Is there a role for renin profiling in selecting chronic heart failure patients for ACE inhibitor treatment?
BACKGROUND
It remains uncertain whether angiotensin converting enzyme (ACE) inhibitors benefit all heart failure patients or just those with renin-angiotensin-aldosterone system (RAAS) activation.


OBJECTIVE
To determine whether the response to an ACE inhibitor, assessed by urine sodium excretion, was different in patients with low renin versus those with high renin.


METHODS
Plasma renin activity (PRA) was measured in 38 patients with stable chronic heart failure (21 male, 17 female; mean (SD) age 71 (6) years, range 59-82 years) on chronic diuretic treatment alone. They were divided into three groups: low (PRA </= 1.5 ng/ml/h, n = 11); normal (1.5 < PRA < 5, n = 14); and high (PRA > 5, n = 13). The effect of ACE inhibition was then assessed on diuretic induced natriuresis with respect to renin status.


RESULTS
There were no significant differences in age and sex distribution between the groups. Plasma angiotensin II and aldosterone increased serially from low to high renin groups, while 24 h urinary sodium concentrations fell from low to high renin groups (low PRA, 96.7 (39.5); normal PRA, 90.4 (26.7); high PRA, 66. 3 (18.9) mmol/l; p = 0.033), despite a higher diuretic dose in the high renin group. This blunted natriuretic effect of loop diuretics was caused by RAAS activation, which could partly be reversed by ACE inhibition. ACE inhibitors increased natriuresis by 22% in the high renin group (p = 0.029), but had no effect in the normal and low renin groups. Within the low renin group, five of the 11 patients had persistently low renin levels despite ACE inhibition. There was a non-significant reduction in natriuresis (-9.6%, p = 0.335) following ACE inhibition in this subgroup of patients.


CONCLUSIONS
About one third of heart failure patients in our study had low renin status and a non-activated RAAS, despite diuretic treatment. ACE inhibitors did not alter natriuresis significantly in this subgroup of patients, and enhanced natriuresis only in patients with high renin. There is thus tentative support for renin profiling in targeting ACE inhibitors to the most deserving, by showing that short term sodium retention does not occur in low renin patients if ACE inhibitors are withdrawn.
Lim
P O
PO
Cardiovascular Research Group, Department of Clinical Pharmacology and Therapeutics, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK. pitt@clinpharm.dundee.ac.uk
MacFadyen
R J
RJ
Struthers
A D
AD
D000368:Aged; D000369:Aged, 80 and over; D000450:Aldosterone / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D012083:Renin / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000187:drug effects*; D012964:Sodium / Q000652:urine*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II; D000450:Aldosterone; D012964:Sodium; D012083:Renin