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LDL – The Lower the Better

Low density lipoprotein cholesterol is the well-known culprit in terms of cardiovascular risk.

Courtesy of a large meta-analysis of statin trials done in 2010 (the Cholesterol Treatment Trialists Collaboration), we know that for people starting with higher LDL-C levels (approximately 3.4 mmol/L), they can lower their risk of having a major adverse vascular event by 22%, every time they lower their LDL-C level by 1mmol/L.

But what happens once your LDL level is lower? Can you continue to increase your protection by lowering your LDL levels further? Or does the beneficial effect plateau at a certain level? Or, worse still can very low LDL levels actually cause harm?

A new meta-analysis just published in JAMA Cardiology has gone some way in answering these questions.

The researchers analysed data from the 26 statin studies in the CTTC as well as three large trials of non-statin, cholesterol-lowering therapy looking at those patients who had an LDL-C level of 1.8 mmol/L or less at baseline.

They found the cardioprotective benefits continued as LDL-C levels declined to even lower levels.

“We found consistent clinical benefit from further LDL-C lowering in patient populations starting as low as a median of 1.6 mmol/L and achieving levels as low as a median of 0.5 mmol/L”.

What’s more, the incremental benefit was of an almost identical magnitude to that seen when the LDL-C levels were higher – 21% relative risk reduction per 1-mmol/L reduction in LDL-C through this range.

“This relative risk reduction is virtually the same as the 22% reduction seen in the overall CTTC analysis in which the starting LDL-C was nearly twice as high,” they said.

And even though very low cholesterol levels have been rumoured to be associated with everything from cancer to dementia, across all these studies there were no offsetting safety concerns with LDL-C lowering, even when extremely low levels were recorded, levels that were lower than those seen in newborns.

Given the weight of benefit over risk, the study authors suggest the current targets for LDL-C could be lowered further, to even as low as 0.5 mmol/L to reduce cardiovascular risk. This suggestion is supported by an accompanying editorial, in which the author, Dr Antonio Gotto, a New York cardiologist, predicts the findings will be included as part of the revision of the American Heart Association National Cholesterol guidelines which is currently underway.

He said the study findings would provide much needed evidence to help clinicians manage patients with these extremely low achieved cholesterol levels, that until recently have been very rare.

“Whether one calls it a target or a threshold, practicing physicians need some guidance as they venture into achieved levels of LDL-C levels that are as foreign as travel to outer space. I have confidence that the new guidelines will be closer to a global positioning system map rather than just a compass and the stars”, he concluded.


JAMA Cardiol. Published online August 1, 2018. doi:10.1001/jamacardio.2018.2258