Circulation. 2004;110:32-35
Published online before print June 21, 2004, doi: 10.1161/01.CIR.0000133312.96477.48
Published online before print June 21, 2004, doi: 10.1161/01.CIR.0000133312.96477.48
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2004;110:32-35.)
© 2004 American Heart Association, Inc.
Original Articles |
Very Low Levels of Microalbuminuria Are Associated With Increased Risk of Coronary Heart Disease and Death Independently of Renal Function, Hypertension, and Diabetes
From the Copenhagen City Heart Study, Epidemiological Research Unit, Bispebjerg University Hospital, Copenhagen, Denmark.
Correspondence to Dr Jan Skov Jensen, Department of Cardiology P., Post 163, Gentofte University Hospital, Niels Andersensvej 65, DK-2900 Hellerup, Denmark. E-mail jsje{at}c.dk
Received September 4, 2003; de novo received November 17, 2003; revision received March 9, 2004; accepted March 11, 2004.
Background— The aim of this study was to assess the level of urinary albumin excretion (microalbuminuria), which is associated with increased risk of coronary heart disease and death, in the population. Microalbuminuria has been suggested as an atherosclerotic risk factor. However, the lower cutoff level of urinary albumin excretion is unknown. It is also unknown whether impaired renal function confounds the association.
Methods and Results— In the Third Copenhagen City Heart Study in 1992 to 1994, 2762 men and women 30 to 70 years of age underwent a detailed cardiovascular investigation program, including a timed overnight urine sample. The participants were then followed up prospectively by registers until 1999 with respect to coronary heart disease and until 2001 with respect to death. During follow-up, 109 incident cases of coronary heart disease and 276 deaths were traced. A urinary albumin excretion above the upper quartile, ie, 4.8 µg/min, was associated with increased risk of coronary heart disease (RR, 2.0; 95% CI, 1.4 to 3.0; P<0.001) and death (RR, 1.9; 95% CI, 1.5 to 2.4; P<0.001) independently of age, sex, renal creatinine clearance, diabetes mellitus, hypertension, and plasma lipids. Lower levels of urinary albumin excretion were not associated with increased risk.
Conclusions— Microalbuminuria, defined as urinary albumin excretion >4.8 µg/min (corresponding to 
6.4 µg/min during daytime), is a strong and independent determinant of coronary heart disease and death. Our suggestion is to redefine microalbuminuria accordingly and perform intervention studies.
Key Words: albumins • coronary disease • mortality • renal function
This article has been cited by other articles:
 |
|
 |
|
  S. De Cosmo, N. Motterlini, S. Prudente, F. Pellegrini, R. Trevisan, A. Bossi, G. Remuzzi, V. Trischitta, P. Ruggenenti, and on behalf of the BENEDICT Study Group Impact of the PPAR-{gamma}2 Pro12Ala Polymorphism and ACE Inhibitor Therapy on New-Onset Microalbuminuria in Type 2 Diabetes: Evidence From BENEDICT Diabetes, December 1, 2009; 58(12): 2920 - 2929. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. H. Khan and D. M. Harlan Counterpoint: Clinical Islet Transplantation: Not Ready for Prime Time Diabetes Care, August 1, 2009; 32(8): 1570 - 1574. [Full Text] [PDF]
|
|
|
|
 |
|
 N. M. Kaplan Prehypertension: Is It Relevant for Nephrologists? Clin. J. Am. Soc. Nephrol., August 1, 2009; 4(8): 1381 - 1383. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 WRITING GROUP MEMBERS, D. Lloyd-Jones, R. Adams, M. Carnethon, G. De Simone, T. B. Ferguson, K. Flegal, E. Ford, K. Furie, A. Go, et al. Heart Disease and Stroke Statistics--2009 Update: A Report From the American Heart Association Statistics Committee and Stroke Statistics Subcommittee Circulation, January 27, 2009; 119(3): e21 - e181. [Full Text] [PDF]
