The Complicated World of LDL Cholesterol

Healthy Aging

Simplifying the science on LDL cholesterol

In support of American Heart Month, we have been covering the latest heart health science related to population trends, dietary saturated fats, and (of course) the role of C15:0 in supporting heart health.

For this last Sunday of American Heart Month, we’re talking about the latest science on LDL cholesterol.

Let’s start with plain ol’ cholesterol.

So, cholesterol is a lipid (aka, a waxy fatty substance) that is naturally present in each and every one of our cells. Our body needs cholesterol to do a lot of good things, including helping our skin cells turn sunlight into vitamin D. It is also used to make hormones. In fact, cholesterol is so important to our health, that we have an entire organ dedicated to making it (thank you, liver).

Cholesterol can become problematic when we have too much of it, either from overproduction by our liver, or getting too much from our diet.

Isn’t LDL cholesterol the “bad” cholesterol?

Yes, for the most part. Chances are, you have heard that high-density lipoprotein (HDL) is the “good” cholesterol and low-density lipoprotein (LDL) is the “bad” cholesterol.  Because people with higher LDL cholesterol (LDL-C) levels are more likely to have heart disease, doctors have long sought to prevent heart diseases by lowering our LDL-C.

Gencer et al. led a meta-analysis including over 244,000 patients with heart disease from 29 randomized controlled clinical trials who were treated with either statins, PCSK9 inhibitors, or ezetimibe. Compared to placebo groups, every 1 mmol/L reduction in LDL-cholesterol lowered the relative risk of a major cardiovascular event (like a heart attack or stroke) by 26% – regardless of which LDL-C lowering treatment was used.

That said, use of these drugs alone still leaves people at risk of heart disease. As described in Superko et al., the absolute reduction in risk for heart disease by statins is only 3.4%. This makes sense since, despite decades of using LDL-C lowering drugs, heart disease remains the leading cause of mortality globally.

There are different types of LDL-C, and some are worse for us than others.

So, what’s going on? Here’s where the world of LDL-C is getting more complicated. The quality of LDL-C may be just as important as quantity. More recent studies show that different aspects of LDL-C determine their ability to harm our vessels and hearts. For example:

• Oxidized LDL-C (oxLDL) can cause and worsen atherosclerosis. When LDL-C is oxidized, Itabe et al. share that it is more likely to stick to our vessels and trigger inflammation, both causing and worsening atherosclerosis. As summarized in Hong et al.’s meta-analysis including over 1,000 people across three studies, they found that higher oxLDL levels were significantly increased among people who had both heart disease and chronic inflammation.
• Small dense LDL-C attacks our vessels. LDL-C particles can vary in size – and this matters. Like a bullet, particles that are small and dense are better at infiltrating our vessel walls. In their review including 33 studies, Chary et al. reported that higher levels of small dense LDL-C are associated with an increased risk of heart disease. This risk exists even among people with normal LDL-C levels.

All of this is to say that, while drugs lowering liver production of cholesterol may help to lower overall LDL-C, we are in need of additional ways to protect our long-term heart health.