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Angiotensin-related genetic determinants of cardiovascular disease in patients undergoing hemodialysis.

ABSTRACT: BACKGROUND:Cardiovascular mortality in patients receiving dialysis remains unacceptably high, with unexplained ancestry differences suggesting a genetic component. METHODS:We analyzed DNA samples from 37% of subjects enrolled in the EValuation Of Cinacalcet Hydrochloride (HCl) Therapy to Lower CardioVascular Events (EVOLVE) trial, a randomized trial conducted in patients receiving hemodialysis with secondary hyperparathyroidism, comparing cinacalcet to placebo on a background of usual care. DNA was analyzed for single-nucleotide polymorphisms (SNPs) in the genes encoding the angiotensin-converting enzyme receptor type I (AGTR1) and angiotensin-converting enzyme (ACE). Survival analyses were conducted separately in European Ancestry (EA) and African Ancestry (AfAn) due to known differences in cardiovascular events, minor alleles for the same variant and the frequency of minor alleles. Our primary determination was a meta-analysis across both races. RESULTS:Meta-analysis showed significant associations between rs5186 in AGTR1 and increased rates by 25-34% for the primary endpoint (composite of death or nonfatal myocardial infarction, hospitalization for unstable angina, heart failure or peripheral vascular event), all-cause mortality, cardiovascular mortality and heart failure; all P?

SUBMITTER: Moe SM

PROVIDER: S-EPMC6826165 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Angiotensin-related genetic determinants of cardiovascular disease in patients undergoing hemodialysis.

Moe Sharon M SM Long Jin J Schwantes-An Tae-Hwi Linus TL Decker Brian S BS Wetherill Leah L Edenberg Howard J HJ Xuei Xiaoling X Vatta Matteo M Foroud Tatiana M TM Chertow Glenn M GM

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 20191101 11

<h4>Background</h4>Cardiovascular mortality in patients receiving dialysis remains unacceptably high, with unexplained ancestry differences suggesting a genetic component.<h4>Methods</h4>We analyzed DNA samples from 37% of subjects enrolled in the EValuation Of Cinacalcet Hydrochloride (HCl) Therapy to Lower CardioVascular Events (EVOLVE) trial, a randomized trial conducted in patients receiving hemodialysis with secondary hyperparathyroidism, comparing cinacalcet to placebo on a background of u ...[more]

PMID: 29982608

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Project description:Hemodialysis (HD) is the most commonly-used renal replacement therapy for patients with end-stage renal disease worldwide. Arterio-venous fistula (AVF) is the vascular access of choice for HD patients with lowest risk of infection and thrombosis. In addition to environmental factors, genetic factors may also contribute to malfunction of AVF. Previous studies have demonstrated the effect of genotype polymorphisms of angiotensin converting enzyme on vascular access malfunction. We conducted a multicenter, cross-sectional study to evaluate the association between genetic polymorphisms of renin-angiotensin-aldosterone system and AVF malfunction. Totally, 577 patients were enrolled. Their mean age was 60 years old and 53% were male. HD patients with AVF malfunction had longer duration of HD (92.5 ± 68.1 vs. 61.2 ± 51.9 months, p < 0.001), lower prevalence of hypertension (44.8% vs. 55.3%, p = 0.025), right-sided (31.8% vs. 18.4%, p = 0.002) and upper arm AVF (26.6% vs. 9.7%, p < 0.001), and higher mean dynamic venous pressure (DVP) (147.8 ± 28.3 vs. 139.8 ± 30.0, p = 0.021). In subgroup analysis of different genders, location of AVF and DVP remained significant clinical risk factors of AVF malfunction in univariate and multivariate binary logistic regression in female HD patients. Among male HD patients, univariate binary logistic regression analysis revealed that right-side AVF and upper arm location are two important clinical risk factors. In addition, two single nucleotide polymorphisms (SNPs), rs275653 (Odds ratio 1.90, p = 0.038) and rs1492099 (Odds ratio 2.29, p = 0.017) of angiotensin II receptor 1 (AGTR1), were associated with increased risk of AVF malfunction. After adjustment for age and other clinical factors, minor allele-containing genotype polymorphisms (AA and CA) of rs1492099 still remained to be a significant risk factor of AVF malfunction (Odds ratio 3.63, p = 0.005). In conclusion, we demonstrated that rs1492099, a SNP of AGTR1 gene, could be a potential genetic risk factor of AVF malfunction in male HD patients.

Project description:BackgroundIt is becoming increasingly evident that the accurate assessment of fluid status is critical to ensure optimal care in patients undergoing hemodialysis (HD). Various fluid parameters, including overhydration (OH) and overhydration/extracellular water (OH/ECW%), which can be obtained using a bioimpedance spectroscopy device have been used to indicate the hydration status in such patients. This study aimed to explore the effect of these fluid parameters on cardiovascular events and determine which parameter was a better predictor of cardiovascular events (CVEs).MethodsA total of 227 patients who underwent HD at the Hangzhou Hospital of Traditional Chinese Medicine were enrolled in this prospective study between December 2017 and August 2018. Clinical data were collected, and the fluid status of patients was assessed using a body composition monitor. The patients were followed up until December 2020. The primary outcomes were CVEs. The association between fluid parameters and CVEs was analyzed using Cox proportional hazards models. The areas under the curve (AUCs) of receiver operating characteristic analysis and improvement in the global chi-squared value were used to compare the predictive values of fluid parameters for CVEs.ResultsDuring a median follow-up of 31 months, 66 CVEs were recorded. The patients with a higher absolute hydration index (OH) and a relative hydration index (OH/ECW%) exhibited an increased risk of developing CVEs. After adjusting for confounding factors, both OH [hazard ratio (HR) 1.279 per L, 95% confidence interval (CI) 1.047-1.562; p = 0.016] and OH/ECW% (HR 1.061 per %, 95% CI 1.017-1.108; p = 0.006) were independently associated with CVEs. The predictive ability of the absolute hydration index was superior to the relative hydration index based on AUC calculations for CVEs. Furthermore, a greater change in χ2 in predicting CVEs was noted for the absolute hydration index.ConclusionsBoth absolute hydration index and relative hydration index were found to be independent predictors of CVEs in univariate and multivariate analyses. Furthermore, the absolute hydration index had a better additive predictive value than the relative hydration index in predicting CVEs.

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Dataset Information

Angiotensin-related genetic determinants of cardiovascular disease in patients undergoing hemodialysis.

Publications

Angiotensin-related genetic determinants of cardiovascular disease in patients undergoing hemodialysis.

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