Dataset Information

Arterial stiffness and kidney disease progression in the systolic blood pressure intervention trial?.

ABSTRACT:

Aims

Arterial stiffness increases with both advancing age and chronic kidney disease (CKD) and may contribute to kidney function decline, but evidence is inconsistent. We hypothesized that greater baseline arterial stiffness (assessed as pulse pressure (PP) and carotid-femoral pulse-wave velocity CFPWV)) was independently associated with kidney disease progression over the follow-up period (3.8 years) in the Systolic Blood Pressure Intervention Trial (SPRINT).

Materials and methods

8,815 SPRINT participants were included in the analysis of PP. 592 adults who participated in a SPRINT ancillary study that measured CFPWV were included in subgroup analyses. Cox proportional hazards analysis was used to examine the association between PP and time to kidney disease progression endpoints: (A) incident estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m² in non-CKD participants at baseline; (B) 50% decline in eGFR, initiation of dialysis, or transplant in those with baseline CKD. Mixed model analyses examined the association of baseline PP/CFPWV with follow-up eGFR.

Results and conclusion

Mean ± SD age was 68 ± 10 years, baseline PP was 62 ± 14 mmHg, and CFPWV was 10.8 ± 2.7 m/s. In the fully adjusted model, PP ? median was associated with an increased hazard of kidney disease progression endpoints (HR: 1.93 (1.43 - 2.61)). The association remained significant in individuals without (2.05 (1.47 - 2.87)) but not with baseline CKD (1.28 (0.55 - 2.65)). In fully adjusted models, higher baseline PP associated with eGFR decline (p < 0.0001 (all, CKD, non-CKD)), but baseline CFPWV did not. Among older adults at high risk for cardiovascular events, baseline PP was associated with kidney disease progression.

SUBMITTER: Nowak KL

PROVIDER: S-EPMC7814777 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Publications

Arterial stiffness and kidney disease progression in the systolic blood pressure intervention trial .

Nowak Kristen L KL Chonchol Michel M Jovanovich Anna A You Zhiying Z Ambrosius Walter T WT Cho Monique E ME Glasser Stephen S Lash James J Simmons Debra L DL Taylor Addison A Weiner Daniel D Rastogi Anjay A Oparil Suzanne S Supiano Mark A MA

Clinical nephrology 20200701 1

<h4>Aims</h4>Arterial stiffness increases with both advancing age and chronic kidney disease (CKD) and may contribute to kidney function decline, but evidence is inconsistent. We hypothesized that greater baseline arterial stiffness (assessed as pulse pressure (PP) and carotid-femoral pulse-wave velocity CFPWV)) was independently associated with kidney disease progression over the follow-up period (3.8 years) in the Systolic Blood Pressure Intervention Trial (SPRINT).<h4>Materials and methods</h ...[more]

PMID: 32449678

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Project description:Background Arterial stiffness predicts the risk of cardiovascular events and all-cause mortality and is associated with age and hypertension. However, the magnitude of the relationship between blood pressure (BP) and progression of arterial stiffness is unclear, limiting our understanding of how arterial stiffness mediates clinical effects of hypertension and planning of clinical trials. Methods and Results Medline and EMBASE were searched for prospective studies reporting linear models between baseline BP and progression of arterial stiffness, with and without adjustment for demographic characteristics and baseline stiffness. Standardized and unstandardized β coefficients for pulse wave velocity were combined by fixed and random effects meta-analysis, weighted by the inverse variance. Of 566 fully reviewed articles from 30, 524 titles, 22 populations from 21 reports were included. In 9 cohorts, there were consistent, adjusted associations between baseline systolic BP and progression of arterial stiffness (11 781 patients; standardized β=0.041; 95% CI, 0.026-0.055; P<0.001; P value for heterogeneity=0.70), equivalent to a 1.14-m/s increase in standard carotid-femoral pulse wave velocity per decade per 20-mm Hg systolic BP, independent of age. Unstandardized, adjusted associations were similar (1762 patients; β=0.0047; 95% CI, 0.004-0.006; P<0.001; P value for heterogeneity=0.64), equivalent to a 0.94-m/s increase per decade per 20-mm Hg systolic BP. In limited studies, standardized associations between mean BP and arterial stiffness progression were not significant and heterogeneous (913 patients; β=0.039; 95% CI, -0.008 to 0.086; P=0.11; P value for heterogeneity=0.03). Conclusions Baseline systolic BP was associated with a clinically important progression of arterial stiffness, independent of age, providing a reference for the potential effect of arterial stiffness in mediating changes in clinical outcomes associated with hypertension and providing a reference value to aid clinical trial design.

