Beta2-Microglobulin: A Biomarker for Stroke Risk?

Sue Hughes            

May 11, 2017

Raised levels of β2-microglobulin (B2M) — a protein found on the surface of many cells — was associated with an increased risk for ischemic stroke among women in a new study.

The analysis from the Nurses' Health Study, published online in Neurology May 10, was conducted by a team led by Pamela M. Rist, ScD, Harvard Medical School, Boston, Massachusetts.

"Prior studies have shown that B2M is associated with cardiovascular disease and coronary heart disease," Dr Rist commented to Medscape Medical News. "We were interested to see if it is also associated with ischemic stroke.

"In this study we show that women in the highest quartile of B2M levels had a 56% increased risk of ischemic stroke compared with women in the lowest quartile."

She noted that B2M is a clinically available assay, but it is too soon to be measuring B2M routinely to assess stroke risk.

"The next step would be to look at whether B2M can add to stroke risk prediction models after taking into account all other risk factors," Dr Rist explained. "We couldn't do this in the current study as it had a case-control design which is not appropriate for such use. We did, however, control for many cardiovascular risk factors and still saw an increased risk of stroke associated with B2M levels."

She said that analysis of data from cohort studies will be needed to explore whether adding B2M levels to existing cerebrovascular disease risk prediction scores improves risk prediction further.

She suggested that if B2M were to be verified as an independent risk factor for stroke, it may become a target for intervention. "It would be interesting to see if B2M levels can be modified with lifestyle changes or medication."

Commenting on the study for Medscape Medical News, Mitch Elkind, MD, chair of the American Stroke Association, called this "an interesting finding from a good study group."  

"We are always looking for new biomarkers for the risk of stroke," he said. "I don't think this is the first study to show an association of B2M with stroke, but its relevance depends on how aggressively they controlled for other risk factors."

"Many different biomarkers for stroke risk are being explored, and while there are many that have shown associations, it is always difficult to show that a new biomarker adds much to what we already have," Dr Elkind added. "It is important to show additional value for predicting risk on top of the risk factors we already measure, such as the Framingham risk score profile." 

He added that B2M could be one of several possible biomarkers that could predict stroke or cardiovascular risk. "The one that has received the most attention in recent years is CRP [C-reactive protein], but even there it takes studies of many thousands of people to show anything relevant."

Scientists are investigating thousands of different proteins and biological substances as potential biomarkers for disease risk, he noted. "I would think it is unlikely that any single substance will add much to risk stratification in stroke — it is more likely that a combination of biomarkers may be used together. This could possibly be one of them."

In the Neurology paper, Dr Rist and colleagues explain that elevated B2M levels are associated with systemic inflammation and renal disease and it is thought the protein may be a marker of small vessel disease.

They performed a nested case-control study among women enrolled in the Nurses' Health Study who provided blood samples between 1989 and 1990 and were free of prior stroke and cancer. 

They compared B2M levels in these baseline samples in 473 women who went on to have an ischemic stroke after a median follow-up of 9 years (cases) with 473 controls matched 1:1 to the cases on age, race, date of blood collection, menopausal status, postmenopausal hormone use, and smoking status, with adjustment for traditional stroke risk factors.

Results showed that median levels of B2M were higher among cases (1.86 mg/L) than controls (1.80 mg/L) (P = .009). 

Women in the highest B2M quartile had a multivariable-adjusted increased risk for ischemic stroke compared with those in the lowest quartile (odds ratio, 1.56; 95% confidence interval, 1.02 - 2.39).

In the top quartile, 163 of the 283 women had strokes, compared with 106 of the 227 women in the bottom quartile.

"When we controlled for kidney function the association was attenuated, but when we looked at just those women without kidney disease, we still saw an association, suggesting that the mechanism is not entirely explained by kidney function," Dr Rist noted.

She added that after controlling for CRP, there was still an association between B2M levels and an increased risk for ischemic stroke but it was no longer significant, suggesting that inflammation may explain some, but not all, of the association between B2M and ischemic stroke risk.

She said that there are more data on B2M in women than in men because it was also linked to an increased risk for total stroke and coronary heart disease in the Women's Health Initiative. However, similar associations were seen in the ARIC study in both men and women.

The Nurses' Health Study is funded by the National Institutes of Health. The authors have disclosed no relevant financial relationships.  

Neurology. Published online May 10, 2017.  Abstract

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