PLASMA NEUROENDOCRINE ACTIVITY IN VERY ELDERLY SUBJECTS AND PATIENTS WITH AND WITHOUT HEART-FAILURE

Marked neuro-endocrine activation in patients with heart failure indic ates a worse prognosis and a greater prognostic benefit from the use o f ACE inhibitors. However. although the incidence of heart failure ris es rapidly with age, relatively little is known about activation of th e renin-angiotensin and sympathetic nervous system in patients with he art failure over the age of 75 years. This study was undertaken to inv estigate plasma concentrations of neurohormonal variables in elderly p atients referred to the cardiac clinic with a presumptive but unconfir med, diagnosis of heart failure, and to compare these values to plasma concentrations found in age-matched normal subjects. Fifty patients r efer red with a diagnosis of heart heart failure were studied All were receiving a diuretic but not an ACE inhibitor Patients with renal, ha ematological and valve disease were excluded. Routine biochemistry and neuro-hormonal measurements were performed at their first visit, toge ther with an electrocardiogram, chest X-ray and a full clinical examin ation by an experienced cardiologist. An echocardiogram and Doppler st udy was also performed and the diagnosis of heart failure either confi rmed or refuted. Plasma concentrations of neuro-endocrine variables in healthy elderly subjects were similar to our normal laboratory range in younger subjects with the exception of atrial natriuretic peptide ( ANP) (40 +/- 6 pg.ml(-1), normal range <40) and noradrenaline (5.7 +/- 0.7 nmol.l(-1), normal range <2.8). Impairment of left ventricular. s ystolic function was confirmed in 38 of the 50 symptomatic patients (7 6%) and was associated with increases in plasma concentrations of acti ve renin (58 +/- 8 IU.mol(-1), P<0.01 compared to healthy elderly subj ects), angiotensin II (23 +/- 5 pg.ml(-1), P < 0.008), noradrenaline ( 7.7 +/- 1.2 nmol.l(-1), P<0.01) and atrial natriuretic peptide (121 +/ - 18 pg.ml(-1), P<0.002). Plasma concentrations were similar in normal subjects and those receiving treatment for heart failure but in whom the diagnosis was not confirmed A weak relationship between plasma atr ial natriuretic peptide (ANP) and left ventricular fractional shorteni ng was demonstrated (r = -0.5, P<0.001). Using art upper limit of ANP in the healthy elderly subjects of 62 pmol.ml(-1) (mean + SD), plasma concentrations of ANP in the population with suspected heart failure h ad a sensitivity of 74% and specificity of 66% for the diagnosis of he art failure among elderly patients in the community or where access to echocardiography is limited. Left ventricular diastolic filling (asse ssed by Doppler) was abnormal in healthy elderly subjects and patients with heart failure, and appeared of limited value in the diagnosis of heart failure secondary to diastolic dysfunction. This study confirms that the renin-angiotensin system is activated in elderly patients wi th heart failure treated with diuretics. ANP may be helpful in diagnos ing heart failure where it appears to have a complimentary role to ech ocardiography.