Comparison of three creatinine-based equations to predict adverse outcome in a cardiovascular high-risk cohort: an investigation using the SPRINT research materials
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PROVIDER: S-EPMC10836528 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:Recent studies including the SPRINT trial have shown beneficial effects of intensive systolic blood pressure reduction over the standard approach. The awareness of the J-curve for diastolic blood pressure (DBP) causes some uncertainty regarding the net clinical effects of blood pressure reduction. The current analysis was performed to investigate effects of low on-treatment DBP on cardiovascular risk in the SPRINT population. The primary composite outcome was the occurrence of myocardial infarction, acute coronary syndrome not resulting in myocardial infarction, stroke, acute decompensated heart failure or death from cardiovascular causes. The prevalence of primary outcomes was significantly higher in subjects within low DBP in both standard (44-67 mmHg [10.8%] vs 67-73 mmHg [6.7%] vs 73-78 mmHg [5.1%] vs 78-83 mmHg [4.4%] vs 83-113 mmHg [4.3%], p < 0.001) and intensive treatment (38-61 mmHg [6.7%] vs 61-66 mmHg [4.1%] vs 66-70 mmHg [4.5%] vs 70-74 mmHg [2.7%] vs 74-113 mmHg [3.4%], p < 0.001) arms. After adjusting for covariates, low DBP showed no significant effects on cardiovascular risk. Therefore, while reaching blood pressure targets, low DBP should not be a matter of concern.
| S-EPMC6737094 | biostudies-literature
Project description:BackgroundAtrial fibrillation (AF) is linked to increased risk of dementia and cognitive decline, but whether AF and its ascertainment methods affect cognition in patients with hypertension has received less attention.MethodsWe studied 8469 participants with elevated systolic blood pressure who were free of stroke and diabetes at baseline enrolled in the Systolic Blood Pressure Intervention Trial. AF was ascertained using three approaches: self-report of AF, AF from a safety event, and study electrocardiogram-determined (ECG) AF. Mild cognitive impairment (MCI) and probable dementia (PD) were ascertained from in-person assessments or telephone interviews from the participant or an informant. We used Cox proportional hazard models to estimate hazard ratios for the association of AF (all three sources) with outcomes of MCI, PD, and a composite MCI/PD outcome.ResultsDuring a mean follow-up of 4.6 years, 974 (12%) participants had AF (prevalent or incident), 634 were diagnosed with MCI, and 316 with PD. When comparing those with AF (from any source) to those without, no differences were detected in the risk of MCI or PD. Comparison between AF sources found ECG-AF to be associated with an elevated risk of MCI/PD (hazard ratio (HR) 1.59, 95% confidence interval (95%CI) 1.06, 2.38). Neither AF ascertained through safety events nor self-reported AF were associated with MCI or PD.ConclusionThe association of AF with incidence of MCI/PD differed by method of AF ascertainment. Case definition of AF and quantification of AF burden are important factors in studies evaluating the link between AF and cognitive dysfunction.
| S-EPMC9572519 | biostudies-literature
Project description:Orthostatic hypotension (OH) is frequently observed with hypertension treatment, but its contribution to adverse outcomes is unknown. The SPRINT (Systolic Blood Pressure Intervention Trial) was a randomized trial of adults, age ≥50 years at high risk for cardiovascular disease with a seated systolic blood pressure (BP) of 130 to 180 mm Hg and a standing systolic BP ≥110 mm Hg. Participants were randomized to a systolic BP treatment goal of either <120 or <140 mm Hg. OH was defined as a drop in systolic BP ≥20 or diastolic BP ≥10 mm Hg 1 minute after standing from a seated position. We used Cox models to examine the association of OH with cardiovascular disease or adverse study events by randomized BP goal. During the follow-up period (median 3years), there were 1170 (5.7%) instances of OH among those assigned a standard BP goal and 1057 (5.0%) among those assigned the intensive BP goal. OH was not associated with higher risk of cardiovascular disease events (primary outcome: hazard ratio 1.06 [95% CI, 0.78-1.44]). Moreover, OH was not associated with syncope, electrolyte abnormalities, injurious falls, or acute renal failure. OH was associated with hypotension-related hospitalizations or emergency department visits (hazard ratio, 1.77 [95% CI, 1.11-2.82]) and bradycardia (hazard ratio, 1.94 [95% CI, 1.19-3.15]), but these associations did not differ by BP treatment goal. OH was not associated with a higher risk of cardiovascular disease events, and BP treatment goal had no effect on OH's association with hypotension and bradycardia. Symptomless OH during hypertension treatment should not be viewed as a reason to down-titrate therapy even in the setting of a lower BP goal. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT01206062.
