Peter Attia MD210 - Lp(a) and its impact on heart disease | Benoît Arsenault, Ph.D.& Peter Attia, M.D.
At a glance
WHAT IT’S REALLY ABOUT
Lp(a): Genetics, Biology, Testing, and Emerging Therapies for a Common Risk
- Arsenault explains that early epidemiology on Lp(a) came out negative because of poor assays, and genetic studies from 2009 onward revived the field by showing Lp(a)-raising variants track with cardiovascular events.
- Lp(a) is an LDL-like particle with apolipoprotein(a) attached, made in the liver, and Arsenault says it is more atherogenic per particle because it carries many oxidized phospholipids and shares homology with plasminogen.
- Statins and PCSK9 inhibitors do little or only modestly to Lp(a) (a small rise with statins, roughly 15-30% lowering with PCSK9 inhibitors), so residual risk remains even when LDL is very low.
- The two discuss testing and inheritance: measure Lp(a) once, ideally in nanomoles per liter, levels are largely stable and inherited in a hard-to-predict way, and guidelines differ across the US, Canada and Europe.
- Antisense and siRNA drugs from companies such as Ionis and Amgen can cut Lp(a) by about 80%, and the HORIZON outcomes trial is expected to show whether lowering it reduces events.
IDEAS WORTH REMEMBERING
5 ideasEarly negative Lp(a) studies were an assay problem, not a biology problem.
Arsenault says older antibody assays misjudged isoform size, and genetic association studies from 2009 bypassed that by tracking variants instead of measured levels.
Particle number, not isoform size, drives Lp(a) risk.
Arsenault cites the deCODE sequencing study showing isoform size did not predict heart attack or stroke once Lp(a) levels were accounted for, mirroring how apoB particle count matters for LDL.
Lp(a) is more atherogenic than an equivalent LDL particle.
Arsenault points to its much higher load of oxidized phospholipids, plasminogen-like antifibrinolytic activity, and a distinct protein cargo including autotaxin.
Lp(a) is strongly tied to aortic valve stenosis, even early on.
Arsenault describes PET imaging showing a signal before calcification, and Attia screens patients with high Lp(a) with an echocardiogram because earlier intervention gives better outcomes.
Statins should still be used in people with high Lp(a), despite a small Lp(a) increase.
Arsenault notes the rise is around 10% in most studies, but statins reduce events, possibly even more in those with high Lp(a), so they should not be withheld.
WORDS WORTH SAVING
5 quotesOn a per particle basis, Lp is much more atherogenic than an equivalent, uh, LDL particles.
— Benoît Arsenault
It is by far the most prevalent form of dyslipidemia.
— Benoît Arsenault
If your life isn't worth $14, we shouldn't be having this discussion.
— Peter Attia
The European guidelines and the Canadian guidelines are in line with the available evidence and the United States guidelines are, you know, just 40 years out of date, but that's all.
— Peter Attia
even if, uh, Lp is not fully penetrant, it is so common that, uh, it is by far the most, uh, important form of dyslipidemia that will, uh, explain a lot of cardiovascular events at the population level.
— Benoît Arsenault
High quality AI-generated summary created from speaker-labeled transcript.
