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YKL-40 (Chitinase-3-Like Protein 1) Serum Levels in Aortic Stenosis
Fizza Arain1,2, Aurelija Abraityte1,3,4, Mariia Bogdanova5,6
1Research Institute of Internal Medicine (F.A., A.A., A.E.M., T.L., S.H., B.H., A.V.F., L.-E.V., S.N., T.R., P.A., T.U.), Institute of Basic Medical Sciences, University of Oslo, Norway.
Insights
Elevated YKL-40 (chitinase-3-like protein 1) in aortic stenosis (AS) patients is linked to mortality but not disease severity. Circulating YKL-40 has limited clinical utility as an AS biomarker.
Area of Science:
- Biomarker discovery
- Cardiovascular disease research
- Protein expression analysis
Background:
- Aortic stenosis (AS) diagnosis and risk stratification can be improved with novel biomarkers.
- YKL-40 (chitinase-3-like protein 1) is implicated in atherogenesis and upregulated in calcific aortic valves.
- This study investigated circulating YKL-40 levels in symptomatic AS patients.
Purpose of the Study:
- To determine if circulating YKL-40 is elevated in patients with aortic stenosis (AS).
- To assess the association between YKL-40 levels and AS severity.
- To evaluate the prognostic value of YKL-40 for patient outcomes.
Main Methods:
- Plasma YKL-40 was measured in two AS cohorts (severe AS, n=572; mixed severity, n=67).
- YKL-40 expression was analyzed in human calcified valves and an experimental pressure overload model.
- Long-term mortality was assessed in the severe AS cohort.
Main Results:
- Patients with AS exhibited significantly higher circulating YKL-40 levels than controls (109 vs. 34 ng/mL, P<0.001).
- Elevated YKL-40 (highest quartile) was associated with increased long-term all-cause mortality (aHR, 1.93; P<0.001).
- YKL-40 levels did not correlate with the degree of AS severity; myocardial YKL-40 increased in experimental pressure overload.
Conclusions:
- Circulating YKL-40 is elevated in AS patients and predicts mortality.
- YKL-40 levels do not correlate with AS disease severity.
- The clinical utility of YKL-40 as a biomarker for AS is limited despite its association with mortality.
Background:
Identification of novel biomarkers could provide prognostic information and improve risk stratification in patients with aortic stenosis (AS). YKL-40 (chitinase-3-like protein 1), a protein involved in atherogenesis, is upregulated in human calcific aortic valves. We hypothesized that circulating YKL-40 would be elevated and associated with the degree of AS severity and outcome in patients with symptomatic AS.
Methods:
Plasma YKL-40 was analyzed in 2 AS populations, one severe AS (n=572) with outcome measures and one with mixed severity (n=67). YKL-40 expression in calcified valves and in an experimental pressure overload model was assessed.
Results:
We found (1) patients with AS had upregulated circulating YKL-40 compared with healthy controls (median 109 versus 34 ng/mL, P<0.001), but levels were not related to the degree of AS severity. (2) High YKL-40 levels (quartile 4) were associated with long-term (median follow-up 4.7 years) all-cause mortality (adjusted hazard ratio, 1.93 [95% CI, 1.37-2.73], P<0.001). (3) YKL-40 protein expression in human calcific valves co-localized with its putative receptor IL-13rα2 in close proximity to valve interstitial cells. (4) Myocardial YKL-40 increased in experimental pressure overload (6-fold in decompensated versus sham mice).
Conclusions:
YKL-40 levels were elevated in AS and associated with mortality but not with other metrics of disease severity including the degree of AS severity. Despite scientific rationale for its role in AS, the clinical utility of circulating YKL-40 as a biomarker is limited. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01794832.
