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Is there a role for renin profiling in selecting chronic heart failure patients for ACE inhibitor treatment?
P O Lim1, R J MacFadyen, A D Struthers
1Cardiovascular 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
Insights
Angiotensin converting enzyme (ACE) inhibitors benefit heart failure patients with high renin activity, but not those with low renin activity. Renin profiling may help target ACE inhibitors effectively.
Area of Science:
- Cardiology
- Nephrology
- Pharmacology
Background:
- Uncertainty exists regarding the efficacy of ACE inhibitors in all heart failure patients, particularly concerning renin-angiotensin-aldosterone system (RAAS) activation.
- Heart failure management often involves ACE inhibitors, but their benefit may be stratified by individual RAAS status.
Purpose of the Study:
- To investigate if the response to ACE inhibitors differs between heart failure patients with low renin versus high renin activity.
- To assess the impact of ACE inhibition on natriuresis in relation to plasma renin activity (PRA).
Main Methods:
- 38 stable chronic heart failure patients on diuretics were categorized into low, normal, and high PRA groups.
- The effect of ACE inhibition on diuretic-induced natriuresis was evaluated based on renin status.
- Plasma renin activity (PRA), angiotensin II, aldosterone, and 24-hour urinary sodium excretion were measured.
Main Results:
- Patients with high PRA showed significantly lower 24-hour urinary sodium excretion compared to low and normal PRA groups, indicating blunted natriuresis.
- ACE inhibitors increased natriuresis by 22% in the high PRA group but had no significant effect in the normal and low PRA groups.
- Approximately one-third of patients had low renin status and non-activated RAAS, with no significant natriuresis change upon ACE inhibition.
Conclusions:
- ACE inhibitors primarily enhance natriuresis in heart failure patients with high RAAS activation (high renin).
- Patients with low renin status and non-activated RAAS may not benefit from ACE inhibitors regarding short-term sodium retention.
- Renin profiling could potentially guide the targeted use of ACE inhibitors in heart failure management.
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.
Design:
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 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.
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