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Endothelial dysfunction: implications for therapy of cardiovascular diseases
D M Bell1, T E Johns, L M Lopez
1Clinical Pharmacy, School of Pharmacy, West Virginia University, Morgantown 26506, USA.
Insights
Endothelial dysfunction, a key factor in cardiovascular diseases, is an early sign of atherosclerosis. While some treatments improve endothelial function, consistent restoration remains a challenge.
Area of Science:
- Cardiovascular Research
- Vascular Biology
- Medical Science
Background:
- Endothelial dysfunction is an early event in atherogenesis, characterized by impaired endothelium-dependent vascular relaxation.
- Peripheral endothelial dysfunction can indicate coronary artery impairment, serving as a crucial marker for cardiovascular disease.
- Current diagnostic techniques for endothelial dysfunction offer high specificity and positive predictive value for coronary artery disease but have limited sensitivity.
Purpose of the Study:
- To review the existing literature on endothelial dysfunction in cardiovascular diseases.
- To examine the implications of endothelial dysfunction for treating various cardiovascular disorders.
- To assess the effectiveness of different therapeutic agents in restoring endothelial function.
Main Methods:
- A comprehensive MEDLINE search was conducted for basic science articles on the endothelium's role in atherosclerosis.
- Clinical trials investigating the presence and treatment of impaired endothelium-dependent vascular relaxation were systematically reviewed.
- Selected articles and reviews were included to establish the foundational science for clinical trial analysis.
Main Results:
- Endothelial dysfunction is an early indicator of atherosclerosis and a marker for coronary artery impairment.
- Lipid-lowering agents and estrogen supplementation consistently improve endothelial function.
- Treatments for heart failure and hypertension have not consistently improved endothelial function.
Conclusions:
- Endothelial dysfunction is a significant marker for cardiovascular disease, though pharmacologic interventions do not reliably restore normal function.
- Despite inconsistent functional improvements, some agents used to treat endothelial dysfunction demonstrate positive clinical outcomes.
- Further research is needed to elucidate the impact of common cardiovascular therapies on the pathobiology of endothelial dysfunction.
Objective:
To review current literature regarding endothelial dysfunction in cardiovascular diseases and examine implications of these findings for the treatment of various cardiovascular disorders.
Data Source:
A MEDLINE search of basic science articles pertinent to understanding the role of the endothelium in the atherosclerotic process and of clinical trials examining the presence and treatment of impaired endothelium-dependent vascular relaxation was conducted.
Study Selection:
Selected basic science articles and reviews were included to explain the foundation for subsequent clinical trials. All clinical trials examining the treatment of impaired endothelium-dependent vascular relaxation were reviewed.
Data Synthesis:
Endothelial dysfunction characterized by impaired endothelium-dependent vascular relaxation is an early physiologic event in atherogenesis. Endothelial dysfunction in peripheral vasculature serves as a marker for impairment in coronary arteries. Techniques for measuring endothelium-dependent vascular relaxation are specific and have a high positive predictive value for coronary artery disease, but low sensitivity. Various pharmacologic agents have been used in an attempt to improve endothelial function, but only lipid-lowering agents and estrogen supplementation have been shown to improve endothelium-dependent vascular relaxation consistently. Treatments used in patients with heart failure or hypertension fail to demonstrate consistent improvement.
Conclusions:
Endothelial dysfunction serves as a marker for cardiovascular disease, but pharmacologic treatment does not consistently restore normal endothelial function. Nevertheless, some of these agents are known to have positive clinical outcomes. Future research using these techniques will provide greater insight into the effects of many commonly used therapies for cardiovascular disease on the pathobiology of endothelial dysfunction.