From Inflammation to Action: MPO’s Role in Chronic Disease

From Inflammation to Action: MPO’s Role in Chronic Disease 

[00:00:00] Welcome to Healthier World with Quest Diagnostics. Our goal is to prompt action from insight as we keep you up to date on current clinical and diagnostic topics in cardiovascular, metabolic, endocrine, and wellness medicine.

Maeson: Inflammation plays a critical role in cardiometabolic disease, but traditional markers like LDLC and H-S-A-R-P don't tell the whole story. Myeloperoxidase or MPO is an enzyme linked to oxidative stress in immune activation and it can offer a deeper look into hidden cardiovascular and metabolic risk.

I'm Dr. Mason Latsko. A researcher by training with a passion for learning. And in this episode, Dr. Mark Penn and I unpack his new research examining the association between MPO and risk for chronic disease, like chronic kidney disease and non-alcoholic fatty liver disease, or NAFLD, also known as metabolic dysfunction, associated stenotic liver disease or MASLD. And

[00:01:00] And we expand on what this might mean for prevention and tailored treatment.

Welcome, Dr. Penn. It's great to have you on today.

Marc: Thanks, Maeson. Great to be here

Maeson: So I wanna kick off today's conversation with a little bit of background. When we think and talk about cardiovascular disease risk, we often think about three pillars, lipids, metabolic health and inflammation. But inflammation in particular can feel a bit broad and many clinicians look at markers like high sensitivity CRP to get a sense of what's going on in the body.

But there are more tools available specifically for cardiovascular disease risk, and one of them is Myeloperoxidase  or MPO. Now, I know you know this Dr. Penn, but for our audience listening in today, MPO is an enzyme release by white blood cells. To give us insight into inflammation within the blood vessels themselves, and it helps us better understand the risk for vulnerable plaque.

If you imagine arterial plaque like a volcano, NPL helps us assess whether or not that volcano is on the verge of erupting.

[00:02:00] Dr. Penn, before we dive into the specific role of MPO in A-S-C-V-D and other chronic diseases, can you speak from your perspective on the importance of simply assessing inflammation for cardiovascular disease risk?

Marc: Measuring inflammatory markers in a overall risk stratification assessment of a patient I is really important. LDL only goes so far. Um, no one should ever say that LDL is not important, but as Ger has shown, and as, as we have shown, the reality is. Excess inflammation, even in the setting of low LDL, is still a significant risk factor for myocardial infarction and cardiovascular death.

Um, the challenge with H-S-C-R-P and we've known this for decades now, is it's relatively non-specific. And in populations where we see 40, 50% of the patients having elevated H-S-C-R-P, the reality is, uh, maybe five 10.

[00:03:00] 15% have elevated myeloperoxidase . Um, again, MPO is in response to vulnerable plaque.

H-S-C-R-P is often in response to weight gain and, uh, other forms of inflammation. So, H-S-C-R-P, while a very good marker, I, I think Myeloperoxidase  has been shown to be more specific. Um, so lots of different ways to parse that, but clearly knowing both has been shown clinically to be of, of value.

Um, you know, really the whole push to driving down LDLs is to drive down inflammation. And the reality is. In patients who may have an LDL of 80, if their inflammatory markers are normal, um, there's no real clear evidence that we need to further drive down LDLs in everybody. And if you go back to the Improve-IT trial, which as you'll remember, there was a significant reduction in mortality.

[00:04:00] But if you go back into the supplemental tables, the only population that had a significant reduction in mortality were the diabetics.

And those diabetics are the ones who are associated with greater vascular inflammation typically. Um, and therefore, again, looking at LDL and looking at inflammation together is critically important,

Maeson: Excellent. So when we talk about inflammation, lipids and metabolic dysfunction, we're really describing all of these different processes that converge to increase your risk for cardiovascular disease. And what ties many of these threads together at the molecular level is the activity of specific enzymes that drive oxidative stress an increased vascular injury, and one of the key players here is Myeloperoxidase or MPO.

Dr. Penn, can you take us deeper into what NPO is and how we can utilize this biomarker in the context of cardiovascular risk?

Marc: Myeloperoxidase is a enzyme that exists

[00:05:00] in white blood cells. It's only synthesized while the cells are being made in the bone marrow. The myeloperoxidase  test that we use is looking for free myeloperoxidase  in the bloodstream. Fundamentally, Myeloperoxidase or MPO should not be free in the bloodstream.

The concept of its link to atherosclerosis. Is that when white blood cells, particularly neutrophils or monocytes, see vulnerable plaque or damage to the artery wall, it attacks like it attacks any site where it sees infection or inflammation.

By attacking at the blood tissue interface at the surface of the vessel, the MyoPro, when it's released from the cell, is released free into the bloodstream. The reality is the most common cause of inflammation on the surface of our blood vessels in the westernized world is vulnerable plaque due to [00:06:00] atherosclerosis .

So it's linked to A-S-C-V-D really is the fact that vulnerable plaque is the reason we inflame our vessels in, in America and the westernized world.

Maeson: So looking at inflammation and specifically myeloperoxidase  can give us a more precise understanding of a person's risk for vulnerable plaque, which is a key driver of cardiovascular events. You've been researching the effects of MPO for a long time. In 2023, you published a paper in plus one linking MPO to all cause mortality, and those findings showed that 50% of death in patients with elevated MPO was due to cardiovascular disease and cancer. And more recently, in April of 2025, you authored a paper in scientific report that explored MPO in the context of other comorbid cardiometabolic conditions such as chronic kidney disease and non-alcoholic fatty liver disease. Can you set the stage for us a little bit about that population and what you were looking at specifically?

