title: Clinical risk factors for the development of hypertension in patients treated with inhibitors of the VEGF signaling pathway.
abstract: BACKGROUND
  VEGF signaling pathway inhibitor (anti-VEGF) therapy is associated with hypertension, but little is known about predisposing clinical characteristics. This study describes the real-world association between baseline clinical characteristics, blood pressure (BP) response, and survival in patients prescribed anti-VEGF therapies.
  
  
  METHODS
  Clinical data from Partners HealthCare in Massachusetts was obtained from adults treated with anti-VEGF therapies (2002-2013). Treatment-induced hypertensive response was defined as worsening of preexisting hypertension or new diagnosis of hypertension (if no prior hypertension history).
  
  
  RESULTS
  Data from 1120 patients with renal cell carcinoma (32.2%), hepatocellular carcinoma (11.6%), gastrointestinal stromal tumors (12.5%), and other sarcomas (15.3%) were analyzed. Most patients received sunitinib (52%), sorafenib (25.9%), or pazopanib (18%). A treatment-induced hypertensive response was identified in 49.7% of treated patients. Preexisting hypertension, present in 65.4%, was an independent risk factor for BP elevation (odds ratio [OR], 1.56; 95% confidence interval [CI], 1.27-1.92); other risk factors included age ≥60 years (OR, 1.26; 95% CI, 1.06-1.52), and body mass index (BMI) ≥25 kg/m(2) (OR, 1.26; 95% CI, 1.04-1.53). Race, sex, anti-VEGF therapy prescribed, and baseline antihypertensive class were not significant risk factors. The absolute observed mean increase in BP was 21 mm Hg (systolic)/15 mm Hg (diastolic), both in patients with and without preexisting hypertension. The development of hypertension predicted improved survival (hazard ratio, 0.76; 95% CI, 0.65-0.89).
  
  
  CONCLUSIONS
  Preexisting hypertension, age, and BMI identify patients at risk for significant anti-VEGF therapy-induced BP elevation. Hypertension appears to be a clinical biomarker of efficacy of anti-VEGF therapies in a broad range of malignancies.
authors.affiliation: Brigham and Women's Hospital, Division of Endocrinology, Diabetes and Hypertension, Boston, Massachusetts.
authors.forename: Ole-Petter R
authors.initials: OP
authors.lastname: Hamnvik
authors.forename: Toni K
authors.initials: TK
authors.lastname: Choueiri
authors.forename: Alexander
authors.initials: A
authors.lastname: Turchin
authors.forename: Rana R
authors.initials: RR
authors.lastname: McKay
authors.forename: Lipika
authors.initials: L
authors.lastname: Goyal
authors.forename: Michael
authors.initials: M
authors.lastname: Davis
authors.forename: Marina D
authors.initials: MD
authors.lastname: Kaymakcalan
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Williams
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001794:Blood Pressure / Q000187:drug effects; D015992:Body Mass Index; D018450:Disease Progression; D005260:Female; D006801:Humans; D006973:Hypertension / Q000139:chemically induced* / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy; D011237:Predictive Value of Tests; D018570:Risk Assessment; D012307:Risk Factors; D012737:Sex Factors; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
chemical_list: D000959:Antihypertensive Agents; D000970:Antineoplastic Agents; D042461:Vascular Endothelial Growth Factor A
keywords: angiogenesis inhibitors; antihypertensive agents; hypertension; pazopanib; risk factors; sorafenib; sunitinib; survival