YKL-40: Revolutionizing cardiac risk prediction and therapy in liver transplantation

Table 3 Cardiovascular risk factors in liver transplantation: Traditional and transplant-specific considerations

Risk factor	Description	Category	CVD risk level
HTN	Prevalent in up to 70% of LT candidates, often secondary to cirrhosis-related hemodynamic changes and renal dysfunction. Increased after LT due to CNI therapy	Traditional	High
DM	Strongly associated with CAD in LT candidates. Increases post-LT MACE risk, especially in patients with NAFLD/ NASH-related cirrhosis	Traditional	High
HLP	Often masked by cirrhosis, where severe liver disease leads to low LDL and cholesterol levels. Becomes evident post-LT due to immunosuppressive drugs (CNIs, steroids, mTOR inhibitors)	Traditional	Moderate
Obesity and metabolic syndrome	Increasingly common due to the rising prevalence of NAFLD/NASH, which is now a leading LT indication. Contributes to insulin resistance, HTN, and CAD	Traditional	High
Smoking and CKD	Smoking doubles post-LT cardiovascular risk. CKD is a strong predictor of post-LT cardiovascular events, often worsened by CNI nephrotoxicity	Traditional	High
Cirrhotic cardiomyopathy	Subclinical cardiac dysfunction due to chronic cirrhosis-related myocardial remodeling. Manifests as blunted cardiac response to stress, leading to increased perioperative cardiovascular instability	Nontraditional	High
Portal hypertension and hyperdynamic circulation	Characterized by low SVR and high CO, which can mask underlying cardiac disease. Contributes to high-output HF and pulmonary hypertension in advanced cirrhosis	Nontraditional	Moderate
NAFLD/ NASH-related cardiovascular risk	Strongly associated with CAC and subclinical atherosclerosis. NAFLD-related CVD risk persists post-LT, even after resolution of liver disease	Nontraditional	High
HRS and ESLD	Worsens fluid overload and increases cardiovascular complications, especially in patients requiring pre-transplant renal replacement therapy	Nontraditional	High
Inflammation and endothelial dysfunction	Chronic systemic inflammation in cirrhosis promotes accelerated atherosclerosis. Circulating pro-inflammatory cytokines impair vascular function, increasing CAD risk	Nontraditional	Moderate
QT prolongation and arrhythmias	Common in cirrhosis due to electrolyte imbalances, autonomic dysfunction, and beta-adrenergic receptor desensitization. Increases perioperative arrhythmic risk, particularly in ALD patients	Nontraditional	Moderate

ALD: Alcohol-related liver disease; CAC: Coronary artery calcification; CAD: Coronary artery disease; CKD: Chronic kidney disease; CNI: Calcineurin inhibitor; CO: Cardiac output; CVD: Cardiovascular disease; DM: Diabetes mellitus; ESLD: End-stage liver disease; HF: Heart failure; HLP: Hyperlipidemia; HRS: Hepatorenal syndrome; HTN: Hypertension; LDL: Low density lipoprotein; LT: Liver transplant; LT: Liver transplantation; MACE: Major adverse cardiovascular events; mTOR: Mammalian target of rapamycin; NAFLD: Nonalcoholic fatty liver disease; NASH: Nonalcoholic steatohepatitis; post-LT: Post liver transplantation; SVR: Systemic vascular resistance.