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[Pharmacologic prevention of cardiovascular diseases with calcium antagonists]
1Abt. für Kardiologie, Medizinische Hochschule Hannover.
Abstract:
The major impact of calcium-antagonists in prevention strategies of cardiovascular disease evolves from their modulation of signal transduction and metabolic processes controlled by calcium-ions as "second messenger" in cells participating in the early development of vascular atherosclerotic lesions, namely endothelial cells, vascular smooth muscle cells, monocytes/macrophages, T-lymphocytes and platelets. In accordance with experimental data suppression of angiographically early coronary lesions was documented in four independent clinical studies using quantitative analysis of repeated coronary angiography: Nifedipine and Nicardipine reduce angiographically "new" (minimal) lesions to 30-70%, in some cases already after 1 year of treatment. This anti-atherosclerotic effect is independent of known risk factors and indicates a new strategy in "primary" prevention of atherosclerotic vascular disease. In pre-infarction-syndromes calcium-antagonists demonstrate a tendency in attenuating anginal symptoms and progression into definitive infarction. Analysis of studies in acute infarction showed a neutral effect of calcium-antagonists with unchanged infarct-size, regional and global ventricular function or early mortality. In post-infarction patients only strict selection criteria (up to 60% of patients) as well as delayed onset of therapy (> 7 days after infarction) reduce the number of re-infarction and mortality. Subgroup analysis indicate that calcium antagonists with mild afterload reduction and minimal negative inotropic impact might be preferable. The suppression of "early" lesions should be regarded as the predominant benefit for future strategies in prevention of cardiovascular disease with calcium-antagonists.
Insights
Calcium-antagonists prevent cardiovascular disease by modulating cellular processes involved in early atherosclerotic lesion development. These drugs show significant potential in primary prevention by reducing coronary lesions.
Area of Science:
- Cardiovascular pharmacology
- Cellular signaling
- Atherosclerosis research
Context:
- Calcium ions act as crucial intracellular second messengers in cardiovascular cells.
- Early atherosclerotic lesions involve complex cellular and metabolic processes.
- Calcium antagonists modulate these cellular functions.
Purpose:
- To investigate the impact of calcium antagonists on cardiovascular disease prevention.
- To evaluate their role in modulating cellular signal transduction and metabolic processes.
- To assess their efficacy in preventing early atherosclerotic lesion development.
Summary:
- Calcium antagonists impact signal transduction and metabolism in cells crucial for early atherosclerotic lesions (endothelial cells, smooth muscle cells, monocytes, lymphocytes, platelets).
- Four studies show Nifedipine and Nicardipine reduce coronary lesions by 30-70% within a year, independent of risk factors.
- They show potential in pre-infarction syndromes but have neutral effects in acute infarction.
Impact:
- Calcium antagonists offer a novel primary prevention strategy for atherosclerotic vascular disease.
- Their anti-atherosclerotic effects are independent of traditional risk factors.
- Further research in post-infarction patients suggests specific types may reduce re-infarction and mortality with careful patient selection.