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.