A higher level of the inflammation marker myeloperoxidase (MPO) in circulating blood increases the risk of death from a range of disorders, a new study published in the journal PLOS One shows, with the risk of death nearly 10 times higher over a five-year period in patients in the study with the highest levels of MPO compared to those with the lowest levels.
The study, conducted by researchers from Quest Diagnostics, MD Value in Prevention (MDVIP), and Harvard Medical School was based on de-identified clinical data provided by the Quest Cardiometabolic Center of Excellence at Cleveland HeartLab from 3,700 patients under the care of MDVIP-affiliated physicians.
MPO, a marker of chronic inflammation, has been linked with mortality from cardiovascular disease; this study is the first to show an association of MPO with mortality from other diseases.
However, the researchers theorize that elevated MPO levels are not themselves the cause of the higher mortality risk; instead, high MPO is a signifier of changes in the body caused or aggravated by chronic inflammation that raise the risk of death from a range of disorders including but not limited to cardiovascular disease.
The researchers randomly selected 3,700 patients (mean age 66.5 years; 65% female), with data on age, sex, and laboratory results from 2011 through 2015 for MPO and other markers, including low-density cholesterol (LDL-C) and the diabetes marker hemoglobin A1c (HbA1c). The data also included information on any major acute cardiovascular events such as myocardial infarction or stroke. The study group had a prior myocardial infarction rate of 2.4%, which was relatively low risk. Over the study period, 356 patients had died; the dates and causes of death was included for these patients.
Death rates per 1,000 patient years five years from the first MPO level measurement were 2 for low levels, 15 for moderate levels, and 21 for high levels. Cardiovascular events were the leading cause of death in patients with high MPO levels (23.7%), with cancer the second leading cause (18.7%). Liver, renal, respiratory, and central nervous disorders (i.e., Parkinson's disease and multiple sclerosis) combined were responsible for 20.9% of deaths. Of the remaining deaths among patients with high MPO levels, 15.8% were due to Alzheimer’s dementia or old age (as defined by the treating physician) and 11.2% were due to sepsis.
Even after the researchers adjusted for age, sex, prior cardiovascular events, baseline HbA1c, and baseline LDL-C, the correlation of elevated MPO with risk of death remained significant. Furthermore, patients in the study who lowered their MPO by 100 pmol/L reduced their mortality by 5% over five years. It was noted that Quest and MDVIP researchers had previously demonstrated that after physicians had tested MPO levels in patients and recommended changes in areas such as nutrition, exercise and sleep, and medication, the prevalence of elevated MPO levels declined from 20% to less than 5% five years later, suggesting that the changes made had positive effects on inflammation and consequently their MPO levels.