Metabolic biomarkers related to cardiac dysfunction in metabolic-dysfunction-associated fatty liver disease: a cross-sectional analysis

Abstract

Introduction Hepatic steatosis is associated with cardiac systolic and diastolic dysfunction. Therefore, we evaluated metabolites and their potential cardiovascular effects in metabolic-dysfunction-associated fatty liver disease (MAFLD). Materials and methods We conducted a cross-sectional study involving 75 participants (38 MAFLD and 37 controls). Hepatic steatosis was confirmed by hepatic ultrasonography and SteatoTestTM. Cardiac function was assessed using echocardiography. Metabolomic analysis was conducted using ultra-high-performance liquid chromatography–mass spectrometry. Results The median age for participants’ age was 45 (IQR 30–56.5), with gender distribution of 35 males and 40 females. MAFLD patients had lower levels of glycyl tyrosine (p-value < 0.001), lysophosphatidylcholine (LPC) (18:2/0:0) (p-value < 0.001), LPC (22:6) (p-value < 0.001), and ceramide (Cer) (d18:0/23:0) (p-value 0.003) compared to controls. MAFLD patients presented lower left ventricular ejection fraction (LVEF), E/A ratio, E/e′ ratio, and average global longitudinal strain (GLS) values, with a p-value of 0.047, <0.001, 0.008, and <0.001, respectively. Decreased glycyl tyrosine levels were significantly correlated with reduced LVEF, even after performing multiple linear regression with 95% CI (1.34–3.394, p-value < 0.001). Moreover, decreased LPC (18:2/0:0) levels remained significantly associated with E/A ratio, even after adjusting for confounding factors with 95% CI (0.008–0.258, p-value = 0.042). Conclusion MAFLD patients are at risk for developing cardiac systolic and subclinical systolic dysfunctions, as well as diastolic dysfunction. Decreased glycyl tyrosine levels correlate with reduced LVEF and LPC (18:2/0:0) levels with diastolic dysfunction, even after adjusting for confounding factors, suggesting their potential to be used as metabolic biomarkers in detecting cardiovascular risk.

Metabolic dysfunction-associated fatty liver disease and cardiovascular disease: A meta-analysis

“…Recent findings pointed out cardiac contraction, subclinical contraction dysfunction, and increased risk of diastolic dysfunction in patients with MAFLD. Moreover, a low level of ammonia acyl tyrosine was related to lower left ventricular systolic function; even after adjusting confounding factors, lower lysophosphatidylcholine (LPC) (speech/0-0) levels were also associated with diastolic dysfunction (41). This finding was consistent with previous studies assessing cardiac systolic, subclinical systolic, and diastolic function in patients with NAFLD (42,43).…”

Lysophosphatidylcholine: Potential Target for the Treatment of Chronic Pain

“…At present, the accurate detection of LPC relies on metabolomics or lipidomics technology, which provides assays for exploiting the role of LPC in chronic pain. Apart from chronic pain, LPC or LPC species in body fluids such as blood, urine, cerebrospinal fluid, and tissues are uniquely or collectively related to cancer [ 150 , 151 , 152 ], diabetes [ 153 , 154 , 155 , 156 ], coronary atherosclerosis [ 157 ], Alzheimer’s disease [ 158 , 159 ], rheumatoid arthritis [ 83 ], COVID-19 [ 160 ], liver and kidney damage [ 161 , 162 ], etc. Whether LPC is necessary for other chronic pain conditions, such as cancer pain, has not been confirmed.…”

Non-invasive assessment of metabolic dysfunction–associated fatty liver disease

“…The performances of the aforementioned blood-based biomarkers and scores for NASH or fibrotic NASH is summarized in Table 2. Some recent studies have focused on 'omic markers' [48][49][50] to corroborate the findings of raised production of lipidomic, 51,52 proteomic, metabolomics, 53 and microbiome markers 54 in patients with NAFLD. Nevertheless, these require further validation; and while attempting to improve accuracy, the key to obtaining an effective non-invasive biomarker to diagnose at-risk or fibrotic NASH in clinical practice is for it to be simple, low cost, and easily available.…”