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Lipid-lowering therapy corrects endothelial cell dysfunction in a short time but does not affect hypercoagulable
1Department of Cardiology, Jichi Medical School, Tochigi, Japan. kak2012@mail.med.cornell.edu
Insights
Simvastatin therapy improves endothelial dysfunction in hyperlipidemic patients by reducing von Willebrand factor (vWF) levels. However, it does not affect hypercoagulability markers, suggesting endothelial improvement contributes to reduced cardiac events.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
- Biochemistry
Background:
- Hyperlipidemia is associated with increased cardiac events, partly due to endothelial dysfunction and hypercoagulability.
- Lipid-lowering therapies aim to reduce cardiovascular risk, but the mechanisms beyond direct atherosclerosis regression are not fully understood.
Purpose of the Study:
- To investigate the effects of simvastatin on endothelial dysfunction and hypercoagulability in hyperlipidemic patients.
- To compare these effects with those observed in hypertensive patients.
Main Methods:
- Prospective study measuring coagulation factors (FVIIa, FVIIc, FVIIAg, fibrinogen), coagulation activation markers (F1 + 2), and endothelial dysfunction markers (vWF).
- Evaluated 20 hyperlipidemic patients, 20 hypertensive patients, and 20 controls.
- Measured parameters in hyperlipidemic patients before and after simvastatin therapy for up to 24 months.
Main Results:
- Hyperlipidemic patients showed higher levels of FVIIa, FVIIc, FVIIAg, F1 + 2, and vWF compared to controls.
- Simvastatin therapy significantly reduced vWF levels in hyperlipidemic patients after 3 months, an effect sustained for 2 years.
- Levels of fibrinogen, FVIIc, FVIIAg, FVIIa, and F1 + 2 remained unchanged during simvastatin treatment.
Conclusions:
- Lipid reduction with simvastatin effectively corrects endothelial cell dysfunction in hyperlipidemic patients.
- Simvastatin does not improve hypercoagulability in this patient group.
- The improvement in endothelial function may explain the rapid reduction in cardiac events observed with lipid-lowering therapy.
Abstract:
Lipid-lowering therapy reduces cardiac events to an extent that is disproportionate to the small degree of regression of coronary atherosclerosis observed among hyperlipidemic patients. We prospectively investigated the effects of lipid reduction using simvastatin on the endothelial dysfunction and hypercoagulability found in hyperlipidemic patients. We measured levels of coagulation factors [factor VII (FVII) coagulant activity (FVIIc), FVII antigen (FVIIAg), activated FVII (FVIIa), and fibrinogen], and markers of coagulation activation [prothrombin fragment 1 + 2 (F1 + 2)] and endothelial cell dysfunction [von Willebrand factor (vWF)] in 20 hyperlipidemic patients, 20 hypertensive patients, and 20 normotensive normolipidemic controls. The levels of FVIIa, FVIIc, FVIIAg, F1 + 2, and vWF were all higher in hyperlipidemic patients, but only FVIIa, F1 + 2, and vWF levels were higher in hypertensive patients than in controls. We measured the above parameters in 13 hyperlipidemic patients before and after 1, 3, 6, 12 and 24 months of simvastatin therapy and compared these values with those in 15 hypertensive patients at baseline and after 12 and 24 months. The median (25th-75th percentile) level of total cholesterol was decreased from 259 (255-278) to 206 (176-220) mg/dl after 1 month of simvastatin therapy and this reduction persisted for 2 years. The plasma level of vWF [136% (113-158%)] was not changed after 1 month of administration of simvastatin [132% (115-153%)], but was decreased after 3 months of treatment [114% (96-128%), P<0.01]. This decrease also persisted for 2 years during simvastatin therapy and both of these reductions were significant, compared with levels in hypertensive patients. In contrast, levels of fibrinogen, FVIIc, FVIIAg, FVIIa, and F1 + 2 did not change throughout the 2 years of simvastatin therapy. We conclude that lipid reduction using simvastatin corrects endothelial cell dysfunction but not hypercoagulability in hyperlipidemic patients. The improvement in endothelial cell function brought about by lipid-lowering therapy might contribute to the reduction in cardiac events within a relatively short time period in hyperlipidemic patients.