To the Editor,
We read with great interest the excellent article by Górriz Teruel et al.1 on renal assessment in patients with cardiovascular disease. This extensive and excellent update did not mention cystatin C (CC), a biological marker that estimates kidney function and has lately gained importance due to its role in cardiovascular risk stratification.
Chronic kidney disease is usually associated with cardiovascular disease and greatly increases the patient's risk. Recent studies have shown that even mild renal impairment is associated with high risk, hence kidney function markers are now being considered true sentinel indicators of cardiovascular risk.2
CC is a cysteine protease inhibitor protein produced by all nucleated cells and exhibits a highly stable synthesis rate. Its low molecular weight and high isoelectric point mean that the protein is almost entirely excreted by glomerular filtration. Concentrations of the protein are unaffected by age, sex, or protein intake, and there is greater sensitivity to small changes in glomerular filtration rate. Because of these characteristics, plasma CC concentrations are one of the best markers of glomerular filtration rate.3 Several recent publications report a correlation between elevated CC concentrations and the development of cardiovascular complications in patients with coronary disease.
Koenig et al.4 studied the usefulness of CC to predict future cardiovascular events in a cohort of 1033 patients who had been diagnosed with coronary disease within 3 months before inclusion. Patients with renal failure as assessed by plasma creatinine or creatinine clearance (CrCl) presented CC values in the top quintile, compared to those who had mild renal impairment or normal kidney function. No significant differences in the incidence of cardiovascular adverse events were found among patients with differing degrees of renal dysfunction as assessed by plasma creatinine (5.4% incidence of events with creatinine >106μmol/L vs 7% incidence with creatinine<106 μmol/L; P=.63) or by CrCl (7% incidence of events in patients with CrCl<60 mL/min, 9% in patients with CrCl 60-90 mL/min, and 6.3% in patients with CrCl>90mL/min; P=.1). There were significant CC-related differences in the probability of developing a cardiovascular event according to CC quintile (14% for the top quintile and 7.7%, 4.3%, 3.9%, and 5% for the remaining quintiles in descending order; P<.0001).
A Spanish study among patients with acute coronary syndrome showed that those with higher CC concentrations presented worse cardiovascular prognosis, even in the group of patients with normal estimated glomerular filtration rate, which could have implications for risk stratification in this patient group.5 Additionally, Cepeda et al.6 conducted the first study in Spain to determine the prevalence of high CC and its correlation with cardiovascular risk factors among the general population.
Based on the scientific evidence published in the literature in recent years, we believe that CC should be considered a better marker of kidney function than other common measurements (serum creatinine and glomerular filtration rate) and a practical application is likely to be found for the various clinical settings for cardiovascular diseases.
Corresponding author: adrvdg@hotmail.com