Worsening calcification propensity precedes all-cause and cardiovascular mortality in haemodialyzed patients.
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ABSTRACT:
SUBMITTER: Lorenz G
PROVIDER: S-EPMC5645333 | biostudies-literature | 2017 Oct
REPOSITORIES: biostudies-literature
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Worsening calcification propensity precedes all-cause and cardiovascular mortality in haemodialyzed patients.
Lorenz Georg G Steubl Dominik D Kemmner Stephan S Pasch Andreas A Koch-Sembdner Wilhelm W Pham Dang D Haller Bernhard B Bachmann Quirin Q Mayer Christopher C CC Wassertheurer Siegfried S Angermann Susanne S Lech Maciej M Moog Philipp P Bauer Axel A Heemann Uwe U Schmaderer Christoph C
Scientific reports 20171017 1
A novel in-vitro test (T<sub>50</sub>-test) assesses ex-vivo serum calcification propensity which predicts mortality in HD patients. The association of longitudinal changes of T<sub>50</sub> with all-cause and cardiovascular mortality has not been investigated. We assessed T<sub>50</sub> in paired sera collected at baseline and at 24 months in 188 prevalent European HD patients from the ISAR cohort, most of whom were Caucasians. Patients were followed for another 19 [interquartile range: 11-37] ...[more]
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Project description:Medial arterial calcification is accelerated in patients with CKD and strongly associated with increased arterial rigidity and cardiovascular mortality. Recently, a novel in vitro blood test that provides an overall measure of calcification propensity by monitoring the maturation time (T50) of calciprotein particles in serum was described. We used this test to measure serum T50 in a prospective cohort of 184 patients with stages 3 and 4 CKD, with a median of 5.3 years of follow-up. At baseline, the major determinants of serum calcification propensity included higher serum phosphate, ionized calcium, increased bone osteoclastic activity, and lower free fetuin-A, plasma pyrophosphate, and albumin concentrations, which accounted for 49% of the variation in this parameter. Increased serum calcification propensity at baseline independently associated with aortic pulse wave velocity in the complete cohort and progressive aortic stiffening over 30 months in a subgroup of 93 patients. After adjustment for demographic, renal, cardiovascular, and biochemical covariates, including serum phosphate, risk of death among patients in the lowest T50 tertile was more than two times the risk among patients in the highest T50 tertile (adjusted hazard ratio, 2.2; 95% confidence interval, 1.1 to 5.4; P=0.04). This effect was lost, however, after additional adjustment for aortic stiffness, suggesting a shared causal pathway. Longitudinally, serum calcification propensity measurements remained temporally stable (intraclass correlation=0.81). These results suggest that serum T50 may be helpful as a biomarker in designing methods to improve defenses against vascular calcification.
| S-EPMC3904573 | biostudies-other
Project description:BackgroundVascular calcification is a major contributor to the high cardiac burden among hemodialysis patients. A novel in vitro T50-test, which determines calcification propensity of human serum, may identify patients at high risk for cardiovascular (CV) disease and mortality. We evaluated whether T50 predicts mortality and hospitalizations among an unselected cohort of hemodialysis patients.MethodsThis prospective clinical study included 776 incident and prevalent hemodialysis patients from 8 dialysis centers in Spain. T50 and fetuin-A were determined at Calciscon AG, all other clinical data were retrieved from the European Clinical Database. After their baseline T50 measurement, patients were followed for two years for the occurrence of all-cause mortality, CV-related mortality, all-cause and CV-related hospitalizations. Outcome assessment was performed with proportional subdistribution hazards regression modelling.ResultsPatients who died during follow-up had a significantly lower T50 at baseline as compared to those who survived (269.6 vs. 287.7 min, p = 0.001). A cross-validated model (mean c statistic: 0.5767) identified T50 as a linear predictor of all-cause-mortality (subdistribution hazard ratio (per min): 0.9957, 95% CI [0.9933;0.9981]). T50 remained significant after inclusion of known predictors. There was no evidence for prediction of CV-related outcomes, but for all-cause hospitalizations (mean c statistic: 0.5284).ConclusionT50 was identified as an independent predictor of all-cause mortality among an unselected cohort of hemodialysis patients. However, the additional predictive value of T50 added to known mortality predictors was limited. Future studies are needed to assess the predictive value of T50 for CV-related events in unselected hemodialysis patients.
