Effects of valsartan on fibrinolysis in hypertensive patients with metabolic syndrome

Circ J. 2012;76(4):843-51. doi: 10.1253/circj.cj-12-0153.

Abstract

Background: The purpose of this study was to analyze the effect of valsartan on abnormal adipocyte metabolism and prothrombotic state in hypertensive patients with metabolic syndrome (MetS).

Methods and results: We conducted a multicenter, prospective, randomized, parallel-group controlled trial in 150 hypertensive patients with MetS. They were randomly assigned to receive either 80-160 mg valsartan per day (valsartan group, n=79) or other conventional treatment without a renin-angiotensin system (RAS) inhibitor (non-RAS inhibitor group, n=71). After 1 year, there were no significant differences between the 2 groups in the changes in systolic and diastolic blood pressures (valsartan: 153±15/86±15 to 138±16/77±12 mmHg; non-RAS inhibitor: 150±14/82±15 to 137±15/76±10 mmHg). There was a significant difference in the change in the levels of plasminogen activator inhibitor-1 (PAI-1) between the 2 groups after 1 year (valsartan: 3.7±3.2 ng/ml; non-RAS inhibitor: 5.8±3.3 ng/ml, P=0.04). There was no significant difference between groups in the change in the concentration of adiponectin after 1 year (valsartan: 0.3±0.4 µg/ml; non-RAS inhibitor: 0.9±0.4 µg/ml, P=0.22). The animal study showed aortic PAI-1 protein expression was reduced in double knockout mice of angiotensin II type 1a receptor and apolipoprotein E (apoE) compared with the apoE knockout mice.

Conclusions: Valsartan reduced plasma PAI-1 levels compared to non-RAS inhibitor in hypertensive patients with MetS, which suggests it may be useful for improving fibrinolytic function.

Trial registration: ClinicalTrials.gov NCT00790946.

Publication types

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

MeSH terms

  • Adipocytes / drug effects
  • Adipocytes / metabolism
  • Adiponectin / blood
  • Aged
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use*
  • Animals
  • Antihypertensive Agents / therapeutic use*
  • Aorta / drug effects
  • Aorta / metabolism
  • Apolipoproteins E / deficiency
  • Apolipoproteins E / genetics
  • Biomarkers / blood
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / prevention & control*
  • Disease Models, Animal
  • Female
  • Fibrinolysis / drug effects*
  • Humans
  • Hypertension / blood
  • Hypertension / complications
  • Hypertension / drug therapy*
  • Japan
  • Male
  • Metabolic Syndrome / blood
  • Metabolic Syndrome / complications*
  • Mice
  • Mice, Knockout
  • Middle Aged
  • Plasminogen Activator Inhibitor 1 / blood
  • Prospective Studies
  • Receptor, Angiotensin, Type 1 / deficiency
  • Receptor, Angiotensin, Type 1 / genetics
  • Tetrazoles / therapeutic use*
  • Time Factors
  • Treatment Outcome
  • Valine / analogs & derivatives*
  • Valine / therapeutic use
  • Valsartan

Substances

  • ADIPOQ protein, human
  • Adiponectin
  • Agtr1a protein, mouse
  • Angiotensin II Type 1 Receptor Blockers
  • Antihypertensive Agents
  • Apolipoproteins E
  • Biomarkers
  • Plasminogen Activator Inhibitor 1
  • Receptor, Angiotensin, Type 1
  • SERPINE1 protein, human
  • Tetrazoles
  • Valsartan
  • Valine

Associated data

  • ClinicalTrials.gov/NCT00790946