Role for Cystatin C–Based Risk Stratification for Patients After Acute Coronary Syndrome in the Era of High Sensitivity Cardiac Troponin Assays

R enal dysfunction plays a fundamental role in the physiopathological characteristics of cardiovascular diseases. Impaired renal function in heart failure and coronary heart disease correlates independently with higher risk of death and hospitalization. Renal function evaluation is a primary feature when studying comorbidities in a cardiovascular disease population. In patients with coronary heart disease and especially in a population with acute coronary syndrome (ACS), even mild stages of renal dysfunction are associated with an increased risk of death and other cardiovascular events independent of other risk factors. To assess renal function, estimated glomerular filtration rate (eGFR), generally a serum creatinine (SCr)–based, formula is recommended unless there are circumstances that may affect the accuracy of the eGFR with creatinine. In such instances, the measurement of eGFR with a cystatin C–based equation may be more accurate. Cystatin C is a low-molecular-weight protein (a member of the family of papainlike cysteine proteinase inhibitors) expressed in all nucleated cells, with essentially a constant quantity produced over time. It is filtered by the glomerular basement membrane, almost completely reabsorbed in the proximal tubular ducts, and then catabolized. Cystatin C concentration versus SCr is less affected by demographic features (age and sex) and cardiovascular comorbidities and medical conditions (except for thyroid illness). In practice, cystatin C has been identified during the past 15 years as a valuable estimator of GFR, comparable to SCr in the population at large and slightly superior to SCr eGFR calculations in the population with mildly impaired GFR. For these reasons, there has been an interest to determine if a cystatin C–based eGFR would be more accurate for prognostication in patients with coronary heart disease. Multiple studies spanning from “at-risk” individuals, such as older adults, to those presenting with ACS have demonstrated that cystatin C is strongly associated with all-cause mortality, independent of SCr levels. Cystatin C is also an independent predictor of major adverse cardiovascular events, in addition to the natriuretic peptides, in studies of patients with ACS and in those with stable coronary heart disease. Furthermore, cystatin C–based eGFR calculations may have particular prognostic advantages when substituted for SCrbased eGFR in the well-established GRACE (Global Registry of Acute Coronary Events) score. The Table is a summary of ACS studies using cystatin C as a prognosticator for major adverse cardiovascular events that typically include in their multivariate models conventional cardiac troponin (cTn) assay results and natriuretic peptides when available. Unlike conventional or sensitive cTn results, cTn measured by a high sensitivity assay is measurable in most of a healthy population. High sensitive cTn assays have been evaluated in clinical trials for >10 years, are commonly used in clinical practice throughout the world, and were recently approved by the US Food and Drug Administration for use in the United States. B-type natriuretic peptide and NT-proBNP (N-terminal pro-B-type natriuretic peptide) are also 2 nearly ubiquitously available cardiac-specific biomarkers in clinical practice; although predominantly used to diagnose and prognosticate heart failure, they have been shown to be independent prognosticators in patients with ACS. Therefore, the SOLIDTIMI 52 (Stabilization of plaques usIngDarapladib-Thrombolysis in Myocardial Infarction) substudy by Correa et al in this issue of the Journal of the AmericanHeart Association (JAHA), inclusive of 4965 (predefined biomarker subset) from a total 13 026 patients enrolled with ACS within 30 days, who had cystatin C and both an hs-cTnI and NT-proBNP measured, represents an important update to contemporary practice to the studies noted The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association. From the University of Brescia, Italy (F.L.); and Inova Heart and Vascular Institute, Falls Church, VA (C.d.). Correspondence to: Christopher deFilippi, MD, Inova Heart and Vascular Institute, 3300 Gallows Rd, Ste 1225, Falls Church, VA 22042. E-mail christopher.defilippi@inova.org J Am Heart Assoc. 2018;7:e010589. DOI: 10.1161/JAHA.118. 010589. a 2018 The Author. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.