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Lowering blood lipids to treat atherosclerosis: vascular tone, plaques, events, and mortality
Insights
Lowering high cholesterol (hypercholesterolemia) improves blood vessel function and can reverse arterial damage. Significant cholesterol reduction is key for preventing coronary heart disease.
Area of Science:
- Cardiovascular Medicine
- Vascular Biology
- Pharmacology
Background:
- Hypercholesterolemia impairs endothelium-dependent relaxation, increasing vascular tone.
- Endothelial dysfunction precedes detectable atherosclerotic lesions.
- Correction of hypercholesterolemia improves hemodynamics in animal models and humans.
Discussion:
- Cholesterol-lowering drugs halt or reverse arterial lesion progression.
- Arteriography shows lumen but not vessel wall status.
- Noninvasive B-mode ultrasound visualizes arterial walls (e.g., carotid bifurcation).
Key Insights:
- Arterial wall and lesion measurements are crucial clinical trial endpoints.
- Cholesterol reduction impacts coronary heart disease incidence.
- A minimum 8-9% cholesterol reduction is needed for mortality benefits.
Outlook:
- Further research into noninvasive imaging for atherosclerosis.
- Optimizing cholesterol-lowering therapies for cardiovascular prevention.
- Investigating the precise mechanisms of endothelial dysfunction in hypercholesterolemia.
Abstract:
Hypercholesterolemia has been associated with an increase in vascular tone, mainly because of an impairment of endothelium-dependent relaxation. This endothelial dysfunction occurs before any definite atherosclerotic lesion is demonstrated. In both animal models and humans the correction of hypercholesterolemia has been associated with hemodynamic improvement. Several controlled trials have demonstrated that long-term treatment with cholesterol-lowering drugs is effective in blocking progression and in some cases in inducing regression of angiographically detected arterial lesions. Arteriographies produce a negative image of the arterial lumen but do not provide sufficient information on vessel wall status. Noninvasive B-mode ultrasound has allowed a direct visualization of the arterial wall in superficial vascular districts, such as the carotid bifurcation. Wall and lesion measures are increasingly used as end points for clinical trials of antiatherosclerotic drugs. In secondary prevention, cholesterol reduction is associated with a lower incidence of coronary heart disease, although the cholesterol reduction should be at least 8-9% to have an impact on total mortality.