Carmen A Peralta1, Leslie A McClure2, Rebecca Scherzer2, Michelle C Odden2, Carole L White2, Michael Shlipak2, Oscar Benavente2, Pablo Pergola2. 1. From The Kidney Health Research Collaborative at University of California San Francisco and San Francisco VA Medical Center (C.A.P., R.S., M.S.); University of Alabama at Birmingham (L.A.M.); Oregon State University, Corvallis (M.C.O.); University of Texas Health Science Center at San Antonio (C.L.W., P.P.); and University of British Columbia, Vancouver, Canada (O.B.). carmenalicia.peralta@ucsf.edu. 2. From The Kidney Health Research Collaborative at University of California San Francisco and San Francisco VA Medical Center (C.A.P., R.S., M.S.); University of Alabama at Birmingham (L.A.M.); Oregon State University, Corvallis (M.C.O.); University of Texas Health Science Center at San Antonio (C.L.W., P.P.); and University of British Columbia, Vancouver, Canada (O.B.).
Abstract
BACKGROUND: The effect of intensive blood pressure (BP) lowering on kidney function among individuals with established cerebrovascular disease and preserved estimated glomerular filtration rate (eGFR) is not established. METHODS AND RESULTS: Among 2610 participants randomized to a lower (<130 mm Hg) versus higher (130-149 mm Hg) systolic BP target with repeated measures of serum creatinine, we evaluated differences by study arm in annualized eGFR decline and rapid decline (eGFR decline >30%) using linear mixed models and logistic regression, respectively. We assessed associations of both treatment and kidney function decline with stroke, major vascular events, and the composite of stroke, death, major vascular events, or myocardial infarction using multivariable Cox regression, separately and jointly including a test for interaction. Analyses were conducted by treatment arm. Mean age was 63±11 years; 949 participants (36%) were diabetic; and mean eGFR was 80±19 mL·min(-1)·1.73 m(-2). At 9 months, achieved systolic BP was 137±15 versus 127±14 mm Hg in the higher versus lower BP group, and differences were maintained throughout follow-up (mean, 3.2 years). Compared with the higher target, the lower BP target had a -0.50-mL·min(-1)·1.73 m(-2) per year (95% confidence interval [CI], -0.79 to -0.21) faster eGFR decline. Differences were most pronounced during the first year (-2.1 mL·min(-1)·1.73 m(-2); 95% CI, -0.97 to -3.2), whereas rates of eGFR decline did not differ after year 1 (-0.095; 95% CI, -0.47 to 0.23). A total of 313 patients (24%) in the lower BP group had rapid kidney function decline compared with 247 (19%) in the higher BP group (odds ratio, 1.4; 95% CI, 1.1-1.6). Differences in rapid decline by treatment arm were apparent in the first year (odds ratio, 1.4; 95% CI, 1.1-1.8) but were not significant after year 1 (odds ratio, 1.0; 95% CI, 0.73-1.4). Rapid decline was associated with higher risk for stroke, major vascular events, and composite after full adjustment among individuals randomized to the higher BP target (stroke hazard ratio, 1.93; 95% CI, 1.15-3.21) but not the lower BP arm (stroke hazard ratio, 0.93; 95% CI, 0.50-1.75; all P for interaction <0.06). CONCLUSIONS: In patients with prior lacunar stroke and relatively preserved kidney function, intensive BP lowering was associated with a greater likelihood of rapid kidney function decline. Differences were observed primarily during the first year of antihypertensive treatment. Rapid kidney function decline was not associated with increased risk for clinical events among those undergoing intensive BP lowering. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicalTrials.gov. Unique identifier: NCT00059306.
RCT Entities:
BACKGROUND: The effect of intensive blood pressure (BP) lowering on kidney function among individuals with established cerebrovascular disease and preserved estimated glomerular filtration rate (eGFR) is not established. METHODS AND RESULTS: Among 2610 participants randomized to a lower (<130 mm Hg) versus higher (130-149 mm Hg) systolic BP target with repeated measures of serum creatinine, we evaluated differences by study arm in annualized eGFR decline and rapid decline (eGFR decline >30%) using linear mixed models and logistic regression, respectively. We assessed associations of both treatment and kidney function decline with stroke, major vascular events, and the composite of stroke, death, major vascular events, or myocardial infarction using multivariable Cox regression, separately and jointly including a test for interaction. Analyses were conducted by treatment arm. Mean age was 63±11 years; 949 participants (36%) were diabetic; and mean eGFR was 80±19 mL·min(-1)·1.73 m(-2). At 9 months, achieved systolic BP was 137±15 versus 127±14 mm Hg in the higher versus lower BP group, and differences were maintained throughout follow-up (mean, 3.2 years). Compared with the higher target, the lower BP target had a -0.50-mL·min(-1)·1.73 m(-2) per year (95% confidence interval [CI], -0.79 to -0.21) faster eGFR decline. Differences were most pronounced during the first year (-2.1 mL·min(-1)·1.73 m(-2); 95% CI, -0.97 to -3.2), whereas rates of eGFR decline did not differ after year 1 (-0.095; 95% CI, -0.47 to 0.23). A total of 313 patients (24%) in the lower BP group had rapid kidney function decline compared with 247 (19%) in the higher BP group (odds ratio, 1.4; 95% CI, 1.1-1.6). Differences in rapid decline by treatment arm were apparent in the first year (odds ratio, 1.4; 95% CI, 1.1-1.8) but were not significant after year 1 (odds ratio, 1.0; 95% CI, 0.73-1.4). Rapid decline was associated with higher risk for stroke, major vascular events, and composite after full adjustment among individuals randomized to the higher BP target (stroke hazard ratio, 1.93; 95% CI, 1.15-3.21) but not the lower BP arm (stroke hazard ratio, 0.93; 95% CI, 0.50-1.75; all P for interaction <0.06). CONCLUSIONS: In patients with prior lacunar stroke and relatively preserved kidney function, intensive BP lowering was associated with a greater likelihood of rapid kidney function decline. Differences were observed primarily during the first year of antihypertensive treatment. Rapid kidney function decline was not associated with increased risk for clinical events among those undergoing intensive BP lowering. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicalTrials.gov. Unique identifier: NCT00059306.
