Download PDF
Exp Clin Endocrinol Diabetes 2011; 119(10): 649-655
DOI: 10.1055/s-0031-1287791
Article
© J. A. Barth Verlag in George Thieme Verlag KG Stuttgart · New York

Relationship between Plasma Aldosterone Concentration and Soluble Cellular Adhesion Molecules in Patients Referred to Coronary Angiography

A. Tomaschitz   *
1   Department of Internal Medicine, Division of Endocrinology and Metabolism, Medical University of Graz, Graz, Austria
,
S. Pilz
1   Department of Internal Medicine, Division of Endocrinology and Metabolism, Medical University of Graz, Graz, Austria
2   Department of Epidemiology and Biostatistics, EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands
,
E. Ritz
3   Department of Nephrology, University of Heidelberg, Heidelberg, Germany
,
T. Grammer
4   Mannheim Institute of Public Health, Rupertus Carola University ­Heidelberg, Medical Faculty Mannheim, Mannheim, Germany
,
K. Amrein
1   Department of Internal Medicine, Division of Endocrinology and Metabolism, Medical University of Graz, Graz, Austria
,
S. Merger
5   Division of Endocrinology, Diabetes and Metabolism, Graduate School of ­Molecular Diabetology and Endocrinology, Ulm University, Ulm, Germany
,
A. Meinitzer
6   Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
,
B. R. Winkelmann
7   Cardiology Group Sachsenhausen, Frankfurt, Germany
,
B. O. Boehm   *
5   Division of Endocrinology, Diabetes and Metabolism, Graduate School of ­Molecular Diabetology and Endocrinology, Ulm University, Ulm, Germany
,
W. März   *
4   Mannheim Institute of Public Health, Rupertus Carola University ­Heidelberg, Medical Faculty Mannheim, Mannheim, Germany
6   Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
8   Synlab Centre of Laboratory Diagnostics, Heidelberg, Germany
› Author Affiliations
Further Information

Publication History

received 26 March 2011
first decision 18 July 2011

accepted 06 September 2011

Publication Date:
08 November 2011 (online)

Also available at
    Permissions and Reprints

Abstract

Objective:

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.

Methods:

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.

Results:

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.

Conclusion:

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.

Key words

plasma aldosterone - soluble cellular adhesion molecules
*

* These authors contributed equally to this work.


 

