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

Authors

L Parker Gregg
S Susan Hedayati
Hui Yang
Peter N Van Buren
Subhash Banerjee
Sankar D Navaneethan
Salim S Virani
Wolfgang C Winkelmayer
Carlos A Alvarez

Publication Date

3-3-2021

Journal

Hypertension

DOI

10.1161/HYPERTENSIONAHA.120.16117

PMID

33423525

PMCID

PMC7878423

PubMedCentral® Posted Date

3-3-2022

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes

Keywords

Aged, Aged, 80 and over, Antihypertensive Agents, Blood Pressure, Cardiovascular Diseases, Cohort Studies, Diuretics, Female, Humans, Hypertension, Kidney Failure, Chronic, Male, Middle Aged, Outcome Assessment, Health Care, Proportional Hazards Models, Renal Insufficiency, Chronic, chronic kidney disease, blood pressure variability, diuretics, cardiovascular events, death

Abstract

Visit-to-visit blood pressure variability (BPV) is associated with cardiovascular events in the general population. Data are scarce in chronic kidney disease (CKD). 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 CKD.

We studied U.S. Veterans with non-dialysis CKD stages 1-5 and hypertension on non-diuretic antihypertensive monotherapy. At the time of second antihypertensive agent prescription, we propensity-matched for exposure to a loop or thiazide diuretic vs. 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 non-fatal myocardial infarction or ischemic stroke; heart failure hospitalization). Secondary outcomes included all-cause death, each primary outcome component, ESKD, and cardiovascular death.

There were 31,394 participants in each group. BPV was associated with composite cardiovascular events, hazard ratio (95% confidence interval) at second, third, fourth, and fifth vs. 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 (P_interaction=0.03 and 0.04, respectively). BPV was associated with all secondary outcomes except ESKD, with no diuretic interactions.

BPV was associated with cardiovascular events and death but not ESKD in patients with CKD, with attenuated associations with CV events in the diuretic-treated group at high BPV quintiles. Future studies should investigate whether other antihypertensive classes modify these risks.

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