Results of an international trial suggest that once statins have lowered LDL or "bad" cholesterol, the level of HDL or "good"
cholesterol is less important in terms of predicting cardiovascular risk than it is during pre-treatment assessment.
You can read about the research behind these particular findings from the JUPITER trial in a report published in the early online issue of The Lancet on 22 July. The study was led by Dr Paul Ridker, Eugene Braunwald Professor of Medicine at the Harvard Medical School and director of the Center for Cardiovascular Disease Prevention at the Brigham and Women's Hospital, both in Boston, Massachusetts.
The JUPITER (Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin) trial, which ran from February 2003 to August 2008, showed that compared to placebo, long term use of AstraZeneca's statin Crestor (rosuvastatin) may lower risk of heart attacks and strokes in people with normal levels of cholesterol.
The participants were 17,802 men over 50 and women over 60 years of age, in over 850 locations worldwide, with no previous cardiovascular disease, and without diabetes, with low to normal levels of LDL (the "bad" cholesterol) and high levels of high sensitivity C-reactive protein (hs-CRP, a blood marker of inflammation, used as a rough indicator of heart disease risk).
A computer randomly assigned the participants to receive either Crestor (rosuvastatin) 20 mg per day, or a placebo (8,901 in each group); neither the administrators nor the participants knew whether the treatment contained the active drug or the placebo (double blind).
For this particular study, Ridker and colleagues divided the participants into four groups, according to their levels of "good" cholesterol (HDL), from low to high, and looked for links between HDL levels and significant cardiovascular events such as first non-fatal heart attacks or strokes, hospital attendances for unstable angina, arterial revascularisations, and of course, death due to cardiovascular causes.
Their results showed that:
- There were 44 per cent fewer cardiovascular events in the statin group compared to the placebo group (p
- In the placebo group, HDL levels were inversely linked to cardiovascular risk, both at the start of the study (baseline), and on treatment (top vs bottom quartile hazard ratios HR were 0·54 and 0.55, with 95 per cent confidence interval CI, ranging from 0· 35 to 0·83, and 0.35 to 0.87, p=0·0039 and p=0·0047, in each case).
- In comparison, the statin group showed no significant relationship between quartiles of HDL levels and cardiovascular risk, either at the baseline or on treatment (HR 1·12, 95% CI 0·62-2·03, p=0·82 and HR 1·03, 95% 0·57-1·87, p=0·97, in each case).
- A parallel analysis of apolipoprotein A1 (a major protein in HDL), showed an equivalent strong relationship with cardiovascular events in the placebo group but little association in the statin group.
Although measurement of HDL-cholesterol concentration is useful as part of initial cardiovascular risk assessment, HDL-cholesterol concentrations are not predictive of residual vascular risk among patients treated with potent statin therapy who attain very low concentrations of LDL cholesterol."
Several companies are developing drugs that raise HDL, with the idea of combining them with statins to offer greater protection against heart attacks and strokes.
But these findings appear to question the need for drugs to raise HDL to prevent heart attacks, Ridker said in a telephone interview reported by Reuters.
"Once we get LDL into these very low ranges with very potent statins, HDL no longer predicts future risk of heart disease," he said.
The study was funded by AstraZeneca, who make Crestor, the statin used in the trial.
"HDL cholesterol and residual risk of first cardiovascular events after treatment with potent statin therapy: an analysis from the JUPITER trial."
Paul M Ridker, Jacques Genest, Matthijs Boekholdt, Peter Libby, Antonio M Gotto, Børge G Nordestgaard, Samia Mora, Jean G MacFadyen, Robert J Glynn, John JP Kastelein, for the JUPITER Trial Study Group.
The Lancet, Early Online Publication, 22 July 2010
Additional source: BWH, Reuters.
Written by: Catharine Paddock, PhD