Best of Pappas Health: Labs and Studies

Here’s our first installment of the best of 2024. We begin with a review of some of the more interesting lab tests and studies that have caught our attention and found especially useful this past year.

HDL function panel (HDLfx Test) 

The Cleveland Heart lab in association with Quest labs has a test that looks at HDL function

The research demonstrates:

HDL cholesterol particles are considered to be cardioprotective because of their anti-atherogenic properties, which include increasing reverse cholesterol transport, promoting endothelial nitric oxide production, and anti-inflammatory and antithrombotic effects. Low HDL-C, a component of metabolic syndrome, is predictive of cardiovascular risk, but clinical trials have shown therapeutically increased HDL-C levels do not reduce rates of cardiovascular events.

These findings led to an understanding that the physiological impact of HDL may be dependent on its functionality, more so than low or high HDL-C levels. The importance of HDL function to CVD is highlighted by findings that patients who have the highest cholesterol efflux capacity (CEC), a marker of HDL function, have a 67% reduction in cardiovascular risk compared to the lowest quartile CEC.

HDL Function Testing provides Unique Insight into Cardiovascular Disease

In early 2019, the Journal of American College of Cardiology published a study that found that the HDL function test may be independently associated with cardiovascular death in individuals with coronary artery disease. “This study provides tantalizing evidence that HDL function testing will complement other methods of evaluating an individual’s cardiovascular health, enhancing risk detection and patient management,” said study co-author Marc Penn, MD, PhD, FACC, Founder, Cleveland Heart Lab, and Medical Director, Cardiometabolic Endocrine Division, Quest Diagnostics.

New HDL Concepts:

Dr. Mark Houston reviews this concept in this video here- New HDL Cholesterol Concepts for Coronary Heart Disease

My comment:
Is your good cholesterol good enough? HDL has simplistically been considered as the protective or good type of cholesterol. We are now starting to learn that HDL comes in many forms and that the forms may not always function well. My senior resident and excellent mentor was Dr Marc Penn during our time in training together at the University Hospitals of Cleveland. He went on to found the Cleveland Heart Lab and helped to develop this novel test and other important cardiac labs. More than just your number of HDL or even the size, knowing the function may be a more important piece of information and help to better classify cardiovascular risk. 

ADMA

The ADMA/SDMA biomarker blood test, now available through Cleveland HeartLab (CHL), measures levels of asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA). Elevated levels of these biomarkers can signal damage to the endothelium, the inner lining of blood vessels.

“Not only does this test help medical practitioners do a better job of assessing the health of the arterial wall, but it can also help identify the cause of problems like high blood pressure and vascular inflammation” says Amy Doneen, DNP, ARNP, medical director of the Heart Attack & Stroke Prevention Center in Spokane, Washington.

“When ADMA or SDMA are elevated, the endothelium is robbed of one of the most powerful nutrients it needs to maintain health: nitric oxide,” continues Dr. Doneen. Levels of both biomarkers, which are naturally produced as proteins are broken down, may rise in people who smoke, eat a poor diet, or have high cholesterol, high blood pressure or high blood sugar.

My comment:
We’ve been using this test for quite some time and have found it to be a very useful tool to help us optimize cardiovascular and metabolic health. ADMA elevation is associated with a decrease in Nitric Oxide and a dysfunction in the endothelium, often an early step on the way to atherosclerosis. It also has been linked to glucose dysregulation and kidney problems. An increased ADMA can also be seen with blood pressure changes. 

Adiponectin

The adipose tissue is an active endocrine organ that synthesizes and secretes a variety of adipokines, including adiponectin with its anti-inflammatory properties.

Adiponectin is the most abundant peptide secreted by adipocytes, being a key component in the interrelationship between adiposity, insulin resistance, and inflammation. Adiponectin presents antineoplastic, cardioprotective, and anti-inflammatory properties.

Additionally, it sensitizes tissues to insulin activity which contributes to its hypoglycemic properties. This means that it helps the body use glucose more efficiently and it also helps to break down fatty acids and reduce overall fat. The fewer fat cells you have, the more adiponectin you produce.

The higher the number the better. Low levels of adiponectin are associated with obesity, metabolic syndrome, heart disease, increased inflammation, and diabetes. Lower levels are seen in men than women. 

My comment:
The good news with this metabolic marker is that there are many ways to improve it. Adiponectin is raised by Intense Lifestyle Intervention (ILI)- regular and consistent exercise and a clean diet. In particular, research has shown that healthy fats such as olive oil, nuts, fish, and avocados, help to raise adiponectin levels. Another great argument for a Mediterranean diet! Other studies demonstrate that coffee, fish oil, turmeric, and aged garlic extract can help to raise adiponectin. 

You can find more information on adiponectin within the following links: 

Galectin-3

Galectin-3 is an emerging all-out player in the metabolic disorders and their complications. Galectin-3 has been increasingly recognized as an important modulator of several biological functions, by interacting with several molecules inside and outside the cell, and an emerging player in numerous disease conditions.

It regulates chronic and acute inflammatory responses and contributes to fibrosis. We’ve been testing for a novel marker of fibrosis and inflammation for some time now as many of you are aware. Here’s a good video link from one of the pioneers in this field:

Galectin-3: A New Target For Inflammation with Dr Isaac Eliaz

Emerging research is linking Galectin-3 to prognostic factors in the presence/ severity of a variety of illnesses from heart disease, Covid-19 and other viral infections, neurodegenerative disorders, autoimmune diseases, and cancers. Its original research highlighted its link to heart failure, and it remains listed under cardiac panels but it is applicable to a number of areas and not just the cardiac system.

