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Relation between lipids and atherosclerosis: epidemiologic evidence and clinical implications
1Division of Endocrinology and Hypertension, Wayne State University School of Medicine, Detroit, Michigan 48201.
Insights
Coronary artery disease (CAD) risk factors include cholesterol levels. While lowering cholesterol reduces CAD risk, some blood pressure medications may worsen it, necessitating new treatment approaches.
Area of Science:
- Cardiovascular Medicine
- Epidemiology
- Pharmacology
Background:
- Coronary artery disease (CAD) is a primary cause of mortality globally.
- Established risk factors include dyslipidemia (abnormal cholesterol levels) and hypertension.
- Previous research identified adverse effects of high total and low-density lipoprotein cholesterol, and protective effects of high-density lipoprotein cholesterol.
Purpose of the Study:
- To review the established and emerging risk factors for coronary artery disease.
- To evaluate the impact of antihypertensive therapies on CAD morbidity and mortality.
- To explore newer pharmacological agents for CAD risk reduction.
Main Methods:
- Review of large-scale epidemiologic studies (e.g., Framingham Heart Study).
- Analysis of clinical trial data (e.g., Lipid Research Clinics Trial, Helsinki Heart Study).
- Examination of the metabolic effects of various antihypertensive drug classes.
Main Results:
- Lowering total cholesterol and increasing high-density lipoprotein cholesterol significantly reduce CAD risk.
- Diuretics and beta-blockers, despite lowering blood pressure, did not significantly decrease CAD morbidity or mortality.
- Adverse effects of traditional antihypertensives on lipid and glucose metabolism may explain their limited efficacy.
Conclusions:
- Traditional antihypertensives like diuretics and beta-blockers may not be optimal for reducing CAD risk due to metabolic side effects.
- Newer antihypertensive agents, such as ACE inhibitors and calcium channel blockers, show promise for CAD risk reduction.
- Further research is needed to confirm the cardiovascular benefits of newer antihypertensive classes.
Abstract:
Coronary artery disease (CAD) is the leading cause of death in most developed countries. Therefore, elucidation of risk factors and associated mechanisms for CAD has been a high priority. Data from the Framingham Heart Study and other large-scale epidemiologic studies have identified major risk factors associated with CAD, demonstrating the adverse effects of increased total and low-density lipoprotein cholesterol levels and the protective effect of high-density lipoprotein cholesterol. Other more recent investigations, including the Lipid Research Clinics Trial and the Helsinki Heart Study, have shown that lowering total cholesterol and raising high-density lipoprotein cholesterol significantly reduce the risk for CAD. Because hypertension is also a significant risk factor for CAD, the assumption has been that blood pressure reduction should offer significant benefits in terms of CAD risk. However, despite their antihypertensive efficacy, diuretics and beta blockers have failed to significantly reduce CAD morbidity or mortality. The adverse effects of these antihypertensive agents on lipid profiles, glucose metabolism and other metabolic parameters may account for their disappointing performance in reducing CAD morbidity and mortality. As a result, newer agents such as angiotensin-converting enzyme inhibitors and calcium antagonists that appear to be free of such adverse effects have garnered considerable attention for their potential to reduce CAD risk.