Albuminuria and Cardiovascular Risk in Hypertensive Patients with Left Ventricular Hypertrophy: The LIFE Study

  1. Kristian Wachtell, MD, PhD;
  2. Hans Ibsen, MD;
  3. Michael H. Olsen, MD, PhD;
  4. Knut Borch-Johnsen, MD;
  5. Lars H. Lindholm, MD;
  6. Carl Erik Mogensen, MD;
  7. Björn Dahlöf, MD, PhD;
  8. Richard B. Devereux, MD;
  9. Gareth Beevers, MD;
  10. Ulf de Faire, MD;
  11. Frej Fyhrquist, MD;
  12. Stevo Julius, MD;
  13. Sverre E. Kjeldsen, MD;
  14. Krister Kristianson, PhD;
  15. Ole Lederballe-Pedersen, MD;
  16. Markku S. Nieminen, MD;
  17. Peter M. Okin, MD;
  18. Per Omvik, MD;
  19. Suzanne Oparil, MD;
  20. Hans Wedel, PhD;
  21. Steven M. Snapinn, PhD; and
  22. Peter Aurup, MD
  1. 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.

    Abstract

    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.

    Article and Author Information

    • 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.

    Summary for Patients

    • Summaries for Patients:Microalbuminuria Increases Risk for Heart Attacks and Strokes in Hypertensive Patients Ann Intern Med December 2, 2003 139:I-26
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    1. Ann Intern Med December 2, 2003 vol. 139 no. 11 901-906
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