Background and purpose CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is a rare genetic disease caused by NOTCH3 gene mutations. A dysfunction in vasoreactivity has been proposed as an early event in the pathogenesis of the disease. The aim of this study was to verify whether endothelium dependent and/or independent function is altered in CADASIL patients with respect to controls.

Methods Vasoreactivity was studied by a non-invasive pletismographic method in 49 mildly disabled CADASIL patients (30–65 years, 58% male, Rankin scale ≤2) and 25 controls. Endothelium dependent vasodilatation was assessed by reactive hyperaemia (flow mediated dilation–peripheral arterial tone (FMD-PAT)) and endothelium independent vasoreactivity by glyceryl trinitrate (GTN) administration (GTN-PAT).

Results Patients and controls showed comparable age, gender and cardiovascular risk factor distribution. GTN-PAT values were significantly lower in CADASIL patients (1.54 (1.01 to 2.25)) than in controls (1.89 (1.61 to 2.59); p=0.041). FMD-PAT scores did not differ between patients and controls (1.88 (1.57 to 2.43) vs 2.08 (1.81 to 2.58); p=0.126) but 17 CADASIL patients (35%) had FMD-PAT scores below the fifth percentile of controls. FMD-PAT and GTN-PAT values correlated both in controls (ρ=0.648, p<0.001) and CADASIL patients (ρ=0.563, p<0.001). By multivariable logistic regression for clinical and laboratory variables, only GTN-PAT (OR 0.39, 95% CI 0.15 to 0.97; p=0.044) was independently associated with FMD-PAT below the fifth percentile in CADASIL patients.

Conclusions The impaired vasoreactivity observed in CADASIL patients highlights the fact that both endothelial and smooth muscle functional alterations may already be present in mildly disabled subjects. The improvement in vascular function could be a new target for pharmacological trials in CADASIL patients.