Department of Medicine, Weill Cornell Medical College, New York, New York, USA.
Am J Hypertens. 2013 Jun;26(6):727-38. doi: 10.1093/ajh/hpt034. Epub 2013 Apr 2.
Four recent reports revealed differences in survival rates among treated cardiovascular patients taking renin-angiotensin system-blocking drugs. Patients with higher on-treatment plasma renin activity (PRA) levels died sooner of cardiovascular mortality than those with lower levels. We investigated whether excessive sodium depletion might have induced the higher PRA levels and contributed to the greater morbidity and mortality.
Using published data, ranges of PRA, blood pressures, drug usage, and biochemical parameters were compared among various groups of cardiovascular patients.
We showed (i) that PRA levels are usually medium to low in treated cardiovascular patients, but are sometimes abnormally high, (ii) that excessive sodium depletion can induce such high PRA levels, (iii) that the higher PRA patients exhibited evidence of sodium depletion: lower blood pressures, more frequent natriuretic drug usage, lower N-terminal pro b-type natriuretic peptide (NT-proBNP), and higher blood urea nitrogen and uric acid levels, with similar usage of renin-angiotensin blocking drugs.
We hypothesize that patients with high on-treatment PRA levels die sooner of cardiovascular events because they are excessively sodium-volume depleted. Moreover, renin-angiotensin system-blocking drugs may be harmful in such patients because they can functionally interfere with the effects of reactive rises in PRA that are triggered to prevent potentially dangerous falls in blood pressure, increases in plasma potassium, and falls in glomerular filtration rate. Careful liberalization of salt intake and subtraction of natriuretic drugs, sufficient to reduce reactive hyperreninemia without inducing unacceptable increases in blood pressure, might benefit such patients and decrease risk of adverse effects from drugs that block the renin-angiotensin system.
四项最近的报告揭示了接受肾素-血管紧张素系统阻断药物治疗的心血管患者生存率存在差异。与较低水平相比，治疗后血浆肾素活性（PRA）水平较高的患者心血管死亡率更高，更早死亡。我们调查了过度钠耗竭是否可能导致较高的 PRA 水平，并导致更高的发病率和死亡率。
利用已发表的数据，比较了各种心血管患者群体的 PRA、血压、药物使用和生化参数的范围。
我们表明：（i）治疗中的心血管患者的 PRA 水平通常处于中等至低水平，但有时会异常升高；（ii）过度钠耗竭可诱导这种高 PRA 水平；（iii）PRA 较高的患者表现出钠耗竭的证据：较低的血压、更频繁地使用利钠药物、较低的 N 末端 pro B 型利钠肽（NT-proBNP）以及更高的血尿素氮和尿酸水平，同时使用肾素-血管紧张素阻断药物相似。
我们假设治疗后 PRA 水平较高的患者因过度钠-容量耗竭而更早死于心血管事件。此外，在这些患者中，肾素-血管紧张素系统阻断药物可能是有害的，因为它们可能会对反应性升高的 PRA 产生功能性干扰，这种升高是为了防止潜在危险的血压下降、血浆钾升高和肾小球滤过率下降。谨慎放宽盐摄入量并减去利钠药物，足以减少反应性高肾素血症而不会引起不可接受的血压升高，可能会使这些患者受益，并降低阻断肾素-血管紧张素系统的药物的不良反应风险。
