Do sex differences exist in cardiovascular mortality among patients with chronic kidney disease (CKD)?: a systematic review and meta-analysis

Although it is known that sex differences exist in cardiovascular mortality among the general population, the evidence regarding these differences among men and women with chronic kidney disease (CKD) is inconclusive and inconsistent. This thesis aims to systematically review the current literature regarding sex differences in cardiovascular mortality among CKD patients. PubMed, Medline, EMBASE, Scopus and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched systematically and studies were included if they looked at sex-stratified cardiovascular mortality outcomes among adult CKD patients of any stage from 2004 up to May 2019, and excluded if their patient population were exclusively diabetic or had a renal transplant, malignancy, non-conventional treatments or surgical interventions. Reported risk estimates (hazard ratios (HR) with 95% confidence intervals (CI)) were pooled and risk ratios (RR) and cardiovascular mortality rates were calculated where data was available. Thirty eight studies and one registry report (ANZDATA) involving 110,568 participants were included, and the results demonstrated that there was no significant association of sex with overall cardiovascular mortality among CKD patients, both in reported risk estimates (HR 1.10, 95% CI 0.95-1.28), and calculated risk estimates from additional data in the included studies together with ANZDATA (RR 1.16, 95% CI 1.02-1.32). However, there was some heterogeneity among both the reported HRs (I2= 41.6%, p= 0.013), and calculated RRs (I2= 69.1%, p= 0.000). Subgroup analysis and risk of bias assessment revealed there were considerable bias at study and outcome level that contributed to heterogeneity of results. The findings from the study show that men and women with CKD share equal risk of cardiovascular mortality, which is contradictory to the prevalent opinion that cardiovascular risk is higher in men with CKD. Therefore, further research is required to understand whether this shift in cardiovascular mortality is due to a reduction in mortality in men, or an increased risk in women with CKD, and strategies to address these inequalities in cardiovascular disease prevention and management in CKD patients -- abstract.