Can change in high-density lipoprotein cholesterol levels reduce cardiovascular risk?

Area of Science:

• Cardiovascular Medicine
• Pharmacology
• Epidemiology

Background:

• Cardiovascular risk reduction from lipid-lowering agents often exceeds predictions based solely on low-density lipoprotein cholesterol (LDL-C) reduction.
• The role of high-density lipoprotein cholesterol (HDL-C) in mediating this additional risk reduction requires further investigation.

Purpose of the Study:

• To explore the extent to which changes in HDL-C levels explain the observed cardiovascular risk reduction beyond LDL-C.
• To analyze the association between HDL-C level changes and coronary heart disease (CHD) risk reduction in trials of lipid-lowering agents.

Main Methods:

• A systematic review of 51 trials of lipid-lowering agents was conducted, focusing on changes in HDL-C and LDL-C levels and CHD incidence.
• Relative risk reduction (RRR) in CHD morbidity and mortality was calculated and compared to expected RRR based on total cholesterol reduction.
• The difference between observed and expected RRR was analyzed against HDL-C level changes using regression analysis.

Main Results:

• Nineteen statin trials were analyzed for the association between HDL-C and CHD.
• Statins significantly reduced total cholesterol (up to 32%) and LDL-C (up to 45%), with HDL-C increases generally below 10%.
• Changes in HDL-C levels did not significantly predict the difference between observed and expected CHD risk reduction for mortality (P=.08) or morbidity (P=.20), though a trend was observed.

Conclusions:

• While a trend suggested greater CHD risk reduction with increased HDL-C effects, this association was not statistically significant.
• The limited range of HDL-C increases in the included statin trials may have hindered the detection of a significant beneficial HDL-C effect.
• Further studies with a wider range of HDL-C changes are needed to definitively assess HDL-C's role in cardiovascular risk reduction.