I see it every week in my practice: Patients obsessed with their cholesterol numbers. LDL, HDL, triglycerides, the full alphabet soup. They have been trained to believe these numbers hold the keys to life and death.

But here is something I cannot stop thinking about: When you look under the microscope, an atherosclerotic plaque (the thing that clogs arteries and leads to heart attacks) looks an awful lot like a tuberculosis granuloma.

In tuberculosis, the granuloma forms as an immune attempt to wall off Mycobacterium tuberculosis. Its center (the caseous necrosis) is a soft, cheese-like mass made up of dead macrophages, neutrophils, T cells, bacterial debris, and a good amount of cholesterol derived from all those broken cell membranes. Cholesterol crystals are often seen on histology, but no one blames cholesterol for causing tuberculosis. We blame the infection and the immune system’s overreaction to it.

Now look at an atheroma: It, too, has a necrotic core filled with dead and dying macrophages (foam cells), lymphocytes, smooth muscle cells, extracellular lipids (including cholesterol and cholesterol esters), cellular debris, and often calcification. We call it a lipid plaque, but really, it is an immune cemetery.

So why, in one disease, do we call the immune-driven mess an infectious granuloma; and in the other, we pin the blame entirely on cholesterol?

For decades, we have been locked into the “lipid hypothesis,” that LDL cholesterol clogs arteries like grease in a pipe. But maybe we have been looking at it backward. Maybe LDL is just part of the wreckage left behind after the immune system goes haywire, possibly in response to chronic infectious triggers (Chlamydia pneumoniae comes to mind), metabolic stress, or other inflammatory insults.

We do not blame cholesterol in syphilitic gummas, leprosy nodules, or TB granulomas, all of which are packed with immune debris and lipid material. We recognize those as inflammatory or infectious diseases. Yet with atherosclerosis, we declared war on cholesterol, and built an entire medical and pharmaceutical empire around fighting it.

And if we followed that logic consistently, we would be treating tuberculosis with statins.

Do statins reduce cardiovascular events? Yes, but probably not just because they lower LDL; they also have potent anti-inflammatory effects. And the repeated failures of HDL-raising drugs (niacin, CETP inhibitors, fibrates) should have been our clue that the story is not as simple as “more or less cholesterol.”

So here is what I tell my patients: Cholesterol may matter, but it is probably more of a marker than a maker of disease. And if that is true, we have spent decades fighting the wrong enemy, and maybe ignoring the real cause.

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.