Lipoprotein-a and white matter abnormalities: predicting small vessel disease in young patients with ischemic cerebrovascular events

Introduction: Post-stroke cognitive impairment (PSCI) affects 15-70% of ischemic stroke survivors, with vascular dementia contributing significantly to long-term disability. Lipoprotein(a) [Lp(a)] has emerged as a key risk factor for cardiovascular and cerebrovascular diseases, but its role in cerebral small vessel disease (cSVD) remains unclear. This study investigates the association between elevated Lp(a) levels and Fazekas scores (≥ 2), a marker of white matter hyperintensities (WMHs) indicative of cSVD, in young patients (< 65 years) with ischemic stroke or transient ischemic attack (TIA). Methods: We retrospectively analysed data of 217 patients with ischemic stroke/TIA, age 18-65, and Lp(a) measurement within four weeks of the event. Data included clinical history, imaging (MRI Fazekas scores), and Lp(a) levels (> 50 mg/dL). Multivariable logistic regression and ROC analysis were performed to identify predictors of higher Fazekas scores. Results: Elevated Lp(a) levels were independently associated with Fazekas scores ≥ 2 (OR 2.83, 95% CI 1.13-7.10, p = 0.03) alongside older age, hypertension, prior stroke/TIA, and elevated non-HDL cholesterol. The predictive model demonstrated high accuracy (AUC = 0.81). Patients with elevated Lp(a) exhibited greater WMH burden, indicating advanced small vessel damage. Conclusions: Elevated Lp(a) levels are a significant biomarker for WMHs and cSVD in young stroke patients, offering prognostic value beyond traditional risk factors. Incorporating Lp(a) testing into routine stroke evaluations could enable early identification and tailored management strategies to mitigate further vascular damage and cognitive decline.