Project description:Rationale & objectiveThe Systolic Blood Pressure Intervention Trial (SPRINT) compared the effect of intensive versus standard systolic blood pressure targets on cardiovascular morbidity and mortality. In this ancillary study, we evaluated the use of exploratory factor analysis (EFA) to combine biomarkers of kidney tubule health in urine and plasma and then study their role in longitudinal estimated glomerular filtration rate (eGFR) change and risk of acute kidney injury (AKI).Study designObservational cohort nested in a clinical trial.Setting & participants2,351 SPRINT participants with eGFR < 60 mL/min/1.73 m2 at baseline.ExposureLevels of neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18), chitinase-3-like protein (YKL-40), kidney injury molecule 1 (KIM-1), monocyte chemoattractant protein 1 (MCP-1), α1-microglobulin (A1M) and β2-microglobulin (B2M), uromodulin (UMOD), fibroblast growth factor 23 (FGF-23), and intact parathyroid hormone (PTH).OutcomeLongitudinal changes in eGFR and risk of AKI.Analytical approachWe performed EFA to capture different tubule pathophysiologic processes. We used linear mixed effects models to evaluate the association of each factor with longitudinal changes in eGFR. We evaluated the association of the tubular factors scores with AKI using Cox proportional hazards regression.ResultsFrom 10 biomarkers, EFA generated 4 factors reflecting tubule injury/repair (NGAL, IL-18, and YKL-40), tubule injury/fibrosis (KIM-1 and MCP-1), tubule reabsorption (A1M and B2M), and tubule reserve/mineral metabolism (UMOD, FGF-23, and PTH). Each 1-SD higher tubule reserve/mineral metabolism factor score was associated with a 0.58% (95% CI, 0.39%-0.67%) faster eGFR decline independent of baseline eGFR and albuminuria. Both the tubule injury/repair and tubule injury/fibrosis factors were independently associated with future risk of AKI (per 1 SD higher, HRs of 1.18 [95% CI, 1.10-1.37] and 1.23 [95% CI, 1.02-1.48], respectively).LimitationsThe factors require validation in other settings.ConclusionsEFA allows parsimonious subgrouping of biomarkers into factors that are differentially associated with progressive eGFR decline and AKI. These subgroups may provide insights into the pathological processes driving adverse kidney outcomes.

Project description:BackgroundChronic kidney disease is common and is associated with cardiovascular disease, cerebrovascular disease, and cognitive function, although the nature of this relationship remains uncertain.Study designCross-sectional cohort using baseline data from the Systolic Blood Pressure Intervention Trial (SPRINT).Setting & participantsParticipants in SPRINT, a randomized clinical trial of blood pressure targets in older community-dwelling adults with cardiovascular disease, chronic kidney disease, or high cardiovascular disease risk and without diabetes or known stroke, who underwent detailed neurocognitive testing in the cognition substudy, SPRINT-Memory and Cognition in Decreased Hypertension (SPRINT-MIND).PredictorsUrine albumin-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR).OutcomesCognitive function, a priori defined as 5 cognitive domains based on 11 cognitive tests using z scores, and abnormal white matter volume quantified by brain magnetic resonance imaging.ResultsOf 9,361 SPRINT participants, 2,800 participated in SPRINT-MIND and 2,707 had complete data; 637 had brain imaging. Mean age was 68 years, 37% were women, 30% were black, and 20% had known cardiovascular disease. Mean eGFR was 70.8±20.9mL/min/1.73m2 and median urine ACR was 9.7 (IQR, 5.7-22.5) mg/g. In adjusted analyses, higher ACR was associated with worse global cognitive function, executive function, memory, and attention, such that each doubling of urine ACR had the same association with cognitive performance as being 7, 10, 6, and 14 months older, respectively. Lower eGFR was independently associated with worse global cognitive function and memory. In adjusted models, higher ACR, but not eGFR, was associated with larger abnormal white matter volume.LimitationsCross-sectional only, no patients with diabetes were included.ConclusionsIn older adults, higher urine ACR and lower eGFR have independent associations with global cognitive performance with different affected domains. Albuminuria concurrently identifies a higher burden of abnormal brain white matter disease, suggesting that vascular disease may mediate these relationships.

