Dataset Information

Mediation analysis for estimating cardioprotection of longitudinal RAS inhibition beyond lowering blood pressure and albuminuria in type 1 diabetes.

ABSTRACT:

Purpose

We assessed the extent of cardiovascular benefit of renin-angiotensin system (RAS) inhibition beyond lowering blood pressure (BP) and albuminuria in type 1 diabetes (T1D).

Methods

This cohort study included 605 T1D participants from the Pittsburgh Epidemiology of Diabetes Complications study without baseline coronary artery disease (CAD). Participant follow-up extended through 25 years. We implemented marginal structural models to estimate total effect of and controlled direct effect by isolating the role of BP or albuminuria in mediating the relation between RAS inhibitors and CAD.

Results

Total effect of longitudinal RAS inhibition treatment was associated with 38% decreased CAD risk (HR [95% CI]: 0.62 [0.23, 1.77]). The controlled direct effect of RAS inhibition was a 27% risk reduction (HR: 0.73 [0.20, 2.59]) when isolating the role of BP and 26% risk reduction (HR: 0.74 [0.16, 3.35]) when isolating the role of albuminuria. The mediation proportion for each 10 mm Hg systolic BP and each 1 log unit of albumin excretion rate were 34% and 37%, respectively.

Conclusion

Our findings suggest that BP regulation and albuminuria reduction can only partially explain cardiovascular benefit of RAS inhibition on CAD in T1D, supporting the assertion that RAS inhibitors provide additional cardioprotection beyond lowering BP and albuminuria.

SUBMITTER: Guo J

PROVIDER: S-EPMC7024023 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Publications

Mediation analysis for estimating cardioprotection of longitudinal RAS inhibition beyond lowering blood pressure and albuminuria in type 1 diabetes.

Guo Jingchuan J Naimi Ashley I AI Brooks Maria M MM Muldoon Matthew F MF Orchard Trevor J TJ Costacou Tina T

Annals of epidemiology 20191206

<h4>Purpose</h4>We assessed the extent of cardiovascular benefit of renin-angiotensin system (RAS) inhibition beyond lowering blood pressure (BP) and albuminuria in type 1 diabetes (T1D).<h4>Methods</h4>This cohort study included 605 T1D participants from the Pittsburgh Epidemiology of Diabetes Complications study without baseline coronary artery disease (CAD). Participant follow-up extended through 25 years. We implemented marginal structural models to estimate total effect of and controlled di ...[more]

PMID: 31928894

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Project description:BACKGROUND:Random assignment to the intensive systolic blood pressure (SBP) arm (<120mmHg) in the Systolic Blood Pressure Intervention Trial (SPRINT) resulted in more rapid declines in estimated glomerular filtration rates (eGFRs) than in the standard arm (SBP<140mmHg). Whether this change reflects hemodynamic effects or accelerated intrinsic kidney damage is unknown. STUDY DESIGN:Longitudinal subgroup analysis of clinical trial participants. SETTINGS & PARTICIPANTS:Random sample of SPRINT participants with prevalent chronic kidney disease (CKD) defined as eGFR<60mL/min/1.73m2 by the CKD-EPI (CKD Epidemiology Collaboration) creatinine-cystatin C equation at baseline. OUTCOMES & MEASUREMENTS:Urine biomarkers of tubule function (?2-microglobulin [B2M], ?1-microglobulin [A1M]), and uromodulin), injury (interleukin 18, kidney injury molecule 1, and neutrophil gelatinase-associated lipocalin), inflammation (monocyte chemoattractant protein 1), and repair (human cartilage glycoprotein 40) at baseline, year 1, and year 4. Biomarkers were indexed to urine creatinine concentration and changes between arms were evaluated using mixed-effects linear models and an intention-to-treat approach. RESULTS:978 SPRINT participants (519 in the intensive and 459 in the standard arm) with prevalent CKD were included. Mean age was 72±9 years and eGFR was 46.1±9.4mL/min/1.73m2 at baseline. Clinical characteristics, eGFR, urinary albumin-creatinine ratio, and all 8 biomarker values were similar across arms at baseline. Compared to the standard arm, eGFR was lower by 2.9 and 3.3mL/min/1.73m2 in the intensive arm at year 1 and year 4. None of the 8 tubule marker levels was higher in the intensive arm compared to the standard arm at year 1 or year 4. Two tubule function markers (B2M and A1M) were 29% (95% CI, 10%-43%) and 24% (95% CI, 10%-36%) lower at year 1 in the intensive versus standard arm, respectively. LIMITATIONS:Exclusion of persons with diabetes, and few participants had advanced CKD. CONCLUSIONS:Among participants with CKD in SPRINT, random assignment to the intensive SBP arm did not increase any levels of 8 urine biomarkers of tubule cell damage despite loss of eGFR. These findings support the hypothesis that eGFR declines in the intensive arm of SPRINT predominantly reflect hemodynamic changes rather than intrinsic damage to kidney tubule cells.

Dataset Information

Mediation analysis for estimating cardioprotection of longitudinal RAS inhibition beyond lowering blood pressure and albuminuria in type 1 diabetes.

Purpose

Methods

Results

Conclusion

Publications

Mediation analysis for estimating cardioprotection of longitudinal RAS inhibition beyond lowering blood pressure and albuminuria in type 1 diabetes.

Similar Datasets

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