Thread by @POhukainen

(Thread alert!) This review provides some extremely clear figures that explain not just why #LDL matters for #heartdisease but also HOW it matters | onlinejacc.org/content/72/10/… (1/10)

First of all, it's never about what your LDL happens to be right now. It's about what you've been exposed to your whole life. Sometimes you see denialists cite cross-sectional studies (with no follow-up time) as evidence that LDL doesn't matter. This is why that's wrong. (2/10)

This is a very clear illustration how risk manifests over time. Most of us get CVD at some age - with lower lifetime exposure, you can push it further and further. Perhaps until you die of something else. (3/10)

But of course other risk factors also have an effect. They determine your vulnerability to LDL. With higher vulnerability due to non-lipid risk factors, less LDL is needed to initiate and progress CVD. (4/10)

And here's how and why the timing of intervention matters. If you're already at high risk, a modest reduction in LDL will yield only a modest benefit. However, if you begin earlier in life, even a modest reduction yields greater benefit over time due to cumulative exposure (5/10)

It's common to see LDL-denialists cite clinical trials where reduction in LDL yields small benefit. However, these are usually done on patients with either advanced disease ("too late") or otherwise low risk (takes a long time to see the outcome benefit). (6/10)

Again, the cumulative exposure matters and it's illustrated here when comparing the genetic effects of low LDL and reduction via statins (7/10)

The benefit is proportional to lowering, which is a very clear (but just one of many) indication of a causal effect. (8/10)

Those who claim that LDL doesn't matter ( = LDL-deniers) are dangerous quacks. Please don't listen to them. (9/10)

On a personal note, I have somewhat bad LDL genetics myself. I also love the taste of foods that elevate it. I have strong cognitive bias to believe that LDL is harmless. However, the evidence is so overwhelming I can't. (10/10)