Our main finding in this study is that an increased AST/ALT ratio could predict functional status decline in HFrEF patients, as shown by the less favorable cardiac profile in Group-2.
Moreover, the predictive value of the AST/ALT ratio is independent after adjustment for age, BMI, hypertension, diabetes mellitus, and NT-proBNP.
Our explanation for this main finding is multi-factorial; it is known that AST is released from many tissues, including the myocardium and the liver, while ALT is only released from the liver. Therefore, more severe myocardial pathology would lead to an anticipated increase in the AST/ALT ratio [21]. Additionally, higher the AST/ALT ratio, greater the probability of hepatic fibrosis, which is associated with cardiovascular disease (CVD) pathogenesis through different mechanisms, including increased plasma inflammatory mediators, insulin resistance, oxidative stress, and metabolic syndrome [22].
Based on their medical records, our patients did not have any primary hepatic disorders to justify the increased AST/ALT ratio. It is known that an increased AST/ALT ratio is also caused by alcoholic liver disease [23]. However, our records did not include those with alcohol drinking habits.
Hypoxic hepatitis is another cause of increased AST/ALT ratio in its early phase; however, our data showed that ALT and AST values were far less than those required for diagnosing classic hypoxic hepatitis [24].
Previous research has focused on the value of hepatic transaminases as CVD predictors. Lazo et al. [25] showed that elevated levels of liver transaminases were significantly correlated with the cardiac biomarkers; troponin T and NT-proBNP. Consequently, they concluded that liver transaminases could be used as predictors in patients at risk of CVD. However, they did not enroll heart failure patients in their study, as they were only concerned with predicting subclinical myocardial injury.
Yokoyama et al. [26] recently concluded that an increased AST/ALT ratio positively correlates with NT-proBNP levels, yet their study was not specific for HFrEF patients.
Zoppini et al. [27] studied patients with type 2 diabetes mellitus and found that the AST/ALT ratio positively correlated with CVD mortality; however, as in the above studies, they did not include HFrEF patients.
On the other hand, there are some studies that did not show significant correlation between ALT and CVD, as seen by both Ruhl et al. [28] and Fraser et al. [29] However, they did not include AST or the AST/ALT ratio in their correlations with CVD, which could be an explanation for the non-significant result.
In our study, we found that 0.9 was the best predictive cut-off value of the AST/ALT ratio when considering functional severity in HFrEF patients. Our finding was in agreement with the finding of Long et al. [30] that 1 was the best cut-off value of the AST/ALT ratio that predicted cardio-metabolic risk in their study.
To our knowledge, our study is the first in Saudi Arabia and other Arabian countries to correlate the AST/ALT ratio with functional severity in HFrEF patients. Consequently, we could not find comparable AST/ALT cut-off values in the Arab population.
Our cut-off value could be very helpful in monitoring the functional status of HFrEF patients in primary healthcare settings and accordingly adjusting their follow-up investigations/management plans.