| S-EPMC9933331 | biostudies-literature
Project description:Studies on aortic arch calcification (AAC) and mortality risk in maintenance dialysis patients have yielded conflicting findings. We conducted this meta-analysis to investigate the association between the presence of AAC and cardiovascular or all-cause and mortality risk in maintenance dialysis patients. Observational studies evaluating baseline AAC and cardiovascular or all-cause mortality risk in maintenance dialysis patients were searched through the PubMed and Embase, CNKI, VIP and Wanfang databases until January 2016. A total of 8 studies with 3,256 dialysis patients were identified. Compared with patients without AAC, the presence of AAC was associated with greater risk of cardiovascular mortality (hazard risk [HR] 2.30; 95% confidence intervals [CI] 1.78-2.97) and all-cause mortality (HR 1.44; 95% CI 1.19-1.75). Subgroup analyses indicated that the pooled HR for cardiovascular and all-cause mortality was 2.31 (95% CI 1.57-3.40) and 1.45 (95% CI 1.08-1.96) for the grade 2/3 AAC. Peritoneal dialysis patients with AAC had greater cardiovascular (HR 3.93 vs. HR 2.10) and all-cause mortality (HR 2.36 vs. HR 1.33) than hemodialysis patients. The AAC appears to be independently associated with excessive cardiovascular and all-cause mortality in maintenance dialysis patients. Regular follow-up AAC might be helpful to stratify mortality risk in dialysis patients.
| S-EPMC5066315 | biostudies-literature
Project description:Unlabelled?BackgroundThis study aimed to examine whether the coronary artery calcification score (CaCS) was associated with the prognosis of peritoneal dialysis (PD) patients. ?MethodsAdult PD patients who were clinically stable for at least 2 months were recruited for this prospective, observational cohort study. Coronary artery calcification was assessed using multislice spiral computed tomography and was recorded according to the Agatston score. The endpoints including all-cause mortality, cardiovascular events, and cardiovascular mortality were assessed. Multivariate Cox regression was used to identify independent predictors of all-cause mortality, cardiovascular events (CVEs), and cardiovascular mortality. ?ResultsA total of 179 PD patients (86 men) with a mean age of 63.5 ± 14.8 years were recruited for this study. Coronary artery calcification scores ranging from 0 to 5,257 were stratified as follows: no (CaCS = 0, n = 54), low (0 < CaCS < 400, n = 72), and high (CaCS ? 400, n = 53) calcification. The follow-up duration was 30.6 ± 16.2 (24-63) months. Compared with the no calcification group, patients with a higher CaCS were older and had lower diastolic blood pressure, residual renal function, and serum albumin, and higher HbA1C and serum insulin. Multivariate Cox regression revealed that the CaCS was an independent predictor for all the 3 endpoints after adjustment in PD patients. ?ConclusionsCaCS was an independent predictor of all-cause mortality, cardiovascular events, and cardiovascular mortality in patients receiving peritoneal dialysis.
| S-EPMC4803361 | biostudies-literature
Project description:Background and aimsCVD risks associated with coronary artery calcification (CAC) and aortic calcification (AC) are well known, but less is known about other calcified arteries. We aimed to assess the associations of arterial calcification in the breast, splenic, and internal and external iliac arteries with CVD risk factors and mortality.MethodsWe conducted a case-cohort study nested in a cohort of 5196 individuals who self-referred or were referred by a health care provider for whole body computed tomography (CT), including a random subcohort (n = 395) and total and CVD mortality cases (n = 298 and n = 90), who died during a median follow-up of 9.4 years. Arterial calcification in the breast, splenic, and internal and external iliac arteries on CT was scored using a simple visual score. AC and CAC were previously measured using the Agatston technique. Logistic regression models were made to study associations of CVD risk factors with calcification in the different vascular beds. Prentice-weighted Cox proportional hazards models adjusted for CVD risk factors, and calcification in other vascular beds, were used to study associations with mortality.ResultsIn the subcohort, the mean age was 56.6 years (SD 11.1) and 41.3% were female. The prevalence of calcification on CT, was 11.6% in the splenic, 47.9% in the internal iliac and 9.5% in the external iliac arteries, while 3.7% of women had breast artery calcification (BAC). Calcification in the splenic and iliac arteries was associated with calcification in the abdominal aorta but differentially associated with other CVD risk factors in logistic regression models. The prevalence of BAC was too low to fit these multivariable models. Calcification of the external iliac arteries was significantly associated with both all-cause and CVD mortality, but no longer significant when adjusted for CVD risk factors. Breast artery calcification was associated with both all-cause and CVD mortality independent of CVD risk factors and AAC and CAC (all-cause HR 5.67 [95% CI 1.50-21.41]).ConclusionsRisk factors associated with calcification, and the association of calcification with risk of mortality differ across vascular beds, possibly reflecting different pathophysiology.
