 |
 |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
2 December 2003 | Volume 139 Issue 11 | Pages 901-906
Background: Several studies have shown that albuminuria is associated with increased risk for fatal and nonfatal cardiovascular events, independent of conventional risk factors. The partition values for urine albumin–creatinine ratio (UACR) used to identify microalbuminuria have been based on studies that predicted risk in diabetic patients.
Objective: To determine whether the relation between albuminuria and cardiovascular risk can be used to predict cardiovascular morbidity and mortality in hypertensive patients.
Design: Multicenter cohort study derived from a randomized, controlled trial.
Patients: 8206 patients with stage II or III hypertension randomly assigned to double-blind therapy with losartan or atenolol. Follow-up was 39 122 patient-years.
Measurements: Renal glomerular permeability evaluated by UACR.
Results: In nondiabetic hypertensive patients with left ventricular hypertrophy, the risk for the composite cardiovascular end point increased continuously as albuminuria increased (P < 0.001 for trend). There was no specific threshold for increased risk. For every 10-fold increase in UACR, hazard ratios in nondiabetic patients increased as follows: composite end point, by 57% (95% CI, 40.6% to 75.0%); cardiovascular mortality, by 97.7% (CI, 66.5% to 235%); all-cause mortality, by 75.2% (CI, 54.0% to 99.4%); stroke, by 51.0% (CI, 28.8% to 76.9%); and myocardial infarction, by 45% (CI, 19.9% to 75.4%) (P < 0.001 for all comparisons). Values were similar in diabetic patients, although for myocardial infarction the trend was weaker and not significant.
Conclusion: Increased UACR resulted in increasing risk for cardiovascular morbidity and mortality among hypertensive patients with left ventricular hypertrophy. We found no thresholds or plateaus. Risk increases at much lower UACR values than has been reported among diabetic patients.
Editors' Notes
Context
Contribution
Implications
Cautions
–The Editors
Author and Article Information
From Glostrup University Hospital, Glostrup, Denmark; Steno Diabetes Centre, Gentofte, Denmark; Norrland University Hospital, Umeå, Sweden; Århus University Hospital, Århus, Denmark; Sahlgrenska University Hospital-Östra and The Nordic School of Public Health, Göteborg, Sweden; The Weill Medical College of Cornell University, New York, New York; Dudley Road Hospital, Birmingham, United Kingdom; Institute of Environmental Medicine, Stockholm, Sweden, Helsinki University Hospital, Helsinki, Finland; University of Michigan Medical Center, Ann Arbor, Michigan; Ullevål Sykehus, Oslo, Norway; Merck Research Laboratories, Sollentuna, Sweden; Viborg University Hospital, Viborg, Denmark; Haukeland University Hospital, Bergen, Norway; University of Alabama, Birmingham, Alabama; and Merck & Co., Inc., Whitehouse Station, New Jersey.
Acknowledgments: The authors thank Sigrid Helle Berg for her extensive work on the LIFE study.
Grant Support: By unrestricted grants from Merck & Co., Inc.
Potential Financial Conflicts of Interest:Employment: K. Kristianson, S.M. Snapinn, P. Aurup (Merck & Co., Inc.); Consultancies: K. Wachtell, H. Ibsen, M.H. Olsen, L.H. Lindholm, B. Dahlöf, R.B. Devereux, G. Beevers, U. de Faire, F. Fyhrquist, S. Julius, S.E. Kjeldsen, O. Lederballe-Pedersen, M.S. Nieminen, P.M. Okin, P. Omvik, S. Oparil (Merck & Co., Inc.); Stock ownership: K. Kristianson, S.M. Snapinn, P. Aurup (Merck & Co., Inc.); Grants received: K. Wachtell, H. Ibsen, M.H. Olsen, B. Dahlöf, R.B. Devereux, G. Beevers, U. de Faire, F. Fyhrquist, S. Julius, S.E. Kjeldsen, M.S. Nieminen, P.M. Okin, P. Omvik, S. Oparil (Merck & Co., Inc.).
Requests for Single Reprints: Kristian Wachtell, MD, PhD, Department of Medicine (M41), Glostrup University Hospital, Glostrup, DK-2600 Glostrup, Denmark; e-mail, kristian{at}wachtell.net.
Current Author Addresses: Drs. Wachtell, Ibsen, and Olsen: Department of Medicine (M41), Glostrup University Hospital, DK-2600 Glostrup, Denmark.
Dr. Borch-Johnsen: Steno Diabetes Centre, Niels Steensens Vej 2, DK-2820 Gentofte, Denmark.
Dr. Lindholm: Department of Preventive Medicine, Norrland University Hospital, S-901 85 Umeå, Sweden.
