Implications of Early Decline in eGFR due to Intensive BP Control for Cardiovascular Outcomes in SPRINT

Srinivasan Beddhu, Jincheng Shen, Alfred K. Cheung, Paul L. Kimmel, Glenn M. Chertow, Guo Wei, Robert E. Boucher, Michel Chonchol, Farid Arman, Ruth C. Campbell, Gabriel Contreras, Jamie P. Dwyer, Barry I. Freedman, Joachim H. Ix, Kent Kirchner, Vasilios Papademetriou, Roberto Pisoni, Michael V. Rocco, Paul K. Whelton, Tom Greene

Research output: Contribution to journalArticle

Abstract

BACKGROUND: The Systolic BP Intervention Trial (SPRINT) found that intensive versus standard systolic BP control (targeting <120 or <140 mm Hg, respectively) reduced the risks of death and major cardiovascular events in persons with elevated cardiovascular disease risk. However, the intensive intervention was associated with an early decline in eGFR, and the clinical implications of this early decline are unclear. METHODS: In a post hoc analysis of SPRINT, we defined change in eGFR as the percentage change in eGFR at 6 months compared with baseline. We performed causal mediation analyses to separate the overall effects of the randomized systolic BP intervention on the SPRINT primary cardiovascular composite and all-cause mortality into indirect effects (mediated by percentage change in eGFR) and direct effects (mediated through pathways other than percentage change in eGFR). RESULTS: About 10.3% of the 4270 participants in the intensive group had a ≥20% eGFR decline versus 4.4% of the 4256 participants in the standard arm (P<0.001). After the 6-month visit, there were 591 cardiovascular composite events during 27,849 person-years of follow-up. The hazard ratios for total effect, direct effect, and indirect effect of the intervention on the cardiovascular composite were 0.67 (95% confidence interval [95% CI], 0.56 to 0.78), 0.68 (95% CI, 0.57 to 0.79), and 0.99 (95% CI, 0.95 to 1.03), respectively. All-cause mortality results were similar. CONCLUSIONS: Although intensive systolic BP lowering resulted in greater early decline in eGFR, there was no evidence that the reduction in eGFR owing to intensive systolic BP lowering attenuated the beneficial effects of this intervention on cardiovascular events or all-cause mortality.

Original languageEnglish (US)
Pages (from-to)1523-1533
Number of pages11
JournalJournal of the American Society of Nephrology : JASN
Volume30
Issue number8
DOIs
StatePublished - Aug 1 2019

Fingerprint

Confidence Intervals
Mortality
Cardiovascular Diseases

Keywords

  • cardiovascular disease
  • hypertension
  • mortality
  • renal hemodynamics

ASJC Scopus subject areas

  • Nephrology

Cite this

Implications of Early Decline in eGFR due to Intensive BP Control for Cardiovascular Outcomes in SPRINT. / Beddhu, Srinivasan; Shen, Jincheng; Cheung, Alfred K.; Kimmel, Paul L.; Chertow, Glenn M.; Wei, Guo; Boucher, Robert E.; Chonchol, Michel; Arman, Farid; Campbell, Ruth C.; Contreras, Gabriel; Dwyer, Jamie P.; Freedman, Barry I.; Ix, Joachim H.; Kirchner, Kent; Papademetriou, Vasilios; Pisoni, Roberto; Rocco, Michael V.; Whelton, Paul K.; Greene, Tom.

In: Journal of the American Society of Nephrology : JASN, Vol. 30, No. 8, 01.08.2019, p. 1523-1533.