| S-EPMC7261502 | biostudies-literature
Project description:SPRINT (Systolic Blood Pressure Intervention Trial) highlighted the benefits of intensive targeted antihypertensive therapy but resulted in higher rates of treatment-related adverse events. Blood pressure (BP) variability has emerged as a significant predictor of outcomes over and above levels of BP. Using the SPRINT data set, we aimed to determine the relationship of BP variability with cardiovascular outcomes and side effects of antihypertensive therapy. The analyses included all participants randomized in SPRINT who reached the target systolic BP (SBP) for their respective groups (intensive < 120 mm Hg; standard < 140 mm Hg). Coefficients of variation (CV) for SBP, diastolic BP (DBP), and PP for each patient characterized variability. Student t test was used to compare treatment arms for each CV metric. Cox proportional hazards regression was used to identify independent predictors of the SPRINT primary outcome and adverse events. P < .15 on univariate analysis was required to enter the model and P < .05 to remain in it. A total of 8884 patients (4561 standard group; 4323 intensive group) met inclusion criteria. DBP CV differed between the groups (9.12 ± 3.20 standard group; 9.47 ± 3.49 intensive group [P < .0001]). DBP CV predicted a greater hazard for the primary outcome (hazard ratio [HR], 1.14) in the overall model as well as separate analyses by treatment arms (standard group HR, 1.15; intensive group HR, 1.19), each P < .0001. DBP CV also independently predicted a greater hazard for acute kidney injury (HR, 1.12) and hypotensive events (HR, 1.12). Visit-to-visit DBP variability independently predicted worse cardiovascular outcomes and hypoperfusion-related adverse events in SPRINT.
| S-EPMC8031192 | biostudies-literature
Project description:BackgroundAccurate estimation of glomerular filtration rate (GFR) is important for diagnosis and risk stratification in chronic kidney disease and for selection of living donors. Ethnic differences have required correction factors in the originally developed creatinine-based GFR estimation equations for populations around the world. Existing equations have not been validated in the vegetarian Indian population. We examined the performance of creatinine and cystatin-based GFR estimating equations in Indians.MethodsGFR was measured by urinary clearance of inulin. Serum creatinine was measured using IDMS-traceable Jaffe's and enzymatic assays, and cystatin C by colloidal gold immunoassay. Dietary protein intake was calculated by measuring urinary nitrogen appearance. Bias, precision and accuracy were calculated for the eGFR equations.ResultsA total of 130 participants (63 healthy kidney donors and 67 with CKD) were studied. About 50% were vegetarians, and the remainder ate meat 3.8 times every month. The average creatinine excretion were 14.7 mg/kg/day (95% CI: 13.5 to 15.9 mg/kg/day) and 12.4 mg/kg/day (95% CI: 11.2 to 13.6 mg/kg/day) in males and females, respectively. The average daily protein intake was 46.1 g/day (95% CI: 43.2 to 48.8 g/day). The mean mGFR in the study population was 51.66 ± 31.68 ml/min/1.73m2. All creatinine-based eGFR equations overestimated GFR (p < 0.01 for each creatinine based eGFR equation). However, eGFR by CKD-EPICys was not significantly different from mGFR (p = 0.38). The CKD-EPICys exhibited lowest bias [mean bias: -3.53 ± 14.70 ml/min/1.73m2 (95% CI: -0.608 to -0.98)] and highest accuracy (P30: 74.6%). The GFR in the healthy population was 79.44 ± 20.19 (range: 41.90-134.50) ml/min/1.73m2.ConclusionExisting creatinine-based GFR estimating equations overestimate GFR in Indians. An appropriately powered study is needed to develop either a correction factor or a new equation for accurate assessment of kidney function in the Indian population.
