Urinary Cystatin C Has Prognostic Value in Peripheral Artery Disease

Abstract

Despite its association with adverse outcomes, peripheral artery disease (PAD) remains undertreated. Cystatin C is elevated in patients with renal disease and may be a marker of cardiovascular disease. We examined the prognostic ability of urinary Cystatin C (uCystatinC) in predicting adverse PAD-related events. In this prospective case-control study, urine samples were collected from patients with PAD (n = 121) and without PAD (n = 77). The cohort was followed for 2 years. uCystatinC was normalized to urinary creatinine (uCr) (uCystatinC/uCr; μg/g). The primary outcome was major adverse limb event (MALE; composite of vascular intervention (open or endovascular) or major limb amputation). The secondary outcome was worsening PAD status (drop in ABI ≥ 0.15). Multivariable Cox regression and Kaplan–Meier analyses were performed to assess the prognostic value of uCystatinC/uCr with regards to predicting MALE and worsening PAD status. Our analysis demonstrated that patients with PAD had significantly higher median [IQR] uCystatinC/uCr levels (24.9 μg/g [14.2–32.9] vs. 20.9 μg/g [11.1–27.8], p = 0.018). Worsening PAD status and MALE were observed in 39 (20%) and 34 (17%) patients, respectively. uCystatinC/uCr predicted worsening PAD status with a hazard ratio (HR) of 1.78 (95% CI 1.12–2.83, p = 0.015), which persisted after controlling for baseline demographic and clinical characteristics (adjusted HR 1.79 [95% CI 1.11–2.87], p = 0.017). Patients with high uCystatinC/uCr had a lower 2-year freedom from MALE (77% vs. 89%, p = 0.025) and worsening PAD status (63% vs. 87%, p = 0.001). Based on these data, higher uCystatinC/uCr levels are associated with adverse PAD-related events and have prognostic value in risk-stratifying individuals for further diagnostic vascular evaluation or aggressive medical management.

The Urinary Concentrations of Neutrophil Gelatinase-Associated Lipocalin, Cystatin C and Osteopontin in the Healthy Term and Stable Preterm Neonates: A Pilot Study

“…ratio in healthy term neonates are similar than the values observed in the adult population. However, in stable preterm neonates, they are significantly higher than in healthy adults [29]. Our study found that the cystatin C/cr.…”

The prognostic capability of inflammatory proteins in predicting peripheral artery disease related adverse events

“…This suggests that PAD patients with higher baseline levels of inflammation, as measured by AGP, are more likely to have limb-related complications over the long term. Our paper provides some evidence that AGP can be used as a potential prognostication biomarker for PAD, adding to our repository of potential biomarkers to improve prognosis of this condition via a multifaceted approach ( 7 – 10 ).…”

“…These findings were replicated in urinary FABP3 ( 8 , 9 ). More recently, we showed that higher levels of Cystatin C correlated with long-term adverse PAD-related events ( 10 ). These results suggest that there is potential to develop a multifaceted approach to risk stratifying PAD patients using a panel of biomarkers.…”

Hypertension in Patients With Peripheral Artery Disease: An Updated Literature Review

“…Urinary cystatin C is a marker classically associated with kidney function. However, the elevated urine cystatin C:urine creatinine ratio is associated with PAD and is a predictive of major adverse limb events [22]. During angiography, myeloperoxidase levels were assessed in patients with PAD and CAD.…”