Kidney Disease, Intensive Hypertension Treatment, and Risk for Dementia and Mild Cognitive Impairment: The Systolic Blood Pressure Intervention Trial

the SPRINT Research Group

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Abstract

Background Intensively treating hypertension may benefit cardiovascular disease and cognitive function, but at the short-term expense of reduced kidney function. Methods We investigated markers of kidney function and the effect of intensive hypertension treatment on incidence of dementia and mild cognitive impairment (MCI) in 9361 participants in the randomized Systolic Blood Pressure Intervention Trial, which compared intensive versus standard systolic BP lowering (targeting,120 mm Hg versus,140 mm Hg, respectively). We categorized participants according to baseline and longitudinal changes in eGFR and urinary albumin-to-creatinine ratio. Primary outcomes were occurrence of adjudicated probable dementia and MCI. Results Among 8563 participants who completed at least one cognitive assessment during follow-up (median 5.1 years), probable dementia occurred in 325 (3.8%) and MCI in 640 (7.6%) participants. In multivariable adjusted analyses, there was no significant association between baseline eGFR,60 ml/min per 1.73 m2 and risk for dementia or MCI. In time-varying analyses, eGFR decline $30% was associated with a higher risk for probable dementia. Incident eGFR,60 ml/min per 1.73 m2 was associated with a higher risk for MCI and a composite of dementia or MCI. Although these kidney events occurred more frequently in the intensive treatment group, there was no evidence that they modified or attenuated the effect of intensive treatment on dementia and MCI incidence. Baseline and incident urinary ACR $30 mg/g were not associated with probable dementia or MCI, nor did the urinary ACR modify the effect of intensive treatment on cognitive outcomes. Conclusions Among hypertensive adults, declining kidney function measured by eGFR is associated with increased risk for probable dementia and MCI, independent of the intensity of hypertension treatment.

Original languageEnglish (US)
Pages (from-to)2122-2132
Number of pages11
JournalJournal of the American Society of Nephrology
Volume31
Issue number9
DOIs
StatePublished - Sep 2020

Bibliographical note

Funding Information:
S. Oparil reports grants and nonfinancial support from National Institutes of Health (NIH)/National Heart, Lung and Blood Institute, during the conduct of the study; and outside the submitted work, has received personal fees from 98point6, Inc, Actelion Clinical Research Inc, CinCor, Novo Nordisk, Pfizer, and Rox Medical, research/grant funding from Bayer, George Clinical Pty Ltd/Actelion/Idorsia Pharmaceuticals, Idorsia Pharmaceuticals, and Novartis, and currently serves as Editor-in-Chief for Current Hypertension Reports (publisher: Springer); and receives an annual stipend of $5000 (from Springer). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH, the US Department of Veterans Affairs, or the US Government. For a full list of contributors to SPRINT, please see the supplementary acknowledgement list: https://www.sprinttrial.org/public/dspScience.cfm. All remaining authors have nothing to disclose.

Funding Information:
This study was supported by National Institutes of Health (NIH) grants R01DK092241 (to M. Kurella Tamura) and R01AG055606 (to PI: Dr. Reboussin), as well as funding from the Alzheimer?s Association (to J.D. Williamson). The Systolic Blood Pressure Intervention Trial is funded with Federal funds from the NIH, including the National Heart, Lung, and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Aging, and the National Institute of Neurological Disorders and Stroke, under contract numbers HHSN268200900040C, HHSN268200900046C, HHSN268200900047C, HHSN268200900048C, and HHSN268200900049C, and interagency agreement number A-HL-13-002-001. We also acknowledge support from the following Clinical and Translational Science Awards funded by National Center for Advancing Translational Science: Case Western Reserve University, UL1TR000439; OSU, UL1RR025755; U Penn, UL1RR024134 and UL1TR000003; Boston, UL1RR025771; Stanford, UL1TR000093; Tufts, UL1RR025752, UL1TR000073, and UL1TR001064; University of Illinois, UL1TR000050; University of Pittsburgh, UL1TR000005; UT Southwestern, 9U54TR000017-06; University of Utah, UL1TR000105-05; Vanderbilt University, UL1TR000445; George Washington University, UL1TR000075; University of CA, Davis, UL1TR000002; University of Florida, UL1TR000064; University of Michigan, UL1TR000433; Tulane University, P30GM103337 COBRE Award NIGMS; Wake Forest University, UL1TR001420.

Funding Information:
Dr. Manjula Kurella Tamura reports grants from National Institutes of Health (NIH), during the conduct of the study. Ms. Sarah Gaussoin reports grants from NIH, during the conduct of the study. Dr. Nicholas M. Pajewski reports grants from National Institute on Aging and Alzheimer’s Association, during the conduct of the study. Dr. Gorden Chelune reports grants from NIH during the conduct of the study. Dr. Barry I. Freedman reports grants from NIH, during the conduct of the study. Dr. Anthony Killeen reports grants from NIH/NIDDK, during the conduct of the study. Dr. Mark Supiano reports grants from NIH, during the conduct of the study. Dr. Daniel E. Weiner reports grants from National Institutes of Health, during the conduct of the study. Dr. Jeff D. Williamson reports grants from National Institutes of Health, grants from Biogen, and grants from Alzheimer’s Association, outside the submitted work.

Funding Information:
This study was supported by National Institutes of Health (NIH) grants R01DK092241 (to M. Kurella Tamura) and R01AG055606 (to PI: Dr. Re-boussin), as well as funding from the Alzheimer’s Association (to J.D. Williamson). The Systolic Blood Pressure Intervention Trial is funded with Federal funds from the NIH, including the National Heart, Lung, and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Aging, and the National Institute of Neurological Disorders and Stroke, under contract numbers HHSN268200900040C, HHSN268200900046C, HHSN268200900047C, HHSN268200900048C, and HHSN268200900049C, and interagency agreement number A-HL-13-002-001.

Funding Information:
This study was also supported in part by resources and use of facilities through the US Department of Veterans Affairs. The SPRINT investigators acknowledge the contribution of study medications (azilsartan and azilsartan combined with chlorthalidone) from Takeda Pharmaceuticals International, Inc.

Funding Information:
We also acknowledge support from the following Clinical and Translational Science Awards funded by National Center for Advancing Translational Science: Case Western Reserve University, UL1TR000439; OSU, UL1RR025755; U Penn, UL1RR024134 and UL1TR000003; Boston, UL1RR025771; Stanford, UL1TR000093; Tufts, UL1RR025752, UL1TR000073, and UL1TR001064; University of Illinois, UL1TR000050; University of Pittsburgh, UL1TR000005; UT Southwestern, 9U54TR000017-06; University of Utah, UL1TR000105-05; Vanderbilt University, UL1TR000445; George Washington University, UL1TR000075; University of CA, Davis, UL1TR000002; University of Florida, UL1TR000064; University of Michigan, UL1TR000433; Tulane University, P30GM103337 COBRE Award NIGMS; Wake Forest University, UL1TR001420.

Publisher Copyright:
Copyright © 2020 by the American Society of Nephrology.

PubMed: MeSH publication types

  • Journal Article
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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