Project description:BACKGROUND:Treating to a lower blood pressure (BP) may increase acute kidney injury (AKI) events. STUDY DESIGN:Data for AKI resulting in or during hospitalization or emergency department visits were collected as part of the serious adverse events reporting process of the Systolic Blood Pressure Intervention Trial (SPRINT). SETTING & PARTICIPANTS:9,361 participants 50 years or older with 1 or more risk factors for cardiovascular disease. INTERVENTIONS:Participants were randomly assigned to a systolic BP target of <120 (intensive arm) or <140mmHg (standard arm). OUTCOMES & MEASUREMENTS:Primary outcome was the number of adjudicated AKI events. Secondary outcomes included severity of AKI and degree of recovery of kidney function after an AKI event. Baseline creatinine concentration was defined as the most recent SPRINT outpatient creatinine value before the date of the AKI event. RESULTS:There were 179 participants with AKI events in the intensive arm and 109 in the standard arm (3.8% vs 2.3%; HR, 1.64; 95% CI, 1.30-2.10; P<0.001). Of 288 participants with an AKI event, 248 (86.1%) had a single AKI event during the trial. Based on modified KDIGO (Kidney Disease: Improving Global Outcomes) criteria for severity of AKI, the number of AKI events in the intensive versus standard arm by KDIGO stage was 128 (58.5%) versus 81 (62.8%) for AKI stage 1, 42 (19.2%) versus 18 (14.0%) for AKI stage 2, and 42 (19.2%) versus 25 (19.4%) for AKI stage 3 (P=0.5). For participants with sufficient data, complete or partial resolution of AKI was seen for 169 (90.4%) and 9 (4.8%) of 187 AKI events in the intensive arm and 86 (86.9%) and 4 (4.0%) of 99 AKI events in the standard arm, respectively. LIMITATIONS:Trial results are not generalizable to patients with diabetes mellitus or without risk factors for cardiovascular disease. CONCLUSIONS:More intensive BP lowering resulted in more frequent episodes of AKI. Most cases were mild and most participants had complete recovery of kidney function. TRIAL REGISTRATION:Registered at ClinicalTrials.gov with study number NCT01206062.

