There is a varying hormonal activation in heart failure. To be able to evaluate this activation and relate it to prognosis, we took blood samples at baseline and after 6 weeks from 239 patients with severe heart failure (all in New York Heart Association class IV) randomized to additional treatment with enalapril or placebo. In this study (CONSENSUS), which has previously been reported, there was a significant reduction in mortality among patients treated with enalapril. The present data show in the placebo group a significant positive relation between mortality and levels of angiotensin II (p<0.05), aldosterone (p=0.003), noradrenaline (p<0.001), adrenaline (p=0.001), and atrial natriuretic factor (p=0.003). A similar relation was not observed among the patients treated with enalapril. Significant reductions in mortality in the groups of patients treated with enalapril were consistently found among patients with baseline hormone levels above median values. There were significant reductions in hormone levels from baseline to 6 weeks in the group of patients treated with enalapril for all hormones except adrenaline. There were no correlations between these changes in hormone levels. Summarily, there is a pronounced but variable neurohormonal activation in heart failure even in patients with similar clinical findings. This activation is reduced by enalapril therapy. The results suggest that the effect of enalapril on mortality is related to hormonal activation in general and the renin-angiotensin system in particular. (Circulation 1990;82:1730-1736 T he long-term prognosis for patients with severe congestive heart failure has been very poor.1 In severe congestive heart failure, compensatory activation of neurohormonal mechanisms,2 the importance of which is unclear, takes place. The increased sympathetic activity may even induce myocardial deterioration in certain types of congestive heart failure.3 The neurohormonal activation may increase myocardial oxygen consumption by elevating heart rate and afterload and may also induce coronary vasoconstriction. A direct cardiotoxic effect of angiotensin II has also been recently

A sample of 73 men and women aged 22-63 years and working in six different occupations (air traffic controllers, waiters, physicians, symphony orchestra musicians, baggagehandlers, and airplane mechanics)participated in a longitudinal study four times during a year. The spontaneous variations in job strain (determined as the self-reported ratio between psychologicaldemands and decision latitude) were substantial. The average difference between the occasion with the highest level of strain and the occasion with the lowest level was 25 Ofo of the total mean. Systolic blood pressureduring workhours, as well as self-reported sleepdisturbance,increased whendemands increased in relation to decision latitude. Among men with a depressive tendency (according to a diary) morning plasma prolactin levels increased markedly with increasing job strain. Among subjects with a positive family history of hypertension the increase in systolic blood pressure at work was particularly pronounced, and among the men in this group a lower than expected levelof morning cortisol was found measured during the period with the highest level of strain.

Job strain, a high level of psychological demands combined with a low level of decision latitude, has been hypothesized to induce mobilization of energy and inhibition of anabolism. In the present project this hypothesis was tested using four repeated observations every third month in a group of 44 men working in six widely different occupations. On each occasion scores of self-reported demands and decision latitude were calculated for every participant. An earlier report has shown that systolic blood pressure during work hours--an indicator of mobilization of energy--increased with increasing job strain (ratio between demands and decision latitude). Blood samples were drawn in the morning at the work site. For each man the plasma testosterone levels--representing the general level of anabolic activity--on the two occasions with the worst strain (ratio between demands and decision latitude) were compared with the plasma testosterone levels on the two occasions with the least strain. The results indicated that total plasma testosterone (but not free testosterone) levels increased when strain diminished in sedentary but not in physically demanding work. Subjects with a family history of hypertension showed a greater decrease in testosterone levels than others when job strain increased.

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