High-Normal Albumin Excretion Predicts Hypertension Risk

By Charles Bankhead
BOSTON, 27 JUNE 2008 -- Albumin excretion at the upper end of the normal range significantly increases the risk of hypertension in otherwise low-risk women, according to new analyses of the Nurses' Health Study.
A high-normal albumin/creatinine ratio increased the risk of hypertension by 75% in older women and by 35% in younger women, compared with those who had ratios at the lower end of the normal range, John P. Forman, M.D., of Harvard, and colleagues reported online in the Journal of the American Society of Nephrology.
"The findings of this study, in conjunction with the findings of numerous others . . . suggest that it may be time to reevaluate our current concept of 'normal' albumin excretion," the authors concluded.
Microalbuminuria has long been recognized as a risk factor for progressive kidney disease, diabetic complications, and adverse cardiovascular outcomes. The association with pathology has led to speculation that microalbuminuria is a generalized marker of vascular damage and a reflection of endothelial dysfunction and abnormal vascular permeability, the authors said.
More recently, data from the Framingham Heart Study and other investigations have suggested that higher albumin-creatinine ratios, even within the normal range, increase the risk of hypertension, the researchers continued. In many instances, however, the higher ratios have been accompanied by microalbuminuria.
In attempt to clarify the risk imparted by high-normal albumin excretion, Dr. Forman and colleagues analyzed data from the first and second Nurses' Health Study. The analysis included 1,065 postmenopausal women (median age 65) from NHS I and 1,114 younger women (median age 44) from NHS II. All women were normotensive, nondiabetic, and had normal albumin excretion rates.
Participants from NHS I had a median albumin-creatinine ratio of 2.7 mg/g, and the NHS II cohort had a median ratio of 2.4 mg/g.
During follow-up, 271 NHS I participants developed hypertension over four years, as did 296 participants from NHS II over eight years. In multivariate analysis, comparison of the highest and lowest quartiles of albumin excretion revealed a hypertension hazard ratio of 1.76 (P=0.004 for the trend) among women in NHS I and 1.35 (P=0.06 for the trend) among NHS II participants.
The results remained unchanged in further analyses that adjusted for alcohol and sodium intake, for use of aspirin, acetaminophen, and nonsteroidal anti-inflammatory drugs, and for exclusion of women with undiagnosed diabetes at baseline or who developed diabetes during follow-up.
The authors suggested several potential mechanistic explanations for the findings, all involving glomerular endothelial cell dysfunction or abnormalities leading to increased filtration of albumin.
"What seems to be clear is that the glomerular endothelial cell does play some role, however large, in the filtration barrier, and dysfunction of these endothelial cells may therefore lead to increased albumin excretion," they said.
The findings mesh with those from other laboratory and clinical studies and suggest that "higher levels of urine albumin excretion may reflect systemic endothelial dysfunction, which in turn may be a precursor to hypertension."
The authors noted several limitations to the study. Each participant submitted only a single morning specimen, BP measurements were reported and not directly measnured. The cohorts studied were predominantly white and entirely female so the results may not be generalizable.
The authors reported no disclosures.
Primary source: Journal of the American Society of NephrologySource reference:Forman JP, et al "Higher levels of albuminuria within the normal range predict incident hypertension" J Am Soc Nephrol 2008; DOI: 10.1681/ASN.2008010038.