Anti-oxidative properties of beta-blockers and angiotensin-converting enzyme inhibitors in congestive heart failure.
BACKGROUND
Chronic elevation of plasma catecholamines and sympathetic stimulation in chronic heart failure (CHF) leads to increased production of free radicals, and so possibly to endothelial damage/dysfunction and atheroma formation. Abnormal oxidative stress may therefore be related to some of the high mortality and morbidity in CHF. The objective of the present prospective open study was to compare the effects of beta-blockers and ACE inhibitors in relation to oxidative stress and endothelial damage in CHF.


METHODS
We studied 66 outpatients with CHF: 46 patients were established on an ACE inhibitor and were then started on a beta-blocker, and 20 patients not previously on ACE-inhibitors were started on lisinopril. Baseline levels of the measured parameters were compared to 22 healthy control subjects. Serum lipid hydroperoxides (LHP) and total antioxidant capacity (TAC) were determined as indices of oxidative damage and antioxidant defence, and plasma von Willebrand factor (vWf) as an index of endothelial damage/dysfunction.


RESULTS
Baseline indices for the measures of oxidative damage and endothelial function in the 66 CHF patients were significantly higher than healthy control subjects [median LHP 7.5 (5.9-12.6) vs. 4.8 micromol/l, P=0.0022; TAC 428 (365-567) vs. 336 Trollox Eq. Units, P=0.0005; mean vWf 134+/-27 vs. 89+/-23 IU/dl, P<0.0001]. Following 3 months of maintenance therapy with beta-blockers, there was significant reduction in LHP levels, but not TAC or vWf. ACE inhibitor therapy also significantly reduced vWf levels, but failed to have any statistically significant effects on LHP or TAC.


CONCLUSIONS
This pilot study suggests that oxidative stress in CHF may be due to increased free radical production or inefficient free radical clearance by scavengers. beta-Blockers, but not ACE inhibitors, reduced lipid peroxidation in patients with CHF. No relation was demonstrated between a reduction in oxidative damage and endothelial damage/dysfunction.
Chin
Bernard S P
BS
University of Birmingham, Division of Medical Sciences, City Hospital, Birmingham, UK.
Langford
Nigel J
NJ
Nuttall
Sarah L
SL
Gibbs
Christopher R
CR
Blann
Andrew D
AD
Lip
Gregory Y H
GY
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D017298:Bisoprolol / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D002227:Carbazoles / Q000627:therapeutic use; D000077261:Carvedilol; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D008054:Lipid Peroxides / Q000097:blood; D017706:Lisinopril / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology*; D011412:Propanolamines / Q000627:therapeutic use; D011446:Prospective Studies; D012307:Risk Factors; D016896:Treatment Outcome; D014841:von Willebrand Factor / Q000378:metabolism
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D002227:Carbazoles; D008054:Lipid Peroxides; D011412:Propanolamines; D014841:von Willebrand Factor; D000077261:Carvedilol; D017706:Lisinopril; D017298:Bisoprolol