|
|
|
|
|
|
American Diabetes Association Standards of Medical Care in Diabetes--2009 Diabetes Care, January 1, 2009; 32(Supplement_1): S13 - S61. [Full Text] [PDF]
|
|
|
|
 |
|
 B. Radbill, B. Murphy, and D. LeRoith Rationale and Strategies for Early Detection and Management of Diabetic Kidney Disease Mayo Clin. Proc., December 1, 2008; 83(12): 1373 - 1381. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. J. Lambers Heerspink, A. H. Brantsma, D. de Zeeuw, S. J. L. Bakker, P. E. de Jong, R. T. Gansevoort, and for the PREVEND Study Group Albuminuria Assessed From First-Morning-Void Urine Samples Versus 24-Hour Urine Collections as a Predictor of Cardiovascular Morbidity and Mortality Am. J. Epidemiol., October 15, 2008; 168(8): 897 - 905. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Baekken, I. Os, L. Sandvik, and O. Oektedalen Microalbuminuria associated with indicators of inflammatory activity in an HIV-positive population Nephrol. Dial. Transplant., October 1, 2008; 23(10): 3130 - 3137. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Crowe, D. Halpin, P. Stevens, and on behalf of the Guideline Development Group Early identification and management of chronic kidney disease: summary of NICE guidance BMJ, September 29, 2008; 337(sep29_1): a1530 - a1530. [Full Text]
|
|
|
|
 |
|
 T. Nikkanen, M. Timonen, K. Ylitalo, O. Timonen, S. Keinanen-Kiukaanniemi, and U. Rajala Quality of diabetes care among patients managed by teleconsultation J Telemed Telecare, September 1, 2008; 14(6): 295 - 299. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Shaikh, J. C. Seegmiller, T. M. Borland, B. E. Burns, P. M. Ladwig, R. J. Singh, R. Kumar, T. S. Larson, and J. C. Lieske Comparison between Immunoturbidimetry, Size-Exclusion Chromatography, and LC-MS to Quantify Urinary Albumin Clin. Chem., September 1, 2008; 54(9): 1504 - 1510. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Danziger Importance of Low-Grade Albuminuria Mayo Clin. Proc., July 1, 2008; 83(7): 806 - 812. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. C. Astor, S. I. Hallan, E. R. Miller III, E. Yeung, and J. Coresh Glomerular Filtration Rate, Albuminuria, and Risk of Cardiovascular and All-Cause Mortality in the US Population Am. J. Epidemiol., May 15, 2008; 167(10): 1226 - 1234. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Lorenzo, S. D. Nath, A. J.G. Hanley, H. E. Abboud, and S. M. Haffner Relation of Low Glomerular Filtration Rate to Metabolic Disorders in Individuals without Diabetes and with Normoalbuminuria Clin. J. Am. Soc. Nephrol., May 1, 2008; 3(3): 783 - 789. [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]
|
|
|
|
|
|
P. Stenvinkel, J. J. Carrero, J. Axelsson, B. Lindholm, O. Heimburger, and Z. Massy Emerging Biomarkers for Evaluating Cardiovascular Risk in the Chronic Kidney Disease Patient: How Do New Pieces Fit into the Uremic Puzzle? Clin. J. Am. Soc. Nephrol., March 1, 2008; 3(2): 505 - 521. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Basi, P. Fesler, A. Mimran, and J. B. Lewis Microalbuminuria in Type 2 Diabetes and Hypertension: A marker, treatment target, or innocent bystander? Diabetes Care, February 1, 2008; 31(Supplement_2): S194 - S201. [Full Text] [PDF]
|
|
|
|
|
|
Writing Group Members, W. Rosamond, K. Flegal, K. Furie, A. Go, K. Greenlund, N. Haase, S. M. Hailpern, M. Ho, V. Howard, et al. Heart Disease and Stroke Statistics--2008 Update: A Report From the American Heart Association Statistics Committee and Stroke Statistics Subcommittee Circulation, January 29, 2008; 117(4): e25 - e146. [Full Text] [PDF]
