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Does Albuminuria Predict Cardiovascular Outcomes on Treatment With Losartan Versus Atenolol in Patients With Diabetes, Hypertension, and Left Ventricular Hypertrophy?

The LIFE study

¹ Department of Medicine, Glostrup University Hospital, Glostrup, Denmark
² Steno Diabetes Centre, Gentofte, Denmark
³ Department of Preventive Medicine, Umeå University Hospital, Umeå, Sweden
⁴ Department of Medicine M, Århus University Hospital, Århus, Denmark
⁵ Department of Medicine, Sahlgrenska University Hospital/Östra, Göteborg, Sweden
⁶ Merck Research Laboratories, West Point, Pennsylvania

Address correspondencereprint requests to Hans Ibsen, Chief Physician, Medical Department M, Glostrup Hospital, DK-2600 Glostrup, Denmark. E-mail: haib{at}glostruphosp.kbhamt.dk

OBJECTIVE—Our current aims were to investigate whether 1) baseline urinary albumin-to-creatinine ratio (UACR) predicted cardiovascular outcomes, 2) changes in UACR differed between treatments, 3) benefits of losartan were related to its influence on UACR, and 4) reduction in albuminuria reduced cardiovascular events.

RESEARCH DESIGN AND METHODS—In 1,063 patients with diabetes, hypertension, and left ventricular hypertrophy, UACR was measured for a mean of 4.7 years. The primary composite end point included cardiovascular death, myocardial infarction, and stroke. Cox models were run including and excluding baseline and time-varying UACR.

RESULTS—Increasing baseline albuminuria related to increased risk for cardiovascular events. Reductions in UACR at years 1 and 2 were 33% for losartan vs. 15% for atenolol (P < 0.001). Benefits of losartan seem to be most prominent in patients with the highest level of baseline UACR, although treatment by albuminuria interaction was only significant for total mortality. Approximately one-fifth of the superiority of losartan was explained by the greater reduction of albuminuria. Risk of the primary end point was related to the in-treatment UACR.

CONCLUSIONS—Lowering of albuminuria in patients with hypertension and diabetes appears to be beneficial and should be the subject of additional study in future clinical trials.

Abbreviations: ECG, electrocardiogram • LIFE, Losartan Intervention For Endpoint reduction in hypertension • UACR, urinary albumin-to-creatinine ratio

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