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Research paper
Impaired vasoreactivity in mildly disabled CADASIL patients
  1. Jonica Campolo1,
  2. Renata De Maria1,
  3. Marina Frontali2,
  4. Franco Taroni3,
  5. Domenico Inzitari4,
  6. Antonio Federico5,
  7. Silvia Romano6,
  8. Emanuele Puca7,
  9. Caterina Mariotti3,
  10. Chiara Tomasello3,
  11. Leonardo Pantoni4,
  12. Francesca Pescini4,
  13. Maria Teresa Dotti5,
  14. Maria Laura Stromillo5,
  15. Nicola De Stefano5,
  16. Alessandra Tavani8,
  17. Oberdan Parodi1
  1. 1CNR Clinical Physiology Institute, Cardiovascular Department, Niguarda Ca' Granda Hospital, Milan, Italy
  2. 2Institute of Translational Pharmacology, CNR, Rome, Italy
  3. 3Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy
  4. 4Department of Neurological and Psychiatric Sciences, University of Florence, Florence, Italy
  5. 5Department of Neurological, Neurosurgical and Behavioural Sciences, University of Siena, Siena, Italy
  6. 6Center for Experimental Neurological Therapy, S Andrea Hospital, University of Rome, La Sapienza, Rome, Italy
  7. 7Neurovascular Treatment Unit, University of Rome, La Sapienza, Rome, Italy
  8. 8Department of Epidemiology, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy
  1. Correspondence to Dr J Campolo, CNR Clinical Physiology Institute, Niguarda Hospital, Piazza Ospedale Maggiore 3, 20162 Milan, Italy; jonica.campolo{at}


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.

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  • For the list of study participants see the appendix.

  • Funding The study was supported by grant FARM659PTX from the Italian Medicine Agency (AIFA).

  • Competing interests None.

  • Ethics approval The study was approved by the institutional review boards of the participating units.

  • Provenance and peer review Not commissioned; externally peer reviewed.