People with extremely low levels of "bad" cholesterol as a result of taking statins don't seem to benefit from increased levels of "good" cholesterol, a new study suggests.
The conventional wisdom has been that to reduce the risk of heart attack and stroke you should lower your LDL, or "bad," cholesterol and increase your HDL, or "good," cholesterol. But researchers made a surprising discovery: for those with rock-bottom levels of LDL cholesterol induced by high-dose statin therapy, high HDL levels don't seem to matter.
Statins include widely used medications such as Crestor, Lipitor and Zocor.
For people not taking a statin (in the case of this study, Crestor), high concentrations of good cholesterol still offered heart protection, the researchers found.
"HDL cholesterol is a well-established 'protective risk factor' for heart disease, which has lead to speculation that drugs capable of increasing HDL cholesterol might be beneficial," said lead researcher Dr. Paul Ridker, the Eugene Braunwald Professor of Medicine at Harvard Medical School and director of the Center for Cardiovascular Disease Prevention at Brigham and Women's Hospital in Boston.
However, most of that data comes from studies of patients in the West with high levels of LDL cholesterol, he said. "In this work, we wanted to know if HDL cholesterol levels remain an important predictor of risk when we dropped LDL cholesterol down to very low ranges rarely seen in the West," he said.
The report on the randomized, double-blind trial is published in the July 22 online edition of The Lancet.
For the study, Ridker's team used data from the JUPITER trial, in which people with average to low levels of bad cholesterol were given 20 milligrams of rosuvastatin (Crestor) daily.
In many patients, the drug reduced LDL cholesterol levels to the low levels seen among Aboriginal populations, but not usually seen among people in developed countries, the researchers noted.
During a follow-up of up to five years, people taking Crestor had a 54 percent reduction in heart attack and 48 percent decrease in stroke.
In addition, people taking Crestor had a 46 percent reduction in revascularization (surgery to restore an adequate blood supply to part of the body through a blood vessel graft, like a coronary bypass) and a 43 percent decrease in venous thromboembolism (a blood clot in the leg). There was also a 20 percent decrease in total mortality.
However, when the researchers looked at the effect of "good" cholesterol on reducing the risk of heart attack and stroke, they found no significant relationship between levels of good cholesterol and cardiovascular risk among people taking Crestor.
Among people in the trial given a placebo, levels of good cholesterol remained predictive of cardiovascular risk. Among people with the highest levels of HDL cholesterol, the risk of heart attack or stroke was about half that of those with the lowest HDL levels, Ridker's group found.
"One of the implications of this work is to rethink just how important HDL cholesterol remains once we get LDL levels very low with potent statin therapy," Ridker said. "Clinically, these data suggest that once on a high-dose statin, it is unclear if HDL cholesterol remains an important determinant of residual risk."
"These data do not diminish our need to find out once and for all whether potent HDL-raising agents might improve cardiovascular outcomes," Ridker said. The researchers said that further clincial trials were needed to make that determination.
The JUPITER trial was funded by the pharmaceutical giant AstraZeneca, the maker of Crestor.
Dr. Gregg C. Fonarow, director of the Ahmanson-UCLA Cardiomyopathy Center at the University of California, Los Angeles, said that "while statin therapy lowers the risk of cardiovascular events by 25 to 50 percent, it has been speculated that low HDL cholesterol levels may account for a large component of the residual vascular risk that remains despite statin therapy."
In the cases of primary prevention patients treated with statins, this latest finding challenges that hypothesis, Fonarow said.
"The most evidence-based and effective approach to reduce the risk of heart attack and stroke is lowering LDL cholesterol with maximally tolerated doses of statin therapy, along with lifestyle modification, even in the setting of low HDL," he said. - (HealthDay News, July 2010)
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