Elsevier

Atherosclerosis

Volume 209, Issue 1, March 2010, Pages 300-305
Atherosclerosis

Plasma cystatin C for prediction of 1-year cardiac events in Mediterranean patients with non-ST elevation acute coronary syndrome

https://doi.org/10.1016/j.atherosclerosis.2009.09.022Get rights and content

Abstract

Objective

Evaluation of renal function (RF) is important for management of patients with non-ST elevation acute coronary syndrome (NSTE-ACS). Cystatin C, a sensitive marker of RF, appears to be also a marker of cardiovascular risk. Little is known regarding its predictive role in NSTE-ACS patients.

Methods

We assessed 525 patients taking part in the “Systemic Inflammation Evaluation in patients with NSTE-ACS” (SIESTA) study. Patients were subdivided in quartiles according to cystatin C plasma concentrations (mg/L), i.e., Q1 < 0.81; Q2 = 0.81–0.92; Q3 = 0.93–1.10; Q4  1.11. Glomerular filtration rate (eGFR) was estimated using the modification of diet in renal disease (MDRD) equation. The study end-point was the composite of cardiac death, non-fatal myocardial infarction and unstable angina at 1-year follow up.

Results

Few patients (0.8%) had severely impaired RF (MDRD < 30 ml/min/1.73 m2). 157 patients reached (30%) the study end-point. Patients in Q3 and Q4 showed a higher cumulative probability of cardiac events compared to patients in the lowest quartile. On multivariable analysis, patients in Q3 and Q4 had an increased incidence of cardiac events (adjusted HR = 1.57 95%CI 1.04–2.49; p = 0.036). Patients with TIMI risk score ≥3 or in-hospital heart failure were also at higher risk for acute cardiac events. Conventional markers of RF, i.e., serum creatinine and eGRF, were not predictors for the study end-point.

Conclusions

Increased levels of cystatin C were an independent predictor of cardiac events at 1-year follow up in this contemporary series of Mediterranean patients with NSTE-ACS.

Introduction

Chronic kidney disease (CKD) represents an important public health problem worldwide with an estimated prevalence of 13% in the Western world [1], [2]. CKD patients are at an increased risk of developing cardiovascular disease (CVD) and serious CV events compared to subjects with normal renal function (RF) [2], [3], [4], [5], [6]. Cystatin C, a marker of RF, is particularly useful for the estimation of small reductions in glomerular filtration rate (GFR) [7], [8], [9] and has been also proposed to represent a marker of cardiovascular risk [10], [11], [12], [13].

Risk stratification plays a crucial role in the management of patients with non-ST elevation acute coronary syndrome (NSTE-ACS) and it has been shown that risk stratification score systems that incorporate markers of RF perform better than score systems without RF markers [14], [15].

Few studies to date have evaluated specifically the prognostic role of cystatin C in patients with NSTE-ACS. Of these, only one study carried out in patients recruited over 10 years ago, focused exclusively on NSTE-ACS patients [16]. Moreover, the prognostic role of cystatin C has not been evaluated in Mediterranean patients with ACS, who in epidemiological studies appear to have lower cardiovascular mortality rates [17].

We therefore sought to assess prospectively the prognostic value of cystatin C in Spanish patients with established NSTE-ACS receiving treatment in accordance to current guidelines.

Section snippets

Patients

Five hundred and twenty-five (86%) of 610 patients enrolled in the multicentre SIESTA (systemic inflammation evaluation in patients with NSTE-ACS) study were assessed. Eighty-five (14%) patients in whom we lacked complete information on creatinine and/or cystatin C data were excluded from analysis. The two groups were similar in terms of baseline clinical, procedural and laboratory characteristics. However, there were less smokers (15.5% vs. 28.2%; p = 0.019) and less people with BMI > 30 (16.5%

Results

Baseline demographics, clinical, procedural and biochemical data in the study patients are listed in Table 1. Of the patients recruited, 329 (63%) had NSTEMI and 196 (37%) unstable angina. One hundred and thirty-five (26%) patients were women. Patients in the highest cystatin C quartile were older and showed a higher prevalence of diabetes and hypertension. They also had a higher TIMI risk score, increased BMI values and higher CRP concentrations. Cystatin C concentrations correlated with age (r

Discussion

The present prospective study showed, for the first time, that increased cystatin C levels were an independent predictor of cardiac events in a contemporary series of Mediterranean patients with confirmed NSTE-ACS. Our results thus confirm and expand the predictive role of cystatin C in ischemic heart disease patients, as suggested by other investigators [16], [23], [24], [25]. Moreover, our study supports the existence of a threshold effect for cystatin C. These findings are consistent with

Conclusions

Our study showed that cystatin C is an independent predictor of 1-year cardiac events in Mediterranean patients with NSTE-ACS. The potential clinical usefulness of this molecule as a clinical marker of cardiovascular risk, as suggested by our data, requires further confirmation in larger studies. Moreover, studies are also needed to elucidate the true pathogenic link between increased cystatin C levels and the development of further serious atherosclerotic cardiovascular events in patients with

Conflict of interest

None declared.

Acknowledgments

We are grateful to Mrs Gerlinde Trischler for excellent technical assistance. Reagents for measurement of cystatin C were a gift from Dade-Behring, Germany.

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    The SIESTA study was supported by unrestricted grants from Bristol Myers Squibb (Madrid, Spain), and the Spanish Society of Cardiology.

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    Daniel J. Fernández-Bergés was supported by the Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III and fundesalud (Grupo emergente GRIMEX).

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    Luciano Consuegra Sánchez was supported by grants by the Spanish Society of Cardiology and Fundación de Investigación del Hospital Clínico de Valencia.

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