Inflammation Marker Signifies Increased Mortality Risk, Finds New Study in PLOS ONE

Ten-fold increase in death risk in individuals with high levels of myeloperoxidase, or MPO, compared to those with low levels, according to analysis of 3,700 patients of MDVIP tested by Quest Diagnostics

SECAUCUS, N.J., and BOCA RATON, Fla., Aug. 2, 2023 /PRNewswire/ -- The higher the level of a marker of inflammation in circulating blood, the greater the risk of dying from a range of medical disorders, according to a new study published in PLOS ONE. The analysis is the first to demonstrate that lowering levels of myeloperoxidase, or MPO, a marker of chronic inflammation traditionally associated with heart disease, may help provide insight into an individual's mortality risks from a range of diseases beyond heart disease. With these insights, individuals with their healthcare providers may be able to take more aggressive actions to lower personal risk.

Researchers from Quest Diagnostics (NYSE: DGX), MDVIP and Harvard Medical School conducted the analysis. It is based on de-identified clinical MPO laboratory data from testing provided by the Quest Cardiometabolic Center of Excellence at Cleveland HeartLab in Ohio on 3,700 patients under the care of MDVIP-affiliated physicians. As part of the MDVIP Annual Wellness Program, physicians provide their patients MPO screening based on a Quest MPO blood test.

"This study provides strong evidence that not only does a high MPO level signify heightened mortality risk from a range of diseases, but that lowering an MPO level reflects a reduction in that risk," said lead author Marc S. Penn, MD, PhD, FACC, co-author of the study and Medical Director for the Quest Cardiometabolic Center of Excellence at Cleveland HeartLab, as well as physician at Summa Health Heart and Vascular Institute. "This finding raises the prospect MPO can help identify individuals at significantly elevated risk for death, so physicians can direct more aggressive care to patients who may benefit as compared to those of lower risk."

White blood cells (called neutrophils) help the body fight infections and heal injuries through a process that involves a limited and local inflammatory response. When inflammation turns chronic, white blood cell activation may trigger adverse changes in the body. One of these changes is the activation of the white blood cells that then release MPO into the blood stream.

Risk of Death Nearly 10 Times Higher in Individuals with Highest MPO vs. Lowest MPO Scores After Five Years

For the study, the researchers randomly selected 3,700 patients enrolled in MDVIP (mean age 66.5 years, 65% female), with data on age, sex and serial laboratory results from 2011 through 2015 for MPO and several other laboratory markers, including low-density cholesterol (LDL) and hemoglobin A1c (HbA1c), a diabetes marker. The team also included information on incidence and dates of major acute cardiovascular events (MACE), including myocardial infarction ("heart attack") and stroke, as well as date and cause of death. Compared to other studies, the population was relatively low risk, with a prior myocardial infarction rate of 2.4%. 

The analysis utilized medically recognized cutoffs for MPO levels of low (<470 pmol/L), moderate (470-539 pmol/L) and high (≥540 pmol/L). Over the study period, approximately 356 patients died for which cause of death could be determined. 

Among the key findings:

• Death rates (per 1,000 patient years)¹ 5 years from first MPO measure were 2 for low MPO levels, 15 for moderate levels and 21 for high MPO levels.
• Fifty percent of deaths in patients with an elevated MPO were due to cardiovascular death (23.7%) or cancer (18.7%). Liver, renal, respiratory and central nervous disorders (Parkinson's and multiple sclerosis) contributed another 20.9% of deaths, with most other causes due to Alzheimer's dementia and the classifier old age (as defined by treating physician) (15.8%) and sepsis (11.2%).
• The correlation of elevated MPO with risk of death remained significant after adjusting for age, sex, prior cardiovascular events, baseline HbA1c, and baseline LDL-C.
• Individuals under the care of an MDVIP doctor who lowered their MPO (by 100 pmol/L) reduced mortality by 5% over 5 years.
• The researchers also noted MPO's performance in the study raises the prospect it may be a more specific predictor of mortality than high-sensitivity CRP, a well-established marker of inflammation described in other research.

