Discrepancy between improvement of insulin sensitivity and that of arterial endothelial function in patients receiving antihypertensive medication

OBJECTIVES: 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. METHODS AND 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: CONCLUSION: 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.