Simvastatin Combined With Ramipril Treatment in Hypercholesterolemic Patients
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 30±5% and 53±6%, respectively ( P <0.001), and reduced plasma levels of malondialdehyde by 4±7% ( P =0.026) and 25±4% ( P <0.001), respectively. Monocyte chemoattractant protein-1 levels decreased by 3±3% and 12±2%, respectively ( P =0.049 and P =0.001, respectively), C-reactive protein levels changed by 0% and 18%, respectively ( P =0.036 and P <0.001, respectively), and plasminogen activator inhibitor-1 antigen levels changed by −7±7% and 17±5%, respectively ( P =0.828 and P <0.001, 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 ( P <0.001 and P =0.048 by ANOVA, respectively). Ramipril alone or simvastatin combined with ramipril significantly improved the percent flow-mediated dilator response to hyperemia (both P <0.001), however, simvastatin combined with ramipril showed significantly more improvement than ramipril alone ( P <0.001 by ANOVA). Simvastatin combined with ramipril significantly improved endothelium-dependent vasodilation and fibrinolysis potential and reduced plasma levels of oxidant stress and inflammation markers in hypercholesterolemic patients.
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Emerging evidence indicates that adding a statin to angiotensin II system inhibition or AT-1 receptor blockade yields greater improvements in endothelial dysfunction, inflammation, and oxidative stress.
“On the other hand, evidence for the possibility of obtaining a more marked effect on endothelial dysfunction, inflammation, and oxidative stress by combining statins with the inhibition of angiotensin II system or blocking AT-1 recep- tors is emerging.[41][42][43][44]”
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- Authors
- Koh, K. K., Son, J. W., Ahn, J. Y., Kim, D. S., Jin, D. K., Kim, H. S., Han, S. H., Seo, Y.-H., Chung, W.-J., Kang, W. C., & Shin, E. K.
- Affiliations
- From the Departments of Cardiology (K.K.K., J.W.S., D.K.J., S.H.H., W.-J.C., W.C.K., E.K.S.), Clinical Pathology (J.Y.A.,Y.-H.S.), Radiology (H.S.K.), and Preventive Medicine (Biostatistics) (D.S.K.), Gachon Medical School, Incheon, Korea.
- ORCID
- Venue
- Hypertension
- Published
- 2004-08
- Volume
- 44
- Issue
- 2
- Pages
- 180-185
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- OpenAlex
- W2162960610
- Cited by
- 45
- References
- 36
- Citations by year
- 2023: 2 · 2021: 1 · 2019: 4 · 2017: 2 · 2016: 2 · 2015: 1 · 2014: 3 · 2013: 1 · 2012: 3
- FWCI
- 6.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Hypertension (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Center for Complementary and Alternative Medicine
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Keywords
- simvastatin, ramipril, combination therapy, hypercholesterolemia, diabetic patients, endothelium-dependent vasodilation, flow-mediated dilation, blood pressure reduction, lipoproteins, malondialdehyde, oxidative stress, MCP-1, C-reactive protein, plasminogen activator inhibitor-1
- MeSH terms
- Angina Pectoris, C-Reactive Protein, Cholesterol, Double-Blind Method, Drug Therapy, Combination, Endothelium, Vascular, Female, Humans, Hypercholesterolemia, Hypertension, Cholesterol, HDL, Cholesterol, LDL, Male, Middle Aged, Nitric Oxide, Triglycerides, Vasodilation, Biomarkers, Ramipril, Plasminogen Activator Inhibitor 1, Cross-Over Studies, Chemokine CCL2, Simvastatin, Diabetes Complications
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