I have written here before about my growing conviction that coronary artery disease is not just about LDL, inflammation, or bad luck. It is time to talk about what might be the elephant in the cath lab: infection.

A recent pathology study out of Japan looked at coronary plaque samples from patients with symptomatic CAD. Using both immunohistochemistry and PCR, they found Chlamydia pneumoniae in every single sample. All fifty plaques tested positive (one hundred percent), regardless of whether the patient had stable or unstable disease.

Think about that.

This was not some serology correlation or “maybe it is there” PCR noise. This was direct tissue confirmation in real, living patients. And when you pair that with decades of mechanistic work showing how this bug can trigger oxidative stress, mitochondrial injury, and vascular smooth muscle cell migration; it is hard to keep calling it an innocent bystander.

Yes, we have been down this road before. We had the antibiotic trials. We had the headlines. And when they did not deliver in advanced disease, we packed it all up and went back to statins and stents. But maybe we were asking the wrong question, in the wrong patients, at the wrong stage of disease.

We do not throw out the tuberculosis hypothesis because late-stage antibiotics cannot reverse cavitary lesions. We do not dismiss HIV antivirals because they do not work in advanced AIDS dementia. Timing matters. Targeting matters.

This new pathology data should be our wake-up call. Let us resurrect the clinical trials, this time aimed at early disease, using combinations that hit different stages of the C. pneumoniae life cycle, and with non-invasive imaging endpoints that can actually detect a change before it is too late.

If you have been reading my past KevinMD posts, you know I am not ready to declare C. pneumoniae the sole cause of CAD. But I am saying the case is strong enough (and the stakes high enough) that abandoning the infectious hypothesis without a fair trial is bad science and bad medicine.

It is time to reopen the file.

To my colleagues designing cardiovascular trials (and to the NIH, NHLBI, and other funding agencies), this is your moment. The tools are better, the imaging is better, and the hypothesis is stronger than it has ever been. The next “statin moment” in cardiology might not be a lipid drug at all, but an antimicrobial strategy. We will not know unless we have the courage to test it, properly, and soon.

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.