| S-EPMC5796440 | biostudies-literature
Project description:Patients with acute myeloid leukemia (AML) suffer dismal prognosis and the most adverse subpopulation within each tumor determines patient’s prognosis. To better understand challenging features in AML, we studied individual stem cells from a single AML sample, complementing genomic with in vivo functional studies. Primary tumor cells from an AML patient’s first and second relapse were transplanted into NSG mice to establish serially transplantable patient derived xenografts (PDX). In an innovative approach, twelve derivative PDX clones were generated thereof, each derived from a single AML stem cell as proven by molecular barcoding, and were color-marked to facilitate multiplex competitive in vivo assays. PDX clones consisted of four different genomic clusters; one cluster displayed resistance against Cytarabine treatment, while two other clusters harbored increased stem cell potential, indicating that stemness and treatment resistance had evolved independently in the sample. In vivo functional data correlated closely with the phylogenetic tree calculated from exome data. The Cytarabine-resistant cluster was characterized by a distinct gene expression profile, and a score thereof predicted outcome in large clinical patient data cohorts. Taken together, we provide proof of concept that intra-sample heterogeneity mimics inter-sample heterogeneity in AML. Stem cell disparities within a single sample allow insights into adverse characteristics of general importance for AML.
2022-04-04 | PXD026296 | Pride
Project description:Metabolic mechanisms underlying the heterogeneity of major adverse cardiovascular (CV) event (MACE) risk in individuals with type 2 diabetes mellitus (T2D) remain unclear. We hypothesized that circulating metabolites reflecting mitochondrial dysfunction predict incident MACE in T2D. Targeted mass-spectrometry profiling of 60 metabolites was performed on baseline plasma samples from the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS; discovery cohort) and Exenatide Study of Cardiovascular Event Lowering (EXSCEL; validation cohort) biomarker substudy cohorts. A principal components analysis metabolite factor comprising medium-chain acylcarnitines (MCACs) was associated with MACE in TECOS and validated in EXSCEL, with higher levels associated with higher MACE risk. Meta-analysis showed that long-chain acylcarnitines (LCACs) and dicarboxylacylcarnitines were also associated with MACE. Metabolites remained associated with MACE in multivariate models and favorably changed with exenatide therapy. A third cohort (Cardiac Catheterization Genetics [CATHGEN]) with T2D was assessed to determine whether these metabolites improved discriminative capability of multivariate models for MACE. Nine metabolites (MCACs and LCACs and 1 dicarboxylacylcarnitine) were associated with time to MACE in the CATHGEN cohort. Addition of these metabolites to clinical models minimally improved the discriminative capability for MACE but did significantly down reclassify risk. Thus, metabolites reporting on dysregulated mitochondrial fatty acid oxidation are present in higher levels in individuals with T2D who experience subsequent MACE. These biomarkers may improve CV risk prediction models, be therapy responsive, and highlight emerging risk mechanisms.
