysis to patients younger than 65 years, these associations remained significant and occurred at a greater magnitude.

Association Observed Regardless of Diabetes

Woolley and colleagues acknowledged that the study was limited by the fact that the NHANES survey only recently began including VCTE measurements, meaning they could not use data from earlier cycles of the survey’s conduct, as well as the cross-sectional design, possible limitations in discerning MASH and fibrosis status in the data, and the fact that certain variables came from self-reported data and therefore may be incomplete or misleading.

“In this study, a significant association between MASH and primary CV event risk was observed, independent of diabetes, particularly in adults between 30 and 64 years of age,” Woolley and colleagues concluded. “The incremental risk was greater for estimated fibrosis stages F2-F4, suggesting the importance of accounting for fibrosis stage in predicting CV risk. This analysis suggests that MASH with significant fibrosis confers increased CV risk above that associated with diabetes.”

Key Takeaways 

• Estimating cardiovascular event risk associated with MASH and the potential confounding of type 2 diabetes can inform clinical understanding of the relationship between MASH and cardiovascular disease.
• Woolley and colleagues found that patients with MASH and significant fibrosis had an increased 10-year risk for cardiovascular disease versus controls.
• The significant association between MASH and primary cardiovascular event risk was observed independent of diabetes status.
• The findings underscore the importance of accounting for fibrosis in predicting cardiovascular risk, as such risk increased in step with fibrosis stage.