Authors: Jackson T Wright; George Bakris; Tom Greene; Larry Y Agodoa; Lawrence J Appel; Jeanne Charleston; DeAnna Cheek; Janice G Douglas-Baltimore; Jennifer Gassman; Richard Glassock; Lee Hebert; Kenneth Jamerson; Julia Lewis; Robert A Phillips; Robert D Toto; John P Middleton; Stephen G Rostand Journal: JAMA Date: 2002-11-20 Impact factor: 56.272
Authors: Mark J Sarnak; Tom Greene; Xuelei Wang; Gerald Beck; John W Kusek; Allan J Collins; Andrew S Levey Journal: Ann Intern Med Date: 2005-03-01 Impact factor: 25.391
Authors: Mahboob Rahman; Sara Pressel; Barry R Davis; Chuke Nwachuku; Jackson T Wright; Paul K Whelton; Joshua Barzilay; Vecihi Batuman; John H Eckfeldt; Michael Farber; Mario Henriquez; Nelson Kopyt; Gail T Louis; Mohammad Saklayen; Carol Stanford; Candace Walworth; Harry Ward; Thomas Wiegmann Journal: Arch Intern Med Date: 2005-04-25
Authors: Anushka Patel; S MacMahon; J Chalmers; B Neal; M Woodward; L Billot; S Harrap; N Poulter; M Marre; M Cooper; P Glasziou; D E Grobbee; P Hamet; S Heller; L S Liu; G Mancia; C E Mogensen; C Y Pan; A Rodgers; B Williams Journal: Lancet Date: 2007-09-08 Impact factor: 79.321
Authors: Nigel S Beckett; Ruth Peters; Astrid E Fletcher; Jan A Staessen; Lisheng Liu; Dan Dumitrascu; Vassil Stoyanovsky; Riitta L Antikainen; Yuri Nikitin; Craig Anderson; Alli Belhani; Françoise Forette; Chakravarthi Rajkumar; Lutgarde Thijs; Winston Banya; Christopher J Bulpitt Journal: N Engl J Med Date: 2008-03-31 Impact factor: 91.245
Authors: Jesse C Ikeme; Pablo E Pergola; Rebecca Scherzer; Michael G Shlipak; Oscar R Benavente; Carmen A Peralta Journal: Clin J Am Soc Nephrol Date: 2017-04-26 Impact factor: 8.237
Authors: Rakesh Malhotra; Hoang Anh Nguyen; Oscar Benavente; Mihriye Mete; Barbara V Howard; Jonathan Mant; Michelle C Odden; Carmen A Peralta; Alfred K Cheung; Girish N Nadkarni; Ruth L Coleman; Rury R Holman; Alberto Zanchetti; Ruth Peters; Nigel Beckett; Jan A Staessen; Joachim H Ix Journal: JAMA Intern Med Date: 2017-10-01 Impact factor: 21.873
Authors: Gregory L Judson; Anna D Rubinsky; Michael G Shlipak; Ronit Katz; Holly Kramer; David R Jacobs; Michelle C Odden; Carmen A Peralta Journal: Am J Hypertens Date: 2018-04-13 Impact factor: 2.689
Authors: William R Zhang; Timothy E Craven; Rakesh Malhotra; Alfred K Cheung; Michel Chonchol; Paul Drawz; Mark J Sarnak; Chirag R Parikh; Michael G Shlipak; Joachim H Ix Journal: Ann Intern Med Date: 2018-10-23 Impact factor: 25.391
Authors: Carmen A Peralta; Leslie A McClure; Rebecca Scherzer; Michelle C Odden; Carole L White; Michael Shlipak; Oscar Benavente; Pablo E Pergola Journal: Circulation Date: 2016-07-26 Impact factor: 29.690