Association of liver related biomarkers with incident cardiovascular disease and all-cause mortality in the Hispanic community health study/study of Latinos (HCHS/SOL), a population-based cohort study

Abstract

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) increases risk of cardiovascular disease (CVD). Despite the high prevalence of MASLD among Hispanic populations, there is a scarcity of research on the associations between non-invasive markers of liver disease and incident CVD and all-cause mortality. In this study we investigated the association of liver related biomarkers with CVD events and all-cause mortality in a population based Hispanic/Latino cohort.

Methods: We included 15,216 participants from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) aged 18-74 years with no pre-existing CVD. The composite outcome combined incident CVD and all-cause mortality. Having "elevated ALT/AST" was defined as ALT > 40 IU/mL or AST > 37 IU/mL for males, and ALT or AST > 31 IU/mL for females. We estimated adjusted hazard ratios (HR) and 95% confidence intervals (CI) relating our composite outcome to elevated ALT/AST, FIB-4 and MASLD. Using interaction terms, we assessed whether the relationship between elevated ALT/AST and the composite outcome differed by MASLD status.

Results: The study population was 40 years old on average, 52.7% female and had 740 CVD or all-cause mortality events. Elevated FIB-4 had the strongest association with incident CVD or all-cause mortality (comparing FIB-4 > 2.67 versus ≤ 2.67, HR:3.47; CI:2.34-5.14). Elevated AST was found to be associated with incident CVD or all-cause mortality (HR:1.53; CI:1.14-2.05). MASLD was not associated with incident CVD or all-cause mortality (HR:1.14; CI: 0.94-1.40), but it was associated with incident CVD alone (HR:1.69; CI:1.19-2.39). The relationship between elevated ALT/AST and incident or all-cause mortality was modified by MASLD, such that the strongest association between elevated ALT/AST and incident CVD or all-cause mortality was in the absence of MASLD (HR:1.95; CI:1.20-3.18).

Conclusions: Among Hispanic adults FIB-4 was strongly associated with CVD or all-cause mortality and among persons without MASLD, elevated ALT/AST were associated with CVD or all-cause mortality.

Keywords: All-cause Mortality; Cardiovascular Disease (CVD); FIB-4; Liver Enzymes; MASLD.

Fig. 1

Hispanic Community Health Study/Study of Latinos (HCHS/SOL) participant flow diagram. CVD: Cardiovascular disease. Prevalent CVD at baseline: defined as self-reported coronary heart disease (electrocardiogram indicating major Q wave abnormalities or minor Q, QS waves with ST, T abnormalities, self-report myocardial infarction, balloon angioplasty, stent, or bypass surgery), stroke or heart failure

Fig. 2

Elevated enzymes prevalence with standard error bars among those who developed CVD or all-cause mortality compared to those who did not develop CVD or all-cause mortality. ALT: Alanine aminotransferase AST: Aspartate aminotransferase; CVD: Cardiovascular disease; GGT: Gamma-glutamyl transpeptidase. Elevated ALT were values above 31 IU/mL for women and above 40 IU/mL for men. Elevated AST were values above 31 IU/mL for women and above 37 IU/mL for men. Elevated GGT were values above 36 U/L. Elevated FIB-4 were values indicative of high fibrosis (>2.67)