Effect of administration of low-dose irbesartan and hydrochlorothiazide combined with levamlodipine at different times on the circadian rhythm of blood pressure and the levels of MMPs and TIMPs in non-dipper patients with grade 1 and 2 hypertension

J Clin Hypertens (Greenwich). 2023 Feb;25(2):137-145. doi: 10.1111/jch.14630. Epub 2023 Jan 14.

Abstract

This study aimed to probe the effects of low-dose irbesartan and hydrochlorothiazide in combination with levamlodipine at different times on the circadian rhythm of blood pressure, matrix metalloproteinases (MMPs), and tissue inhibitors of metalloproteinases (TIMPs) levels in patients with non-dipper hypertension (NDH). In this prospective randomized controlled trial, 124 patients with NDH who visited our hospital between August 2018 and July 2021 were enrolled and divided into morning (62 patients) and night (62 patients) medication groups according to the random number table method. All patients received low-dose irbesartan and hydrochlorothiazide combined with levamlodipine, with the morning medication group taking the medication between 7:00 and 10:00 and the night medication group taking the medication between 19:00 and 22:00 for 24 weeks. The effect of antihypertensive medication in both groups was measured, and changes in ambulatory blood pressure, blood pressure circadian rhythm, left ventricular structure, vascular endothelial function, MMPs, and TIMPs levels were observed before treatment initiation and after 24 weeks of treatment in both groups. The percentage of the dipper type was higher in the night medication group than in the morning medication group, while the percentage of the non-dipper type was lower in the morning medication group (p < .05). Low-dose irbesartan and hydrochlorothiazide combined with levamlodipine at different times can effectively treat NDH, but bedtime dosing is more beneficial in reducing nocturnal blood pressure, reversing NDH, improving the circadian rhythm of blood pressure, left ventricular structure, regulating vascular endothelial function, increasing MMPs levels, and reducing TIMP levels.

Keywords: MMPs; chronotherapeutics; circadian rhythm of blood pressure; hydrochlorothiazide; irbesartan; levamlodipine; non-dipper hypertension.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antihypertensive Agents / pharmacology
  • Antihypertensive Agents / therapeutic use
  • Blood Pressure / physiology
  • Blood Pressure Monitoring, Ambulatory
  • Circadian Rhythm / physiology
  • Humans
  • Hydrochlorothiazide / pharmacology
  • Hydrochlorothiazide / therapeutic use
  • Hypertension* / drug therapy
  • Hypotension*
  • Irbesartan / therapeutic use
  • Prospective Studies

Substances

  • Irbesartan
  • Hydrochlorothiazide
  • levamlodipine
  • Antihypertensive Agents