Cardiorenal Biomarkers and Cerebrovascular Risk in Patients with Congenital Heart Disease

Background/Objectives: Adults with congenital heart disease (CHD) have a substantially higher risk of ischemic stroke than the general population. Circulating biomarkers such as N-terminal pro B-type natriuretic peptide (NT-pro-BNP), high-sensitivity C-reactive protein (hs-CRP), and microalbuminuria have been associated with adverse cardiovascular outcomes in CHD, but their role in predicting cerebrovascular events remains uncertain. Methods: Prospective cohort study including 372 adults with CHD [median age 34 years (IQR 23-42); 57.8% male] followed at a tertiary center between 2017 and 2022. Baseline assessments included demographic characteristics, CHD anatomical complexity, cardiovascular risk factors, NT-pro-BNP, hs-CRP, lipid profile, and 24-h urinary albumin excretion. The primary endpoint was incident ischemic stroke during a median follow-up of 6.3 years (IQR 3.9-8.3). Univariable Cox proportional hazards models were used to identify predictors of stroke. Results: During follow-up, 13 patients (3.5%) experienced ischemic stroke. Patients with stroke were significantly older [51 (46-64) vs. 30 (23-40) years; p < 0.001] and had a higher prevalence of dyslipidemia (61.5% vs. 15.0%; p < 0.001). NT-pro-BNP levels were markedly higher in patients with stroke [369 (218-604) vs. 64 (21-172) pg/mL; p < 0.001]. No significant differences were observed between groups in renal function parameters, hs-CRP, thyroid-stimulating hormone, or urinary albumin excretion rate. In Cox analyses, older age and dyslipidemia were the strongest predictors of stroke (p < 0.001). Arterial hypertension, diabetes mellitus, and higher NT-pro-BNP levels were also associated with increased stroke risk (p < 0.05), whereas CHD anatomical complexity, NYHA functional class, and cyanosis were not. Conclusions: In adults with CHD, ischemic stroke was mainly associated with traditional cardiovascular risk factors and elevated NT-pro-BNP levels rather than anatomical disease complexity or functional status.