Dr. Mogensen: Å rhus University Hospital, Nørrebrogade 44, DK-8000 Århus, Denmark.
Dr. Dahlöf: Department of Medicine, Sahlgrenska University Hospital-Östra, S-416 85 Göteborg, Sweden.
Drs. Wachtell, Devereux, and Okin: Department of Cardiology, The Weill Medical College of Cornell University, 525 East 68th Street, New York, NY 10021.
Dr. Beevers: Dudley Road Hospital, Dudley Road, Birmingham B18 7QH, United Kingdom.
Dr. de Faire: Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institute, PO Box 210, S-171 77 Stockholm, Sweden.
Dr. Fyhrquist: Department of Cardiology, Helsinki University Hospital, Haartmaninkatu 4, SF-00290 Helsinki, Finland.
Dr. Julius: University of Michigan Medical Center, 3918 Taubman Center, Ann Arbor, MI 48109-0356.
Dr. Kjeldsen: Department of Cardiology, Ullevål Sykehus, N-0407 Oslo, Norway.
Dr. Kristianson: Merck Research Laboratories, Box 7125, S-192 07, Sollentuna, Sweden.
Dr. Lederballe-Pedersen: Department of Medicine, Viborg University Hospital, DK-8800 Viborg, Denmark.
Dr. Nieminen: Department of Cardiology, Helsinki University Hospital, Haartmaninkatu 4, SF-00290 Helsinki, Finland.
Dr. Omvik: Department of Cardiology, Haukeland University Hospital, N-5021 Bergen, Norway.
Dr. Oparil: Department of Physiology and Biophysics, University of Alabama, MCLM 704, 1918 University Boulevard, Birmingham, AL 35294-0005.
Dr. Wedel: The Nordic School of Public Health, Box 12133, S-402 42 Göteborg, Sweden.
Drs. Snapinn and Aurup: Merck & Co., Inc., 1 Merck Drive, Whitehouse Station, NJ 08889-0100.
Author Contributions: Conception and design: K. Wachtell, H. Ibsen, M.H. Olsen, K. Borch-Johnsen, L.H. Lindholm.
Analysis and interpretation of the data: K. Wachtell, H. Ibsen, M.H. Olsen, K. Borch-Johnsen, L.H. Lindholm, S.M. Snapinn.
Drafting of the article: K. Wachtell, H. Ibsen, M.H. Olsen, K. Borch-Johnsen, L.H. Lindholm.
Critical revision of the article for important intellectual content: K. Wachtell, H. Ibsen, M.H. Olsen, K. Borch-Johnsen, L.H. Lindholm, B. Dahlöf, R.B. Devereux, S.M. Snapinn.
Final approval of the article: K. Wachtell, H. Ibsen, M.H. Olsen, K. Borch-Johnsen, L.H. Lindholm, B. Dahlöf, R.B. Devereux, G. Beevers, U. de Faire, F. Fyhrquist, S. Julius, S.E. Kjeldsen, K. Kristianson, O. Lederballe-Pedersen, M.S. Nieminen, P.M. Okin, P. Omvik, S. Oparil, H. Wedel, S.M. Snapinn, P. Aurup.
Provision of study materials or patients: K. Wachtell, H. Ibsen, M.H. Olsen, K. Borch-Johnsen, L.H. Lindholm, B. Dahlöf, R.B. Devereux, G. Beevers, U. de Faire, F. Fyhrquist, S. Julius, S.E. Kjeldsen, K. Kristianson, O. Lederballe-Pedersen, M.S. Nieminen, P.M. Okin, P. Omvik, S. Oparil, H. Wedel, S.M. Snapinn, P. Aurup.
Statistical expertise: K. Wachtell, S.M. Snapinn.
Obtaining of funding: K. Kristianson, P. Aurup.
Administrative, technical, or logistic support: K. Wachtell, B. Dahlöf, K. Kristianson, P. Aurup.
