title: Cardiovascular risk factors may moderate pharmacological treatment effects in major depressive disorder.
abstract: OBJECTIVE
  An increased association between depression and cardiovascular disease, as well as cardiovascular risk factors, led to the "vascular depression" hypothesis. This subtype of depression is postulated to have a different clinical presentation and to be more treatment-resistant. In this study, we measured the impact of cardiovascular risk factors on the outcome of antidepressant treatment in major depressive disorder (MDD).
  
  
  METHODS
  We enrolled 348 MDD subjects, ages 19 to 65 years, in an 8-week treatment study with 20 mg fluoxetine per day. We recorded for each subject 6 cardiovascular risk factors: age (male > or =45, female > or =55), smoking, family history, hypertension, diabetes, hypercholesterolemia; and we defined a cardiovascular risk score (range, 0-6) by the number of risk factors present. Treatment outcome was measured as response (> or =50% improvement on the 17-item Hamilton Rating Scale for Depression [Ham-D-17]) and remission (final Ham-D-17< or =7).
  
  
  RESULTS
  In logistic regression analyses, the cardiovascular risk score was significantly associated with treatment nonresponse and lack of remission when adjusting for age of onset of MDD and baseline severity of depression. The cardiovascular risk score remained significantly associated with treatment nonresponse when we additionally controlled for overall medical burden (measured with the Cumulative Illness Rating Scale). Among individual cardiovascular risk factors, elevated total cholesterol was a significant predictor of treatment nonresponse and lack of remission.
  
  
  CONCLUSIONS
  Cardiovascular risk factors may have negative effects on the course of treatment in MDD. These results support the concept of "vascular depression" in younger subjects.
authors.affiliation: Depression Clinical and Research Program, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA. diosifescu@partners.org
authors.forename: Dan V
authors.initials: DV
authors.lastname: Iosifescu
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Clementi-Craven
authors.forename: Renerio
authors.initials: R
authors.lastname: Fraguas
authors.forename: George I
authors.initials: GI
authors.lastname: Papakostas
authors.forename: Timothy
authors.initials: T
authors.lastname: Petersen
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Alpert
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Nierenberg
authors.forename: Maurizio
authors.initials: M
authors.lastname: Fava
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D000368:Aged; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000453:epidemiology*; D015897:Comorbidity; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000453:epidemiology*; D003920:Diabetes Mellitus / Q000175:diagnosis / Q000453:epidemiology; D005473:Fluoxetine / Q000627:therapeutic use; D006801:Humans; D006937:Hypercholesterolemia / Q000175:diagnosis / Q000453:epidemiology; D006973:Hypertension / Q000175:diagnosis / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D012044:Regression Analysis; D012307:Risk Factors; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use; D012720:Severity of Illness Index; D012737:Sex Factors; D012907:Smoking / Q000453:epidemiology; D016896:Treatment Outcome
chemical_list: D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors