For the first time, researchers have found that low levels of an anti-inflammatory antibody predispose older women as well as men to cardiovascular (CV) disease.
The findings, published in the Journal of the American College of Cardiology, could eventually lead to a vaccine against ischemic heart disease (IHD).
The natural antibody against phosphorylcholine acted independently of other, previously known risk markers in predicting a combination of CV outcomes.
Postmenopausal women in the highest third of levels had a 73% lower risk of these adverse events compared with women who had the lowest of levels, after adjusting for potential confounders.
Johan Frostegård, PhD, head of the immunology and chronic disease unit at the Karolinska Institute in Stockholm, said the precision medicine research had shown very strong results for women.
“My real hope is to develop a vaccine to raise these antibodies,” he told Inside Precision Medicine. “Those with lower levels would be eligible.”
Phosphorylcholine is abundant in cell membranes and lipoproteins and is believed to be central to immune activation by oxidized low-density lipoprotein (oxLDL), which contributes to its proinflammatory effects.
IgM antibodies against phosphorylcholine circulate at relatively high levels and have been previously associated with protection against CV disease in studies predominantly involving men.
These antibodies only recognize phosphorylcholine when it is exposed, as occurs in dead cells and oxLDL, and could potentially act through anti-inflammatory mechanisms, the clearance of dead cells, and inhibiting the effects of ox-LDL.
In a study first, the researchers explored the association between serum IgM antibodies against phosphorylcholine (anti-PC) and composite CV disease, specifically ischemic heart disease, myocardial infarction, and ischemic stroke.
Among the 932 female participants, with a mean age of 66 years, who came from a population-based Swedish mammography study, there were 113 cases of the composite CV disease outcome over the course of 16 years—equivalent to 13,033 person-years.
This included 69 cases of ischemic heart disease, 44 cases of myocardial infarction, and 50 cases of ischemic stroke.
IgM anti-PC was statistically significantly inversely associated with the risk of the composite endpoint as well as each individual outcome apart from ischemic stroke.
For example, women in highest third of anti-PC levels, at a mean of 131 U/ml, had a multivariable-adjusted hazard ratio of 0.27 for myocardial infarction compared with women in the lowest third of levels, at a mean of 25 U/ml.
“IgM anti-PC may thus represent a risk marker in these disease conditions,” the researchers concluded.
“The possibility that raising anti-PC through immunization in order to prevent and/or delay IHD deserves further investigations.”
