Association of Blood Pressure Variability and Diuretics With Cardiovascular Events in Patients With Chronic Kidney Disease Stages 1-5

Hypertension. 2021 Mar 3;77(3):948-959. doi: 10.1161/HYPERTENSIONAHA.120.16117. Epub 2021 Jan 11.


Visit-to-visit blood pressure variability (BPV) is associated with cardiovascular events in the general population. Data are scarce in chronic kidney disease. We hypothesized that BPV would be associated with cardiovascular outcomes, death, and end-stage kidney disease (ESKD) and that diuretics would modify these associations in patients with chronic kidney disease. We studied US Veterans with nondialysis chronic kidney disease stages 1-5 and hypertension on nondiuretic antihypertensive monotherapy. At the time of second antihypertensive agent prescription, we propensity-matched for exposure to a loop or thiazide diuretic versus any other antihypertensive. BPV was defined as the coefficient of variation of systolic blood pressure over 6 months after second agent prescription. Cox proportional hazards regression measured associations of BPV with a primary cardiovascular event composite (fatal or nonfatal myocardial infarction or ischemic stroke; heart failure hospitalization). Secondary outcomes included all-cause death, each primary outcome component, end-stage kidney disease, and cardiovascular death. There were 31 394 participants in each group. BPV was associated with composite cardiovascular events, hazard ratio (95% CI) at second, third, fourth, and fifth versus first quintile: 1.79 (1.53-2.11), 2.32 (1.99-2.71), 2.60 (2.24-3.02), and 3.12 (2.68-3.62). Diuretics attenuated associations between the fourth and fifth BPV quintiles with composite events (Pinteraction=0.03 and 0.04, respectively). BPV was associated with all secondary outcomes except end-stage kidney disease, with no diuretic interactions. BPV was associated with cardiovascular events and death but not end-stage kidney disease in patients with chronic kidney disease, with attenuated associations with cardiovascular events in the diuretic-treated group at high BPV quintiles. Future studies should investigate whether other antihypertensive classes modify these risks.

Keywords: blood pressure; death; diuretics; heart failure; population.

Publication types

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

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antihypertensive Agents / therapeutic use*
  • Blood Pressure / drug effects*
  • Blood Pressure / physiology
  • Cardiovascular Diseases / physiopathology
  • Cardiovascular Diseases / prevention & control
  • Cohort Studies
  • Diuretics / therapeutic use*
  • Female
  • Humans
  • Hypertension / complications
  • Hypertension / drug therapy*
  • Hypertension / physiopathology
  • Kidney Failure, Chronic / physiopathology
  • Kidney Failure, Chronic / prevention & control
  • Male
  • Middle Aged
  • Outcome Assessment, Health Care / methods
  • Outcome Assessment, Health Care / statistics & numerical data
  • Proportional Hazards Models
  • Renal Insufficiency, Chronic / complications
  • Renal Insufficiency, Chronic / physiopathology
  • Renal Insufficiency, Chronic / prevention & control*


  • Antihypertensive Agents
  • Diuretics