Advanced glycation end-products, anti-hypertensive treatment and diastolic function in patients with hypertension and diastolic dysfunction

Eur J Heart Fail. 2010 Apr;12(4):397-403. doi: 10.1093/eurjhf/hfq001. Epub 2010 Feb 12.

Abstract

Aims: To investigate the relationship between advanced glycation end-products (AGEs) and diastolic function and the response to blood pressure treatment in patients with hypertension and diastolic dysfunction.

Methods and results: Data were analysed from 97 patients (aged 65 +/- 10 years, 36% male) who were randomly assigned to 6 months open-label treatment with either eprosartan on top of other anti-hypertensive drugs (n = 47) or other anti-hypertensive drugs alone (n = 50). Tissue AGE accumulation was measured using a validated skin-autofluorescence (skin-AF) reader (n = 26). Plasma N(epsilon)-(carboxymethyl)lysine (CML), N(epsilon)-(carboxyethyl)lysine (CEL), and pentosidine were measured by LC-MS/MS and HPLC. Diastolic function was assessed using echocardiography. Blood pressure was reduced from 157/91 to 145/84 mmHg (P < 0.001) in the eprosartan group and from 158/91 to 141/83 mmHg (P < 0.001) in the control group. No effect of eprosartan was found on AGE levels. In patients with baseline skin-AF < median, E/A ratio (P = 0.04) and the mean peak early-diastolic filling velocity (E') improved (P = 0.001). In contrast, in patients with skin-AF levels > median, E/A ratio (P = 0.84) and mean E' (P = 0.32) remained unchanged.

Conclusion: Although eprosartan did not decrease levels of AGEs, patients with lower skin-AF at baseline showed a larger improvement in diastolic function in response to either anti-hypertensive treatment compared with patients with higher skin-AF.

Publication types

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

MeSH terms

  • Acrylates / therapeutic use
  • Aged
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use*
  • Antihypertensive Agents / therapeutic use*
  • Diastole / drug effects
  • Female
  • Glycation End Products, Advanced*
  • Humans
  • Hypertension / drug therapy*
  • Imidazoles / therapeutic use
  • Linear Models
  • Lysine / analogs & derivatives
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Netherlands
  • Skin
  • Statistics as Topic
  • Statistics, Nonparametric
  • Stroke Volume
  • Thiophenes / therapeutic use
  • Ventricular Function, Left

Substances

  • Acrylates
  • Angiotensin II Type 1 Receptor Blockers
  • Antihypertensive Agents
  • Glycation End Products, Advanced
  • Imidazoles
  • Thiophenes
  • eprosartan
  • N(6)-carboxymethyllysine
  • Lysine