Research output: Contribution to journalArticle

Beddhu, S, Shen, J, Cheung, AK, Kimmel, PL, Chertow, GM, Wei, G, Boucher, RE, Chonchol, M, Arman, F, Campbell, RC, Contreras, G, Dwyer, JP, Freedman, BI, Ix, JH, Kirchner, K, Papademetriou, V, Pisoni, R, Rocco, MV, Whelton, PK & Greene, T 2019, 'Implications of Early Decline in eGFR due to Intensive BP Control for Cardiovascular Outcomes in SPRINT', Journal of the American Society of Nephrology : JASN, vol. 30, no. 8, pp. 1523-1533. https://doi.org/10.1681/ASN.2018121261
Beddhu, Srinivasan ; Shen, Jincheng ; Cheung, Alfred K. ; Kimmel, Paul L. ; Chertow, Glenn M. ; Wei, Guo ; Boucher, Robert E. ; Chonchol, Michel ; Arman, Farid ; Campbell, Ruth C. ; Contreras, Gabriel ; Dwyer, Jamie P. ; Freedman, Barry I. ; Ix, Joachim H. ; Kirchner, Kent ; Papademetriou, Vasilios ; Pisoni, Roberto ; Rocco, Michael V. ; Whelton, Paul K. ; Greene, Tom. / Implications of Early Decline in eGFR due to Intensive BP Control for Cardiovascular Outcomes in SPRINT. In: Journal of the American Society of Nephrology : JASN. 2019 ; Vol. 30, No. 8. pp. 1523-1533.
@article{2a85388e89c54707b97e91001a9786aa,
title = "Implications of Early Decline in eGFR due to Intensive BP Control for Cardiovascular Outcomes in SPRINT",
abstract = "BACKGROUND: The Systolic BP Intervention Trial (SPRINT) found that intensive versus standard systolic BP control (targeting <120 or <140 mm Hg, respectively) reduced the risks of death and major cardiovascular events in persons with elevated cardiovascular disease risk. However, the intensive intervention was associated with an early decline in eGFR, and the clinical implications of this early decline are unclear. METHODS: In a post hoc analysis of SPRINT, we defined change in eGFR as the percentage change in eGFR at 6 months compared with baseline. We performed causal mediation analyses to separate the overall effects of the randomized systolic BP intervention on the SPRINT primary cardiovascular composite and all-cause mortality into indirect effects (mediated by percentage change in eGFR) and direct effects (mediated through pathways other than percentage change in eGFR). RESULTS: About 10.3{\%} of the 4270 participants in the intensive group had a ≥20{\%} eGFR decline versus 4.4{\%} of the 4256 participants in the standard arm (P<0.001). After the 6-month visit, there were 591 cardiovascular composite events during 27,849 person-years of follow-up. The hazard ratios for total effect, direct effect, and indirect effect of the intervention on the cardiovascular composite were 0.67 (95{\%} confidence interval [95{\%} CI], 0.56 to 0.78), 0.68 (95{\%} CI, 0.57 to 0.79), and 0.99 (95{\%} CI, 0.95 to 1.03), respectively. All-cause mortality results were similar. CONCLUSIONS: Although intensive systolic BP lowering resulted in greater early decline in eGFR, there was no evidence that the reduction in eGFR owing to intensive systolic BP lowering attenuated the beneficial effects of this intervention on cardiovascular events or all-cause mortality.",
keywords = "cardiovascular disease, hypertension, mortality, renal hemodynamics",
author = "Srinivasan Beddhu and Jincheng Shen and Cheung, {Alfred K.} and Kimmel, {Paul L.} and Chertow, {Glenn M.} and Guo Wei and Boucher, {Robert E.} and Michel Chonchol and Farid Arman and Campbell, {Ruth C.} and Gabriel Contreras and Dwyer, {Jamie P.} and Freedman, {Barry I.} and Ix, {Joachim H.} and Kent Kirchner and Vasilios Papademetriou and Roberto Pisoni and Rocco, {Michael V.} and Whelton, {Paul K.} and Tom Greene",
year = "2019",
month = "8",
day = "1",
doi = "10.1681/ASN.2018121261",
language = "English (US)",
volume = "30",
pages = "1523--1533",
journal = "Journal of the American Society of Nephrology",
issn = "1046-6673",
publisher = "American Society of Nephrology",
number = "8",

}

TY - JOUR

T1 - Implications of Early Decline in eGFR due to Intensive BP Control for Cardiovascular Outcomes in SPRINT

AU - Beddhu, Srinivasan

AU - Shen, Jincheng

AU - Cheung, Alfred K.

AU - Kimmel, Paul L.

AU - Chertow, Glenn M.

AU - Wei, Guo

AU - Boucher, Robert E.

AU - Chonchol, Michel

AU - Arman, Farid

AU - Campbell, Ruth C.

