Cerebral White Matter Hyperintensities, Kidney Function Decline, and Recurrent Stroke After Intensive Blood Pressure Lowering: Results From the Secondary Prevention of Small Subcortical Strokes ( SPS 3) Trial

J Am Heart Assoc. 2019 Feb 5;8(3):e010091. doi: 10.1161/JAHA.118.010091.


Background We aimed to determine whether cerebral white matter hyperintensities ( WMHs ) can distinguish stroke survivors susceptible to rapid kidney function decline from intensive blood pressure ( BP ) lowering. Methods and Results The SPS3 (Secondary Prevention of Small Subcortical Strokes) trial randomized participants with recent lacunar stroke to systolic BP targets of 130 to 149 and <130 mm Hg. We included 2454 participants with WMH measured by clinical magnetic resonance imaging at baseline and serum creatinine measured during follow-up. We tested interactions between BP target and WMH burden on the incidence of rapid kidney function decline (≥30% decrease from baseline estimated glomerular filtration rate at 1-year follow-up) and recurrent stroke. Rapid kidney function decline incidence was 11.0% in the lower- BP -target arm and 8.1% in the higher-target arm (odds ratio=1.40; 95% CI=1.07-1.84). Odds ratio for rapid kidney function decline between lower- and higher-target groups ranged from 1.26 in the lowest WMH tertile (95% CI , 0.80-1.98) to 1.71 in the highest tertile (95% CI , 1.05-2.80; P for interaction=0.65). Overall incidence of recurrent stroke was 7.9% in the lower-target arm and 9.6% in the higher-target arm (hazard ratio=0.80; 95% CI , 0.63-1.03). Hazard ratio for recurrent stroke in the lower-target group was 1.13 (95% CI , 0.73-1.75) within the lowest WMH tertile compared with 0.73 (95% CI , 0.49-1.09) within the highest WMH tertile ( P for interaction=0.04). Conclusions Participants with higher WMH burden appeared to experience greater benefit from intensive BP lowering in prevention of recurrent stroke. By contrast, intensive BP lowering increased the odds of kidney function decline, but WMH burden did not significantly distinguish this risk. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 00059306.

Trial registration: ClinicalTrials.gov NCT00059306.

Keywords: blood pressure; creatinine; estimated glomerular filtration rate; kidney; lacunar stroke; secondary prevention of small subcortical strokes; white matter disease.

Publication types

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

MeSH terms

  • Aged
  • Antihypertensive Agents / administration & dosage
  • Antihypertensive Agents / adverse effects*
  • Blood Pressure / drug effects
  • Blood Pressure / physiology*
  • Creatinine / blood
  • Dose-Response Relationship, Drug
  • Female
  • Follow-Up Studies
  • Glomerular Filtration Rate / physiology
  • Humans
  • Hypertension / complications
  • Hypertension / drug therapy*
  • Incidence
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Prospective Studies
  • Recurrence
  • Renal Insufficiency / epidemiology
  • Renal Insufficiency / etiology
  • Renal Insufficiency / prevention & control*
  • Secondary Prevention / methods*
  • Stroke, Lacunar / epidemiology
  • Stroke, Lacunar / etiology
  • Stroke, Lacunar / prevention & control*
  • United States / epidemiology
  • White Matter / pathology*


  • Antihypertensive Agents
  • Creatinine

Associated data

  • ClinicalTrials.gov/NCT00059306