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 3 – Classification of patients and variables included in multivariate regression analysis of Cox proportional hazards in selected studies Author/Year Classification of patients Variables included in the multivariate regression analysis Sai et al., 2016 19 Patients with cystatin C levels above (n = 138) and below (n = 139) median. (Median = 0.637) BMI, hypertension, HbA1c, HDL, BNP, cystatin C. Bansal et al., 2016 15 GFR between 60 and 75 mL/min/1.73 m 2 (n = 29). GFR between 76 and 90 mL/min/1.73m 2 (n = 153). GFR > 90 mL/min/1.73 m 2 (n = 2228). Age, gender, race, smoking, DM, LDL, HDL, albuminuria, BMI, systolic blood pressure. Abid et al., 2016 7 Patients who developed fatal (n = 6) or non-fatal (n = 26) cardiovascular events and patients who did not develop these events. Patients with cystatin C levels> 1.2 mg/L and <1.2 mg/L NA Woitas et al., 2013 18 Patients with coronary disease (n = 2,346) and control group (n = 652). First quartile < 0.8 mg/L (n = 731). Second quartile 0.81 to 0.91 mg/L (n=769). Third quartile 0.91 to 1.06 mg/L (n=752). Fourth quartile > 1.07 mg/L (n=746) Hypertension, HDL, LDL, triglycerides, statin use, smoking, DM, usPCR, GFR CKD-EPI based on creatinine, age, gender, BMI Dupont et al., 2012 8 Cystatin C quartiles. NA Gao et al., 2011 21 Patients who developed fatal or non-fatal (n = 21) cardiovascular events and patients who did not develop these events (n = 117). Patients with cystatin C levels above the median and below the median (0.9 mg/L). Male gender, history of hypertension, high creatinine, reduced triglycerides, high homocysteine, high usPCR, high cystatin C. Keller et al., 2009 17 Patients with cardiovascular death (n = 66) and patients without cardiovascular death (n = 1761). Cystatin C quartiles. Age, gender, BMI, smoking, DM, hypertension, LDL/HDL ratio, PCR, GNP. Gao et al., 2009 22 Patients with stable angina (n = 34), patients with unstable angina (n = 56), patients with AMI (n = 36) and control group (n = 34). Patients who developed fatal or non-fatal (n = 26) cardiovascular events and patients who did not develop these events (n = 22). NA Alehagen et al., 2009 20 First quartile: < 1.22 mg/L (n = 109). Second quartile: 1.22 to 1.42 mg/L (n = 120). Third quartile: 1.43 to 1.66 mg/L (n = 117). Fourth quartile: > < 1.66 mg/L (n = 118). NA Acuna et al., 2009 16 Patients with cystatin C levels> 0.95 mg/L (n = 63) and ≤ 0.95 mg/L (n = 76) NA Koenig et al., 2007 24 Patients with high (n = 1261) and reduced levels of cystatin C (n = 1347) NA Ix et al., 2007 23 First quartile: ≤ <0.91 mg/L (n = 239). Second quartile: 0.92 to 1.05 mg/L (n = 248). Third quartile: 1.06 to 1.29 mg/L (n = 262). Fourth quartile:> ≥ <1.30 mg/L (n = 241). Age, gender, race, smoking, DM, hypertension, previous AMI, smoking, HDL, BMI, CRP. DM: Diabetes mellitus; HDL-high density lipoprotein; AMI: Acute Myocardial Infarction; BMI: Body mass index; LDL: low density lipoprotein; NA: Not applicable; CRP: C-reactive protein; GFR: Glomerular filtration rate; usPCR: Ultra-sensitive C-reactive protein. Discussion The present study aimed to evaluate the association between high levels of cystatin C and the risk of cardiovascular events or mortality in subjects with normal renal function through a systematic review of the scientific literature and meta-analysis. The difference between the proportion of patients with high levels of cystatin C who developed cardiovascular events or mortality, compared with the proportion of patients with reduced levels of Cystatin C that developed these events was evaluated by two studies and both of them found a significant difference. The difference between cystatin C levels in patients who developed fatal or non-fatal cardiovascular events and those who did not develop these events was assessed by four studies (33.3%) and all found significantly higher levels of cystatin C in the group of patients who had the events. The risk of developing adverse outcomes was assessed by eight studies (66.66%) calculating the hazard ratio. Among these, six studies found an increased risk of cardiovascular events or mortality. The multivariate regression analysis was performed by six (50%) of these studies, with the risk of developing the adverse outcomes remaining significant after the performance of this analysis in four of these studies. The meta-analysis also demonstrated that there is a significant association between high levels of cystatin C and the risk of all-cause mortality. Thus, the results presented by the studies included in this systematic review and meta-analysis 801