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

Table 7 YKL-40 as a biomarker in adverse cardiovascular events: Associations and clinical implications

	Adverse cardiovascular event	Cardiovascular condition overview	YKL-40 association	Ref.
1	AF	A common cardiac arrhythmia characterized by rapid and irregular beating of the atria, leading to inefficient blood flow and increasing the risk of stroke and HF	General population studies have reported that elevated YKL-40 Levels are associated with an approximately two-fold increased risk of AF. Findings from Kjaergaard et al[50] largely align with these observations. However, the lack of a significant association with AF in this study challenges previous hypotheses linking YKL-40 to thromboembolism. Notably, the prognostic value of YKL-40 for AF appears to be influenced by pre-existing CVEs, as no association was observed in individuals without prior CVEs at enrollment. This discrepancy with previous general population studies, which identified a stronger relationship between YKL-40 and AF in otherwise healthy cohorts, may be attributed to differences in study design. Specifically, earlier research did not adjust for age- and sex-related variations in YKL-40 Levels, potentially leading to overestimation of its predictive value for AF	Kjaergaard et al[50]. Marott et al[55]
2	IS	Occurs when an artery supplying blood to the brain is obstructed, typically by a thrombus or embolus, leading to brain tissue ischemia and potential infarction	General population studies have shown that elevated YKL-40 Levels are associated with an approximately two-fold increased risk of IS. The study by Kjaergaard et al[50] reinforces this association, suggesting that YKL-40 may serve as a more effective prognostic biomarker for IS in individuals with lower CVE risk. This highlights the potential utility of YKL-40 in identifying subclinical vascular inflammation and endothelial dysfunction before overt CVEs develop	Kjaergaard et al[48]. Kjaergaard et al[50]
3	VTE	Includes DVT, where blood clots form in deep veins (commonly in the legs), and PE, where such clots travel to the lungs, causing potentially life-threatening complications	General population studies have reported that elevated YKL-40 Levels are associated with an approximately two-fold increased risk of VTE. Findings from Kjaergaard et al[50] partially align with these observations. However, the lack of a significant association between YKL-40 and VTE in this study challenges previous hypotheses linking YKL-40 to thromboembolic risk. This discrepancy suggests that while YKL-40 is a marker of systemic inflammation, its role in VTE pathogenesis may be less pronounced than previously thought, possibly influenced by differences in study populations or underlying risk factors	Kjaergaard et al[50]. Kjaergaard et al[54]
4	MI	MI occurs when blood flow to a part of the heart muscle is blocked, leading to tissue damage or necrosis	General population studies have found no significant association between elevated YKL-40 Levels and MI. This suggests that YKL-40 may be more closely linked to thromboembolic processes rather than atherosclerotic plaque formation. Its role in CVD appears to be stronger in conditions driven by endothelial dysfunction and systemic inflammation rather than direct arterial occlusion	Chou et al[49]. Kjaergaard et al[50]
5	HF	A clinical syndrome where the heart is unable to pump sufficient blood to meet the body's needs, resulting in symptoms like shortness of breath, fatigue, and fluid retention	YKL-40 has been associated with increased mortality in HF populations. Elevated YKL-40 Levels have also been linked to a higher risk of HF, as demonstrated in a meta-analysis of population-based studies. The study by Kjaergaard et al[50] suggests that YKL-40 may serve as a more effective prognostic biomarker for HF in individuals with lower CVE risk, indicating its potential role in early disease identification and risk stratification	Kjaergaard et al[50]. Henry et al[56]
6	PAD	A circulatory condition characterized by narrowed arteries, reducing blood flow to the limbs, often leading to leg pain and mobility issues	Elevated YKL-40 Levels have been observed in individuals with PAD, particularly among those with prediabetes or diabetes. However, no prospective studies have specifically evaluated YKL-40 as a risk factor for PAD development. The study by Kjaergaard et al[50] suggests that YKL-40 may serve as a more reliable prognostic biomarker for PAD in individuals with lower CVE risk, highlighting its potential role in early vascular risk assessment	Wu et al[46]. Chou et al[49]. Kjaergaard et al[50]

AF: Atrial fibrillation; CAD: Coronary artery disease; CVD: Cardiovascular disease; CVEs: Cardiovascular events; DVT: Deep vein thrombosis; HF: Heart failure; IS: Ischemic stroke; MI: Myocardial infarction; PAD: Peripheral artery disease; PE: Pulmonary embolism; VTE: Venous thromboembolism.