The researchers theorized that high MPO may not cause higher mortality risk, but rather, may indicate changes in the body that raise risk of death from a range of disorders possibly caused or aggravated by chronic inflammation.

"We've long known that chronic inflammation is a significant indicator and contributor of disease risk, which is why MDVIP-affiliated physicians have provided their patients with annual MPO screening for over a decade," said senior author Andrea Klemes, DO, FACE, Chief Medical Officer of MDVIP, who is responsible for leading innovation and medical initiatives for its primary care model. "Published data has already shown that when patients have elevated MPO levels, our physicians have more time to better identify the root causes and work with them on steps they should follow to help reduce their levels. This latest study is powerful in raising the prospect that the doctor-patient relationship can improve clinical outcomes when informed by markers that better identify risks for disease."

Quest and MDVIP researchers previously demonstrated that after physicians identified MPO levels in patients of MDVIP, the prevalence of elevated MPO levels declined from 20% to less than 5% five years later². The study suggests that physician and patient awareness contributed to actions that helped reduce MPO levels, presumably due to more proactive coaching in areas that include nutrition, exercise and sleep, medication changes as well as reducing insulin levels.³

"Our study adds to a growing body of research demonstrating chronic inflammation has systemic adverse impacts on health well beyond heart disease," said author Mouris Saghir, PhD., an expert in lipidemia and Vice President and General Manager, Cardiometabolic and Endocrine, for Quest Diagnostics, from the Quest Cardiometabolic Center of Excellence at Cleveland HeartLab. "Crucially, it also shows individuals who take actions to reduce MPO may reduce their risk of death. Individuals with high or moderate MPO levels may also be advised to be especially proactive in pursuing cancer and other health screenings to identify potential risks in early, treatable stages."

The study's strengths include its large sample size. Limitations include lack of diversity (population was greater than 90% Caucasian) and lack of information on specific drug therapy information on each patient.

The full study can be accessed online at PLOS ONE here.

The Quest Cardiometabolic Center of Excellence at Cleveland HeartLab provides cardiometabolic testing, services, and resources to help identify hidden risk of heart disease and metabolic-associated conditions earlier. The center's multi-marker approach of adding inflammation-specific tests to traditional lipid testing provides additional insight into an individual's cardiovascular risk. In addition, this approach helps measure risk across a spectrum, allowing for long-, mid- and near-term assessment, so healthcare providers to better identify hidden risk and treat more aggressively when appropriate.

About MDVIP
MDVIP leads the market in membership-based healthcare that goes far beyond concierge medicine services with a national network of more than 1,100 primary care physicians serving over 385,000 patients. MDVIP-affiliated physicians limit the size of their practices, which affords them the time needed to provide patients with highly individualized service and attention, including a comprehensive annual preventive care program and customized wellness plan. Published research shows that the MDVIP model delivers more preventive health services and saves the healthcare system hundreds of millions of dollars through reduced hospitalizations and readmissions. For more information, visit www.mdvip.com.

About Quest Diagnostics
Quest Diagnostics empowers people to take action to improve health outcomes. Derived from the world's largest database of clinical lab results, our diagnostic insights reveal new avenues to identify and treat disease, inspire healthy behaviors and improve healthcare management. Quest annually serves one in three adult Americans and half the physicians and hospitals in the United States, and our nearly 50,000 employees understand that, in the right hands and with the right context, our diagnostic insights can inspire actions that transform lives. www.QuestDiagnostics.com

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1} The phrase 1,000 patient years provides an estimate of the number of events each year for the population size over the approximately 5 years of the study.
² Neutrophils in chronic inflammatory diseases | Cellular & Molecular Immunology (nature.com)
³ Inflammation Testing Prompts Care Changes Leading  to Significantly Lower Levels in Patients with Increased Cardiovascular Risk Due to Diabetes or Pre-Diabetes (prnewswire.com)

SOURCE Quest Diagnostics