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. 2022 Jun 21;12(7):860.
doi: 10.3390/biom12070860.

Urinary Cystatin C Has Prognostic Value in Peripheral Artery Disease

Ben Li  1 , Abdelrahman Zamzam  1 , Muzammil H Syed  1 , Niousha Jahanpour  1 , Shubha Jain  1 , Rawand Abdin  2 , Mohammad Qadura  1   3   4
Affiliations

Urinary Cystatin C Has Prognostic Value in Peripheral Artery Disease

Ben Li et al. Biomolecules. .

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.

Keywords: Cystatin C; major adverse limb events; peripheral arterial disease.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Kaplan–Meier analysis of event-free survival rates in patients with low vs. high urinary Cystatin C normalized to urinary creatinine (uCystatinC/uCr) for (A) worsening PAD (ankle-brachial index drop ≥0.15), (B) MALE (major adverse limb event), (C) vascular intervention, and (D) major amputation. SE = standard error.
See this image and copyright information in PMC

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