Association of the Aspartate Aminotransferase to Alanine Aminotransferase Ratio with BNP Level and Cardiovascular Mortality in the General Population: The Yamagata Study 10-Year Follow-Up

Abstract

Background. Early identification of high risk subjects for cardiovascular disease in health check-up is still unmet medical need. Cardiovascular disease is characterized by the superior increase in aspartate aminotransferase (AST) to alanine aminotransferase (ALT). However, the association of AST/ALT ratio with brain natriuretic peptide (BNP) levels and cardiovascular mortality remains unclear in the general population. Methods and Results. This longitudinal cohort study included 3,494 Japanese subjects who participated in a community-based health check-up, with a 10-year follow-up. The AST/ALT ratio increased with increasing BNP levels. And multivariate logistic analysis showed that the AST/ALT ratio was significantly associated with a high BNP (≥100 pg/mL). There were 250 all-cause deaths including 79 cardiovascular deaths. Multivariate Cox proportional hazard regression analysis revealed that a high AST/ALT ratio (>90 percentile) was an independent predictor of all-cause and cardiovascular mortality after adjustment for confounding factors. Kaplan-Meier analysis demonstrated that cardiovascular mortality was higher in subjects with a high AST/ALT ratio than in those without. Conclusions. The AST/ALT ratio was associated with an increase in BNP and was predictive of cardiovascular mortality in a general population. Measuring the AST/ALT ratio during routine health check-ups may be a simple and cost-effective marker for cardiovascular mortality.

Figure 1

The receiver operating characteristics curve to predict high BNP levels. The area under the curve for the AST/ALT ratio was significantly greater than for AST and ALT. ALT, alanine transaminase; AST, aspartate transaminase; BNP, brain natriuretic peptide.

Figure 2

The association between the AST/ALT ratio and BNP level. The AST/ALT ratio was increased with increasing BNP levels (Kruskal-Wallis test, P < 0.0001). ALT, alanine transaminase; AST, aspartate transaminase; BNP, brain natriuretic peptide.

Figure 3

The association between the AST/ALT ratio and log BNP, log H-FABP, eGFR, and BMI. ALT, alanine transaminase; AST, aspartate transaminase; BMI, body mass index; BNP, brain natriuretic peptide; eGFR, estimated glomerular filtration rate; H-FABP, heart type fatty acid binding protein.

Figure 4

The association between the AST/ALT ratio and survival ratio. ALT, alanine transaminase; AST, aspartate transaminase.

Figure 5

Kaplan-Meier analysis to predict all-cause and cardiovascular death between subjects with a high and low AST/ALT ratio. ALT, alanine transaminase; AST, aspartate transaminase.