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Novel filtration markers as predictors of all-cause and cardiovascular mortality in US adults.

ABSTRACT: BACKGROUND:New filtration markers, including ?-trace protein (BTP) and ??-microglobulin (B2M), may, similar to cystatin C, enable a stronger prediction of mortality compared to serum creatinine-based estimated glomerular filtration rate (eGFRcr). We sought to evaluate these mortality associations in a representative sample of US adults. STUDY DESIGN:Prospective cohort study. SETTING & PARTICIPANTS:6,445 adults 20 years or older from the Third National Health and Nutrition Examination Survey (1988-1994) with mortality linkage through December 31, 2006. PREDICTORS:Serum cystatin C, BTP, and B2M levels and eGFRcr categorized into quintiles, with the highest quintile (lowest for eGFRcr) split into tertiles (subquintiles Q5a-Q5c). OUTCOMES:All-cause, cardiovascular disease, and coronary heart disease mortality. MEASUREMENTS:Demographic- and multivariable-adjusted Cox proportional hazard models. RESULTS:During follow-up, 2,392 deaths (cardiovascular, 1,079; coronary heart disease, 605) occurred. Levels of all 4 filtration markers were associated with mortality risk after adjusting for demographics (P trend<0.02). Adjusted for mortality risk factors, compared to the middle quintile, the highest subquintiles for cystatin C (Q5c: HR, 1.94; 95% CI, 1.43-2.62), BTP (Q5c: HR, 2.14; 95% CI, 1.56-2.94), and B2M (Q5c: HR, 2.58; 95% CI, 1.96-3.41) were associated with increased all-cause mortality risk, whereas the association was weaker for eGFRcr (Q5c: HR, 1.31; 95% CI, 0.84-2.04). Associations persisted for the novel markers and not for eGFRcr at eGFRcr ?60 mL/min/1.73 m². Trends were similar for cardiovascular disease and coronary heart disease mortality. LIMITATIONS:Single measurements of markers from long-term stored samples. CONCLUSIONS:The strong association of cystatin C level with mortality compared with serum creatinine estimates is shared by BTP and B2M. This supports the utility of alternative filtration markers beyond creatinine when improved risk prediction related to decreased GFR is needed.

SUBMITTER: Foster MC

PROVIDER: S-EPMC4076821 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Novel filtration markers as predictors of all-cause and cardiovascular mortality in US adults.

Foster Meredith C MC Inker Lesley A LA Levey Andrew S AS Selvin Elizabeth E Eckfeldt John J Juraschek Stephen P SP Coresh Josef J

American journal of kidney diseases : the official journal of the National Kidney Foundation 20130319 1

<h4>Background</h4>New filtration markers, including β-trace protein (BTP) and β₂-microglobulin (B2M), may, similar to cystatin C, enable a stronger prediction of mortality compared to serum creatinine-based estimated glomerular filtration rate (eGFRcr). We sought to evaluate these mortality associations in a representative sample of US adults.<h4>Study design</h4>Prospective cohort study.<h4>Setting & participants</h4>6,445 adults 20 years or older from the Third National Health and Nutrition E ...[more]

