Researchers identify novel protein linked to ischaemic stroke risk in older adult patients


By identifying plasma proteomic determinants of incident cardioembolic and non-cardioembolic ischaemic stroke, researchers in the USA have found a novel protein believed to be associated with stroke risk in patients with left atrial dysfunction.

Detailing findings from the Cardiovascular Health Study—now published in the journal Neurology—corresponding author Rizwan Kalani (University of Washington, Seattle, USA) and colleagues conclude that N-terminal pro-brain natriuretic peptide (NTproBNP) and macrophage metalloelastase (MMP12) were “independently associated” with ischaemic stroke risk.

“Plasma proteomics may elucidate novel insights into the pathophysiology of ischaemic stroke, identify biomarkers of ischaemic stroke risk, and guide development of nascent prevention strategies,” Kalani et al initially note.

On this basis, they set out to evaluate the relationship between plasma proteome and ischaemic stroke risk in the population-based Cardiovascular Health Study.

They report that eligible study participants were free of prevalent stroke and underwent quantification of 1,298 plasma proteins using the aptamer-based SOMAScan assay platform (SomaLogic) from a 1992–1993 study visit.

For plasma protein concentrations independently associated with incident ischaemic stroke—determined via multivariable Cox proportional hazards regression, and following adjustments for demographics, ischaemic stroke risk factors and estimated glomerular filtration rate—a secondary stratified analysis evaluated associations in subgroups defined by sex and race. The authors also state that exploratory analyses evaluated plasma proteomic associations with cardioembolic and non-cardioembolic ischaemic stroke, as well as proteins associated with stroke risk in participants with left atrial dysfunction but without atrial fibrillation.

Across a total of 2,983 eligible participants, the mean age was 74.3 years, 61.2% were women, and 15.4% were Black, according to Kalani et al. And, over a median follow-up period of 12.6 years, 450 participants experienced an incident ischaemic stroke.

Ultimately, NTproBNP (adjusted hazard ratio [HR] 1.37, 95% confidence interval [CI] 1.23–1.53, p=2.08×10-08) and MMP12 (adjusted HR 1.30, 95% CI 1.16–1.45, p=4.55×10-06) were both found to be independently associated with ischaemic stroke risk in a cohort of older adult patients. Kalani et al further detail that these two associations were similar in men and women, and in Black and non-Black participants.

Additionally, in exploratory analyses, there were also independent associations between NTproBNP and incident cardioembolic ischaemic stroke risk; E-selectin and incident non-cardioembolic ischaemic stroke risk; and secreted frizzled-related protein-1 (a negative regulator of androgen receptor activity in prostate cancer) and ischaemic stroke risk, in participants with left atrial dysfunction

It is based on these findings that the researchers conclude both NTproBNP and MMP12 were independently associated with ischaemic stroke risk in their study.


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