Tomaschitz A, Pilz S, Ritz E, Grammer T, Amrein K, Merger S, Meinitzer A, Winkelmann B R, Boehm B O, März W
Department of Internal Medicine, Division of Endocrinology and Metabolism, Medical University of Graz, Graz, Austria.
Exp Clin Endocrinol Diabetes. 2011 Nov;119(10):649-55. doi: 10.1055/s-0031-1287791. Epub 2011 Nov 8.
Evidence is emerging that aldosterone contributes to the development and progression of atherosclerosis and cardiovascular disease. Little is known, however, regarding an association between circulating aldosterone levels and soluble cellular adhesion molecules in humans.
We investigated the relationship between plasma aldosterone concentration (PAC) and soluble cellular adhesion molecules in a large cohort of patients referred to coronary angiography. After exclusion of patients with ongoing mineralocorticoid receptor blocker use, oral contraceptive or hormone replacement therapy, 1,733 patients (mean age: 62.5±10.8 years; 26.4%% women; mean PAC: 101.5±93.5 pg/mL) remained eligible for analyses.
Pearson correlation analysis as well as age and gender adjusted partial correlation analysis revealed a positive association between PAC and soluble (s) E-, L- and P-selectin levels but not with sICAM-1 and sVCAM-1, respectively. In multivariate adjusted analyses of covariance (ANCOVA) sE- (p=0.026), sL- (p=0.049) and sP-selectin (p<0.001) levels increased steadily from the first (reference) to the third gender-specific tertile of PAC. No significant variation across PAC tertiles was found for sICAM-1 (p=0.767) and sVCAM1 (p=0.425) levels, respectively. Finally, multivariate regression analyses revealed circulating aldosterone as an important predictor for soluble selectin levels.
Our findings in a large cohort of patients indicate that upregulation of selectins might represent a novel mechanism of aldosterone mediated development and progression of atherosclerosis. In view of aldosterone as a novel cardiovascular risk factor independent of angiotensin II, our findings warrant further interventional studies which should evaluate anti-atherosclerotic effects of aldosterone blocking treatment strategies in humans.
越来越多的证据表明醛固酮会促进动脉粥样硬化和心血管疾病的发生发展。然而,关于人体循环醛固酮水平与可溶性细胞黏附分子之间的关联,人们所知甚少。
我们在一大群接受冠状动脉造影的患者中研究了血浆醛固酮浓度(PAC)与可溶性细胞黏附分子之间的关系。在排除正在使用盐皮质激素受体阻滞剂、口服避孕药或激素替代疗法的患者后,1733例患者(平均年龄:62.5±10.8岁;26.4%为女性;平均PAC:101.5±93.5 pg/mL)仍符合分析条件。
Pearson相关分析以及年龄和性别校正的偏相关分析显示,PAC与可溶性(s)E-选择素、L-选择素和P-选择素水平呈正相关,但与sICAM-1和sVCAM-1无关。在多变量调整协方差分析(ANCOVA)中,sE-选择素(p=0.026)、sL-选择素(p=0.049)和sP-选择素(p<0.001)水平从PAC的第一个(参考)到第三个性别特异性三分位数稳步升高。sICAM-1(p=0.767)和sVCAM1(p=0.425)水平在PAC三分位数之间未发现显著差异。最后,多变量回归分析显示循环醛固酮是可溶性选择素水平的重要预测因子。
我们在一大群患者中的研究结果表明,选择素的上调可能代表醛固酮介导动脉粥样硬化发生发展的一种新机制。鉴于醛固酮是一种独立于血管紧张素II的新型心血管危险因素,我们的研究结果值得进一步开展干预性研究,以评估醛固酮阻断治疗策略对人体的抗动脉粥样硬化作用。