title: Large artery stiffness and hypertension after antiangiogenic drugs: influence on cancer progression.
abstract: BACKGROUND
  Systemic hypertension is a frequent side effect of antiangiogenic drugs (AADs) and may represent a marker of efficacy on cancer. We hypothesized that large artery properties are affected by AADs, and contribute to the rise of blood pressure and may be better related to cancer progression and mortality than hypertension.
  
  
  RESULTS
  Participants were studied before AADs (V0), 10 days later (V1) and then every 2 weeks for 6 weeks (V1-V4). We included 57 consecutive patients in whom treatment with sorafenib (400 mg twice daily) or sunitinib (37.5-50 mg once daily) was indicated. The target dose could be adjusted according to tolerance and response. Aortic and carotid stiffness, brachial and central blood pressure and augmentation index were measured noninvasively at each visit. Data regarding cancer progression and mortality were collected at 6 months. Twenty-eight patients (49%) developed hypertension. Brachial SBP significantly increased during follow-up (V0-V1: +9.6 ± 15.2 mmHg, P < 0.001; V0-V4: +6.0 ± 17.8 mmHg, P = 0.04). Central BP, and aortic and carotid stiffness increased independently of brachial BP changes. Aortic and carotid stiffening were associated with cancer progression independently of BP changes [hazard risk 1.24 (1.01-1.51) and 1.34 (1.03-1.73), respectively; P < 0.05], but not with cancer mortality. Brachial SBP had no predictive value.
  
  
  CONCLUSIONS
  Large arteries stiffen during AAD treatment partly independently of BP changes. Arterial mechanical properties are associated with BP rise. Arterial stiffening is related with the effects of AAD on cancer progression independently of BP changes. Large artery properties might help monitor AAD therapy in cancer patients.
authors.affiliation: aUniversité Paris-Descartes bINSERM U970 cAssistance Publique-Hôpitaux de Paris dDepartment of Pharmacology eClinical Investigation Center, Hôpital Européen Georges Pompidou fDepartment of Oncology, CERIA, Hôpital Cochin, Paris, France *Maureen Alivon and Julie Giroux contributed equally to the writing of this article.
authors.forename: Maureen
authors.initials: M
authors.lastname: Alivon
authors.forename: Julie
authors.initials: J
authors.lastname: Giroux
authors.forename: Marie
authors.initials: M
authors.lastname: Briet
authors.forename: François
authors.initials: F
authors.lastname: Goldwasser
authors.forename: Stéphane
authors.initials: S
authors.lastname: Laurent
authors.forename: Pierre
authors.initials: P
authors.lastname: Boutouyrie
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D001011:Aorta / Q000503:physiopathology; D001158:Arteries / Q000503:physiopathology; D001794:Blood Pressure / Q000502:physiology; D001795:Blood Pressure Determination; D018450:Disease Progression; D005260:Female; D006801:Humans; D006973:Hypertension / Q000139:chemically induced* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011446:Prospective Studies; D012307:Risk Factors; D059289:Vascular Stiffness / Q000187:drug effects*
chemical_list: D020533:Angiogenesis Inhibitors