Prevalence Of Coronary Artery Calcification And Its Association With Cardiovascular Events And Mortality In Patients With Chronic Kidney Disease:Clinical Study And A Meta-analysis

Background and Purpose:The prevalence of chronic kidney disease(CKD)is highly prevalent,and a serious threat to public health.And the traditional and uremia factors contribute to cardiovascular disease.The traditional factors include hypertension,diabetes mellitus,smoking,obesity,and hyperlipemia.Uremia factors include hyperphoshatemia,secondary hyperparathyroidism(SHPT),and micro-inflammation.Cardiovascular diseases are the most common causes of death in patients with end-stage renal disease(ESRD).Coronary artery calcification(CAC)is common in patients with CKD.Nowadays the prevalence and prognostic role of CAC in patients with CKD is reported in many studies,but the results are inconsistent.To explore the prevalence of CAC and confounding factors in patients with CKD,we conducted the first part of the paper.We conducted the second part of the paper,to understand the prevalence of cardiovascular event(CVE)and related factors.To explore the prevalence of CAC in the population and the association with cardiovascular events and mortality,we conducted the meta-analysis in the third part.Methods: The baseline parameters and CAC scores of 290 patients were collected in the first part of the paper,the value of neutrophil-lymphocyte ratio(NLR)was calculated.And serum samples of 131 patients were collected,the levels of interleukin 6(IL-6)and matrix Gla protein(MGP)were measured by enzyme linked immunosorbent assay(ELISA)method.The level of chemerin was measured in 67 patients with CKD.The prevalence of CAC was calculated,and the related factors were analyzed by binary logistic regressions analysis.The receiver operating characteristic curves for NLR and age were analyzed.We conducted 3-19 intervals visit to explore the prevalence of CVE in 276 CKD patients in the second part of the paper,and the related factors were analyzed by Cox proportional hazard model.Meta-analysis was conducted in the third part of the paper.Relevant literatures were identified and evaluated before July 2018 through multiple search strategies on PubMed,Embase,and Web of science.Cross-sectional or cohort(only baseline data)studies reporting estimates of CAC prevalence were included.Data extracted from eligible studies was synthesized to ES(CAC prevalence)and 95% confidence interval(CI).We performed subgroup and meta-regression analysis to test the source of heterogeneity.A random effects model was applied to calculate the pooled ES and 95%CI.Data extracted from eligible cohort studies was synthesized to ES(CAC prognosis)and 95%CI.We systematically searched databases for observational studies that explored baseline coronary artery calcification and subsequent cardiovascular or all-cause mortality risk in CKD patients with or without dialysis.Results: 290 CKD patients were included in the first part of the paper,168 patients with CAC,122 patients without CAC.The total prevalence of CAC was 57.93%,the prevalence of CAC was 68.87% in dialysis patients,and the prevalence of CAC in non-dialysis patients was 46.04%,the prevalence in dialysis patients was higher than that in non-dialysis patients.There was a higher level of IL-6 level and lower MGP level in CAC patients than that in non-CAC patients.The level of IL-6 was higher in severe CAC patients than that in mild CAC patients and non-CAC patients(P<0.05).The level of MGP was lower in severe CAC patients than that in non-CAC to mild CAC patients(P<0.05).The level of chemerin in moderate to severe CAC patients was lower than that in non-moderate to severe CAC patients(P=0.005).The level of IL-6 was positively correlated with NLR(r=0.330,P=0.001),age(r=0.396,P<0.001).There was a negative correlation between IL-6 and MGP(r=-0.319,P=0.002).The level of MGP was inversely associated with age(r=-0.187,P=0.016),NLR(r=-0.324,P=0.001).The level of MGP was positively associated with albumin(r=0.223,P =0.011).We found that age,diabetes mellitus,hyperphosphatemia,dialysis duration,NLR were risk factors for CAC by binary logistic regressions analysis.Higher IL-6 level was an independent risk factor for CAC,but higher MGP level has a protective effect for CAC by binary logistic regressions analysis.ROC curve showed that area under the receiver operating characteristic curve(AUC)of NLR was 0.704(95%CI 0.643-0.765,P<0.001),the combined AUC of NLR and age was 0.718(95%CI 0.658-0.778,P<0.001).The second part of the paper was conducted in 276 patients with CKD.There were 48 cardiovascular events in CKD patients,up to 17.39%.Cox proportional hazard model demonstrated that moderate to severe CAC was correlated with an increased risk for CVE(HR7.250;95%CI 3.192-16.470),hyperphophatemia was associated with an increased risk for CVE(HR 3.198;95%CI 2.026-5.049),higher MGP level was associated with a reduced risk for CVE(HR 0.340;95%CI 0.124-0.933).The meta-analysis included 47 studies in the third part of the paper.Of all the articles,38 studies were included in final analysis of CAC prevalence.The pooled prevalence of CAC in patients with CKD was 60%(95%CI,53%-68%).Subgroup analysis demonstrated that CKD stages,modality of dialysis,region,sample size,published year,study design may explain the variation.We found that age(r=1.009,P=0.032)and dialysis duration(r=1.005,P=0.021)were positively associated with CAC prevalence by meta-regression,but there was no association between CAC prevalence and the proportion of men in the studies(r=0.996,P=0.136).Twelve studies were analyzed for the association between CAC and prognosis,including three same studies with CAC prevalence.Overall,CAC was associated with an increased risk of all-cause mortality(HR 3.44;95%CI 2.40–4.94)and cardiovascular mortality(HR 3.87;95%CI 2.06–7.26),cardiovascular events(HR 2.09;95%CI 1.19-3.67),when comparing individual in the top CAC score group with those in bottle CAC score group.Conclusions: The prevalence of CAC in CKD3-5 is high,up to 57.93% in the first part of the paper.Older age(≥50),hyperphophatemia,dialysis duration,diabetic mellitus,IL-6,NLR are risk factors for CAC by binary logistic regression analysis.Higher MGP level is a protective factor for CAC.The joint parameter of NLR and age has a predictive value for CAC.The CVE is highly up to 17.39% for three to nineteen months interval visits in patients with CKD.Moderate to severe CAC,hyperphosphatemia,lower MGP level is associated with an increased risk for CVE.The pooled prevalence of CAC is up to 60%(95%CI,53%-68%).CAC is independently associated with cardiovascular,all-cause mortality risk and cardiovascular events among CKD patients.In view of high heterogeneity,large samples and multi-center clinical trials are still needed to explore the prevalence of CAC,and also prognostic role in patients with CKD.