  • References

  • 1 Tomaschitz A, Pilz S, Ritz E et al. Aldosterone and arterial hypertension. Nat Rev Endocrinol 2010; 6: 83-93
    CrossrefPubMedGoogle Scholar
  • 2 Rossi GP, Di Bello V, Ganzaroli C et al. Excess aldosterone is associated with alterations of myocardial texture in primary aldosteronism. Hypertension 2002; 40: 23-27
    Google Scholar
  • 3 Sechi LA, Novello M, Lapenna R et al. Long-term renal outcomes in patients with primary aldosteronism. JAMA 2006; 295: 2638-2645
    Google Scholar
  • 4 Mulatero P, Caserta M, Bertello C et al. Aldosterone as an independent factor in cerebrovascular damage. Clin Exp Hypertens 2008; 30: 785-797
    CrossrefPubMedGoogle Scholar
  • 5 Connell JM, MacKenzie SM, Freel EM et al. A lifetime of aldosterone excess: long-term consequences of altered regulation of aldosterone production for cardiovascular function. Endocr Rev 2008; 29: 133-154
    Google Scholar
  • 6 Tomaschitz A, März W, Pilz S et al. Aldosterone/renin ratio determines peripheral and central blood pressure values over a broad range. J Am Coll Cardiol 2010; 55: 2171-2180
    Google Scholar
  • 7 Tomaschitz A, Pilz S, Ritz E et al. Plasma aldosterone levels are associated with increased cardiovascular mortality: the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. Eur Heart J 2010; 31: 1237-1247
    CrossrefPubMedGoogle Scholar
  • 8 Tomaschitz A, Pilz S, Ritz E et al. Association of Plasma Aldosterone With Cardiovascular Mortality in Patients With Low Estimated GFR: The Ludwigshafen Risk and Cardiovascular Health (LURIC) Study. Am J Kidney Dis 2011; 57 (03) 403-414
    CrossrefPubMedGoogle Scholar
  • 9 Pitt B, Zannad F, Remme WJ et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med 1999; 341: 709-717
    Google Scholar
  • 10 Pitt B, Remme W, Zannad F et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 2003; 348: 1309-1321
    Google Scholar
  • 11 Zannad F, McMurray JJ, Krum H et al. Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms. N Engl J Med 2011; 364 (01) 11-21
    Google Scholar
  • 12 Schiffrin EL. Effects of aldosterone on the vasculature. Hypertension 2006; 47: 312-318
    CrossrefPubMedGoogle Scholar
  • 13 Suzuki J, Iwai M, Mogi M et al. Eplerenone with valsartan effectively reduces atherosclerotic lesion by attenuation of oxidative stress and inflammation. Arterioscler Thromb Vasc Biol 2006; 26: 917-921
    CrossrefPubMedGoogle Scholar
  • 14 Takai S, Jin D, Muramatsu M et al. Eplerenone inhibits atherosclerosis in nonhuman primates. Hypertension 2005; 46: 1135-1139
    CrossrefPubMedGoogle Scholar
  • 15 Blankenberg S, Barbaux S, Tiret L. Adhesion molecules and atherosclerosis. Atherosclerosis 2003; 170: 191-203
    CrossrefPubMedGoogle Scholar
  • 16 Petrak O, Widimsky Jr J, Zelinka T et al. Biochemical markers of endothelial dysfunction in patients with endocrine and essential hypertension. Physiol Res 2006; 55: 597-602
    PubMedGoogle Scholar
  • 17 Winkelmann BR, Marz W, Boehm BO et al. Rationale and design of the LURIC study – a resource for functional genomics, pharmacogenomics and long-term prognosis of cardiovascular disease. Pharmacogenomics 2001; 2: S1-S73
    CrossrefPubMedGoogle Scholar
  • 18 Trenkel S, Seifarth C, Schobel H et al. Ratio of serum aldosterone to plasma renin concentration in essential hypertension and primary aldosteronism. Exp Clin Endocrinol Diabetes 2002; 110: 80-85
    Article in Thieme ConnectPubMedGoogle Scholar
  • 19 Ritz E, Tomaschitz A. Aldosterone, a vasculotoxic agent – novel functions for an old hormone. Nephrol Dial Transplant 2009; 24: 2302-2305
    CrossrefPubMedGoogle Scholar
  • 20 Gamliel-Lazarovich A, Gantman A, Coleman R et al. FAD286, an aldosterone synthase inhibitor, reduced atherosclerosis and inflammation in apolipoprotein E-deficient mice. J Hypertens 2010; 28 (09) 1900-1907
    CrossrefPubMedGoogle Scholar
  • 21 Jeong Y, Chaupin DF, Matsushita K et al. Aldosterone activates endothelial exocytosis. Proc Natl Acad Sci USA 2009; 106: 3782-3787
    CrossrefPubMedGoogle Scholar
  • 22 Schafer A, Fraccarollo D, Hildemann S et al. Inhibition of platelet activation in congestive heart failure by aldosterone receptor antagonism and ACE inhibition. Thromb Haemost 2003; 89: 1024-1030
    PubMedGoogle Scholar
  • 23 Kobayashi N, Hara K, Tojo A et al. Eplerenone shows renoprotective effect by reducing LOX-1-mediated adhesion molecule, PKCepsilon-MAPK-p90RSK, and Rho-kinase pathway. Hypertension 2005; 45: 538-544
    CrossrefPubMedGoogle Scholar
  • 24 Pu Q, Neves MF, Virdis A et al. Endothelin antagonism on aldosterone-induced oxidative stress and vascular remodeling. Hypertension 2003; 42: 49-55
    CrossrefPubMedGoogle Scholar
  • 25 Rocha R, Rudolph AE, Frierdich GE et al. Aldosterone induces a vascular inflammatory phenotype in the rat heart. Am J Physiol Heart Circ Physiol 2002; 283: H1802-H1810
    CrossrefPubMedGoogle Scholar
  • 26 Oberleithner H, Riethmuller C, Schillers H et al. Plasma sodium stiffens vascular endothelium and reduces nitric oxide release. Proc Natl Acad Sci USA 2007; 104: 16281-16286
    CrossrefPubMedGoogle Scholar
  • 27 Caprio M, Newfell BG, la Sala A et al. Functional mineralocorticoid receptors in human vascular endothelial cells regulate intercellular adhesion molecule-1 expression and promote leukocyte adhesion. Circ Res 2008; 102: 1359-1367
    CrossrefPubMedGoogle Scholar
  • 28 Tomaschitz A, Pilz S. Aldosterone to renin ratio – a reliable screening tool for primary aldosteronism?. Horm Metab Res 2011; 42: 382-391
    Article in Thieme ConnectPubMedGoogle Scholar