| S-EPMC10544215 | biostudies-literature
Project description:BackgroundWith the increasing prevalence of childhood obesity and related development of chronic kidney disease (CKD), there is a critical need to understand how best to assess kidney function in children with obesity. Since serum creatinine (SCr) is recommended as marker of first choice for GFR estimation, we evaluated and compared creatinine-based GFR equations in children with overweight and obesity.MethodsSix hundred children with overweight and obesity (53.5% female; mean age 12.20 ± 3.28 years; mean BMI z-score 3.31 ± 0.75) were included from the Centre for Overweight Adolescent and Children's Healthcare (COACH).ResultsSerum creatinine (SCr), normalized using Q-age polynomials obtained from reference values, results in median and mean SCr/Q value close to "1" for all age groups, and 96.5% of the children have a SCr/Q within the reference band [0.67-1.33], corresponding to the 2.5th and 97.5th percentile. eGFR CKiD (bedside Schwartz equation) and Schwartz-Lyon decreased with age, whereas eGFR EKFC and modified CKD-EPI40 showed no age-dependency, but the distribution of eGFR values was not symmetrical. eGFR CKiD under 25 (CKiDU25) demonstrated no age-dependency but major sex differences were observed. eGFR FAS age, FAS height, and adjusted-creatinine revised Lund-Malmö (LMR18) showed a relatively symmetrical distribution and no age-dependency.ConclusionsSerum creatinine (SCr) values of children with overweight and obesity are mostly within the reference range for children. Normalization of SCr using reference Q-age polynomials works very well in this cohort. After evaluation of the different equations, we suggest that FAS age, FAS height, and LMR18 are the preferred creatinine-based GFR-estimating equations in children with overweight and obesity.Clinical trial registrationClinicaltrialgov; Registration Number: NCT02091544. A higher resolution version of the Graphical abstract is available as Supplementary information.
| S-EPMC9395456 | biostudies-literature
Project description:BackgroundUrine albumin-to-creatinine ratio (ACR) and protein-to-creatinine ratio (PCR) are used to measure urine protein. Recent guidelines endorse ACR use, and equations have been developed incorporating ACR to predict risk of kidney failure. For situations in which PCR only is available, having a method to estimate ACR from PCR as accurately as possible would be useful.MethodsWe used data from a population-based cohort of 47,714 adults in Alberta, Canada, who had simultaneous assessments of urine ACR and PCR. After log-transforming ACR and PCR, we used cubic splines and quantile regression to estimate the median ACR from a PCR, allowing for modification by specified covariates. On the basis of the cubic splines, we created models using linear splines to develop equations to estimate ACR from PCR. In a subcohort with eGFR<60 ml/min per 1.73 m2, we then used the kidney failure risk equation to compare kidney failure risk using measured ACR as well as estimated ACR that had been derived from PCR.ResultsWe found a nonlinear association between log(ACR) and log(PCR), with the implied albumin-to-protein ratio increasing from <30% in normal to mild proteinuria to about 70% in severe proteinuria, and with wider prediction intervals at lower levels. Sex was the most important modifier of the relationship between ACR and PCR, with men generally having a higher albumin-to-protein ratio. Estimates of kidney failure risk were similar using measured ACR and ACR estimated from PCR.ConclusionsWe developed equations to estimate the median ACR from a PCR, optionally including specified covariates. These equations may prove useful in certain retrospective clinical or research applications where only PCR is available.
| S-EPMC7062208 | biostudies-literature
Project description:Cyclosporine A (CsA) is a substrate of P-glycoprotein, an efflux transporter encoded by the ABCB1 gene. Compared with carriers of the wild-type gene, carriers of T allelic variants in exons 21 or 26 have reduced P-glycoprotein activity and, secondarily, increased intracellular concentration of CsA; therefore, carriers of T variants might be at increased risk for CsA-related adverse events. We evaluated the associations between ABCB1 genotypes (in exons 12, 21, and 26) and CsA-related outcomes in 147 renal transplant recipients who were receiving CsA-based immunosuppression and were included in the Mycophenolate Steroids Sparing study. During a median of 65.5 mo follow-up, carriers of T allelic variants in exons 21 or 26 had a three-fold risk for delayed graft function (DGF), a trend to slower recovery of renal function and lower GFR at study end, and significantly higher incidences of new-onset diabetes and cytomegalovirus reactivation compared with carriers of the wild-type genotype. T variants in both exons 21 and 26 were independently associated with 3.8- and 3.5-fold higher risk for DGF, respectively (P = 0.022 and P = 0.034). The incidence of acute rejection and the mean CsA dose and blood levels were comparable in genotype groups. In conclusion, renal transplant recipients with T allelic variants in ABCB1 exons 21 or 26 are at increased risk for CsA-related adverse events. Genetic evaluation may help to identify patients at risk and to modulate CsA therapy to optimize graft and patient outcomes.
| S-EPMC2689900 | biostudies-literature