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Original Investigation
October 26, 2009

Evaluating the Incremental Benefits of Raising High-Density Lipoprotein Cholesterol Levels During Lipid Therapy After Adjustment for the Reductions in Other Blood Lipid Levels

Author Affiliations

Author Affiliations: McGill Cardiovascular Health Improvement Program and Divisions of General Internal Medicine and Clinical Epidemiology, McGill University Health Centre (Dr Grover and Mr Kaouache), Departments of Medicine (Dr Grover) and Epidemiology and Biostatistics (Dr Joseph), McGill University, and Hyperlipidemia and Atherosclerosis Research Group, Clinical Research Institute of Montreal (Dr Davignon), Montreal, Quebec; and Heart Research Institute, Sydney, Australia (Dr Barter).

Arch Intern Med. 2009;169(19):1775-1780. doi:10.1001/archinternmed.2009.328

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 β-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.