| S-EPMC5376519 | biostudies-literature
Project description:To investigate the association of the thiazolidinediones (TZDs), rosiglitazone, and pioglitazone, together and individually on the risk of cardiovascular outcomes and all-cause mortality, using time-updated propensity score adjusted analysis.We conducted a retrospective cohort study in a large vertically integrated health system in southeast Michigan. Cohort inclusion criteria included adult patients with diabetes treated with oral medications and followed longitudinally within the health system between 1 January 2000 and 1 December 2006. The primary outcome was fatal and non-fatal acute myocardial infarction (AMI). Secondary outcomes included hospitalizations for congestive heart failure (CHF), fatal, and non-fatal cerebrovascular accidents (CVA) and transient ischemic attacks (TIA), combined coronary heart disease (CHD) events, and all-cause mortality.19,171 patients were included in this study. Use of TZDs (adjusted hazard ratio (aHR) with propensity adjustment (PA), 0.92; 95% confidence interval (CI) 0.73-1.17), rosiglitazone (aHR with PA, 1.06; 95%CI 0.66-1.70), and pioglitazone (aHR with PA, 0.91; 95%CI 0.69-1.21) was not associated with a higher risk of AMI. However, pioglitazone use was associated with a reduction in all-cause mortality (aHR with PA, 0.60; 95%CI 0.42-0.96). Compared with rosiglitazone, pioglitazone use was associated with a lower risk of all outcomes assessed, particularly CHF (p = 0.013) and combined CHD events (p = 0.048).Our findings suggest that pioglitazone may have a more favorable risk profile when compared to rosiglitazone, arguing against a singular effect for TZDs on cardiovascular outcomes.
| S-EPMC2919167 | biostudies-literature
Project description:BACKGROUND AND OBJECTIVES:Patients receiving hemodialysis are at risk of cardiovascular events. A novel blood test (T50 test) determines the individual calcification propensity of blood. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:T50 was determined in 2785 baseline serum samples of patients receiving hemodialysis enrolled in the Evaluation of Cinacalcet Therapy to Lower Cardiovascular Events (EVOLVE) trial and the T50 results were related to patient outcomes. RESULTS:Serum albumin, bicarbonate, HDL cholesterol, and creatinine were the main factors positively/directly and phosphate was the main factor negatively/inversely associated with T50. The primary composite end point (all-cause mortality, myocardial infarction [MI], hospitalization for unstable angina, heart failure, or peripheral vascular event [PVE]) was reached in 1350 patients after a median follow-up time of 619 days. After adjustments for confounding, a lower T50 was independently associated with a higher risk of the primary composite end point as a continuous measure (hazard ratio [HR] per 1 SD lower T50, 1.15; 95% confidence interval [95% CI], 1.08 to 1.22; P<0.001). Furthermore, lower T50 was associated with a higher risk in all-cause mortality (HR per 1 SD lower T50, 1.10; 95% CI, 1.02 to 1.17; P=0.001), MI (HR per 1 SD lower T50, 1.38; 95% CI, 1.19 to 1.60; P<0.001), and PVE (HR per 1 SD lower T50, 1.22; 95% CI, 1.05 to 1.42; P=0.01). T50 improved risk prediction (integrated discrimination improvement and net reclassification improvement, P<0.001 and P=0.001) of the primary composite end point. CONCLUSIONS:Blood calcification propensity was independently associated with the primary composite end point, all-cause mortality, MI, and PVE in the EVOLVE study and improved risk prediction. Prospective trials should clarify whether T50-guided therapies improve outcomes.
| S-EPMC5293330 | biostudies-literature
Project description:Background: The propensity of serum to calcify, as assessed by the T50-test, associates with mortality in patients with chronic kidney disease. In chronic heart failure, phosphate and fibroblast growth factor-23 (FGF-23), which are important components of the vascular calcification pathway, have been linked to patient survival. Here, we investigated whether T50 associates with overall and cardiovascular survival in patients with chronic heart failure with reduced ejection fraction (HFrEF). Methods: We measured T50, intact and c-terminal FGF-23 levels in a cohort of 306 HFrEF patients. Associations with overall and cardiovascular mortality were analyzed in survival analysis and Cox-regression models. Results: After a median follow-up time of 3.2 years (25th-75th percentile: 2.0-4.9 years), 114 patients (37.3%) died due to any cause and 76 patients (24.8%) died due to cardiovascular causes. 139 patients (45.4%) had ischemic and 167 patients (54.6%) had non-ischemic HFrEF. Patients with ischemic HFrEF in the lowest T50-tertile had significantly greater 2-year cardiovascular mortality compared to patients in higher tertiles (p = 0.011). In ischemic but not in non-ischemic HFrEF, T50 was significantly associated with cardiovascular mortality in univariate (p = 0.041) and fully adjusted (p = 0.046) Cox regression analysis. Significant associations of intact and c-terminal FGF-23 with all-cause and cardiovascular mortality in univariate Cox regression analysis did not remain significant after adjustment for confounding factors. Conclusion: T50 is associated with 2-year cardiovascular mortality in patients with ischemic HFrEF but not in non-ischemic HFrEF. More research on the role of T50 measurements in coronary artery disease is warranted.
