NEW YORK — In elderly people, the ratio of LDL cholesterol to HDL cholesterol was the most powerful measure of cardiovascular disease risk in a retrospective analysis of data collected in a trial with almost 6,000 patients.
The analysis also suggested that elderly patients—those who are at least 70 years old—will not benefit from statin therapy if their serum level of HDL cholesterol at baseline is greater than 45 mg/dL.
“We need to study this more, but that's what our new analysis suggests,” said Chris J. Packard, Ph.D., at an international symposium on triglycerides and HDL.
The results of several previous studies have shown that an elevated level of LDL cholesterol is not a risk factor for cardiovascular disease in the elderly. Despite this, the results from a large trial that were first reported in 2002 showed that during a follow-up period that averaged 3.2 years, a regimen of 40 mg pravastatin/day cut the risk of new cardiovascular disease events by a statistically significant 15%, compared with placebo, in patients aged 70–82 who had either established vascular disease or elevated risk factors for vascular disease (Lancet 2002;360:1623–30).
This finding from the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) trial raised the question of why statins were effective at lowering risk in patients with an average age of 75 who are usually not harmed by high LDL cholesterol levels, said Dr. Packard, a biochemist and research director at Glasgow Royal Infirmary, Scotland.
One element of the new analysis was to assess the impact of pravastatin treatment by quintile of HDL cholesterol level. This assessment showed that all of the benefit of pravastatin treatment was confined to the two quintiles with the lowest levels of HDL cholesterol at baseline. In these patients, whose levels were all less than 45 mg/dL, pravastatin treatment was associated with a 33% reduction in cardiovascular events, compared with the group treated with placebo. Among the other 60% of patients, who all started the study with an HDL cholesterol level of more than 45 mg/dL, pravastatin treatment was not linked with any reduction in events, compared with the placebo group.
The impact of statin treatment on HDL cholesterol levels was greatest in the 25% of patients whose HDL cholesterol levels were the lowest at baseline. In this group, pravastatin treatment was linked with an average increase of 10.7%. In contrast, among the 25% who started with the highest HDL cholesterol levels, statin treatment was linked with a 4.8% increase. But further analysis showed that the change in HDL cholesterol level, by itself, was not linked to the change in risk, said Dr. Packard at the symposium, sponsored by the Giovanni Lorenzini Medical Foundation. Nor was the change in risk linked with changes in serum levels of C-reactive protein.
But significant reductions in risk were linked with changes in the ratio of LDL to HDL cholesterol. Elderly patients who had a significant reduction in this ratio had, on average, a statistically significant reduction in their cardiovascular disease risk, Dr. Packard said.