Free accessResearch articleFirst published online 2008-10
Relative Effects of Telmisartan,Candesartan and Losartan on Alleviating Arterial Stiffness in Patients with Hypertension Complicated by Diabetes Mellitus: An Evaluation Using the Cardio-Ankle Vascular Index (CAVI)
Using the cardio-ankle vascular index (CAVI) as an indicator, we assessed improvement of arterial stiffness in 95 outpatients with hypertension complicated by type 2 diabetes mellitus who were treated orally for ≤ 12 months with telmisartan 40 mg/day, losartan 50 mg/day or candesartan 8 mg/day. At 1 year, in the telmisartan and losartan groups CAVI did not change whereas in the candesartan group CAVI showed a statistically significant decrease of 2.70%. Although telmisartan is believed to enhance the activity of peroxisome proliferator-activated receptor (PPAR-γ) in vitro, it did not ameliorate arterial stiffness in our patients. Candesartan, however, improved arterial stiffness independently of blood pressure lowering and without PPAR-γ agonist action, possibly by direct action resulting from its potent affinity and binding capacity for the angiotensin II type 1 receptor. We conclude that candesartan is a potentially useful therapy against arterial stiffness in hypertensive patients with type 2 diabetes mellitus.
American Diabetes Association: Standards of medical care in diabetes–2006. Diabetes Care2006; 29 (suppl 1): S4–S42.
2.
ZiemanSJMelenovskyVKassDA: Mechanisms, pathophysiology, and therapy of arterial stiffness. Arterioscler Thromb Vasc Biol2005; 25: 932–943.
3.
LeeACeramiA: Role of glycation in aging. Ann NY Acad Sci1992; 663: 63–70.
4.
YanSDSchmidtAMAndersonGM: Enhanced cellular oxidant stress by the interaction of advanced glycation end products with their receptors/binding proteins. J Biol Chem1994; 269: 9889–9897.
5.
DzauVJ: Significance of the vascular renin–angiotensin pathway. Hypertension1986; 8: 553–559.
6.
BenetosASaberME: Aortic collagen, aortic stiffness, and AT1 receptors in experimental and human hypertension. Can J Physiol Pharmacol1996; 74: 862–866.
7.
KatoHSuzukiHTajimaS: Angiotensin II stimulates collagen synthesis in cultured vascular smooth muscle cells. J Hypertens1991; 9: 17–22.
8.
GibbonsGHPrattREDzauVJ: Vascular smooth muscle cell hypertrophy vs. hyperplasia. Autocrine transforming growth factor-beta 1 expression determines growth response to angiotensin II. J Clin Invest1992; 90: 456–461.
9.
RosenEDSpiegelmanBM: A nuclear regulator of metabolism, differentiation, and cell growth. J Biol Chem2001; 276: 37731–37734.
10.
DiepQNEl MaroukMCohnJS: Structure, endothelial function, cell growth, and inflammation in blood vessels of angiotensin II-infused rats. Role of peroxisome proliferator-activated receptor-γ. Circulation2002; 105: 2296–2302.
11.
SugawaraATakeuchiKUrunoA: Effects of mitogen-activated protein kinase pathway and co-activator CREP-binding protein on peroxisome proliferator-activated receptor-γ-mediated transcription suppression of angiotensin II type 1 receptor gene. Hypertens Res2003; 26: 623–628.
BensonSCPershadsinghHAHoCI: Identification of telmisartan as a unique angiotensin II receptor antagonist with selective PPAR-γ-modulating activity. Hypertension2004; 43: 993–1002.
14.
OliverJJWebbDJ: Noninvasive assessment of arterial stiffness and risk of atherosclerotic events. Arterioscler Thromb Vasc Biol2003; 23: 554–566.
15.
LaurentSBoutouyriePAsmarR: Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients. Hypertension2001; 37: 1236–1241.
16.
AsmarRBenetosATopouchianJ: Assessment of arterial distensibility by automatic pulse wave velocity measurement: Validation and clinical application studies. Hypertension1995; 26: 485–490.