| S-EPMC8249741 | biostudies-literature
Project description:BackgroundThere were no reports on the associations of aortic arch calcification (AAC) measured by chest X-ray with all-cause mortality and cardiovascular disease (CVD) in older general population. Moreover, previous studies of hemodialysis patients showed that AAC was correlated with left ventricular hypertrophy (LVH) and predicted CVD jointly. Whether the effects remained in the general population is unknown. We examined the associations of AAC with all-cause mortality and CVD in general population and the risk associated with the coexistence of AAC and LVH.MethodsPresence and severity (grades 0-2) of AAC were measured by chest X-ray, and LVH was identified by 12-lead electrocardiogram in 27,166 Chinese aged 50+ years free of CVD from Guangzhou Biobank Cohort Study. Multivariate Cox regressions were used to examine associations of AAC and LVH with outcomes.FindingsDuring an average follow-up of 14·3 years, 5,350 deaths and 4,012 CVD occurred. Compared to those without AAC at baseline, those with AAC had higher risks of all-cause mortality (HR 1·24, 95% CI 1·17-1·31) and CVD (HR 1·22, 95% CI 1·14-1·30), with dose-response relationship (P ≤ 0·001). Furthermore, those with coexistence of AAC and LVH had higher risks of all-cause mortality (HR 1·72, 95% CI 1·37-2·15) and CVD (HR 1·80, 95% CI 1·40-2·32) than those without AAC and LVH.InterpretationAs chest X-ray has been performed commonly for health screening and in hospital patients when first admitted, AAC measured by chest X-ray can be further applied to assist cardiovascular risk stratification in the community and clinical settings.FundingThe Natural Science Foundation of China (No. 81941019).
| S-EPMC9079300 | biostudies-literature
Project description:Importance:Few data are available to guide clinical recommendations for individuals with high levels of physical activity in the presence of clinically significant coronary artery calcification (CAC). Objective:To assess the association among high levels of physical activity, prevalent CAC, and subsequent mortality risk. Design, Setting, and Participants:The Cooper Center Longitudinal Study is a prospective observational study of patients from the Cooper Clinic, a preventive medicine facility. The present study included participants seen from January 13, 1998, through December 30, 2013, with mortality follow-up through December 31, 2014. A total of 21 758 generally healthy men without prevalent cardiovascular disease (CVD) were included if they reported their physical activity level and underwent CAC scanning. Data were analyzed from September 26, 2017, through May 2, 2018. Exposures:Self-reported physical activity was categorized into at least 3000 (n = 1561), 1500 to 2999 (n = 3750), and less than 1500 (n = 16 447) metabolic equivalent of task (MET)-minutes/week (min/wk). The CAC scores were categorized into at least 100 (n = 5314) and less than 100 (n = 16 444) Agatston units (AU). Main Outcomes and Measures:All-cause and CVD mortality collected from the National Death Index Plus. Results:Among the 21 758 male participants, baseline mean (SD) age was 51.7 (8.4) years. Men with at least 3000 MET-min/wk were more likely to have prevalent CAC of at least 100 AU (relative risk, 1.11; 95% CI, 1.03-1.20) compared with those accumulating less physical activity. In the group with physical activity of at least 3000 MET-min/wk and CAC of at least 100 AU, mean (SD) CAC level was 807 (1120) AU. After a mean (SD) follow-up of 10.4 (4.3) years, 759 all-cause and 180 CVD deaths occurred, including 40 all-cause and 10 CVD deaths among those with physical activity of at least 3000 MET-min/wk. Men with CAC of less than 100 AU and physical activity of at least 3000 MET-min/wk were about half as likely to die compared with men with less than 1500 MET-min/wk (hazard ratio [HR], 0.52; 95% CI, 0.29-0.91). In the group with CAC of at least 100 AU, men with at least 3000 MET-min/wk did not have a significant increase in all-cause mortality (HR, 0.77; 95% CI, 0.52-1.15) when compared with men with physical activity of less than 1500 MET-min/wk. In the least active men, those with CAC of at least 100 AU were twice as likely to die of CVD compared with those with CAC of less than 100 AU (HR, 1.93; 95% CI, 1.34-2.78). Conclusions and Relevance:This study suggests there is evidence that high levels of physical activity (≥3000 MET-min/wk) are associated with prevalent CAC but are not associated with increased all-cause or CVD mortality after a decade of follow-up, even in the presence of clinically significant CAC levels.
| S-EPMC6439619 | biostudies-literature