Angiotensin receptor blocker vs ACE inhibitor effects on HDL functionality in patients on maintenance hemodialysis

Nutr Metab Cardiovasc Dis. 2018 Jun;28(6):582-591. doi: 10.1016/j.numecd.2018.02.020. Epub 2018 Mar 8.

Abstract

Background and aims: Angiotensin receptor blockers (ARB) and angiotensin converting enzyme inhibitors (ACEI) reduce cardiovascular events in the general population. Maintenance hemodialysis (MHD) patients are at high cardiovascular risk but few studies have directly addressed the comparative efficacy of these drugs. MHD disrupts the normally atheroprotective actions of high density lipoprotein (HDL), therefore, we compared ACEI or ARB treatment on HDL functions in MHD.

Methods and results: HDL was isolated at the starting point (pre) and 3-6 months later (post) in 30 MHD randomly assigned to placebo, ramipril or valsartan. Outcomes included cholesterol efflux, inflammatory cytokine response, effects on Toll-like receptors (TLR), superoxide production, methylarginine and serum amyloid A (SAA) levels. HDL from ARB- or ACEI-treated subjects was more effective in maintaining efflux than HDL of placebo. HDL from ARB- or ACEI-treated subjects but not placebo lessened cellular superoxide production. In contrast, neither ARB nor ACEI improved HDL anti-inflammatory effect. Indeed, HDL of ACEI-treated subjects potentiated the cytokine responses in association with activation of TLR but did not alter the HDL content of methylarginines or SAA.

Conclusion: Both ACEI and ARB stabilized HDL cholesterol acceptor function and sustained cellular anti-oxidative effects but not anti-inflammatory effects, and ACEI-treatment instead amplified the HDL inflammatory response. The findings reveal possible utility of antagonizing angiotensin actions in MDH and suggest a possible mechanism for superiority of ARB vs ACEI in the setting of advanced kidney disease.

Keywords: Angiotensin receptor blocker; Angiotensin-converting enzyme inhibitors; Cholesterol; HDL; Oxidant stress.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Angiotensin II Type 1 Receptor Blockers / adverse effects
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use*
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Biomarkers / blood
  • Cholesterol, HDL / blood*
  • Double-Blind Method
  • Female
  • Humans
  • Inflammation Mediators / blood
  • Kidney Failure, Chronic / blood
  • Kidney Failure, Chronic / diagnosis
  • Kidney Failure, Chronic / therapy*
  • Male
  • Middle Aged
  • Oxidative Stress / drug effects
  • Ramipril / adverse effects
  • Ramipril / therapeutic use*
  • Renal Dialysis* / adverse effects
  • Tennessee
  • Time Factors
  • Treatment Outcome
  • Valsartan / adverse effects
  • Valsartan / therapeutic use*

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Angiotensin-Converting Enzyme Inhibitors
  • Biomarkers
  • Cholesterol, HDL
  • Inflammation Mediators
  • Valsartan
  • Ramipril