Project description:Rational & objectiveMany drugs, metabolites, and toxins are cleared by the kidneys via tubular secretion. Whether novel endogenous measures of tubular secretion provide information about kidney, cardiovascular, and mortality risk is uncertain.Study designLongitudinal subgroup analysis of clinical trial participants.Setting & participants2,089 Systolic Blood Pressure Intervention Trial participants with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 at baseline.ExposureSummary score incorporating urine-to-plasma ratios of 10 endogenous secretion markers measured in paired urine and plasma samples at baseline.OutcomeThe primary outcome was longitudinal change in eGFR. Secondary outcomes included chronic kidney disease (CKD) progression (≥50% eGFR decline or incident kidney failure requiring dialysis or kidney transplantation), a cardiovascular disease (CVD) composite (myocardial infarction, acute coronary syndrome, stroke, acute decompensated heart failure, or death from cardiovascular causes), and mortality.Analytical approachLinear mixed-effect models were used to evaluate the association between the secretion score and change in eGFR, and Cox proportional hazards models were used to evaluate associations with CKD progression, CVD, and mortality.ResultsAt baseline, mean age was 73 ± 9 years and eGFR was 46 ± 11 mL/min/1.73 m2. During a median follow-up of 3.3 years, mean change in eGFR was -1.44% per year, and 72 CKD progression events, 272 CVD events, and 144 deaths occurred. In multivariable analyses, lower secretion score was associated with faster eGFR decline and greater risk of CKD progression, CVD, and mortality. After further adjustment for baseline eGFR and albuminuria, each 1-standard deviation lower secretion score was associated with faster eGFR decline (-0.65% per year; 95% CI, -0.84% to -0.46%), but not CKD progression (HR, 1.23; 95% CI, 0.96-1.58), CVD (HR, 1.02; 95% CI, 0.89-1.18), or mortality (HR, 0.90; 95% CI, 0.74-1.09). The secretion score association with eGFR decline appeared stronger in participants with baseline eGFR <45 mL/min/1.73 m2 (P for interaction < 0.001).LimitationsPersons with diabetes and proteinuria >1 g/d were excluded.ConclusionsAmong SPRINT participants with CKD, lower estimated tubular secretion was associated with faster eGFR decline, independent of baseline eGFR and albuminuria, but not with CKD progression, CVD, or mortality.

Project description:Rationale and objectiveIn the Systolic Blood Pressure Intervention Trial, the possible relationships between acute kidney injury (AKI) and risk of major cardiovascular events and death are not known.Study designPost hoc analysis of a multicenter, randomized, controlled, open-label clinical trial.Setting and participantsHypertensive adults without diabetes who were ≥50 years of age with prior cardiovascular disease, chronic kidney disease (CKD), 10-year Framingham risk score > 15%, or age > 75 years were assigned to a systolic blood pressure target of < 120 mm Hg (intensive) or < 140 mm Hg (standard).PredictorAKI episodes.OutcomesThe primary outcome was a composite of myocardial infarction, acute coronary syndrome, stroke, decompensated heart failure, or cardiovascular death. The secondary outcome was death from any cause. Analytical Approach: AKI was defined using the Kidney Disease: Improving Global Outcomes modified criteria based solely upon serum creatinine. AKI episodes were identified by serious adverse events or emergency room visits. Cox proportional hazards models assessed the risk for the primary and secondary outcomes by AKI status.ResultsParticipants were 68 ± 9 years of age, 36% women (3,332/9,361), and 30% Black race (2,802/9,361), and 17% (1,562/9,361) with cardiovascular disease. Systolic blood pressure was 140 ± 16 mm Hg at study entry. AKI occurred in 4.4% (204/4,678) and 2.6% (120/4,683) in the intensive and standard treatment groups respectively (p < 0.001). Those who experienced AKI had higher risk of cardiovascular events (hazard ratio [HR] 1.52, 95% CI 1.05-2.20, p = 0.026) and death from any cause (HR 2.33, 95% CI 1.56-3.48, p < 0.001) controlling for age, sex, race, baseline systolic blood pressure, body mass index, number of antihypertensive medications, cardiovascular disease and CKD status, hypotensive episodes, and treatment assignment.LimitationsThe study was not prospectively designed to determine relationships between AKI, cardiovascular events, and death.ConclusionsAmong older adults with hypertension at high cardiovascular risk, intensive treatment of blood pressure independently increased risk of AKI, which substantially raised risks of major cardiovascular events and death.

Dataset Information

Arterial stiffness and kidney disease progression in the systolic blood pressure intervention trial?.

Aims

Materials and methods

Results and conclusion

Publications

Arterial stiffness and kidney disease progression in the systolic blood pressure intervention trial .

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Arterial stiffness and kidney disease progression in the systolic blood pressure intervention trial?.

Aims

Materials and methods

Results and conclusion

Publications

Arterial stiffness and kidney disease progression in the systolic blood pressure intervention trial .

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Arterial stiffness and kidney disease progression in the systolic blood pressure intervention trial .