Neuroendocrine activation is known to occur in patients with congestive heart failure, but there is uncertainty as to whether this occurs before or after the presence of overt symptoms. In the Studies of Left Ventricular Dysfunction (SOLVD), a multicenter study of patients with ejection fractions of 35% or less, we compared baseline plasma norepinephrine, plasma renin activity, plasma atrial natriuretic factor, and plasma arginine vasopressin in 56 control subjects, 151 patients with left ventricular dysfunction (no overt heart failure), and 81 patients with overt heart failure before randomization. Median values for plasma norepinephrine (p=9.0001), plasma atrial natriuretic factor (p<0.0001), plasma arginine vasopressin (p=0.006), and plasma renin activity (p=0.03) were significantly higher in patients with left ventricular dysfunction than in normal control subjects. Neuroendocrine values were highest in patients with overt heart failure. Plasma renin activity was normal in patients with left ventricular dysfunction without heart failure who were not receiving diuretics and was significantly increased (p<0.05) in patients on diuretic therapy. We conclude that neuroendocrine activation occurs in patients with left ventricular dysfunction and no heart failure. Neuroendocrine activation is further increased as overt heart failure ensues and diuretics are added to therapy. (Circulation 1990;82:1724-1729 C ongestive heart failure is a complex clinical syndrome with varying pathophysiology and clinical expression. It is well known that overt heart failure is characterized by activation of several neuroendocrine systems.' Plasma norepinephrine (PNE)2 and plasma atrial natriuretic factor (ANF)3 are increased and known to be prognostic factors in patients with heart failure. Activation of the renin-angiotensin system is common in patients with advanced heart failure. Angiotensin converting enzyme inhibitor therapy improves survival in patients with advanced heart failure,4 suggesting that

Background-Electrocardiographic markers of left ventricular hypertrophy (LVH) predict poor prognosis. We determined whether the ACE inhibitor ramipril prevents the development and causes regression of ECG-LVH and whether these changes are associated with improved prognosis independent of blood pressure reduction. Methods and Results-In the Heart Outcomes Prevention Evaluation (HOPE) study, patients at high risk were randomly assigned to ramipril or placebo and followed for 4.5years. ECGs were recorded at baseline and at study end. We compared prevention/regression and development/persistence of ECG-LVH in the two groups and related these changes to outcomes. At baseline, 676 patients had LVH (321 in the ramipril group and 355 in the placebo group) and 7605 patients did not have LVH (3814 in the ramipril group and 3791 in the placebo group). By study end, 336 patients in the ramipril group (8.1%) compared with 406 in the placebo group (9.8%) had development/persistence of LVH; in contrast, 3799 patients in the ramipril group (91.9%) compared with 3740 in the placebo group (90.2%) had regression/prevention of LVH (Pϭ0.007). The effect of ramipril on LVH was independent of blood pressure changes. Patients who had regression/prevention of LVH had a lower risk of the predefined primary outcome (cardiovascular death, myocardial infarction, or stroke) compared with those who had development/persistence of LVH (12.3% versus 15.8%, Pϭ0.006) and of congestive heart failure (9.3% versus 15.4%, PϽ0.0001). Conclusions-The ACE inhibitor ramipril decreases the development and causes regression of ECG-LVH independent of blood pressure reduction, and these changes are associated with reduced risk of death, myocardial infarction, stroke, and congestive heart failure. (Circulation. 2001;104:1615-1621.)