Collection and assembly of data: K. Wachtell, K. Kristianson, S.M. Snapinn, P. Aurup. ARTICLE
Albuminuria and Cardiovascular Risk in Hypertensive Patients with Left Ventricular Hypertrophy: The LIFE Study
Related articles in Annals:
This article has been cited by other articles:
|
|
 |
|
  R. T. Gansevoort and E. Ritz Hermann Senator and albuminuria--forgotten pioneering work in the 19th century Nephrol. Dial. Transplant., December 10, 2008; (2008) gfn741v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. S. A. Naderi and R. F. Reilly Primary Care Approach to Proteinuria J Am Board Fam Med, November 1, 2008; 21(6): 569 - 574. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Forman, N. D.L. Fisher, E. L. Schopick, and G. C. Curhan Higher Levels of Albuminuria within the Normal Range Predict Incident Hypertension J. Am. Soc. Nephrol., October 1, 2008; 19(10): 1983 - 1988. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Farbom, B. Wahlstrand, P. Almgren, S. Skrtic, J. Lanke, L. Weiss, S. Kjeldsen, T. Hedner, and O. Melander Interaction Between Renal Function and Microalbuminuria for Cardiovascular Risk in Hypertension: The Nordic Diltiazem Study Hypertension, July 1, 2008; 52(1): 115 - 122. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Palmas, T. G. Pickering, J. Teresi, J. E. Schwartz, L. Field, R. S. Weinstock, and S. Shea Telemedicine Home Blood Pressure Measurements and Progression of Albuminuria in Elderly People With Diabetes Hypertension, May 1, 2008; 51(5): 1282 - 1288. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Gill Cardiovascular Disease in Transplant Recipients: Current and Future Treatment Strategies Clin. J. Am. Soc. Nephrol., March 1, 2008; 3(Supplement_2): S29 - S37. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Oliveira, G. B. Silva Jr, C. J. Souza, E. F. Vieira, R. M. S. Mota, A. M. C. Martins, A. B. Liborio, and E. F. Daher Evaluation of renal function in leprosy: a study of 59 consecutive patients Nephrol. Dial. Transplant., January 1, 2008; 23(1): 256 - 262. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. D. Solomon, J. Lin, C. G. Solomon, K. A. Jablonski, M. M. Rice, M. Steffes, M. Domanski, J. Hsia, B. J. Gersh, J. M. O. Arnold, et al. Influence of Albuminuria on Cardiovascular Risk in Patients With Stable Coronary Artery Disease Circulation, December 4, 2007; 116(23): 2687 - 2693. [Abstract] [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]
|
|
|
|
|
|
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. C. Foster, S.-J. Hwang, M. G. Larson, N. I. Parikh, J. B. Meigs, R. S. Vasan, T. J. Wang, D. Levy, and C. S. Fox Cross-Classification of Microalbuminuria and Reduced Glomerular Filtration Rate: Associations Between Cardiovascular Disease Risk Factors and Clinical Outcomes Arch Intern Med, July 9, 2007; 167(13): 1386 - 1392. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. K. Chandie Shaw, S. P. Berger, M. Mallat, M. Frolich, F. W. Dekker, and T. J. Rabelink Central Obesity Is an Independent Risk Factor for Albuminuria in Nondiabetic South Asian Subjects Diabetes Care, July 1, 2007; 30(7): 1840 - 1844. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Authors/Task Force Members:, G. Mancia, G. De Backer, A. Dominiczak, R. Cifkova, R. Fagard, G. Germano, G. Grassi, A. M. Heagerty, S. E. Kjeldsen, et al. 2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) Eur. Heart J., June 11, 2007; (2007) ehm236v1. [Full Text] [PDF]
|
|
|
|
|
|
R. Marin, P. Rodriguez, S. Tranche, J. Redon, F. Morales-Olivas, A. Galgo, M. A. Brito, J. Mediavilla, J. V. Lozano, C. Filozof, et al. Prevalence of Abnormal Urinary Albumin Excretion Rate in Hypertensive Patients with Impaired Fasting Glucose and Its Association with Cardiovascular Disease J. Am. Soc. Nephrol., December 1, 2006; 17(12_suppl_3): S178 - S188. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Redon, F. Morales-Olivas, A. Galgo, M. A. Brito, J. Mediavilla, R. Marin, P. Rodriguez, S. Tranche, J. V. Lozano, C. Filozof, et al. Urinary Albumin Excretion and Glomerular Filtration Rate across the Spectrum of Glucose Abnormalities in Essential Hypertension J. Am. Soc. Nephrol., December 1, 2006; 17(12_suppl_3): S236 - S245. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Nobakhthaghighi, M. Kamgar, M. R. Bekheirnia, K. McFann, R. Estacio, and R. W. Schrier Relationship between Urinary Albumin Excretion and Left Ventricular Mass with Mortality in Patients with Type 2 Diabetes Clin. J. Am. Soc. Nephrol., November 1, 2006; 1(6): 1187 - 1190. [Abstract] [Full Text] [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]
