Associations Between Plasma Proteomic Profiles and Incident Ischemic Stroke in Older Adults

Jun 6, 2023

The following is a summary of "Plasma Proteomic Associations With Incident Ischemic Stroke in Older Adults," published in the May 2023 issue of Neurology by Kalani, et al.

Plasma proteomics has the potential to provide valuable insights into the underlying mechanisms of ischemic stroke (IS), identify biomarkers for IS risk assessment, and contribute to the development of preventive strategies. For a study, researchers sought to investigate the relationship between the plasma proteome and the risk of IS using data from the population-based Cardiovascular Health Study (CHS).

Participants from the CHS who were free of prevalent stroke were included in the analysis. Plasma protein quantification was performed using the SOMAScan assay platform, which measured 1,298 plasma proteins during the 1992-1993 study visit. Cox proportional hazards regression, adjusted for demographics, IS risk factors, and estimated glomerular filtration rate, was used to assess the associations between a 1-standard deviation increase in log2-transformed estimated plasma protein concentrations and incident IS. In addition, subgroup analyses were conducted to evaluate associations in sex- and race-defined subgroups. Additional exploratory analyses examined the associations between plasma proteomic markers and cardioembolic and non-cardioembolic IS and proteins associated with IS risk in participants with left atrial dysfunction but without atrial fibrillation.

Among the 2,983 eligible participants with a mean age of 74.3 (±4.8) years, 61.2% were women, and 15.4% were Black. Over a median follow-up period of 12.6 years, 450 participants experienced an incident IS.

N-terminal probrain natriuretic peptide (NTproBNP) and macrophage metalloelastase (MMP12) were independently associated with IS risk (adjusted hazard ratio [HR] 1.37, 95% CI 1.23-1.53, P = 2.08 × 10 for NTproBNP; adjusted HR 1.30, 95% CI 1.16-1.45, P = 4.55 × 10-6 for MMP12). The associations were consistent across sex and race subgroups. Exploratory analyses revealed that NTproBNP was specifically associated with incident cardioembolic IS, E-selectin with incident non-cardioembolic IS, and secreted frizzled-related protein 1 with IS risk in participants with left atrial dysfunction.

The study involving older adults identified NTproBNP and MMP12 as independent determinants of IS risk. Furthermore, specific plasma proteomic markers were associated with incident cardioembolic and noncardioembolic IS and IS risk in participants with left atrial dysfunction.

The findings contributed to the understanding of the plasma proteome concerning IS risk and highlighted potential biomarkers for IS prevention and management.

Source: n.neurology.org/content/100/21/e2182