Influence of age on neurohormonal activation and prognosis in patients with chronic heart failure.

Heart failure is a major medical problem in the elderly. Neurohormonal activation plays a role in the pathophysiology of heart failure, but is also affected by ageing. The present study was carried out to examine the influence of age on neurohormonal activation and prognosis in patients with chronic heart failure. We studied 372 patients with moderate to severe chronic heart failure (New York Heart Association [NYHA] functional class III-IV), who were treated with angiotensin converting enzyme (ACE) inhibitors (95%), diuretics (99%), and digoxin (59%). Their mean age was 68 +/- 8 years (range 38-80), left ventricular ejection fraction 0.23 +/- 0.08, and 77% were males. The relationship between age and plasma neurohormones (norepineprine, epinephrine, dopamine, renin, aldosterone, atrial natriuretic peptide, N-terminal atrial natriuretic peptide, and endothelin), and age and prognosis was examined. Only atrial natriuretic peptide and N-terminal atrial natriuretic peptide showed an independent, positive correlation with age (P < 0.0001). On univariate analysis, norepinephrine also increased, while renin and aldosterone decreased (all P < 0.05). As regards mortality (25%), there was no linear increase with ageing for the group as a whole during follow-up, but patients in the highest age quartile (> 74 years) had a significantly higher mortality (risk ratio 1.9) than younger patients (P < 0.05). Although several plasma neurohormones are affected by ageing on univariate analysis, only atrial natriuretic peptide and N-terminal atrial natriuretic peptide show a highly significant increase with ageing on multivariate analysis. There is no linear increase in mortality with ageing, but in the truly elderly heart failure patients (> 74 years), age alone was an independent predictor for mortality.