Abstract T P130: Determinants of White Matter Hyperintensity Burden Differ at the Extremes of Age of Ischemic Stroke Onset

Abstract

Background: White matter hyperintensity (WMH) detected on MRI scans of patients with acute ischemic stroke (AIS) is associated with greater risk of infarct progression, poor post-stroke outcomes, and recurrent stroke. Age is strongly linked to risk of stroke and WMH. We hypothesized that determinants of WMH severity differ across the lifetime and sought to test it in a prospective cohort of AIS patients with early (<55 years), late (>75 years) versus average age of stroke onset. Methods: Clinical characteristics as well as laboratory and radiographic data were ascertained on admission for AIS in all consecutive patients ≥ 18 years. WMH volume (WMHv) was measured using a previously validated, semi-automated method, normalized for intracranial area, and natural log-transformed for univariate and multivariate linear regression analyses. Results: Of 754 AIS patients, 175 (23.2%) developed early-onset (mean age 46.4 ± 7.5 years) and 237 (31.4%) late-onset (mean age 82.1 ± 5.2 years) stroke. Median WMHv differed between the early-onset AIS (2.4cc, IQR 1.6 - 4.5), late-onset AIS (11cc, IQR 5.8 - 23.2) and average-age-of-onset stroke patients (mean age 65.6 ± 5.8 years, median WMHv 6.4cc, IQR 3.2 - 13.0). In univariate analysis, WMHv burden was associated with age (p = 0.03) and history of tobacco use (p = 6.6E-3) in early-onset AIS, with gender (p = 0.03) in late-onset AIS, versus age (p = 1.8E-8) and hyperlipidemia (p = 0.045) in average-age-of-onset AIS. Although backward stepwise selection confirmed male gender (ß = -0.26, p = 0.04) in late-onset AIS patients as well as age (ß = 0.05, p = 3.9E-8) and hyperlipidemia (ß = -0.26, p = 0.02) in patients with average age of AIS onset as predictors of WMHv, only tobacco use (ß = 0.35, p = 8.8E-3) remained an independent predictor of WMHv severity in early-onset AIS patients. Conclusions: Phenotypic determinants of WMH severity in AIS patients differ at the extremes of age of stroke onset, including a strong link between tobacco use in patients with early-onset stroke and burden of small cerebral vessel disease. While age remains a major risk factor for WMH, modifiable determinants - such as smoking - should be targeted in the future to reduce WMH and mitigate stroke risk in each age group.