Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria.
Clin Chem. 2013 Apr;59(4):692-702. doi: 10.1373/clinchem.2012.193656. Epub 2013 Jan 11.
Plasma concentrations of the peptides midregional proadrenomedullin (MR-proADM), midregional proatrial natriuretic peptide (MR-proANP), and C-terminal endothelin-1 precursor fragment (CT-proET-1) are increased in various cardiovascular conditions. However, there is limited information about the association and comparative performance of these peptides in peripheral arterial disease (PAD).
The associations of MR-proADM, MR-proANP, and CT-proET-1 plasma concentrations with symptomatic PAD were investigated in the CAVASIC (Cardiovascular Disease in Intermittent Claudication) Study. Study participants were a male cohort of 238 patients with a diagnosis of intermittent claudication (IC) and 245 age- and diabetes-matched controls. Results were compared to those for N-terminal pro-B-type natriuretic peptide (NT-proBNP).
Each increase of MR-proADM, MR-proANP, and CT-proET-1 by 1 SD was significantly associated with symptomatic PAD: odds ratio (OR) = 1.78 (95% CI, 1.41-2.25, P < 0.001), OR = 1.32 (95% CI, 1.06-1.66, P = 0.014), and OR = 1.80 (95% CI, 1.43-2.28, P < 0.001), respectively. The association remained significant for all 3 markers after additional adjustment for log C-reactive protein, serum creatinine, HDL cholesterol, and current smoking. When one adjusts for log NT-proBNP and excluding individuals with prevalent cardiovascular disease, MR-proADM and CT-proET-1 still predicted symptomatic PAD. Extended adjustment models including MR-proADM or CT-proET-1 showed significantly improved model fits compared to models including classical cardiac risk factors or NT-proBNP and led to significant reclassification (P < 0.05).
This study in a male cohort of patients with IC and age- and diabetes-matched controls indicates a significant association of high MR-proADM, MR-proANP, and CT-proET-1 concentrations with PAD. MR-proADM and CT-proET-1 provide additive information in comparison to NT-proBNP. Moreover, MR-proADM and CT-proET-1 significantly predict PAD in those patients and controls free from prevalent CVD.
在各种心血管疾病中，肽中段促肾上腺髓质素（MR-proADM）、中段心房利钠肽（MR-proANP）和 C 端内皮素前体片段（CT-proET-1）的血浆浓度升高。然而，关于这些肽在周围动脉疾病（PAD）中的关联和比较表现的信息有限。
在 CAVASIC（间歇性跛行中的心血管疾病）研究中，研究了 MR-proADM、MR-proANP 和 CT-proET-1 血浆浓度与有症状 PAD 的相关性。研究参与者是 238 名间歇性跛行（IC）诊断男性患者和 245 名年龄和糖尿病匹配的对照组。将结果与 N 末端 pro-B 型利钠肽（NT-proBNP）进行比较。
MR-proADM、MR-proANP 和 CT-proET-1 每增加 1 个标准差与有症状 PAD 显著相关：比值比（OR）=1.78（95%CI，1.41-2.25，P<0.001），OR=1.32（95%CI，1.06-1.66，P=0.014），OR=1.80（95%CI，1.43-2.28，P<0.001）。在进一步调整 log C 反应蛋白、血清肌酐、高密度脂蛋白胆固醇和当前吸烟状态后，所有 3 种标志物的相关性仍然显著。当调整 log NT-proBNP 并排除有心血管疾病病史的个体时，MR-proADM 和 CT-proET-1 仍然预测有症状 PAD。与包括经典心脏危险因素或 NT-proBNP 的模型相比，包含 MR-proADM 或 CT-proET-1 的扩展调整模型显示出显著改善的模型拟合度，并导致显著的重新分类（P<0.05）。
本研究对 IC 男性患者和年龄及糖尿病匹配的对照组进行了研究，表明高浓度的 MR-proADM、MR-proANP 和 CT-proET-1 与 PAD 显著相关。与 NT-proBNP 相比，MR-proADM 和 CT-proET-1 提供了附加信息。此外，MR-proADM 和 CT-proET-1 在那些没有心血管疾病病史的患者和对照组中显著预测 PAD。
