Rationale and Objective:

Coronary Heart Disease (CHD) is a leading cause of death for men and women in Canada and worldwide. Current evidence indicates that reducing low-density lipoprotein cholesterol (LDL-C) significantly reduces an individual's risk for CHD-related events. Although an inverse relationship between high-density lipoprotein cholesterol (HDL-C) and incidence of CHD has been established, whether increasing HDL-C protects against CHD is still under debate. The objective of this systematic review was to examine the effects of increasing HDL-C on CHD-related events and mortality.

Methods:

A systematic literature search of the PubMed and Web of Science databases (1977 to 2005), as well as a bibliographic search of relevant articles, was conducted. All randomized controlled trials of lipid-modifying agents that assessed changes in HDL-C and subsequent effects on CHD events were identified. Percent changes in lipid levels due to treatment were compared to the relative risk reduction (RRR) for major CHD-related events and for total mortality.

Results:

Nine randomized controlled trials that met the inclusion criteria were identified. Statin therapy increased HDL-C by 3.8% to 8% and achieved a RRR between 27% and 41%. Fibric acid therapy increased HDL-C by 6% to 18% and achieved a RRR between 9% and 34%. Combination therapy achieved the greatest increase in HDL-C (29% to 38%) and the greatest RRR in CHD-related events (53% to 80%). Most trials achieved a difference in HDL-C levels between treatment and control groups of <10%. However, there were also simultaneous changes in other lipid fractions such as LDL-C. Significant RRR's ranged from 22% to 80%. In three statin trials a significant CHD risk reduction was associated with a rise in low HDL-C at baseline, regardless of whether LDL-C levels were reduced. Two post-hoc analyses found that a 1% increase in HDL-C indicated a 2-3% reduction in CHD risk. No considerable beneficial effect on total mortality was associated with treatment.

Conclusions:

There appears to be a linear relationship between higher HDL-C levels and reduced risk of CHD outcomes. However, whether or not this relationship remains significant in the absence of simultaneous changes in other lipids needs to be determined. The lack of consistency among these trials regarding definitions of CHD and of normal and abnormal baseline lipid profiles of subjects limits the ability to accurately predict and compare the effects of increasing HDL-C. More clinical trials are essential to directly assess the benefits of increasing HDL-C on the reduction of CHD risk.

Section Description

For more information, contact Marilyn Thomas (204) 488-5854