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Prevention and regression of coronary atherosclerosis. Is it safe and efficacious therapy?
T Montague1, R Tsuyuki, J Burton
1Epidemiology and Coordinating Research (EPICORE) Centre, University of Alberta, Edmonton, Canada.
Insights
High cholesterol levels directly increase coronary heart disease (CHD) risk. Reducing high cholesterol effectively lowers CHD events and mortality, but safety in patients with desirable levels is uncertain.
Area of Science:
- Cardiology
- Epidemiology
- Preventive Medicine
Background:
- Coronary heart disease (CHD) is a leading cause of mortality in Western societies.
- Evidence links serum cholesterol levels to CHD risk, prompting population-wide cholesterol reduction strategies.
- Concerns exist regarding potential non-CHD risks associated with very low cholesterol levels.
Purpose of the Study:
- To evaluate the safety and efficacy of prevention and regression therapies for atherosclerotic coronary heart disease (CHD).
- To synthesize evidence from epidemiologic studies and clinical trials on cholesterol management and CHD outcomes.
Main Methods:
- Review of epidemiologic studies with large sample sizes and long follow-up periods.
- Analysis of primary and secondary prevention trials with clinical endpoints (CHD events, mortality).
- Evaluation of secondary prevention trials using coronary angiography to assess atherosclerosis regression.
Main Results:
- A direct relationship exists between total and LDL cholesterol levels and CHD risk across various demographics.
- Cholesterol-lowering therapies consistently reduced CHD events and mortality, but not total mortality.
- Regression trials showed improvement in coronary atherosclerosis, particularly in patients with high baseline cholesterol.
Conclusions:
- Serum cholesterol levels are directly associated with CHD risk, with no identifiable safe threshold.
- Reduction of elevated cholesterol levels demonstrably lowers CHD risk.
- The safety and efficacy of lipid-lowering therapies in patients with desirable or borderline cholesterol levels require further investigation.
Objective:
Atherosclerotic coronary heart disease (CHD) continues to be the dominant disease in Western society. A large body of evidence directly linking serum cholesterol levels and CHD risk has stimulated population treatment strategies designed to reduce cholesterol and CHD risk. Data indicating a relation between low cholesterol and non-CHD risk have, however, suggested that cholesterol reduction may not always be desirable. The primary goal of this evaluative review of the available evidence was to answer the following question: Is prevention/regression therapy for CHD safe and effective?
Data Sources:
Three lines of evidence were reviewed: epidemiologic studies; primary and secondary prevention trials with clinical end points; and secondary prevention trials with quantitative coronary angiography as a surrogate end point for clinical CHD.
Study Selection:
Original studies and meta-analyses were reviewed. The principal selection criteria for the epidemiologic studies were large size and prolonged follow-up; for the trials, randomization and viable clinical (CHD events, CHD mortality, total mortality) or angiographic end points.
Data Extraction:
The data were initially extracted by a single reviewer using common qualitative guidelines. The data were then evaluated by all authors acting as a data interpretation team.
Data Synthesis:
Overall, the epidemiologic data revealed excess risk of fatal and nonfatal CHD events was directly related to total cholesterol and low-density lipoprotein (LDL) cholesterol levels, for both men and women and for both younger (< 65 years) and older (> or = 65 years) patients, over a wide range of serum cholesterol levels. The predictive value was higher in younger men than older men and women, although part of this quantitative interaction may be due to fewer studies, with fewer end points, in the older and female populations. The CHD events and CHD mortality, but not total mortality, were consistently reduced in trials of cholesterol-lowering therapy. The regression trials, predominantly in CHD patients with high cholesterol values (mean 7.1 mmol/L), demonstrated improvement in angiographic atherosclerosis in every study. The evidence for elevated risk of non-CHD death at very low levels of cholesterol is uncertain and controversial. The most likely possibilities for this apparent relationship are unknown confounding variables and the play of chance.
Conclusions:
Serum cholesterol levels are directly associated with CHD risk, and there is no threshold level below which there is no risk. Reduction of high serum cholesterol levels reduces CHD risk. Whether lipid-lowering and adjunctive antiatherosclerotic therapies are effective and safe in the majority of CHD patients who have desirable or borderline cholesterol levels remains undetermined.