PMID: 23518194

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Project description:Background and objectivesSerum ?-trace protein (BTP) and ?-2 microglobulin (B2M) are associated with risk of ESRD and death in the general population and in populations at high risk for these outcomes (GP/HR) and those with CKD, but results differ among studies.Design, setting, participants, & measurementsWe performed an individual patient-level meta-analysis including three GP/HR studies (n=17,903 participants) and three CKD studies (n=5415). We compared associations, risk prediction, and improvement in reclassification of eGFR using BTP (eGFRBTP) and B2M (eGFRB2M) alone and the average (eGFRavg) of eGFRBTP, eGFRB2M, creatinine (eGFRcr), and cystatin C (eGFRcys), to eGFRcr, eGFRcys, and their combination (eGFRcr-cys) for ESRD (2075 events) and death (7275 events).ResultsMean (SD) follow up times for ESRD and mortality for GP/HR and CKD studies were 13 (4), 6.2 (3.2), 14 (5), and 7.5 (3.9) years, respectively. Compared with eGFRcr, eGFRBTP and eGFRB2M improved risk associations and modestly improved prediction for ESRD and death even after adjustment for established risk factors. eGFRavg provided the most consistent improvement in associations and prediction across both outcomes and populations. Assessment of heterogeneity did not yield clinically relevant differences. For ESRD, addition of albuminuria substantially attenuated the improvement in risk prediction and risk classification with novel filtration markers. For mortality, addition of albuminuria did not affect the improvement in risk prediction with the use of novel markers, but lessened improvement in risk classification, especially for the CKD cohort.ConclusionsThese markers do not provide substantial additional prognostic information to eGFRcr and albuminuria, but may be appropriate in circumstances where eGFRcr is not accurate or albuminuria is not available. Educational efforts to increase measurement of albuminuria in clinical practice may be more cost-effective than measurement of BTP and B2M for improving prognostic information.

Project description:Background and objectivesKidney disease progression, assessed by change in eGFR on the basis of creatinine, is an independent risk factor for cardiovascular disease and death. This study aimed to evaluate whether changes in multiple filtration markers, individually and combined, were associated with cardiovascular disease and death.Design, setting, participants, & measurementsCreatinine, cystatin C, and ?2-microglobulin were measured among 9716 Atherosclerosis Risk in Communities Study participants in 1990-1992 and 1996-1998. Percentage change in three filtration markers (eGFR on the basis of creatinine, eGFR on the basis of cystatin C, and 1/?2-microglobulin) individually and the average of percentage change across all three filtration markers were calculated. Cardiovascular events and deaths were ascertained from 1996 to 2011. Cox regression models were adjusted for established risk factors for cardiovascular disease and mortality and first measurement of eGFR on the basis of creatinine.ResultsDuring a median follow-up of 14 years, there were 1922 cardiovascular events and 2285 deaths from any cause. Decline of >30% in each filtration marker was significantly associated with higher risk of mortality compared with stable kidney function (-9.9% to +9.9% change in the filtration marker) with hazard ratios (95% confidence intervals) of 1.91 (1.67 to 2.18) for eGFR on the basis of creatinine, 2.29 (1.99 to 2.63) for eGFR on the basis of cystatin C, and 2.48 (2.15 to 2.86) for 1/?2-microglobulin, with similar associations for cardiovascular disease. An average decline of >30% across the three markers was strongly associated with higher risk of all-cause mortality (hazard ratio, 2.82; 95% confidence interval, 2.42 to 3.29).ConclusionsKidney disease progression was assessed using >30% decline in eGFR on the basis of creatinine, eGFR on the basis of cystatin C, and 1/?2-microglobulin and average decline of >30% across the three filtration markers is strongly associated with risk of cardiovascular disease and death.

Project description:BACKGROUND:A growing number of serum filtration markers are associated with mortality and end-stage renal disease (ESRD) in adults. Whether ?-trace protein (BTP) and ?2-microglobulin (B2M) are associated with these outcomes in adults with type 2 diabetes is not known. STUDY DESIGN:Longitudinal cohort study. SETTING & PARTICIPANTS:250 Pima Indians with type 2 diabetes (69% women; mean age, 42 years; mean diabetes duration, 11 years). PREDICTORS:Serum BTP, B2M, and glomerular filtration rate measured by iothalamate clearance (mGFR) or estimated using creatinine (eGFRcr) or cystatin C level (eGFRcys). OUTCOMES & MEASUREMENTS:Incident ESRD and all-cause mortality through December 2013. HRs were reported per interquartile range decrease of the inverse of BTP and B2M (1/BTP and 1/B2M) using Cox regression. Improvement in risk prediction with the addition of BTP or B2M level to established markers (eGFRcys with mGFR or eGFRcr) was evaluated using C statistics, continuous net reclassification improvement, and relative integrated discrimination improvement (RIDI). RESULTS:During a median follow-up of 14 years, 69 participants developed ESRD and 95 died. Both novel markers were associated with ESRD in multivariable models. BTP level remained statistically significant after further adjustment for mGFR (1/BTP, 1.53 [95% CI, 1.01-2.30]; 1/B2M, 1.54 [95% CI, 0.98-2.42]). B2M level was associated with mortality in multivariable models and after further adjustment for mGFR (HR, 2.12; 95% CI, 1.38-3.26). The addition of B2M level to established markers increased the C statistic for mortality but only weakly when assessed by either continuous net reclassification improvement or RIDI; none was improved for ESRD by the addition of these markers. LIMITATIONS:Small sample size, single measurements of markers. CONCLUSIONS:In Pima Indians with type 2 diabetes, BTP and, to a lesser extent, B2M levels were associated with ESRD. B2M level was associated with mortality after adjustment for traditional risk factors and established filtration markers. Further studies are warranted to confirm whether inclusion of B2M level in a multimarker approach leads to improved risk prediction for mortality in this population.

