Evaluating the incremental benefits of raising high-density lipoprotein cholesterol levels during lipid therapy after adjustment for the reductions in other blood lipid levels.
BACKGROUND
The role of high-density lipoprotein cholesterol (HDL-C) as a therapeutic target to prevent cardiovascular (CV) events remains unclear. We examined data from the Framingham Offspring Study from 1975 through 2003 to determine whether increases in HDL-C levels after lipid therapy was started were independently associated with a reduction in CV events.


METHODS
Using Cox proportional-hazards regression, we evaluated the risk of a CV event associated with changes in blood lipid levels among individuals who started lipid therapy. The independent effect of HDL-C levels on future CV risk (average follow-up, 8 years) was estimated after adjustment for changes in low-density lipoprotein cholesterol, plasma triglycerides, and pretreatment blood lipid levels. Potential confounders (eg, smoking status, weight, and the use of beta-blockers) were then added to the model. Interactions between blood lipid levels were also explored.


RESULTS
The change in HDL-C level was a strong independent risk factor for CV events (hazard ratio, 0.79 per 5-mg/dL increase; 95% confidence interval, 0.67-0.93) after adjustment for the other lipid changes associated with treatment. This relationship remained stable across a wide range of patient subgroups and did not appear to be associated with a specific drug class. An important interaction was observed: the lower the pretreatment low-density lipoprotein cholesterol level, the greater the impact of raising the HDL-C.


CONCLUSIONS
Raising HDL-C levels with commonly used lipid medications appears to be an important determinant of the benefits associated with lipid therapy. These results support the further evaluation of therapies to raise HDL-C levels to prevent CV events.
Grover
Steven A
SA
McGill Cardiovascular Health Improvement Program and Division of General Internal Medicine, McGill University Health Centre, Montreal, Quebec, Canada. steven.grover@mcgill.ca
Kaouache
Mohammed
M
Joseph
Lawrence
L
Barter
Philip
P
Davignon
Jean
J
D000368:Aged; D000369:Aged, 80 and over; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000097:blood / Q000517:prevention & control*; D008076:Cholesterol, HDL / Q000097:blood* / Q000187:drug effects*; D008078:Cholesterol, LDL / Q000097:blood; D015897:Comorbidity; D005260:Female; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D015415:Biomarkers; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D000960:Hypolipidemic Agents; D014280:Triglycerides