|
|
|
|
|
|
P. A. Sarafidis and G. L. Bakris Microalbuminuria and chronic kidney disease as risk factors for cardiovascular disease Nephrol. Dial. Transplant., September 1, 2006; 21(9): 2366 - 2374. [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]
|
|
|
|
|
|
W. Palmas, A. Moran, T. Pickering, J. P. Eimicke, J. Teresi, J. E. Schwartz, L. Field, R. S. Weinstock, and S. Shea Ambulatory Pulse Pressure and Progression of Urinary Albumin Excretion in Older Patients With Type 2 Diabetes Mellitus Hypertension, August 1, 2006; 48(2): 301 - 308. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Douglas, P. G. O'Malley, and J. L. Jackson Meta-Analysis: The Effect of Statins on Albuminuria Ann Intern Med, July 18, 2006; 145(2): 117 - 124. [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]
|
|
|
|
|
|
R. Pontremoli, G. Leoncini, F. Viazzi, E. Ratto, V. Vaccaro, V. Falqui, A. Parodi, N. Conti, C. Tomolillo, and G. Deferrari Evaluation of Subclinical Organ Damage for Risk Assessment and Treatment in the Hypertensive Patient: Role of Microalbuminuria. J. Am. Soc. Nephrol., April 1, 2006; 17(4_suppl_2): S112 - S114. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Ibsen, M. H. Olsen, K. Wachtell, K. Borch-Johnsen, L. H. Lindholm, C. E. Mogensen, B. Dahlof, S. M. Snapinn, Y. Wan, and P. A. Lyle Does Albuminuria Predict Cardiovascular Outcomes on Treatment With Losartan Versus Atenolol in Patients With Diabetes, Hypertension, and Left Ventricular Hypertrophy?: The LIFE study. Diabetes Care, March 1, 2006; 29(3): 595 - 600. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Berl and W. Henrich Kidney-Heart Interactions: Epidemiology, Pathogenesis, and Treatment Clin. J. Am. Soc. Nephrol., January 1, 2006; 1(1): 8 - 18. [Full Text] [PDF]
|
|
|
|
 |
|
 A. Sato, L. Tarnow, F.S. Nielsen, E. Knudsen, and H.-H. Parving Left ventricular hypertrophy in normoalbuminuric type 2 diabetic patients not taking antihypertensive treatment QJM, December 1, 2005; 98(12): 879 - 884. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Afzali and J. E Marsh Commentary: Microalbuminuria -- the next target for vascular disease prevention? The British Journal of Diabetes & Vascular Disease, November 1, 2005; 5(6): 342 - 343. [PDF]
|
|
|
|
|
|
R. E. Schmieder, A. U. Klingbeil, E. H. Fleischmann, R. Veelken, and C. Delles Additional Antiproteinuric Effect of Ultrahigh Dose Candesartan: A Double-Blind, Randomized, Prospective Study J. Am. Soc. Nephrol., October 1, 2005; 16(10): 3038 - 3045. [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]
|
|
|
|
|
|
B. I. Freedman, C. D. Langefeld, K. K. Lohman, D. W. Bowden, J. J. Carr, S. S. Rich, and L. E. Wagenknecht Relationship between Albuminuria and Cardiovascular Disease in Type 2 Diabetes J. Am. Soc. Nephrol., July 1, 2005; 16(7): 2156 - 2161. [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]
|
|
|
|
|
|
R. Pontremoli, G. Leoncini, F. Viazzi, D. Parodi, V. Vaccaro, V. Falqui, A. Parodi, S. Vettoretti, E. Ratto, and G. Deferrari Role of Microalbuminuria in the Assessment of Cardiovascular Risk in Essential Hypertension J. Am. Soc. Nephrol., March 1, 2005; 16(3_suppl_1): S39 - S41. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Weir Reduction in Microalbuminuria: A Biomeasure of Therapeutic Success? Hypertension, February 1, 2005; 45(2): 181 - 182. [Full Text] [PDF]
|
|
|
|
|
|
H. Ibsen, M. H. Olsen, K. Wachtell, K. Borch-Johnsen, L. H. Lindholm, C. E. Mogensen, B. Dahlof, R. B. Devereux, U. de Faire, F. Fyhrquist, et al. Reduction in Albuminuria Translates to Reduction in Cardiovascular Events in Hypertensive Patients: Losartan Intervention for Endpoint Reduction in Hypertension Study Hypertension, February 1, 2005; 45(2): 198 - 202. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. F M Strippoli, M. Craig, J. J Deeks, F. P. Schena, and J. C Craig Effects of angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists on mortality and renal outcomes in diabetic nephropathy: systematic review BMJ, October 9, 2004; 329(7470): 828. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. G. Coca and G. K. Buller Albuminuria and Mortality in Hypertension Ann Intern Med, August 3, 2004; 141(3): 244 - 245. [Full Text] [PDF]
|
|
Article
