Even very low levels of microalbuminuria raise risk of cardiovascular events

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Last Updated: 2001-07-24 16:00:40 EDT (Reuters Health)

By Karla Gale

WESTPORT, CT (Reuters Health) – Any degree of albuminuria is a risk factor for cardiovascular (CV) events in middle-age individuals, according to analysis of data from the Heart Outcomes Prevention Evaluation (HOPE) Study.

Dr. Hertzel C. Gerstein, of McMaster University in Hamilton, Ontario, and associates in North and South America and Europe evaluated outcomes among 3498 individuals with diabetes mellitus and 5545 nondiabetic subjects. The findings appear in the July 25th issue of The Journal of the American Medical Association.

Subjects were at least 55 years old and had a history of previous CV disease or a history of diabetes plus at least one other CV risk factor. Those with dipstick-positive proteinuria were excluded from the study.

"The average risk of a cardiovascular event was about 4% to 5% per year," Dr. Gerstein noted in an interview with Reuters Health.

Microalbuminuria was detected in 32.6% of those with diabetes and 14.8% of those without, where microalbuminuria was defined as an albumin-to-creatinine ratio (ACR) of 2 mg/mmol or more.

During a median follow-up of 4.5 years, baseline microalbuminuria increased the adjusted relative risk for major CV events by 1.83-fold, for all-cause mortality by 2.09-fold, and for hospitalization for heart failure by 3.23-fold.

The continuous, graded relationship between baseline ACR and the risk of CV outcomes and mortality extended as low as 0.22 mg/mmol. For every 0.4-mg/mmol increase in ACR, the risk of CV event increased by 5.9% and for all-cause death by 6.8%.

"One potential argument is that those with the highest levels of microalbuminuria dragged the statistical significance into the positive range," Dr. Gerstein told Reuters Health. "To explore how robust that relationship is, we analyzed the data after removing those with microalbuminuria of over 2 mg/mmol. Even then, the association with risk was statistically significant."

"Thus, an ACR of 2.0 mg/mmol–a threshold used to screen for microalbuminuria and risk for diabetic nephropathy–may not be relevant when considering the risk for CV outcomes," the investigators write. They suggest that albuminuria is a marker of diffuse endothelial dysfunction that reflects underlying macrovascular and microvascular disease.

"Another key finding…is that in people with diabetes and those without diabetes, the presence of microalbuminuria is a risk factor, not just for a CV event, but for death and new-onset heart failure," Dr. Gerstein emphasized.

"The next step is to ask, how do we incorporate these findings into our clinical examination practices," he said. "That will require a whole different kind of research."

JAMA 2001;286:421-426.

-Westport Newsroom 203 319 2700

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