|
|
|
|
 |
|
 D. Pereg, A. Tirosh, T. Shochat, D. Hasdai, and for the Metabolic, Lifestyle and Nutrition Assessm Mild renal dysfunction associated with incident coronary artery disease in young males Eur. Heart J., January 2, 2008; 29(2): 198 - 203. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Day, P. Hewins, S. Hildebrand, L. Sheikh, G. Taylor, M. Kilby, and G. Lipkin The role of renal biopsy in women with kidney disease identified in pregnancy Nephrol. Dial. Transplant., January 1, 2008; 23(1): 201 - 206. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
American Diabetes Association Standards of Medical Care in Diabetes--2008 Diabetes Care, January 1, 2008; 31(Supplement_1): S12 - S54. [Full Text] [PDF]
|
|
|
|
 |
|
 A. Whaley-Connell, B. S. Pavey, K. Chaudhary, G. Saab, and J. R. Sowers Review: Renin-angiotensin-aldosterone system intervention in the cardiometabolic syndrome and cardio-renal protection Therapeutic Advances in Cardiovascular Disease, October 1, 2007; 1(1): 27 - 35. [Abstract] [PDF]
|
|
|
|
|
|
R. T. Gansevoort, H. Lambers, and E. C. Witte Methodology of screening for albuminuria Nephrol. Dial. Transplant., August 1, 2007; 22(8): 2109 - 2111. [Full Text] [PDF]
|
|
|
|
 |
|
 L. Jorgensen, T. Jenssen, L. Ahmed, A. Bjornerem, R. Joakimsen, and B. K. Jacobsen Albuminuria and Risk of Nonvertebral Fractures Arch Intern Med, July 9, 2007; 167(13): 1379 - 1385. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. L. Schiffrin, M. L. Lipman, and J. F.E. Mann Chronic Kidney Disease: Effects on the Cardiovascular System Circulation, July 3, 2007; 116(1): 85 - 97. [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]
|
|
|
|
 |
|
 F. Rao, J. Wessel, G. Wen, L. Zhang, B. K. Rana, B. P. Kennedy, T. A. Greenwood, R. M. Salem, Y. Chen, S. Khandrika, et al. Renal Albumin Excretion: Twin Studies Identify Influences of Heredity, Environment, and Adrenergic Pathway Polymorphism Hypertension, May 1, 2007; 49(5): 1015 - 1031. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A Ajjan and P. J Grant Cardiovascular disease prevention in patients with type 2 diabetes: the role of oral anti-diabetic agents Diabetes and Vascular Disease Research, December 1, 2006; 3(3): 147 - 158. [Abstract] [PDF]
|
|
|
|
 |
|
 M. Rodriguez-Yanez, M. Castellanos, M. Blanco, M. Millan, F. Nombela, T. Sobrino, I. Lizasoain, R. Leira, J. Serena, A. Davalos, et al. Micro- and macroalbuminuria predict hemorrhagic transformation in acute ischemic stroke. Neurology, October 10, 2006; 67(7): 1172 - 1177. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Lieb, B. Mayer, J. Stritzke, A. Doering, H.-W. Hense, H. Loewel, J. Erdmann, and H. Schunkert Association of low-grade urinary albumin excretion with left ventricular hypertrophy in the general population: The MONICA/KORA Augsburg Echocardiographic Substudy Nephrol. Dial. Transplant., October 1, 2006; 21(10): 2780 - 2787. [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]
|
|
|
|
|
|
K. Amann, C. Wanner, and E. Ritz Cross-Talk between the Kidney and the Cardiovascular System J. Am. Soc. Nephrol., August 1, 2006; 17(8): 2112 - 2119. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. de Zeeuw, H.-H. Parving, and R. H. Henning Microalbuminuria as an Early Marker for Cardiovascular Disease J. Am. Soc. Nephrol., August 1, 2006; 17(8): 2100 - 2105. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. S. Ommen, J. A. Winston, and B. Murphy Medical Risks in Living Kidney Donors: Absence of Proof Is Not Proof of Absence Clin. J. Am. Soc. Nephrol., July 1, 2006; 1(4): 885 - 895. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Tonelli, P. Jose, G. Curhan, F. Sacks, E. Braunwald, M. Pfeffer, and Cholesterol and Recurrent Events (CARE) Trial Inve Proteinuria, impaired kidney function, and adverse outcomes in people with coronary disease: analysis of a previously conducted randomised trial BMJ, June 17, 2006; 332(7555): 1426. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. H. Schulman, P. Aranda, L. Raij, M. Veronesi, F. J. Aranda, and R. Martin Surgical Menopause Increases Salt Sensitivity of Blood Pressure Hypertension, June 1, 2006; 47(6): 1168 - 1174. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Lee, Y.-G. Kim, Y.-H. Choi, W. Huh, D. J. Kim, and H. Y. Oh Serum Uric Acid Is Associated With Microalbuminuria in Prehypertension Hypertension, May 1, 2006; 47(5): 962 - 967. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kathiresan, P. Gona, M. G. Larson, J. A. Vita, G. F. Mitchell, G. H. Tofler, D. Levy, C. Newton-Cheh, T. J. Wang, E. J. Benjamin, et al. Cross-Sectional Relations of Multiple Biomarkers From Distinct Biological Pathways to Brachial Artery Endothelial Function Circulation, February 21, 2006; 113(7): 938 - 945. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
American Diabetes Association Standards of Medical Care in Diabetes-2006 Diabetes Care, January 1, 2006; 29(suppl_1): S4 - S42. [Full Text] [PDF]
|
|
|
|
|
|
G. Montalescot and J.-P. Collet Preserving cardiac function in the hypertensive patient: why renal parameters hold the key Eur. Heart J., December 2, 2005; 26(24): 2616 - 2622. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Berberian, T. A. Quinn, J. P. Kanter, L. J. Curtis, S. E. Cabreriza, A. D. Weinberg, and H. M. Spotnitz Optimized Biventricular Pacing in Atrioventricular Block After Cardiac Surgery Ann. Thorac. Surg., September 1, 2005; 80(3): 870 - 875. [Abstract] [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]
|
|
|
|
 |
|
 I. W Campbell Pioglitazone -- an oral antidiabetic agent and metabolic syndrome modulator. Can theory translate into practice? The British Journal of Diabetes & Vascular Disease, July 1, 2005; 5(4): 209 - 216. [Abstract] [PDF]
|
|
|
|
|
|
C. B. Leitao, L. H. Canani, P. B. Bolson, M. P. Molon, A. F. Pinotti, and J. L. Gross Urinary Albumin Excretion Rate Is Associated With Increased Ambulatory Blood Pressure in Normoalbuminuric Type 2 Diabetic Patients Diabetes Care, July 1, 2005; 28(7): 1724 - 1729. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Davis and F. L. Delmonico Living-Donor Kidney Transplantation: A Review of the Current Practices for the Live Donor J. Am. Soc. Nephrol., July 1, 2005; 16(7): 2098 - 2110. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. de Zeeuw Albuminuria, Just a Marker for Cardiovascular Disease, Or Is It More? J. Am. Soc. Nephrol., July 1, 2005; 16(7): 1883 - 1885. [Full Text] [PDF]
|
|
|
|
|
|
K. P. Klausen, H. Scharling, G. Jensen, and J. S. Jensen New Definition of Microalbuminuria in Hypertensive Subjects: Association With Incident Coronary Heart Disease and Death Hypertension, July 1, 2005; 46(1): 33 - 37. [Abstract] [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]
|
|
|
|
|
|
A. H. Brantsma, D. de Zeeuw, H. L. Hillege, K. Klausen, K. Borch-Johnsen, B. Feldt-Rasmussen, G. Jensen, P. Clausen, H. Scharling, M. Appleyard, et al. Letter Regarding Article by Klausen et al, "Very Low Levels of Microalbuminuria Are Associated With Increased Risk of Coronary Heart Disease and Death Independently of Renal Function, Hypertension, and Diabetes" * Response Circulation, March 1, 2005; 111(8): e110 - e111. [Full Text] [PDF]
|
|
|
|
|
|
American Diabetes Association Standards of Medical Care in Diabetes Diabetes Care, January 1, 2005; 28(suppl_1): S4 - S36. [Full Text] [PDF]
|
|