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

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Steven A. Grover, MD, MPA; Mohammed Kaouache, MSc; Lawrence Joseph, PhD; Philip Barter, MD, PhD; Jean Davignon, MD, MSc
Arch Intern Med. 2009;169(19):1775-1780.
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


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