Vantrimpont P, Rouleau J L, Ciampi A, Harel F, de Champlain J, Bichet D, Moyé L A, Pfeffer M
Section of Cardiology Medical Department, Montreal Heart Institute, Canada.
Eur Heart J. 1998 Oct;19(10):1552-63. doi: 10.1053/euhj.1998.1093.
To describe the temporal evolution of neurohumoral activation in survivors of myocardial infarction with left ventricular dysfunction who are initially asymptomatic and to relate this to prognosis.
Patients in the neurohumoral substudy (n = 534) of the Survival and Ventricular Enlargement (SAVE) study had their neurohormones measured at baseline, 3, 12 and 24 months post-infarction, were followed 38 +/- 7 months and had these values related to prognosis. All patients had a left ventricular ejection fraction < or = 40% early post-infarction. Atrial natriuretic peptide, aldosterone, norepinephrine and plasma renin activity decreased progressively over time. Patients with events had a persistent increase in these neurohormones with those dying within the first 24 months of follow-up having the greatest increase. Treatment with captopril affected only plasma renin activity (increase) and aldosterone (decrease). For patients who remained asymptomatic for the first 3 months post-infarction (n = 471), by multivariate analyses (all neurohormones together with non-neurohumoral risk factors), 3-month plasma atrial natriuretic peptide and aldosterone were the most closely related to the development of severe heart failure or to the combined end-points (cardiovascular death, myocardial infarction, or severe heart failure). No neurohormone was related to recurrent myocardial infarction or to cardiovascular mortality. When the last neurohormone measured prior to an event was considered along with non-neurohumoral risk factors (adjusted univariate), atrial natriuretic peptide, aldosterone, norepinephrine and epinephrine were associated with prognosis indicating that a time-dependent analysis identified a closer relationship between neurohormones and events than that identified by 3-month values. However, by multivariate analyses atrial natriuretic peptide was the only neurohormone associated with an event, being associated with the development of severe heart failure (P < 0.001) and the combined end-points (P = 0.022). However, when neurohormones were considered as binary variables, activated or non-activated (defined as > 1.96 SD above the mean of age-matched controls), an association between activation of norepinephrine prior to recurrent myocardial infarction (P < 0.001) and combined end-points (P < 0.01) and between activation of aldosterone and severe heart failure (P < 0.05) was identified.
Neurohumoral activation decreases progressively post-infarction, but only in patients with a good prognosis. In patients with a left ventricular ejection fraction < or = 40% and asymptomatic post-infarction plasma atrial natriuretic peptide at 3 months, aldosterone levels appeared to be the neurohormones most closely associated with prognosis. Increased levels of atrial natriuretic peptide, aldosterone and norepinephrine appear to be temporally most closely associated with events.
描述初始无症状的左心室功能障碍心肌梗死幸存者神经体液激活的时间演变，并将其与预后相关联。
生存与心室扩大（SAVE）研究的神经体液亚研究中的患者（n = 534）在基线、心肌梗死后3、12和24个月测量神经激素，随访38±7个月，并将这些值与预后相关联。所有患者在心肌梗死后早期左心室射血分数≤40%。心房利钠肽、醛固酮、去甲肾上腺素和血浆肾素活性随时间逐渐下降。发生事件的患者这些神经激素持续升高，在随访的前24个月内死亡的患者升高幅度最大。卡托普利治疗仅影响血浆肾素活性（升高）和醛固酮（降低）。对于心肌梗死后前3个月仍无症状的患者（n = 471），通过多变量分析（所有神经激素与非神经体液危险因素一起），3个月时的血浆心房利钠肽和醛固酮与严重心力衰竭的发生或联合终点（心血管死亡、心肌梗死或严重心力衰竭）最密切相关。没有神经激素与复发性心肌梗死或心血管死亡率相关。当将事件发生前最后一次测量的神经激素与非神经体液危险因素一起考虑时（调整后的单变量分析），心房利钠肽、醛固酮、去甲肾上腺素和肾上腺素与预后相关，表明时间依赖性分析确定神经激素与事件之间的关系比3个月时的值确定的关系更密切。然而，通过多变量分析，心房利钠肽是唯一与事件相关的神经激素，与严重心力衰竭的发生（P < 0.001）和联合终点（P = 0.022）相关。然而，当将神经激素视为二元变量，即激活或未激活（定义为高于年龄匹配对照组平均值1.96个标准差）时，发现复发性心肌梗死前去甲肾上腺素激活与联合终点（P < 0.001）以及醛固酮激活与严重心力衰竭（P < 0.05）之间存在关联。
心肌梗死后神经体液激活逐渐降低，但仅在预后良好的患者中如此。对于左心室射血分数≤40%且心肌梗死后无症状的患者，3个月时的血浆心房利钠肽、醛固酮水平似乎是与预后最密切相关的神经激素。心房利钠肽、醛固酮和去甲肾上腺素水平升高似乎在时间上与事件最密切相关。