We see that many of our patients who have post-Covid challenges have persistent Galectin-3 levels. Although, like with other markers of inflammation these tests can be non-specific, persistent changes warrant further attention and a more comprehensive plan. The research highlighted below hints at some potentially exciting possibilities including the monitoring of cancer, heart disease, Covid-19, autoimmune, and neurodegenerative changes through changes in Galectin-3 levels.

Here are some important papers on the multifaceted impact of Galectin-3: 

My comment:
Understanding galectin-3 remains in its infancy but it is emerging as an important modulator of metabolic disorders across all facets of disease. While big pharma is actively studying treatment to block or inhibit its function, the leading player in the treatment of elevated levels of galectin-3 is modified pectin, derived from citrus fruit and best known as Pectasol. I predict tracking this novel marker will help us better understand the status of these multifaceted illnesses. 

Covid-19 Spike Antibody

We’ll take a look at the Covid-19 spike antibody in more detail when we review the latest in Covid-19 studies and research in a future article but it’s important to point out the significance of this lab and why we routinely test for it.

Dr. Peter McCullough, one of the leading researchers and practitioners of all things Covid, has written often about the significance of antibody testing: 

An extended range total antibody against the Spike protein is a useful proxy for prior Spike exposure. The Roche Elecsys Anti-SARS-CoV-2 Spike assay measures antibodies against the receptor binding domain (RBD). Roche Elecsys Anti-SARS-CoV-2 assay has a normal value of <0.8 U/ml, and in my experience 0-1000 is low risk, and >1000 indicates higher risk with either multiple infections or vaccine administrations.

It is not uncommon to find patients with >25,000 U/ml as unmeasurably high even years after vaccination. Antibody concentrations take at least 12 months to taper off. Thus a Spike antigen test measurable in whole blood, plasma, or serum is greatly needed to provide a real-time estimate of Spike concentration and its inferred potential for toxicity.

My comment:
This test is the best proxy we have for prior Covid Spike exposure. It remains an inexact science and undoubtedly many only have a jump in levels after a recent exposure. However, the majority of our patients have persistently elevated antibodies 3-4 years after their last vaccine or infection. Furthermore, many of these patients also have other inflammatory markers such as Galectin-3 and D-Dimer that require further assessments. Dr. McCullough is correct when he says, “- a Spike antigen test measurable in whole blood, plasma, or serum is greatly needed to provide a real-time estimate of Spike concentration and its inferred potential for toxicity.”

A New Revolutionary Technology That Can Predict Cardiovascular Risk With Precision, Part 1 and 2

Precision medicine and the improved imaging of cardiac and arterial structures and function are important emerging concepts. We have been using both CT Angiograms and A.I.-derived plaque assessments to help our patients better differentiate the health of their heart arteries. 

Dr. Ronald Hoffman interviews Dr. James Min the founder of Cleerly Health in this two-part series. They review the difference between Calcium Score scans and CT Angiograms and how to use the latter to better differentiate plaque through an A.I.-generated program run by Cleerly Health. 

Dr. Joel Kahn, an integrative cardiologist interviews Dr. James Earls, the Chief Medical Officer of Cleerly Health: Prove Your Heart Health With Cleerly

Dr. Earls, from the interview:

We do it clearly as we take a CT scan of the heart, and for the first time, we measure coronary atherosclerosis or the disease process itself. So we can separate the plaque from the arteries, and we can accurately determine the quantity of plaque. There are several different types of plaque. These plaques have different risks for patients. So we’re also able to determine how much of each of the different types of plaque is present. sounds like a relatively simple advance, but, for many years we measured many other things about heart disease, but we didn’t measure the disease process itself. So that’s what we have introduced to the marketplace in the last few years.

That’s right. For many years, of course, we predominantly used the calcium score because that was the only type of plaque we were able to follow. But with advances in imaging as well as A.I., we can now look at the other types of plaque, and it’s the other types of plaque that place you at risk. So, yes, certainly there are cases where patients have low calcium scores, and that can give you a sort of false sense of security in some situations because, with a low calcium score, you could still have a relatively high amount of the other types of plaque, which are riskier. Certainly, there are times, of course, when a low calcium score also means there’s a low non-calcified plaque burden, but in some cases, it can go the other way around.

My comment:
These tests are not cheap and not as of yet well covered, if at all. However, they can provide detailed non-invasive assessments of the different types of arterial plaque, help differentiate the plaque that may increase one’s risk for heart attacks, and better look at artery flow and function. 

CNS Vital Signs

The field of neurodegenerative diseases and cognitive health is gaining much-needed attention due to the alarming rates of disorders in this space. There’s an important need to better assess neurocognitive testing. One of the exciting new products we’ve been experimenting with is CNS Vital Signs. This remote and computerized broad-spectrum neurocognitive testing program can help assess many areas of memory and cognitive function and help differentiate cognitive decline from ADHD and other causes such as concussion and Traumatic Brain Injuries. It has a large body of evidence supporting it and is recommended and used by clinicians such as the Neurologist Dale Bredesen. 

You can view a sample report with more information on their website.

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