WakabayashiIMasudaH: Effects of age on the relationship between cardio-ankle vascular index and atherosclerotic progression in patients with type 2 diabetes mellitus. Jpn J Geriatr2006; 43: 217–221.
19.
OkuraTWatanabeSKurataM: Relationship between cardio-ankle vascular index (CAVI) and carotid atherosclerosis in patients with essential hypertension. Hypertens Res2007; 30: 335–340.
20.
YambeTYoshizawaMSaijoY: Brachio-ankle pulse wave velocity and cardio-ankle vascular index (CAVI). Biomed Pharmacother2004; 58: S95–S98.
21.
HuckCJBronasUGWilliamsonEB: Noninvasive measurements of arterial stiffness: Repeatability and interrelationships with endothelial function and arterial morphology measures. Vasc Health Risk Manag2003; 23: 343–349.
22.
ShiraiK: CAVI, a new index of arteriosclerosis and coronary artery disease. Jpn Med J2007; 4334: C1–C4.
23.
AsmarRGossePTopouchianJ: Effects of telmisartan on arterial stiffness in type 2 diabetes patients with essential hypertension. J Renin Angiotensin Aldosterone Syst. 2002; 3: 176–180.
24.
SasamuraHKitamuraYNakamuraM: Effects of the angiotensin receptor blocker candesartan on arterial stiffness and markers of extracellular matrix metabolism in patients with essential hypertension. Clin Exp Hypertens2006; 28: 511–520.
25.
AgataJNagaharaDKinoshitaS: Angiotensin II receptor blocker prevents increased arterial stiffness in patients with essential hypertension. Circ J2004; 68: 1194–1198.
26.
UchidaHNakamuraYMakinoH: Practical efficacy of telmisartan for decreasing morning home blood pressure and pulse wave velocity in patients with mild-to-moderate hypertension. Hypertens Res2004; 27: 545–550.
27.
NakamuraTYamamotoEKim-MitsuyamaS: Beneficial effects of pioglitazone on hypertensive cardiovascular injury are enhanced by combination with candesartan. Hypertension2008; 51: 296–301.
28.
OgiharaTMinamiFKainumaH: Pharmacokinetic evaluation of angiotensin II AT1 receptor antagonist, BIBR277 (telmisartan) in hypertensive patients. Jpn Pharmacol Ther2002; 30: S271–S283.
29.
DorenkampMRiadAStiehlS: Protection against oxidative stress in diabetic rats: Role of angiotensin AT1 receptor and beta 1-adrenoceptor antagonism. Eur J Pharmacol2005; 520: 179–187.
30.
KohEMorimotoSTomitaJ: Effects of an angiotensin II receptor antagonist, CV-11974, on angiotensin II-induced increases in cytosolic free calcium concentration, hyperplasia, and hypertrophy of cultured vascular smooth muscle cells. J Cardiovasc Pharmacol1994; 23: 175–179.
31.
BrowatzkiMLarsenDPfeifferCAH: Angiotensin II stimulates matrix metalloproteinase secretion in human vascular smooth muscle cells via nuclear factor-B and activator protein 1 in a redox-sensitive manner. J Vasc Res2005; 42: 415–423.
32.
TimmermansP: Pharmacologial properties of angiotensin II receptor antagonists. Can J Cardiol1999; 15 (suppl F): 26F–28F.
33.
MaillardMPPerregauxCCentenoC: In vitro and in vivo characterization of the activity of telmisartan: an insurmountable angiotensin II receptor antagonist. J Pharmacol Exp Ther2002; 302: 1089–1095.
34.
FogariR: Efficacy of losartan, valsartan, and telmisartan in patients with mild to moderate hypertension: A double-blind, placebo-controlled, crossover pressure monitoring study. Curr Ther Res Clin Exp2002; 63: 1–14.
35.
AndersonOK: The antihypertensive effect and tolerability of candesartan cilexetil, a new generation angiotensin II antagonist, in comparison with losartan. Blood Press1998; 7: 53–59.
