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(Circulation. 2005;111:1370-1376.)
© 2005 American Heart Association, Inc.

Hypertension

Low-Grade Albuminuria and the Risks of Hypertension and Blood Pressure Progression

Thomas J. Wang, MD; Jane C. Evans, DSc; James B. Meigs, MD, MPH; Nader Rifai, PhD; Caroline S. Fox, MD, MPH; Ralph B. D’Agostino, PhD; Daniel Levy, MD; Ramachandran S. Vasan, MD

From the Framingham Heart Study, Framingham, Mass (T.J.W., J.C.E., C.S.F., R.B.D., D.L., R.S.V.); Cardiology Division (T.J.W.), General Medicine Division (J.B.M.), Massachusetts General Hospital, Harvard Medical School, Boston, Mass; Center for Cardiovascular Disease Prevention (N.R.), Department of Endocrinology, Hypertension, and Diabetes (C.S.F.), Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass; Department of Mathematics (R.B.D.), Statistics and Consulting Unit, Boston University, Boston, Mass; the National Heart, Lung, & Blood Institute (C.S.F., D.L.), Bethesda, Md; and Preventive Medicine and Cardiology Sections (R.S.V.), Boston Medical Center, Boston University School of Medicine, Boston, Mass.

Correspondence to Ramachandran S. Vasan, MD, Framingham Heart Study, 73 Mt. Wayte Ave, #2, Framingham, MA 01702-5827. E-mail vasan{at}bu.edu

Received August 14, 2004; revision received November 25, 2004; accepted December 20, 2004.

Background— It has been postulated that glomerular hyperfiltration and endothelial dysfunction are early features of essential hypertension that may antedate blood pressure elevation. Microalbuminuria, a marker of glomerular hyperfiltration and endothelial dysfunction, has been described in individuals with established hypertension, but its role as a biomarker of preclinical stages of this disease has not been investigated prospectively.

Methods and Results— We examined the association between urinary albumin excretion and the risks of hypertension and blood pressure progression in 1499 nonhypertensive individuals (58% women) without diabetes. During a mean follow-up of 2.9 years, 230 participants (15%) developed hypertension and 499 (33%) progressed to a higher blood pressure category (defined by the sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure). In multivariable logistic regressions that adjusted for known risk factors, the urine albumin-creatinine ratio (UACR) was a significant predictor of incident hypertension (adjusted OR 1.20, 95% CI 1.01 to 1.44, per 1-SD increment in log UACR). Compared with those in the lowest UACR quartile, participants in the highest quartile (men: >6.66 mg/g; women: >15.24 mg/g) had an 2-fold risk of developing hypertension (adjusted OR 1.93, P=0.006) and 1.5-fold risk of blood pressure progression (adjusted OR 1.45, P=0.03).

Conclusions— Urinary albumin excretion predicts blood pressure progression in nondiabetic, nonhypertensive individuals incrementally over established risk factors and at levels well below the conventional threshold for microalbuminuria. UACR may be a useful biomarker for identifying individuals most likely to develop hypertension.

Key Words: blood pressure • risk factors • hypertension • epidemiology

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