Comparative Effects of Diet and Statin on NO Bioactivity and Matrix Metalloproteinases in Hypercholesterolemic Patients With Coronary Artery Disease

Koh, Kwang Kon; Son, Ji Won; Ahn, Jeong Yeal; Jin, Dong Kyu; Kim, Hyung Sik; Choi, YoungRok; Kim, Dae Sung; Jeong, Eui Jun; Park, Gi Soo; Choi, In Suck; Shin, Eak Kyun

doi:10.1161/01.atv.0000030997.02059.bb

Cited by 95 publications

(70 citation statements)

References 34 publications

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“…We and others reported that simvastatin lowers CRP in hyperlipidemic coronary patients (27,28). In the current study, we observed that simvastatin tended to lower CRP in hyperlipidemic patients.…”

Section: Effects On Lipidssupporting

confidence: 70%

Simvastatin Improves Flow-Mediated Dilation but Reduces Adiponectin Levels and Insulin Sensitivity in Hypercholesterolemic Patients

et al. 2008

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OBJECTIVE -We hypothesized that simvastatin may reduce adiponectin levels and insulin sensitivity in hypercholesterolemic patients.RESEARCH DESIGN AND METHODS -This was a randomized, double-blind, placebo-controlled, parallel study. Age, sex, and BMI were matched. Thirty-two patients were given placebo, and 30, 32, 31, and 31 patients were given daily 10, 20, 40, and 80 mg simvastatin, respectively, during a 2-month treatment period.RESULTS -Simvastatin doses of 10, 20, 40, and 80 mg significantly reduced total cholesterol (mean changes 27, 25, 37, and 38%), LDL cholesterol (39, 38, 52, and 54%), and apolipoprotein B levels (24, 30, 36, and 42%) and improved flow-mediated dilation (FMD) (68, 40, 49, and 63%) after 2 months of therapy compared with baseline (P Ͻ 0.001 by paired t test) or compared with placebo (P Ͻ 0.001 by ANOVA). Simvastatin doses of 10, 20, 40, and 80 mg significantly decreased plasma adiponectin levels (4, 12, 5, and 10%) and insulin sensitivity (determined by the Quantitative Insulin-Sensitivity Check Index [QUICKI]) (5,8,6, and 6%) compared with baseline (P Ͻ 0.05 by paired t test) or compared with placebo (P ϭ 0.011 for adiponectin and P ϭ 0.034 for QUICKI by ANOVA). However, the magnitudes of these percent changes (FMD, adiponectin, and QUICKI) were not significantly different among four different doses of simvastatin despite dose-dependent changes in the reduction of apolipoprotein B levels.CONCLUSIONS -Simvastatin significantly improved endothelium-dependent dilation, but reduced adiponectin levels and insulin sensitivity in hypercholesterolemic patients independent of dose and the extent of apolipoprotein B reduction. Diabetes Care 31:776-782, 2008

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Section: Effects On Lipidssupporting

confidence: 70%

Simvastatin Improves Flow-Mediated Dilation but Reduces Adiponectin Levels and Insulin Sensitivity in Hypercholesterolemic Patients

et al. 2008

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“…We calculated that 30 subjects would provide 80% power for detecting a difference of absolute increase, Ն2.1% flow-mediated dilation of the brachial artery between baseline and simvastatin, with ␣ϭ0.05 based on our previous studies. 7,20 The comparison of endothelium-dependent dilation among the 3 treatment schemes was prospectively designated as the primary end point of the study. All other comparisons were considered secondary.…”

Section: Discussionmentioning

confidence: 99%

“…7,8,18,20 Measurements were performed by 2 independent investigators (S.H.H. and W.-J.C.) blinded to the subject's identity and medication status.…”

Section: Vascular Studiesmentioning

confidence: 99%

Additive Beneficial Effects of Losartan Combined With Simvastatin in the Treatment of Hypercholesterolemic, Hypertensive Patients

et al. 2004

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Background-Biological mechanisms underlying statin and angiotensin II type 1 receptor blocker therapies differ.Therefore, we compared vascular and metabolic responses to these therapies either alone or in combination in hypercholesterolemic, hypertensive patients. Methods and Results-This was a randomized, double-blind, placebo-controlled crossover trial with 3 treatment arms (each 2 months) and 2 washout periods (each 2 months). Forty-seven hypertensive, hypercholesterolemic patients were given simvastatin 20 mg and placebo, simvastatin 20 mg and losartan 100 mg, or losartan 100 mg and placebo daily during each 2-month treatment period. Losartan alone or combined therapy significantly reduced blood pressure compared with simvastatin alone. Compared with losartan alone, simvastatin alone or combined therapy significantly changed lipoproteins. All 3 treatment arms significantly improved flow-mediated dilator response to hyperemia and decreased plasma malondialdehyde and monocyte chemoattractant protein-1 levels relative to baseline measurements. However, these parameters were changed to a greater extent with combined therapy compared with simvastatin or losartan alone (both PϽ0.001 and Pϭ0.030 for monocyte chemoattractant protein-1 by ANOVA). Combined therapy or losartan alone significantly increased plasma adiponectin levels and insulin sensitivity (determined by QUICKI) relative to baseline measurements. These changes were significantly greater than in the group treated with simvastatin alone (PϽ0.001 for adiponectin, Pϭ0.029 for QUICKI by ANOVA). Conclusions-Simvastatin combined with losartan improves endothelial function and reduces inflammatory markers to a greater extent than monotherapy with either drug in hypercholesterolemic, hypertensive patients.

