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


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.


CONCLUSIONS
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.
Department of Cardiology, University Medical Center Groningen and University of Groningen, Hanzeplein 1, Groningen, The Netherlands. j.w.l.hartog@thorax.umcg.nl
Jasper W L
JW
Hartog
Ruud M
RM
van de Wal
Casper G
CG
Schalkwijk
Toshio
T
Miyata
Wybren
W
Jaarsma
H W Thijs
HW
Plokker
Leen M
LM
van Wijk
Andries J
AJ
Smit
Dirk J
DJ
van Veldhuisen
Adriaan A
AA
Voors
D000179:Acrylates / Q000627:therapeutic use; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D003971:Diastole / Q000187:drug effects; D005260:Female; D017127:Glycation End Products, Advanced; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007093:Imidazoles / Q000627:therapeutic use; D016014:Linear Models; D008239:Lysine / Q000031:analogs & derivatives; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009426:Netherlands; D012867:Skin; D013223:Statistics as Topic; D018709:Statistics, Nonparametric; D013318:Stroke Volume; D013876:Thiophenes / Q000627:therapeutic use; D016277:Ventricular Function, Left
D000179:Acrylates; D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D017127:Glycation End Products, Advanced; D007093:Imidazoles; D013876:Thiophenes; C068373:eprosartan; C048496:N(6)-carboxymethyllysine; D008239:Lysine