ABC | Volume 111, Nº6, December 2018

Original Article Einwoegerer & Domingueti Cystatin C and cardiovascular event or mortality Arq Bras Cardiol. 2018; 111(6):796-807 Table 1 – Characteristics of selected studies Author/Year Number of patients/ Age group Study population Patient follow-up time Evaluated outcome Sai et al., 2016 19 277/64 Patients undergoing PCI 5 years and 3 months Cardiovascular death, cerebrovascular death, ACS including non-fatal AMI and unstable angina, non-fatal stroke and hospitalization due to worsening CHF Bansal et al., 2016 15 2410/40,2 ± 3,6 Patients at risk for cardiovascular events who underwent echocardiography 10 years Left ventricular hypertrophy Abid et al., 2016 7 127/58 ± 11,65 Patients with STEMI and NSTEMI 1 year Cardiovascular death, myocardial reinfarction, NSTEMI, HF Woitas et al., 2013 18 2356/64 ± 10 Patients with CAD and healthy individuals 10 years Cardiovascular death and death from any cause Dupont et al., 2012 8 615/65 ± 11 Patients with CHF who underwent coronary angiography 3 years Death from any cause, non-fatal AMI and non-fatal stroke Gao et al., 2011 21 13 8/65,4 ± 11,0 Patients with chronic or new onset systolic CHF 3 years Cardiovascular death, development or progression of HF requiring hospitalization, intravenous treatment of HF within the first 3 days after admission, cardiac transplantation Keller et al., 2009 17 1827/62 Patients with stable CAD or ACS 4 years Cardiovascular death Gao et al., 2009 22 160/60 Patients with stable, unstable angina and AMI and healthy individuals 6 months AMI, cardiovascular death, refractory angina, PCI and angiography Alehagen et al., 2009 20 464/65 to 87 Patients with CHF 10 years Cardiovascular death Acuna et al., 2009 16 203/66,6 ± 13,16 Patients with STEMI and NSTEMI 1 years and 3 months Cardiovascular death and HF Koenig et al., 2007 24 466 3/≥ 65 Elderly subjects (≥ 65 years) 9,3 years Death from any cause, cardiovascular death, incident HF, stroke and AMI Ix et al., 2007 23 990/67 Patients with a history of AMI, angiographic evidence of stenosis greater than 50% in 1 or more coronary vessels, evidence of treadmill-induced ischemia or nuclear testing, or history of coronary artery bypass grafting 3 years and 1 month Cardiovascular death, non-fatal AMI, stroke, death from all causes and HF AMI: Acute Myocardial Infarction; HF: Heart failure; CHF: congestive heart failure; NSTEMI: Non-ST-segment elevation myocardial infarction; PCI: Percutaneous coronary intervention; ACS: acute coronary syndrome; STEMI: ST-segment elevation myocardial infarction; CAD: Coronary artery disease. Outcome The main outcomes evaluated by the studies were cardiovascular death (n = 10; 83.33%), 7,16-24 heart failure (n = 6; 50%), 7,16,19,21,23,24 and acute myocardial infarction (n=6; 50%), 7,8,19,22-24 followed by stroke (n=4; 33,33%), 8,19,23,24 death from any cause (n = 3; 35%,) 8,23,24 and unstable angina (n = 2; 16,67%). 19,22 Only one study (8.33%) evaluated each of the following outcomes: cerebrovascular death, 19 left ventricular hypertrophy, 15 myocardial reinfarction, 7 need for percutaneous coronary intervention, 22 and angiography. 22 Method for dosing cystatin C and criteria for the definition of normal renal function The cystatin C dosing method and the criteria used to define normal renal function in the selected studies are shown in Table 2. The methods used for cystatin C dosing were immunonephelometry[41.67%(n=5)], 15‑18,23 immunoturbimetry [33.33% (n = 4)], 7,8,19,20 and immunoenzymatic assay [8.33% (n = 1)]. 22 Two studies (16.66%) 21,24 did not report the method used for cystatin C dosing. The criteria used to define normal renal function were the GFR, estimated by theMDRD equation, above 60 mL/min/1.73 m 2 [66.67% (n = 8)], 7,8,16-19,23,24 the GFR, estimated by the CKD-EPI equation based on cystatin C, above 60 mL/min/1.73 m 2 , and normal albuminuria [8,33% (n = 1)] 15 and serum creatinine levels below 115 μmol/L [8,33% (n=1)]. 20 Two studies (16.67%) 21,22 did not mention themethod of evaluation of renal function. Classification of patients and variables included in the multivariate regression analysis Theway patients were classified in each of the selected studies, and the variables included in the multivariate Cox proportional hazards regression analysis are presented in Table 3, while the results of the studies are presented in Table 4. Among the studies included in this systematic review, five (41.66%) 8,17,18,20,23 classified patients according to cystatin C quartiles; three (25%) 8,21 classified patients according to whether or not there were fatal or non-fatal cardiovascular events; two (16.66%) 19,21 divided the patients according to the median of cystatin C; one study (8.33%) 17 classified patients according to whether or not they developed cardiovascular death; another study (8.33%) 18 compared patients with coronary disease in relation to the healthy control group; 799