title: Specific serotonin reuptake inhibition in major depressive disorder adversely affects novel markers of cardiac risk.
abstract: There exists a growing body of evidence linking depression with cardiovascular events, although the mechanisms responsible remain unknown. We investigated the role of the autonomic nervous system and inflammation in the link between coronary heart disease and major depressive disorder (MDD), and examined the cardiac risk modification following pharmacological treatment of depression. We measured cardiac baroreflex function, heart rate variability, pulse pressure and high sensitivity C-reactive protein (hsCRP), all of which have an impact on cardiac risk, pre- and post-treatment in 25 patients with MDD, with no history of coronary heart disease, and in 15 healthy subjects. Treatment consisted of selective serotonin reuptake inhibitors for approximately 12 weeks. No significant differences were observed between untreated MDD patients and healthy subjects in blood pressure, heart rate, baroreflex sensitivity or heart rate variability. Pulse pressure and hsCRP, however, were significantly elevated in patients with MDD prior to treatment (p=0.023 and p=0.025, respectively). Moreover, while pharmacotherapy was effective in alleviating depression, surprisingly, each of cardiac baroreflex function, heart rate variability, pulse pressure and hsCRP was modified (p<0.05) in a manner likely to increase cardiac risk. In conclusion, this study demonstrated higher pulse pressure and hsCRP plasma levels in patients with MDD, which might contribute to increased cardiac risk. Following treatment vagal activity was reduced, as indicated by reductions in baroreflex sensitivity and heart rate variability, accompanied by increases in pulse pressure and plasma hsCRP levels. Mechanisms potentially responsible for generating cardiac risk in patients treated with selective serotonin reuptake inhibitors may need to be therapeutically targeted to reduce the incidence of coronary heart disease in this population.
authors.affiliation: Baker Heart Research Institute, Melbourne, Australia. tye.dawood@baker.edu.au
authors.forename: Tye
authors.initials: T
authors.lastname: Dawood
authors.forename: Elisabeth A
authors.initials: EA
authors.lastname: Lambert
authors.forename: David A
authors.initials: DA
authors.lastname: Barton
authors.forename: Dominique
authors.initials: D
authors.lastname: Laude
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Elghozi
authors.forename: Murray D
authors.initials: MD
authors.lastname: Esler
authors.forename: Deepak
authors.initials: D
authors.lastname: Haikerwal
authors.forename: David M
authors.initials: DM
authors.lastname: Kaye
authors.forename: Elodie J
authors.initials: EJ
authors.lastname: Hotchkin
authors.forename: Gavin W
authors.initials: GW
authors.lastname: Lambert
mesh_terms: D000328:Adult; D001341:Autonomic Nervous System / Q000502:physiology*; D017704:Baroreflex / Q000502:physiology; D015415:Biomarkers; D001794:Blood Pressure / Q000502:physiology; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000150:complications* / Q000276:immunology / Q000503:physiopathology; D003865:Major Depressive Disorder / Q000150:complications* / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D005260:Female; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use*
chemical_list: D015415:Biomarkers; D002097:C-Reactive Protein; D017367:Selective Serotonin Reuptake Inhibitors