Prognostic value of cartilage intermediate layer protein 1 in chronic heart failure

Abstract

Aims Emerging evidence suggests that cartilage intermediate layer protein 1 (CILP‐1) is associated with myocardial remodelling. However, the prognostic value of circulating CILP‐1 in patients with heart failure (HF) remains to be elucidated. This study aimed to investigate whether circulating CILP‐1 can independently predict the outcome of chronic HF. Methods and results This prospective cohort study included 210 patients with chronic HF and left ventricular ejection fraction <50% between September 2018 and December 2019. The primary endpoint was 1 year all‐cause mortality. During the 1 year follow‐up, 28 patients died. In multivariable Cox proportional hazards regression analysis, higher CILP‐1 levels were independently associated with a higher risk of mortality after adjusting for potential confounding factors. In Kaplan–Meier analysis, patients with CILP‐1 levels above the median had a significantly higher mortality rate than those with CILP‐1 levels below the median (log‐rank P = 0.015). In addition, CILP‐1 significantly improved prognostic prediction over N‐terminal pro‐brain natriuretic peptide by an increase in net reclassification improvement (P = 0.043) and a trend towards an increase in integrated discrimination improvement (P = 0.118). Conclusions Circulating CILP‐1 is a novel independent prognostic predictor in chronic HF.

CILP-1 Is a Biomarker for Backward Failure and Right Ventricular Dysfunction in HFrEF

“…CILP-1 was also a good predictor of a right ventricular function (RVF) of <40%, suggesting that CILP-1 might be a new non-invasive biomarker for RVD [8]. A subsequent study examining chronic HF patients with a left ventricular ejection fraction (LVEF) of ≤50% reported that CILP-1 was a risk factor for increased mortality over a 1-year period [14]. Here, CILP-1 improved the risk prediction beyond NT-proBNP.…”

“…In the other two studies [1,8] conducted by the same group using the Cusabio assay, healthy individuals showed 1389 pg/mL (Q1: 860, Q3: 2214) and 2913 pg/mL (Q1: 2436, Q3: 3293), respectively, while CILP-1 values for HF patients were higher at 3431 pg/mL (Q1: 2383, Q3:4980) and 4164 pg/mL (Q1: 2926, Q3: 5429), respectively [1,8]. Another paper used the Invitrogen assay in HFrEF patients and reported a median CILP-1 level of 3.92 ng/mL (Q1-Q3 2.62-6.12) [14]. These values are consistent with our results.…”

“…Following previous studies on the association of CILP-1 and RVD, data from 210 patients with chronic HF, including patients with LVEF < 50%, were evaluated to assess the ability of CILP-1 to predict the 1-year survival [14]. CILP-1 was significantly associated with all-cause mortality in the crude analysis, with a 1.61-fold increase in mortality per standard deviations, and the association remained significant after adjustment for NT-proBNP and in a model that also included age and renal function [14]. In contrast, the present study, which included 636 patients with a median follow-up period of over 2 years and recorded 156 events, only demonstrated a weak association between CILP-1 and survival.…”

“…Cartilage intermediate layer protein 1 (CILP-1) is an extracellular matrix protein predominantly secreted from chondrocytes in the articular cartilage [11]; however, it is also expressed within the myocardium, where it is supposedly produced by cardiac fibroblasts [1,12]. CILP-1 plays a role in the counterregulatory mechanism of fibrosis and collagen remodeling, presumably by a paracrine mechanism, where it acts as an antagonist of the transforming growth factor beta 1 pathway and profibrotic gene expression [10,13,14]. Animal models have shown less progression of ventricular fibrosis and diastolic dysfunction under the overexpression of CILP-1 [10].…”

Associations of cartilage intermediate layer protein 1 and hypoxia-inducible factor-1-alpha with transthoracic echocardiography results in patients with heart failure with preserved ejection fraction

“…Одним из важнейших биохимических факторов, отражающих процессы фиброза и ремоделирования миокарда при СН, можно считать белок промежуточного слоя хряща 1 типа (CILP-1, Cartilage intermediate layer protein 1) [10]. CILP-1 представляет собой белок экстрацеллюлярного матрикса, экспрессирующийся в соединительной ткани и в миокарде, который рассматривается в качестве биомаркера-кандидата для выявления фиброза и ремоделирова ния миокарда [11,12].…”