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Vascular and Metabolic Effects of Combined Therapy With Ramipril and Simvastatin in Patients With Type 2 Diabetes

Mechanisms underlying biological effects of statin and angiotensin-converting enzyme inhibitor therapies differ. Therefore, we compared vascular and metabolic responses to these therapies either alone or in combination in patients with type 2 diabetes. This was a randomized, double-blind, placebo-co...

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Published in:Hypertension (Dallas, Tex. 1979) Tex. 1979), 2005-06, Vol.45 (6), p.1088-1093
Main Authors: Koh, Kwang Kon, Quon, Michael J, Han, Seung Hwan, Ahn, Jeong Yeal, Jin, Dong Kyu, Kim, Hyung Sik, Kim, Dae Sung, Shin, Eak Kyun
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description Mechanisms underlying biological effects of statin and angiotensin-converting enzyme inhibitor therapies differ. Therefore, we compared vascular and metabolic responses to these therapies either alone or in combination in patients with type 2 diabetes. This was a randomized, double-blind, placebo-controlled crossover trial with 3 treatment arms (each 2 months) and 2 washout periods (each 2 months). Fifty patients with type 2 diabetes were given simvastatin 20 mg and placebo, simvastatin 20 mg and ramipril 10 mg, or ramipril 10 mg and placebo daily during each 2-month treatment period. Ramipril alone or combined therapy significantly reduced blood pressure when compared with simvastatin alone. When compared with ramipril alone, simvastatin alone or combined therapy significantly improved the lipoprotein profile. All 3 treatment arms significantly improved flow-mediated dilator response to hyperemia and reduced plasma levels of malondialdehyde relative to baseline measurements. However, these parameters were changed to a greater extent with combined therapy when compared with simvastatin or ramipril alone (P
doi_str_mv 10.1161/01.HYP.0000166722.91714.ba
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Therefore, we compared vascular and metabolic responses to these therapies either alone or in combination in patients with type 2 diabetes. This was a randomized, double-blind, placebo-controlled crossover trial with 3 treatment arms (each 2 months) and 2 washout periods (each 2 months). Fifty patients with type 2 diabetes were given simvastatin 20 mg and placebo, simvastatin 20 mg and ramipril 10 mg, or ramipril 10 mg and placebo daily during each 2-month treatment period. Ramipril alone or combined therapy significantly reduced blood pressure when compared with simvastatin alone. When compared with ramipril alone, simvastatin alone or combined therapy significantly improved the lipoprotein profile. All 3 treatment arms significantly improved flow-mediated dilator response to hyperemia and reduced plasma levels of malondialdehyde relative to baseline measurements. 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Etiology ; Cross-Over Studies ; Diabetes Mellitus, Type 2 - blood ; Diabetes Mellitus, Type 2 - drug therapy ; Diabetes Mellitus, Type 2 - physiopathology ; Double-Blind Method ; Drug Therapy, Combination ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use ; Insulin Resistance ; Lipids - blood ; Malondialdehyde - blood ; Medical sciences ; Pharmacology. 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Therefore, we compared vascular and metabolic responses to these therapies either alone or in combination in patients with type 2 diabetes. This was a randomized, double-blind, placebo-controlled crossover trial with 3 treatment arms (each 2 months) and 2 washout periods (each 2 months). Fifty patients with type 2 diabetes were given simvastatin 20 mg and placebo, simvastatin 20 mg and ramipril 10 mg, or ramipril 10 mg and placebo daily during each 2-month treatment period. Ramipril alone or combined therapy significantly reduced blood pressure when compared with simvastatin alone. When compared with ramipril alone, simvastatin alone or combined therapy significantly improved the lipoprotein profile. All 3 treatment arms significantly improved flow-mediated dilator response to hyperemia and reduced plasma levels of malondialdehyde relative to baseline measurements. However, these parameters were changed to a greater extent with combined therapy when compared with simvastatin or ramipril alone (P&lt;0.001 by ANOVA). When compared with simvastatin or ramipril alone, combined therapy significantly reduced high-sensitivity C-reactive protein levels (P=0.004 by ANOVA). Interestingly, combined therapy or ramipril alone significantly increased plasma adiponectin levels and insulin sensitivity relative to baseline measurements. These changes were significantly greater than in the group treated with simvastatin alone (P&lt;0.015 by ANOVA). Ramipril combined with simvastatin had beneficial vascular and metabolic effects when compared with monotherapy in patients with type 2 diabetes.</description><subject>Angiotensin-Converting Enzyme Inhibitors - therapeutic use</subject><subject>Antihypertensive agents</subject><subject>Arterial hypertension. Arterial hypotension</subject><subject>Biological and medical sciences</subject><subject>Blood and lymphatic vessels</subject><subject>Blood Pressure - drug effects</subject><subject>C-Reactive Protein - metabolism</subject><subject>Cardiology. Vascular system</subject><subject>Cardiovascular system</subject><subject>Clinical manifestations. Epidemiology. Investigative techniques. Etiology</subject><subject>Cross-Over Studies</subject><subject>Diabetes Mellitus, Type 2 - blood</subject><subject>Diabetes Mellitus, Type 2 - drug therapy</subject><subject>Diabetes Mellitus, Type 2 - physiopathology</subject><subject>Double-Blind Method</subject><subject>Drug Therapy, Combination</subject><subject>Humans</subject><subject>Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use</subject><subject>Insulin Resistance</subject><subject>Lipids - blood</subject><subject>Malondialdehyde - blood</subject><subject>Medical sciences</subject><subject>Pharmacology. 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identifier ISSN: 0194-911X
ispartof Hypertension (Dallas, Tex. 1979), 2005-06, Vol.45 (6), p.1088-1093
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subjects Angiotensin-Converting Enzyme Inhibitors - therapeutic use
Antihypertensive agents
Arterial hypertension. Arterial hypotension
Biological and medical sciences
Blood and lymphatic vessels
Blood Pressure - drug effects
C-Reactive Protein - metabolism
Cardiology. Vascular system
Cardiovascular system
Clinical manifestations. Epidemiology. Investigative techniques. Etiology
Cross-Over Studies
Diabetes Mellitus, Type 2 - blood
Diabetes Mellitus, Type 2 - drug therapy
Diabetes Mellitus, Type 2 - physiopathology
Double-Blind Method
Drug Therapy, Combination
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use
Insulin Resistance
Lipids - blood
Malondialdehyde - blood
Medical sciences
Pharmacology. Drug treatments
Ramipril - therapeutic use
Simvastatin - therapeutic use
Vasodilation - drug effects
title Vascular and Metabolic Effects of Combined Therapy With Ramipril and Simvastatin in Patients With Type 2 Diabetes
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