The inflammatory biomarker YKL-40 as a new prognostic marker for all-cause mortality in patients with heart failure

Harutyunyan, Marina; Christiansen, Michael; Johansen, Julia S.; Køber, Lars; Torp-Petersen, Christian; Kastrup, Jens

doi:10.1016/j.imbio.2011.11.003

Cited by 45 publications

(17 citation statements)

References 32 publications

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“…cardiovascular diseases [5-7], asthma [8], diabetes mellitus type 1 [9] and 2 [10,11], rheumatoid arthritis [12], liver fibrosis [13-15], and cancer [16]. Furthermore, YKL-40 levels have been shown to be a strong predictor of overall mortality in patients admitted to hospital irrespective of diagnosis [17].…”

Section: Introductionmentioning

confidence: 99%

Plasma YKL-40 and all-cause mortality in patients with chronic obstructive pulmonary disease

et al. 2013

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BackgroundChronic obstructive pulmonary disease (COPD) is hallmarked by inflammatory processes and a progressive decline of lung function. YKL-40 is a potential biomarker of inflammation and mortality in patients suffering from inflammatory lung disease, but its prognostic value in patients with COPD remains unknown. We investigated whether high plasma YKL-40 was associated with increased mortality in patients with moderate to very severe COPD.MethodsFour hundred and ninety-three patients with moderate to very severe COPD were followed prospectively for up to 10 years. Patients were divided into two groups according to plasma YKL-40: concentration higher than the 75th percentile for age-matched healthy subjects (i.e. high levels) and normal levels. Outcome was overall survival (OS) and was evaluated in uni- and multivariate proportional hazards Cox regression analyses and adjusted for factors affecting mortality.ResultsMedian plasma YKL-40 was increased in patients with COPD (81 ng/ml, p < 0.001) compared to healthy subjects (40 ng/ml). Patients with high plasma YKL-40 had a hazard ratio (HR) of 1.42 (95% CI: 1.15–1.75, p = 0.001) for all-cause mortality. Multivariate analysis showed that YKL-40 (HR 1.38; 95% CI: 1.11–1.72, p = 0.004), age (HR 1.05; 95% CI: 1.03–1.06, p < 0.0001), Severe COPD (HR 1.35; 95 CI: 1.03-1.76, p = 0.03) very severe COPD (HR 2.19; 95% CI: 1.60 - 2.99 < 0.0001), neutrophil granulocyte count (HR 1.05; 95% CI: 1.01-1.08, p = 0.01), and a smoking history of > 40 years (HR 1.38; 95% CI: 1.11-1.71, p = 0.003) were independent prognostic markers of OS.ConclusionHigh plasmaYKL-40 is associated with increased mortality in patients with moderate to very severe COPD, suggesting a role for YKL-40 as a potential biomarker of mortality in this patient group.Trial registrationClinicalTrials.gov: NCT00132860.

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Section: Introductionmentioning

confidence: 99%

Plasma YKL-40 and all-cause mortality in patients with chronic obstructive pulmonary disease

et al. 2013

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“…Growing clinical evidence has indicated that aberrant expression of YKL-40 is largely associated with endothelial dysfunction [14], [29]–[31] and poor cardiovascular outcome [19], [20], suggesting that serum levels of YKL-40 can serve as a diagnostic and prognostic biomarker. Middle aged OSA patients without clinical evidence for cardiovascular disease have premature atherosclerosis [23] and endothelial dysfunction predicts development of de novo hypertension in post-menopausal women [32].…”

Section: Discussionmentioning

confidence: 99%

“…Elevated plasma YKL-40 level is associated with increased risk of ischemic stroke [16], [17] and found to be a biomarker for myocardial infarction, progression of coronary artery disease, congestive heart failure [18], and cardiovascular death [19], [20]. OSA has been shown to increase population burden of cardiovascular diseases including stroke and hypertension [21], [22].…”

Section: Introductionmentioning

confidence: 99%

Increased Plasma YKL-40/Chitinase-3-Like-Protein-1 Is Associated with Endothelial Dysfunction in Obstructive Sleep Apnea

2014

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PurposeObstructive sleep apnea (OSA) is a common disorder affecting 15–24% of the adults and is associated with increased risk of hypertension and atherosclerosis. The exact mechanisms underlying hypertension in OSA are not entirely clear. YKL-40/Chitinase-3-like protein-1 is a circulating moiety with roles in injury, repair and angiogenesis that is dysregulated in atherosclerosis and a number of other diseases. We sought to determine the role of YKL-40 in endothelial dysfunction and hypertension in OSA.MethodsWe studies 23 normotensive OSA (N-OSA) and 14 hypertensive OSA (H-OSA) without diabetes and apparent cardiovascular disease. Endothelial-dependent nitric oxide-mediated vasodilatory capacity was assessed by flow-mediated vasodilation (FMD). YKL-40, vascular endothelial growth factor (VEGF) and the soluble form of VEGF receptor-1or sFlt-1 were measured in plasma using ELISA methodology.ResultsN-OSA subjects aged 49.1±2.3 years and H-OSA aged 51.3±1.9 years with BMI 36.1±1.6 and 37.6±1.9 kg/m2, respectively. The apnea-hypopnea index (AHI) was 41±5 events/hr in N-OSA and 46±6 in H-OSA with comparable degree of oxygen desaturations during sleep. FMD was markedly impaired in H-OSA (8.3%±0.8) compared to N-OSA (13.2%±0.6, P<0.0001). Plasma YKL-40 was significantly elevated in H-OSA (55.2±7.9 ng/ml vs. 35.6±4.2 ng/ml in N-OSA, P = 0.02) and had an inverse relationship with FMD (r = −0.52, P = 0.013). There was a significant positive correlation between sFlt-1/VEGF, a measure of decreased VEGF availability, and YKL-40 (r = 0.42, P = 0.04).ConclusionThe levels of plasma YKL-40 were elevated in H-OSA group and inversely correlated with the endothelial-dependent vasodilatory capacity whereas there was a positive correlation between sFlt-1/VEGF and YKL-40. These findings suggest that YKL-40 is dysregulated, in part, due to perturbation of VEGF signaling, and may contribute to endothelial dysfunction and hypertension in OSA.

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“…There is a great deal of evidence that serum YKL-40 can be used for prognostication in patients with inflammation. Recently, serum YKL-40 is identified as an independent predictor of mortality in patients with stable coronary artery disease, myocardial infarction and heart failure [35][36][37]. There is evidence that serum or cerebrospinal fluid YKL-40 levels are increased in patients with severe traumatic brain injury and aneurysmal subarachnoid hemorrhage.…”

Section: Discussionmentioning

confidence: 99%

Serum YKL-40 levels as a prognostic factor in patients with intracerebral hemorrhage

Jiang

Zhang

Wang

et al. 2014

Clinical Biochemistry

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The inflammatory biomarker YKL-40 as a new prognostic marker for all-cause mortality in patients with heart failure

Cited by 45 publications

References 32 publications

Plasma YKL-40 and all-cause mortality in patients with chronic obstructive pulmonary disease

Plasma YKL-40 and all-cause mortality in patients with chronic obstructive pulmonary disease

Increased Plasma YKL-40/Chitinase-3-Like-Protein-1 Is Associated with Endothelial Dysfunction in Obstructive Sleep Apnea

Serum YKL-40 levels as a prognostic factor in patients with intracerebral hemorrhage

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