We all know that lowering low-density lipoprotein (LDL, otherwise known as "bad" cholesterol levels) can help reduce our risk of heart attack and other cardiovascular-related diseases. But is there a limit to how low you should go and more importantly, is there any benefit to having very low levels of cholesterol? According to new research led by scientists at Imperial College London, the answer is a resounding "yes."

The study involved a pooled analysis of 10 clinical trials known as ODYSSEY, an ongoing program that lets patients with high cholesterol levels not adequately lowered by statins gain access to experimental drugs. Researchers wanted to find out whether dramatic reductions in cholesterol levels caused by some of these drugs are safe, and if these reduced levels confer more benefits than the current levels achieved with existing drugs.

The 10 studies involved around 5,000 patients with an average age of 60, all of whom were deemed at risk of heart attack or stroke. The average cholesterol reading was around 125 mg/dL (recommended levels are 100 mg/dL or below, though this number depends on a person's risk of cardiovascular disease). Most had cardiovascular disease, and already had some furring of the arteries or were at very high risk of furred arteries.

What the study found was that overall, 33 percent of these patients achieved a cholesterol level lower than 50mg/dL, which is comparable to the levels we have at birth. In placebo-controlled studies, 52.6 percent of those treated with the drug alirocumab achieved these levels compared to 0 percent of placebo-treated patients. Of note is the fact that these results are only achievable in adulthood through medication. Individuals cannot achieve such levels through a healthy lifestyle and exercise alone.

In addition, the authors also found that there was a continuous relationship between lowered LDL cholesterol levels and major adverse cardiovascular events (MACE) all the way down to about 25 mg/dL. For every 39 mg/dL lower on treatment LDL, a patient's risk of MACE – i.e. death from heart disease, heart attack, stroke or angina – went down by about 24 percent.

"We also looked at many of the guidelines [and] actually looked at percentage reductions. If you start with a baseline LDL of X and you achieve a 50 percent further reduction in LDL, how much further benefit does that give you? A 50 percent further reduction gave you a 29 percent further lower risk of MACE. So we didn't find any threshold or limit all the way down to LDLs of about 25," explains lead author Kausik Ray, a professor from the School of Public Health at Imperial College, in the podcast, Circulation on the Run.

Based on the results of the study, one can reasonably conclude that very low cholesterol levels are not only safe but beneficial as well. "Experts have long debated whether very low cholesterol levels are harmful, or beneficial. This study suggests not only are they safe, but they also reduced risk of heart disease, heart attack and stroke," says Ray.

A year's supply of alirocumab, which was approved by the US Food and Drug Administration last year, costs US$14,600. While the results of the study are highly promising, the authors of the study also say that they need to wait till the trials have been fully analyzed to assess the full benefits and long-term effects of low cholesterol levels induced by the drug. That said, this study should encourage people to look at LDL and the associated benefits of reduced levels.

The study was funded by Sanofi and Regeneron Pharmaceuticals.

The results of the study were published in Circulation.

Source: Imperial College