[00:07:00] Marc: We looked at an employer population, not people who were necessarily sick.

We looked at Myeloperoxidase as a marker of risk for cardiovascular disease, but we went a step further and looked to see whether that same level of inflammation was associated with either. An increase in fib four as a measure of hepatic disease or an increase in CKD status, um, as a risk of renal disease with the recognition that cardiometabolic disease is what's now driving inflammation.

20 years ago, 30 years ago, before we were all large and sweet. LDL and cigarette smoking. Was what drove disease. And now it's really, cardiometabolic disease associated with obesity and hyperglycemia, hyperinsulinemia. And what our study ultimately showed was that if you identify risk in one

[00:08:00] organ, liver, kidney or heart, you're highly likely to find disease in other organs.

And that inflammation is a link to all three of those. And that we would be remiss to just focus on cardiac prevention in somebody with an elevated myeloperoxidase. 'cause the reality is we need to assess their liver and their kidneys as well. Um, 'cause again, it's a commonality of risk factors across multiple organs and frankly, dementia gets in there as well, although we're not, we didn't specifically look at it. And if we silo our thoughts, we're missing the evidence that tells us this patient may be at risk for more than just one organ of disease.

Great. So really just to reiterate, the study found that if a patient had elevated MYOP peroxidase, They were more likely to have an elevated FIB four, which is an assessment of non-alcoholic fatty liver disease

Maeson: Using A-S-T-A-L-T age and platelets

[00:09:00] as well as evidence of CKD, and that was using an EGFR by creatinine. And really, it does reiterate the idea that if a patient has elevated myeloperoxidase, the likelihood of inflammation being driven by these comorbid cardiometabolic conditions is high.

So a patient at risk For CVD is also at risk for disease and these other organ systems. How do you think that these findings will help clinicians risk stratify their patients in the future?

Marc: I think it's two things. One is it's, let's recognize that patients have risk. They may not have a disease yet, but they have risk and the risk is going to grow 'cause nothing gets better on its own as you age. and inform the patients that they have this, instead of informing them everything's okay. if you have an A1C of five five and an LDL in 98, your report is all green. And what's missing is the right tests that might come up yellow or red. Now if they get an MPO, they get an

[00:10:00] insulin resistant score.

Their triglycerides are good and their A OB is normal and everything's green. Yeah, they're probably in pretty good shape. But we're just missing an opportunity to truly

prevent. secondly, What we really want to highlight with this paper is the idea that cardiometabolic risk or cardiometabolic disease is across multiple organ systems.

And as much as we're taught to prevent heart disease, prevent kidney disease, prevent liver disease. What we really need to be treating is cardiometabolic disease, and we need to recognize that markers that identify cardiometabolic disease, we may think of ordering because of one organ means all the other organs may also be at risk, and we have to look,

Maeson: Good point. Are there other conditions that providers should be thinking about when they run MPO and they identify that it's high, that go beyond cardiovascular disease risk?

Marc: Um, again, MPO is in response to vulnerable [00:11:00] plaque.

but if patients have temporal arteritis, tatsu arteritis, or any significant inflammation in a blood vessel, Myeloperoxidase  will be released by neutrophils and monocytes into the bloodstream.

Um, also as we've shown in other studies, where significant preventive strategies have been given to patients to prevent heart disease or atherosclerosis. The elevation of MPO is linked to cancer and in fact can be used to identify patients who have early cancer, frankly, long before they're ever sick.

And you know, we, we live in an exciting time that we didn't live in 15, 20 years ago, where if you have somebody who has an elevated myeloperoxidase , yes you can do blood testing to look at the liver. You can do blood testing and urine testing to look at the kidney. A as we all should. But we can also look at coronary, CTA.

[00:12:00] To look to see, does my patient have vulnerable plaque, or I can do whole body MRI or CT looking, does my patient have an occult tumor I don't know about before they're sick? And when you're looking at a marker like myeloperoxidase  that is elevated in, different studies, 8%, 4%, 14%, not 50, 60, 70% of the population when to use these more expensive imaging tests becomes, um, really valuable.

And when we talk about liquid biopsy, again, another way, if I have somebody who truly has risk, because the positive predictive value of these tests often, um, are low. But if we can enrich the risk of these patient populations going to this testing using something like myeloperoxidase, we suddenly are actually identifying disease.

And ruling out disease. and that becomes really valuable.

Maeson: Yeah, that's a great point.

[00:13:00] And for listeners who aren't healthcare providers, Do you have any key takeaways for them?

Marc: I really think what, what they, should take away is the idea that if all you're getting is an A1C and an LDL, you're probably being under assessed.

Uh, and if your A1C is above five, you're absolutely being under assessed. And if your LDL is above a hundred. Or even if it's low, but you don't know your a OB, you're probably being under assessed. if We can identify the patient has a condition. Early cardiometabolic disease we can inform them that diet and exercise at this time will actually work.

Maeson: Right. So essentially just kind of being your own advocate at this point. Yeah and having that knowledge going into your appointments with your providers we'll help you to identify your risk of disease much sooner.

So thank you Dr. Penn so much for being here today. It was a pleasure to talk to you as always, and I look forward to next time.

Marc: Absolutely.

[00:14:00] That's a wrap on this episode of Healthier World with Quest Diagnostics. Please follow us on your favorite podcast app and be sure to check out Quest Diagnostics Clinical Education Center for more resources, including educational webinars and research publications. Thank you for joining us today as we work to create a healthier world, one life at a time.