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“…4,7,21,22 C-reactive protein (CRP) levels were determined with an immunonephelometry system according to methods described by the manufacturer (rate nephelometry; Immage, Beckman Coulter) as previously described. 23,24 …”

Section: Laboratory Assaysmentioning

confidence: 99%

Simvastatin Combined With Ramipril Treatment in Hypercholesterolemic Patients

et al. 2004

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Abstract-Mechanisms underlying biological effects of statin and angiotensin-converting enzyme inhibitor therapies differ. Thus, we studied vascular responses to combination therapy in hypercholesterolemic patients. A randomized, double-blind, placebo-controlled, crossover trial was conducted with 50 hypercholesterolemic patients with simvastatin and either placebo or ramipril (study I) and in 45 hypercholesterolemic diabetic patients with simvastatin or ramipril with placebo or simvastatin combined with ramipril (study II) for 2 months with 2 months washout. In study I simvastatin combined with ramipril significantly reduced blood pressure after 2 months. Simvastatin alone or combined with ramipril significantly changed lipoproteins, improved percent flow-mediated dilator response to hyperemia by 30Ϯ5% and 53Ϯ6%, respectively (PϽ0.001), and reduced plasma levels of malondialdehyde by 4Ϯ7% (Pϭ0.026) and 25Ϯ4% (PϽ0.001), respectively. Monocyte chemoattractant protein-1 levels decreased by 3Ϯ3% and 12Ϯ2%, respectively (Pϭ0.049 and Pϭ0.001, respectively), C-reactive protein levels changed by 0% and 18%, respectively (Pϭ0.036 and PϽ0.001, respectively), and plasminogen activator inhibitor-1 antigen levels changed by Ϫ7Ϯ7% and 17Ϯ5%, respectively (Pϭ0.828 and PϽ0.001, respectively). In study II ramipril alone did not significantly change lipoproteins and C-reactive protein levels, however, simvastatin combined with ramipril significantly changed lipoproteins and C-reactive protein levels more than ramipril alone (PϽ0.001 and Pϭ0.048 by ANOVA, respectively). Ramipril alone or simvastatin combined with ramipril significantly improved the percent flow-mediated dilator response to hyperemia (both PϽ0.001), however, simvastatin combined with ramipril showed significantly more improvement than ramipril alone (PϽ0.001 by ANOVA). Simvastatin combined with ramipril significantly improved endotheliumdependent vasodilation and fibrinolysis potential and reduced plasma levels of oxidant stress and inflammation markers in hypercholesterolemic patients. Key Words: angiotensin-converting enzyme Ⅲ atherosclerosis Ⅲ endothelial growth factors Ⅲ hypercholesterolemia Ⅲ blood pressure L arge-scale clinical studies demonstrate that statins and angiotensin-converting enzyme (ACE) inhibitor prevent or retard the progression of coronary heart disease. 1,2 The mechanisms of this apparent benefit of these therapies may include vascular effects. Statins reduce LDL cholesterol and improve endothelial function, consistent with enhanced NO bioactivity. 3-5 ACE inhibition also improves endothelial function. 6,7 A potential mechanism of this effect is augmented NO bioactivity via diminished bradykinin degradation by ACE with activation of endothelial B 2 kinin receptors and stimulation of NO synthase activity. 8 Alternatively, ACE inhibition may diminish intracellular production of superoxide anions via reduced activity of angiotensin II-dependent oxidases in the endothelium and vascular smooth muscle, 9,10 thus protecting NO from oxidant degradatio...

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Comparative Effects of Diet and Statin on NO Bioactivity and Matrix Metalloproteinases in Hypercholesterolemic Patients With Coronary Artery Disease

Cited by 95 publications

References 34 publications

Simvastatin Improves Flow-Mediated Dilation but Reduces Adiponectin Levels and Insulin Sensitivity in Hypercholesterolemic Patients

Simvastatin Improves Flow-Mediated Dilation but Reduces Adiponectin Levels and Insulin Sensitivity in Hypercholesterolemic Patients

Additive Beneficial Effects of Losartan Combined With Simvastatin in the Treatment of Hypercholesterolemic, Hypertensive Patients

Simvastatin Combined With Ramipril Treatment in Hypercholesterolemic Patients

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