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.
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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
_______________________
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)
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SOURCE Quest Diagnostics