Project description:Importance:Depression is associated with increased disease burden worldwide and with higher risk of mortality in Western populations. Objective:To investigate whether depression is a risk factor for all-cause and cardiovascular disease (CVD) mortality in adults in China. Design, Setting, and Participants:This cohort study prospectively followed adults aged 30 to 79 years in the China Kadoorie Biobank (CKB) study from June 1, 2004, to December 31, 2016, and adults aged 32 to 104 years in the Dongfeng-Tongji (DFTJ) study from September 1, 2008, to December 31, 2016. Data analysis was conducted from June 1, 2018, to March 31, 2019. Main Outcomes and Measures:Depression was evaluated using the Chinese version of the World Health Organization Composite International Diagnostic Interview-Short Form in the CKB cohort and a 7-item symptoms questionnaire modified from the Composite International Diagnostic Interview-Short Form in the DFTJ cohort. Multivariable-adjusted Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs for the association of depression with mortality. Covariates in the final models included sociodemographic characteristics, lifestyle factors, and personal and family medical history. Results:Among 512?712 individuals (mean [SD] age, 52.0 [10.7] years; 302?509 [59.0%] women) in the CKB cohort, there were 44?065 deaths, including 18?273 CVD deaths. The 12-month prevalence of major depressive episode in the CKB cohort was 0.64%, and the 1-month prevalence of clinically significant depressive symptoms was 17.96% in the DFTJ cohort. Among 26?298 individuals (mean [SD] age, 63.6 [7.8] years; 14?508 [55.2%] women) in the DFTJ cohort, there were 2571 deaths, including 1013 CVD deaths. In the multivariable-adjusted model, depression was associated with increased risk of all-cause mortality (CKB cohort: HR, 1.32 [95% CI, 1.20-1.46]; P?<?.001; DFTJ cohort: HR, 1.17 [95% CI, 1.06-1.29]; P?=?.002) and CVD mortality (CKB cohort: HR, 1.22 [95% CI, 1.04-1.44]; P?=?.02; DFTJ cohort: HR, 1.32 [95% CI, 1.14-1.54]; P?<?.001). In both cohorts, men had statistically significantly higher risk of all-cause mortality (CKB cohort: HR, 1.53 [95% CI, 1.32-1.76]; DFTJ cohort: HR, 1.24 [95% CI, 1.10-1.41]) and CVD mortality (CKB cohort: HR, 1.39 [95% CI, 1.10-1.76]; DFTJ cohort: HR, 1.49 [95% CI, 1.23-1.80]), while the association of depression with mortality among women was only significant for all-cause mortality in the CKB cohort (HR, 1.19 [95% CI, 1.03-1.37]). Conclusions and Relevance:These findings suggest that depression is associated with an increased risk of all-cause and CVD mortality in adults in China, particularly in men. These findings highlight the importance and urgency of depression management as a measure for preventing premature deaths in China.

Dataset Information

Novel filtration markers as predictors of all-cause and cardiovascular mortality in US adults.

Publications

Novel filtration markers as predictors of all-cause and cardiovascular mortality in US adults.

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