AU - Contreras, Gabriel

AU - Dwyer, Jamie P.

AU - Freedman, Barry I.

AU - Ix, Joachim H.

AU - Kirchner, Kent

AU - Papademetriou, Vasilios

AU - Pisoni, Roberto

AU - Rocco, Michael V.

AU - Whelton, Paul K.

AU - Greene, Tom

PY - 2019/8/1

Y1 - 2019/8/1

N2 - BACKGROUND: The Systolic BP Intervention Trial (SPRINT) found that intensive versus standard systolic BP control (targeting <120 or <140 mm Hg, respectively) reduced the risks of death and major cardiovascular events in persons with elevated cardiovascular disease risk. However, the intensive intervention was associated with an early decline in eGFR, and the clinical implications of this early decline are unclear. METHODS: In a post hoc analysis of SPRINT, we defined change in eGFR as the percentage change in eGFR at 6 months compared with baseline. We performed causal mediation analyses to separate the overall effects of the randomized systolic BP intervention on the SPRINT primary cardiovascular composite and all-cause mortality into indirect effects (mediated by percentage change in eGFR) and direct effects (mediated through pathways other than percentage change in eGFR). RESULTS: About 10.3% of the 4270 participants in the intensive group had a ≥20% eGFR decline versus 4.4% of the 4256 participants in the standard arm (P<0.001). After the 6-month visit, there were 591 cardiovascular composite events during 27,849 person-years of follow-up. The hazard ratios for total effect, direct effect, and indirect effect of the intervention on the cardiovascular composite were 0.67 (95% confidence interval [95% CI], 0.56 to 0.78), 0.68 (95% CI, 0.57 to 0.79), and 0.99 (95% CI, 0.95 to 1.03), respectively. All-cause mortality results were similar. CONCLUSIONS: Although intensive systolic BP lowering resulted in greater early decline in eGFR, there was no evidence that the reduction in eGFR owing to intensive systolic BP lowering attenuated the beneficial effects of this intervention on cardiovascular events or all-cause mortality.

AB - BACKGROUND: The Systolic BP Intervention Trial (SPRINT) found that intensive versus standard systolic BP control (targeting <120 or <140 mm Hg, respectively) reduced the risks of death and major cardiovascular events in persons with elevated cardiovascular disease risk. However, the intensive intervention was associated with an early decline in eGFR, and the clinical implications of this early decline are unclear. METHODS: In a post hoc analysis of SPRINT, we defined change in eGFR as the percentage change in eGFR at 6 months compared with baseline. We performed causal mediation analyses to separate the overall effects of the randomized systolic BP intervention on the SPRINT primary cardiovascular composite and all-cause mortality into indirect effects (mediated by percentage change in eGFR) and direct effects (mediated through pathways other than percentage change in eGFR). RESULTS: About 10.3% of the 4270 participants in the intensive group had a ≥20% eGFR decline versus 4.4% of the 4256 participants in the standard arm (P<0.001). After the 6-month visit, there were 591 cardiovascular composite events during 27,849 person-years of follow-up. The hazard ratios for total effect, direct effect, and indirect effect of the intervention on the cardiovascular composite were 0.67 (95% confidence interval [95% CI], 0.56 to 0.78), 0.68 (95% CI, 0.57 to 0.79), and 0.99 (95% CI, 0.95 to 1.03), respectively. All-cause mortality results were similar. CONCLUSIONS: Although intensive systolic BP lowering resulted in greater early decline in eGFR, there was no evidence that the reduction in eGFR owing to intensive systolic BP lowering attenuated the beneficial effects of this intervention on cardiovascular events or all-cause mortality.

KW - cardiovascular disease

KW - hypertension

KW - mortality

KW - renal hemodynamics

UR - http://www.scopus.com/inward/record.url?scp=85070850350&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85070850350&partnerID=8YFLogxK

U2 - 10.1681/ASN.2018121261

DO - 10.1681/ASN.2018121261

M3 - Article

C2 - 31324734

AN - SCOPUS:85070850350

VL - 30

SP - 1523

EP - 1533

JO - Journal of the American Society of Nephrology

JF - Journal of the American Society of Nephrology

SN - 1046-6673

IS - 8

ER -