Association between aldehyde dehydrogenase 4 family member A1 plasma concentrations and atherosclerotic disease in patients with ischemic stroke: Results from the prospective multicenter BIOSIGNAL study

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BACKGROUND: The role of Aldehyde Dehydrogenase 4 Family Member A1 (ALDH4A1) in atherosclerotic disease is unclear. Experimental data suggests a possible involvement in atherogenesis. We investigated the association between circulating ALDH4A1 and atherosclerotic disease outcome measures in acute stroke patients. METHODS: Multicenter study using data from the prospective BIOSIGNAL cohort (2014-2017). ALDH4A1 plasma concentrations were measured in stored samples collected within 24 h after stroke onset. Primary outcome measure was large artery atherosclerotic stroke (LAAS) origin. Secondary outcome measures were atherosclerotic disease outcomes such as the maximum intima-media-thickness (IMT), the degree of stenosis on ultrasound, and a composite for atherosclerotic disease burden (large artery atherosclerotic index stroke, history of myocardial infarction, coronary or peripheral artery disease). Logistic regression analyses were performed to examine the association between ALDH4A1 plasma concentrations (absolute and log-transformed) and the primary and secondary outcome measures. RESULTS: Of 1759 stroke patients, 84.5% had available ALDH4A1 measurements. Circulating ALDH4A1 plasma concentrations were neither significantly associated with LAAS (logALDH4A1 aOR 0.97, 95%CI 0.79-1.21, p = 0.81) nor any secondary outcome measure including the maximum IMT, stenosis degree or the composite for atherosclerotic disease burden. Sensitivity analysis using inverse probability of treatment weighting were in line with the main findings. CONCLUSIONS: In acute stroke patients, we found no clear evidence of an association between ALDH4A1 plasma concentrations and clinically relevant atherosclerotic disease outcome measures, including maximum IMT. However, due to the lack of validated and standardized ALDH4A1 assays, and the resulting limited comparability with other cohorts, a potential association cannot be excluded. TRIAL REGISTRATION: NCT02274727 (ClinicalTrials.gov).

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