I just read the new Cleveland Clinic Journal of Medicine introduction by its editor-in-chief, and it’s laying out the usual playbook: demonize lipoprotein(a) (Lp(a)), list all the terrible things it does, and hint that salvation is around the corner, pending results of a major pharmaceutical trial, of course.
It’s a neat narrative arc.
But it’s incomplete.
What’s missing is the one question almost no cardiology article seems willing to ask:
Why does Lp(a) exist at all?
As a recovering lipidologist, I’ve spent decades watching molecules get cast as heroes or villains depending on whether we can drug them. LDL is “bad,” HDL was “good” until it wasn’t, triglycerides are making a comeback as the devil of the month, and now Lp(a) is becoming the franchise player in the next therapeutic rollout.
But biology doesn’t traffic in morality.
And evolution doesn’t waste energy on useless proteins.
If Lp(a) were truly a random design flaw, natural selection would have trimmed it out millions of years ago. Instead, humans expanded the LPA gene. That expansion had a purpose.
Lp(a) was an ancient emergency repair tool.
Apo(a), the unique tail of Lp(a), is almost a mirror image of plasminogen, the enzyme precursor that dissolves clots. But apo(a) doesn’t dissolve them. It competes with plasminogen and helps you clot faster.
In a world of:
- Trauma
- Childbirth hemorrhage
- Infected wounds
- Predation
That was life-saving.
Lp(a) was evolution’s “stop the bleeding now” button.
It scavenges toxic debris.
Lp(a) binds oxidized phospholipids, danger signals released during infection and tissue injury. Today we call them “pro-atherogenic.” Back then, Lp(a) was simply mopping up molecular trash created during an infection or wound.
It likely helped us fight pathogens.
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Those kringle domains? They look suspiciously like proteins used by bacteria and parasites to invade tissue. There are strong evolutionary hints that Lp(a) interfered with those invaders.
This pattern (beneficial early, harmful later) is the same story as sickle cell trait, hemochromatosis, and CCR5-Δ32.
Evolution trades youth survival for old-age consequences.
The real problem isn’t Lp(a). It’s lifespan and environment.
Lp(a) makes perfect sense if you live to 30, walk barefoot, and fight off infections with your bare immune system. It becomes a problem if you live to 80, sit for 10 hours a day, and marinate your arteries in chronic inflammation, sugar, and stress.
The molecule isn’t evil.
It’s just doing what it was designed to do in a world that no longer exists.
So why does medicine keep demonizing it?
Because “dangerous molecule + upcoming drug trial = neat story arc.”
It’s the cholesterol playbook all over again.
The Lp(a)HORIZON results may help patients; we’ll see soon enough. But even if they do, we should tell the whole truth:
Lp(a) is not a villain. It’s an ancient survival protein whose talents don’t age well in modern arteries.
If we’re going to talk about Lp(a), we owe patients more than fear and inevitability.
We owe them the biology, and the humility to admit we’re late to understanding it.
Millions of years of evolution aren’t wrong.
Our storytelling often is.
Larry Kaskel is an internist and “lipidologist in recovery” who has been practicing medicine for more than thirty-five years. He operates a concierge practice in the Chicago area and serves on the teaching faculty at the Northwestern University Feinberg School of Medicine. In addition, he is affiliated with Northwestern Lake Forest Hospital.
Before podcasts entered mainstream culture, Dr. Kaskel hosted Lipid Luminations on ReachMD, where he produced a library of more than four hundred programs featuring leading voices in cardiology, lipidology, and preventive medicine.
He is the author of Dr. Kaskel’s Living in Wellness, Volume One: Let Food Be Thy Medicine, works that combine evidence-based medical practice with accessible strategies for improving healthspan. His current projects focus on reevaluating the cholesterol hypothesis and investigating the infectious origins of atherosclerosis. More information is available at larrykaskel.com.
