Cohn Jay N, Anand Inder S, Latini Roberto, Masson Serge, Chiang Yann-Tong, Glazer Robert
Cardiovascular Division, Department of Medicine, University of Minnesota Medical School, 420 Delaware St SE, Minneapolis, Minn 55455, USA.
Circulation. 2003 Sep 16;108(11):1306-9. doi: 10.1161/01.CIR.0000091234.45664.62. Epub 2003 Aug 25.
Aldosterone has been implicated in the progression of heart failure. The Valsartan Heart Failure Trial (Val-HeFT) provided the first opportunity to examine the long-term effects of an angiotensin receptor blocker on plasma aldosterone levels in patients with NYHA class II through IV heart failure.
Plasma aldosterone was measured by radioimmunoassay in core laboratories at baseline and during follow-up in patients assigned to valsartan at a target dose of 160 mg twice daily or placebo. In the placebo group, aldosterone (baseline, 150+/-160 pg/mL, mean+/-SD; n=2025) increased at 4, 12, and 24 months. In the valsartan group, aldosterone (baseline, 137+/-124 pg/mL, mean+/-SD; n=2023) decreased at 4 months and remained suppressed for up to 2 years. At end point (last measurement in each patient), mean aldosterone increased by 17.8+/-3.0 pg/mL (SEM) (11.9%) in the placebo group and decreased by 23.8+/-3.0 pg/mL (SEM) (-17.4%) in the valsartan group (P<0.00001). The effect of valsartan was similar in all subgroups, including those receiving neither ACE inhibitors (ACE-I) nor beta-blockers (BB) at baseline and those receiving concomitant ACE-I or BB. In contrast, outcome effects varied in the 4 subgroups, with a statistically significant reduction in the combined mortality/morbidity end point in those receiving neither neurohormonal inhibitor and an adverse trend in those treated with both drugs.
Valsartan added to background therapy for heart failure produces sustained reduction in plasma aldosterone, consistent with the observed significant reduction in the combined mortality/morbidity end point. A similar reduction in all subgroups based on ACE-I or BB therapy, despite differing clinical outcomes in these subgroups, suggests that aldosterone plasma levels may not be a critical marker of the progression of heart failure.
醛固酮与心力衰竭的进展有关。缬沙坦心力衰竭试验（Val-HeFT）首次提供了一个机会，来研究血管紧张素受体阻滞剂对纽约心脏病协会（NYHA）心功能II级至IV级心力衰竭患者血浆醛固酮水平的长期影响。
在核心实验室通过放射免疫分析法测定了基线时以及随访期间接受每日两次160mg目标剂量缬沙坦或安慰剂治疗的患者的血浆醛固酮水平。在安慰剂组中，醛固酮（基线水平为150±160pg/mL，均值±标准差；n = 2025）在4个月、12个月和24个月时升高。在缬沙坦组中，醛固酮（基线水平为137±124pg/mL，均值±标准差；n = 2023）在4个月时下降，并在长达2年的时间内持续受到抑制。在终点（每位患者的最后一次测量）时，安慰剂组醛固酮均值升高了17.8±3.0pg/mL（标准误）（11.9%），缬沙坦组下降了23.8±3.0pg/mL（标准误）（-17.4%）（P<0.00001）。缬沙坦在所有亚组中的作用相似，包括那些基线时既未接受血管紧张素转换酶抑制剂（ACE-I）也未接受β受体阻滞剂（BB）治疗的患者以及同时接受ACE-I或BB治疗的患者。相比之下，4个亚组的预后效应各不相同，在那些既未接受神经激素抑制剂治疗的患者中，联合死亡率/发病率终点有统计学意义的降低，而在同时接受这两种药物治疗的患者中有不良趋势。
在心力衰竭背景治疗中加用缬沙坦可使血浆醛固酮持续降低，这与观察到的联合死亡率/发病率终点的显著降低一致。尽管这些亚组的临床结局不同，但基于ACE-I或BB治疗的所有亚组中醛固酮水平都有类似降低，这表明血浆醛固酮水平可能不是心力衰竭进展的关键标志物。
