NEW YORK — The ratio of LDL cholesterol to HDL cholesterol was the most powerful measure of cardiovascular disease risk in a retrospective analysis of data on almost 6,000 elderly patients.
The analysis also suggested that patients over age 70 years won't benefit from statin therapy if their serum level of HDL cholesterol at baseline exceeds 45 mg/dL, Chris J. Packard, Ph.D., said at an international symposium on triglycerides and HDL.
Previous studies showed that elevated LDL cholesterol is not a risk factor for cardiovascular disease in the elderly. Yet in a large trial first reported in 2002, during a mean follow-up of 3.2 years, use of 40 mg pravastatin/day cut the risk of new cardiovascular disease events by a significant 15%, compared with placebo, in patients aged 70–82 who had 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 lowered 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.
In the new analysis, pravastatin's benefit was confined to the two quintiles with the lowest baseline levels of HDL cholesterol (all were below 45 mg/dL). In these patients, the use of pravastatin was associated with a 33% reduction in cardiovascular events, compared with placebo. Among the 60% of patients with a baseline HDL cholesterol level above 45 mg/dL, the use of pravastatin was not linked with any reduction in events.
Statin therapy's impact on HDL was greatest in the 25% of patients with the lowest baseline HDL cholesterol levels. In this group, use of pravastatin was linked to a mean increase of 10.7%. In the 25% who started with the highest HDL cholesterol levels, statin therapy was linked to a 4.8% increase.
Further analysis showed that the change in HDL cholesterol level, by itself, was not linked to the change in risk, Dr. Packard said 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 elderly patients with a significant reduction in the ratio of LDL to HDL cholesterol had, on average, a significant reduction in cardiovascular disease risk.