The potential of cystatin C as a predictive biomarker in pulmonary hypertension

Abstract

Background Cystatin C is a novel biomarker to identify renal dysfunction and cardiovascular risk. Objective The aim of this study was to investigate the role of cystatin C in non-invasive risk prediction in a large cohort of patients with pre-capillary pulmonary hypertension (PH). Method We retrospectively analyzed pre-capillary PH patients with available cystatin C and hemodynamic data derived from right heart catheterization. Results A total of 398 consecutive patients with confirmed pre-capillary PH were recruited from Fuwai Hospital between November 2020 and November 2021. Over a median duration of 282 days, 72 (18.1%) of these patients experienced clinical worsening. Cystatin C levels significantly correlated with cardiac index (r = -0.286, P < 0.001), mixed venous oxygen saturation (r = -0.216, P < 0.001), and tricuspid annular plane systolic excursion (r = -0.236, P < 0.001), and high cystatin C levels independently predicted a poor prognosis after adjusting potential confounders in different models (all P < 0.05). A three-group non-invasive risk model was constructed based on the combined assessment of the cystatin C and WHO-FC using dichotomous cut-off value. Those patients with higher cystatin C (≥ 1.0 mg/L) and a worse WHO-FC experienced the highest risk of endpoint occurrence. The predictive capacity of this model was comparable to that of an existing invasive risk stratification model (area under curve: 0.657 vs 0.643, P = 0.619). Conclusions Cystatin C levels were associated with disease severity and prognosis in patients with pre-capillary PH. A combination of high cystatin C and advanced WHO-FC identifies patients at particularly high risk of clinical deterioration.

Association of serum creatinine to cystatin C to waist circumference ratios and hypertension: evidence from China health and retirement longitudinal study

“…CCR is acknowledged as an indicator of muscle wasting, serving as an alternative measure for assessing muscle mass ( 28 , 29 ). Prior investigations have proposed cystatin C as a predictive biomarker in pulmonary hypertension ( 30 ). However, these investigations did not incorporate the independent influences of muscle mass and adipose tissue measurements when evaluating the risk of hypertension.…”

Circulating Biomarkers in Pulmonary Arterial Hypertension: An Update

“…In addition, the CysC levels are associated with elevated RV systolic pressure and show positive correlations with various RV parameters, including end-diastolic volume, endsystolic volume, mass index, strain, and strain rate [19]. Although CysC proved to be a sensitive biomarker for assessing PAH, offering advantages over standard biomarkers such as BNP and NT-proBNP by being independent of muscle mass, age, and gender [20] and predicting long-term mortality and clinical events in patients with CHD-PAH [21], its utility was demonstrated only in small studies [21]; therefore, to date, CysC has no clinical use. As a result, CysC cannot be considered a good biomarker because it is not widespread and, to the best of our knowledge, there are not data about a correlation of its expression with PAH progression.…”

Correlation Between Cystatin C and the Severity of Cardiac Dysfunction in Patients with Systolic Heart Failure

“…5 Cystatin C levels were associated with disease severity and prognosis in patients with pre-capillary PH. 6 A combination of high cystatin C and advanced WHO-FC identifies patients at particularly high risk of clinical deterioration. 6 Cystatin C is a cysteine protease inhibitor generated by all nucleated cells in mammals at a constant rate, in contrast to creatinine, is less influenced by changes in muscle mass.…”

“…6 A combination of high cystatin C and advanced WHO-FC identifies patients at particularly high risk of clinical deterioration. 6 Cystatin C is a cysteine protease inhibitor generated by all nucleated cells in mammals at a constant rate, in contrast to creatinine, is less influenced by changes in muscle mass. 7 Among HF patients, Cystatin C may more accurately reflect directly measured kidney function 8 and has demonstrated superior prognostic value when compared with creatinine.…”