Published online before print February 28, 2002, doi: 10.1161/01.ATV.0000013786.80104.D4
© 2002 American Heart Association, Inc.
Vascular Biology |
C-Reactive Protein and Soluble Vascular Cell Adhesion Molecule-1 Are Associated With Elevated Urinary Albumin Excretion but Do Not Explain Its Link With Cardiovascular Risk
From the Institute for Research in Extramural Medicine (A.J., P.J.K., G.N., J.M.D., R.J.H., L.M.B., C.D.A.S.), the Institute for Cardiovascular Research (V.V.M.v.H., C.D.A.S.), and the Department of Clinical Epidemiology and Biostatistics (P.J.K.), Vrije Universiteit, and the Department of Internal Medicine (R.J.H., C.D.A.S.), Vrije Universiteit Medical Center, Amsterdam, the Netherlands, and Gaubius Laboratory (V.V.M.v.H., J.J.E.), TNO Prevention and Health, Leiden, the Netherlands.
Correspondence to Prof Coen D.A. Stehouwer, Department of Internal Medicine, Vrije Universiteit Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, Netherlands. E-mail cda.stehouwer{at}azvu.nl
An elevated urinary albumin excretion rate (UAER) is associated with an increased risk of cardiovascular mortality, but the pathophysiological mechanism underlying this association is poorly understood. To investigate the role of endothelial dysfunction, leukocyte adhesion, and low-grade inflammation (1) in the development of elevated UAER (study I) and (2) in linking elevated UAER with risk of cardiovascular mortality (study II), we performed a prospective study in an age–, sex–, and glucose tolerance– stratified sample of a population-based cohort aged 50 to 75 years. High levels of von Willebrand factor, soluble vascular cell adhesion molecule-1 (sVCAM-1), and C-reactive protein (CRP) were used as markers of endothelial dysfunction, leukocyte adhesion, and low-grade inflammation, respectively. For study I, subjects who had normal UAER at baseline (n=316 subjects, 66 with type 2 diabetes) were reexamined after a mean follow-up of 6.1 years. The development of elevated UAER was defined as a mean albumin-to-creatinine ratio >2.0 mg/mmol at follow-up. Age–, sex–, and glucose tolerance– adjusted logistic regression analyses showed the development of elevated UAER to be significantly associated with levels of sVCAM-1 and CRP (odds ratio 1.14 [95% CI 1.02 to 1.27] per 10% increase of sVCAM-1 and odds ratio 1.17 [95% CI 1.04 to 1.32] per 50% increase of CRP). The results were not materially different after additional adjustment for hypertension, body mass index, cardiovascular disease, and creatinine clearance or stratification by the presence of diabetes. For study II, the vital status of all subjects (n= 575) was determined after a mean follow-up of 6.6 years. Eighty-one of 575 subjects died (30 died of cardiovascular disease). The presence of elevated UAER at baseline was associated with a 4.1-fold (1.94 to 8.73) increased risk of cardiovascular death after adjustment for age, sex, and glucose tolerance status. Adjustment for levels of von Willebrand factor, sVCAM-1, or CRP did not materially affect the results, nor did additional adjustment for the presence of hypertension, retinopathy, and cardiovascular disease and for levels of homocysteine, triglycerides, and high density lipoprotein cholesterol. Leukocyte adhesion (sVCAM-1) and low-grade inflammation (CRP) are determinants of the development of elevated UAER. However, these determinants do not explain the association between elevated UAER and cardiovascular mortality.
Key Words: elevated urinary albumin excretion rate • von Willebrand factor • C-reactive protein • soluble vascular cell adhesion molecule-1 • cardiovascular mortality
This article has been cited by other articles:
 |
|
 |
|
  C. N. Rathcke, F. Persson, L. Tarnow, P. Rossing, and H. Vestergaard YKL-40, a Marker of Inflammation and Endothelial Dysfunction, Is Elevated in Patients With Type 1 Diabetes and Increases With Levels of Albuminuria Diabetes Care, February 1, 2009; 32(2): 323 - 328. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Suliman, M. I. Yilmaz, J. J. Carrero, A. R. Qureshi, M. Saglam, O. M. Ipcioglu, M. Yenicesu, M. Tong, O. Heimburger, P. Barany, et al. Novel Links between the Long Pentraxin 3, Endothelial Dysfunction, and Albuminuria in Early and Advanced Chronic Kidney Disease Clin. J. Am. Soc. Nephrol., July 1, 2008; 3(4): 976 - 985. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. I. Yilmaz, M. Saglam, A. R. Qureshi, J. J. Carrero, K. Caglar, T. Eyileten, A. Sonmez, E. Cakir, Y. Oguz, A. Vural, et al. Endothelial dysfunction in type-2 diabetics with early diabetic nephropathy is associated with low circulating adiponectin Nephrol. Dial. Transplant., May 1, 2008; 23(5): 1621 - 1627. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Jorgensen, I. Heuch, T. Jenssen, and B. K. Jacobsen Association of Albuminuria and Cancer Incidence J. Am. Soc. Nephrol., May 1, 2008; 19(5): 992 - 998. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. F. Salles, R. Fiszman, C. R.L. Cardoso, and E. S. Muxfeldt Relation of Left Ventricular Hypertrophy With Systemic Inflammation and Endothelial Damage in Resistant Hypertension Hypertension, October 1, 2007; 50(4): 723 - 728. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Weir Microalbuminuria and Cardiovascular Disease Clin. J. Am. Soc. Nephrol., May 1, 2007; 2(3): 581 - 590. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. D.A. Stehouwer and Y. M. Smulders Microalbuminuria and Risk for Cardiovascular Disease: Analysis of Potential Mechanisms J. Am. Soc. Nephrol., August 1, 2006; 17(8): 2106 - 2111. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Ritz Reduction of Microalbuminuria by {beta} Blockers: Beyond Renin-Angiotensin System Blockade Hypertension, December 1, 2005; 46(6): 1254 - 1255. [Full Text] [PDF]
|
|
|
|
|
|
X. J, L. G, W. P, V. H, Y. X, L. Y, W. Y, P. A, C. S, D. GV, et al. Kidney and Blood Pressure--The Story Unfolds: Renalase Is a Novel, Soluble Monoamine Oxidase That Regulates Cardiac Function and Blood Pressure. J Clin Invest J. Am. Soc. Nephrol., September 1, 2005; 16(9): 2521 - 2527. [Full Text] [PDF]
|
|
|
|
|
|
C. W, Y. PX, L. BM, C. RD, M. DL, M. RH, I. H, O. MH, W. K, B.-J. K, et al. Anorexia and Cachexia in Renal Failure--Is Leptin the Culprit?: Role of Leptin and Melanocortin Signaling in Uremia-Associated Cachexia. J Clin Invest 115: 1659-1665, 2005 J. Am. Soc. Nephrol., August 1, 2005; 16(8): 2245 - 2250. [Full Text] [PDF]
|
|
|
|
|
|
F. Togel, Z. Hu, K. Weiss, J. Isaac, C. Lange, C. Westenfelder, T. Stasko, M.D. Brown, J.A. Carucci, S. Euvrard, et al. Amelioration of Acute Renal Failure by Stem Cell Therapy--Paracrine Secretion Versus Transdifferentiation into Resident Cells: Administered Mesenchymal Stem Cells Protect against Ischemic Acute Renal Failure through Differentiation-Independent Mechanisms. Am J Physiol Renal Physiol E-pub February 15, 2005 J. Am. Soc. Nephrol., May 1, 2005; 16(5): 1153 - 1163. [Full Text] [PDF]
|
|
|
|
|
|
E. M. Stuveling, S. J. L. Bakker, H. L. Hillege, P. E. de Jong, R. O. B. Gans, and D. de Zeeuw Biochemical risk markers: a novel area for better prediction of renal risk? Nephrol. Dial. Transplant., March 1, 2005; 20(3): 497 - 508. [Full Text] [PDF]
|
|
|
|
|
|
M. Dalla Vestra, M. Mussap, P. Gallina, M. Bruseghin, A. M. Cernigoi, A. Saller, M. Plebani, and P. Fioretto Acute-Phase Markers of Inflammation and Glomerular Structure in Patients with Type 2 Diabetes J. Am. Soc. Nephrol., March 1, 2005; 16(3_suppl_1): S78 - S82. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. D. A. Stehouwer Endothelial dysfunction in diabetic nephropathy: state of the art and potential significance for non-diabetic renal disease Nephrol. Dial. Transplant., April 1, 2004; 19(4): 778 - 781. [Full Text] [PDF]
|
|
|
|
|
|
E. M. Stuveling, S. J.L. Bakker, H. L. Hillege, J. G.M. Burgerhof, P. E. de Jong, R. O.B. Gans, D. de Zeeuw, and for the PREVEND Study Group C-Reactive Protein Modifies the Relationship Between Blood Pressure and Microalbuminuria Hypertension, April 1, 2004; 43(4): 791 - 796. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. T. Schram, N. Chaturvedi, C. Schalkwijk, F. Giorgino, P. Ebeling, J. H. Fuller, and C. D. Stehouwer Vascular Risk Factors and Markers of Endothelial Function as Determinants of Inflammatory Markers in Type 1 Diabetes: The EURODIAB Prospective Complications Study Diabetes Care, July 1, 2003; 26(7): 2165 - 2173. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Tonelli, L. Moye, F. M. Sacks, T. Cole, and G. C. Curhan Effect of Pravastatin on Loss of Renal Function in People with Moderate Chronic Renal Insufficiency and Cardiovascular Disease J. Am. Soc. Nephrol., June 1, 2003; 14(6): 1605 - 1613. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Engstrom, L. Stavenow, B. Hedblad, P. Lind, K.-F. Eriksson, L. Janzon, and F. Lindgarde Inflammation-Sensitive Plasma Proteins, Diabetes, and Mortality and Incidence of Myocardial Infarction and Stroke: A Population-Based Study Diabetes, February 1, 2003; 52(2): 442 - 447. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. Ballantyne and M. L. Entman Soluble Adhesion Molecules and the Search for Biomarkers for Atherosclerosis Circulation, August 13, 2002; 106(7): 766 - 767. [Full Text] [PDF]
|
|