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Effects of lisinopril on cardiorespiratory, neuroendocrine, and renal function in patients with asymptomatic left
J G Cleland1, D Shah, S Krikler
1Department of Medicine (Cardiology) and Dietetics, Royal Postgraduate Medical School, Hammersmith Hospital, London.
Insights
Lisinopril significantly improved exercise capacity in men with asymptomatic left ventricular systolic dysfunction. This ACE inhibitor enhanced cardiopulmonary response to exercise, even before heart failure symptoms manifest.
Area of Science:
- Cardiology
- Pharmacology
- Nephrology
- Neuroendocrinology
Background:
- Left ventricular systolic dysfunction (LVSD) is a precursor to heart failure.
- Early intervention may prevent or delay the progression of cardiac dysfunction.
- The effects of angiotensin-converting enzyme (ACE) inhibitors on asymptomatic LVSD require further elucidation.
Purpose of the Study:
- To investigate the cardiac, renal, and neuroendocrine effects of lisinopril in men with untreated, asymptomatic LVSD.
- To assess the impact of lisinopril on exercise capacity and physiological parameters in this patient group.
Main Methods:
- A randomized, double-blind, cross-over trial was conducted with 15 male participants.
- Participants received either lisinopril (10 mg/day) or a matching placebo for six-week treatment periods.
- Primary outcome was peak oxygen consumption; secondary outcomes included cardiac function, renal function, and neuroendocrine markers.
Main Results:
- Lisinopril significantly increased peak oxygen consumption during exercise compared to placebo (p < 0.003).
- No significant improvement in resting cardiac function was observed.
- Lisinopril reduced plasma concentrations of angiotensin II, aldosterone, and atrial natriuretic peptide, while increasing renal blood flow and decreasing glomerular filtration rate.
Conclusions:
- Lisinopril improves the cardiopulmonary response to exercise in patients with systolic ventricular dysfunction, even prior to the development of heart failure symptoms.
- The findings suggest a potential role for ACE inhibitors in managing early-stage LVSD to enhance functional capacity.
Objective:
To determine the cardiac, renal, and neuroendocrine effects of lisinopril in men with untreated, symptom free left ventricular systolic dysfunction.
Design:
A randomised, double blind cross over trial with six week treatment periods to compare lisinopril (10 mg/day) and matching placebo.
Setting:
Hospital outpatient department.
Patients:
Patients with pronounced systolic dysfunction on cross sectional echocardiography due to myocardial infarction at least six months previously, without angina and with no or minimal breathlessness. Eighteen men were identified of whom 15 completed the study.
Interventions:
Lisinopril (10 mg) or placebo given once daily by mouth.
Main Outcome Measures:
Primary: oxygen consumption at peak exercise. Secondary: resting cardiac function as measured by radionuclide ventriculography and echocardiography, renal function estimated radioisotopically, and plasma indices of neuroendocrine activity.
Results:
Compared with placebo, lisinopril increased (mean (SD)) peak oxygen consumption during exercise (19.8(3.1) ml/kg/min v 21.4(3.2) ml/kg/min; p < 0.003). Lisinopril did not improve indices of cardiac function at rest. It reduced plasma concentrations of angiotensin II (median values 7 pg/ml to 5 pg/ml; p < 0.02), aldosterone (median values 113 pg/ml to 66 pg/ml; p < 0.05) and atrial natriuretic peptide (median values 69 pg/ml to 40 pg/ml; p < 0.04), but noradrenaline and antidiuretic hormone concentrations did not change. Renal blood flow increased and glomerular filtration rate declined.
Conclusions:
Even before the onset of heart failure lisinopril improves the cardiopulmonary response to exercise in patients with systolic ventricular dysfunction.