Discrepancy between improvement of insulin sensitivity and that of arterial endothelial function in patients receiving antihypertensive medication.
OBJECTIVE
We evaluated whether the changes in the insulin sensitivity observed in hypertensive patients following treatment with an angiotensin II receptor blocker (candesartan) or calcium-channel antagonist (amlodipine) might be related to improvement of the endothelial function (END) and/or plasma level of high-sensitive C-reactive protein (CRP) following such treatment.


RESULTS
Seventy-one hypertensive patients (age: 58 +/- 10 years) without obvious target organ damage were allocated randomly to treatment with either candesartan at the dose of 8 mg/day or amlodipine at the dose of 5 mg/day. At the start and end of the 8-month treatment period, the homeostasis model assessment index of insulin resistance (HOMA-IR index), plasma CRP and END, as assessed by changes in the forearm blood flow in reactive hyperemia, were determined. While significant improvement of END was observed in patients receiving either drug, only candesartan, but not amlodipine, also reduced the plasma CRP and HOMA-IR index (2.13 +/- 1.92 --> 1.53 +/- 1.47, P < 0.05). In the patients receiving treatment with candesartan, stepwise multivariate linear regression analysis revealed that the percent change in the HOMA-IR index was significantly and independently correlated with that in the plasma CRP (beta = 0.38, P < 0.05), but not with that in END:


CONCLUSIONS
Improvement of the END alone by the antihypertensive medication might not entirely explain the improvement of the insulin sensitivity observed in these patients. Additional mechanisms may be involved, and the anti-inflammatory effects of the medication observed in patients treated with candesartan may also be related, at least in part, to the observed improvement of insulin sensitivity.
Tomiyama
Hirofumi
H
Second Department of Internal Medicine, Tokyo Medical University, Tokyo, Japan.
Yambe
Minoru
M
Yamada
Jiko
J
Motobe
Kohki
K
Koji
Yutaka
Y
Yoshida
Masanobu
M
Shiina
Kazuki
K
Yamashina
Akira
A
D000368:Aged; D017311:Amlodipine / Q000627:therapeutic use; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D001713:Biphenyl Compounds; D002097:C-Reactive Protein / Q000187:drug effects / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D017536:Carotid Artery, Common / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D005542:Forearm / Q000098:blood supply; D006352:Heart Ventricles / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology; D007333:Insulin Resistance; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011446:Prospective Studies; D012039:Regional Blood Flow / Q000187:drug effects; D012107:Research Design; D013777:Tetrazoles / Q000627:therapeutic use; D016896:Treatment Outcome; D017539:Tunica Intima / Q000187:drug effects / Q000503:physiopathology; D017540:Tunica Media / Q000187:drug effects / Q000503:physiopathology; D014655:Vascular Resistance / Q000187:drug effects
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D015415:Biomarkers; D001713:Biphenyl Compounds; D002121:Calcium Channel Blockers; D013777:Tetrazoles; D017311:Amlodipine; D002097:C-Reactive Protein; C081643:candesartan