Serum Phosphorus Tagged as Cardiovascular Risk Factor

FRAMINGHAM, Mass. May 18 -- As serum phosphorus levels increase, so does the risk of cardiovascular disease, even among those with normal kidney function and no evidence of heart troubles, researchers reported here.

Among 3,368 Framingham Offspring study participants followed for more than 16 years, there was a significant dose-dependant relationship between serum phosphorus and cardiovascular outcome, said Ravi Dhingra, M.D., of the National Heart, Lung, and Blood Institute's Framingham Study, and colleagues.

"Values of serum phosphorus higher than 3.5 mg/dL (.382) mmol/L) (defining the lower limit of the highest quartile and well within the reference range) were associated with a 55% increased cardiovascular disease risk," they wrote in the May 14 issue of Archives of Internal Medicine.

Moreover, Dr. Dhingra said the associations remained robust in a subgroup with an estimated glomerular filtration rate greater than 90 mL/min per 1.73 m² and without proteinuria.

According to the authors, the study "is the first to demonstrate a graded independent relation of serum phosphorus levels (within the reference range) to cardiovascular disease risk in a community-based sample of men and women without either chronic kidney disease or cardiovascular disease at baseline."

In an accompanying editorial, Robert N. Foley, M.D., of the U.S. Renal Data System Coordinating Center at the Minneapolis Medical Research Foundation, said that the findings should "excite nephrologists (because it adds a nonnephrological context to a widely held but unproven belief) and to nonnephrologists (because it introduces a new cardiovascular risk factor that may be susceptible to intervention)."

And unlike many cardiovascular risk factors, phosphorus is a risk factor for which "several potential interventions suitable for clinical trials may already exist," Dr. Foley concluded.

Participants, 51% of whom were women, underwent physical examination, anthropometry, and laboratory assessment at four-year intervals. Serum phosphorus and calcium levels were measured using standard colorimetric methods.

There were 524 participants with incident cardiac events during follow-up.

Among the findings:

• In a multivariate analysis serum phosphorus values were positively associated with age, C-reactive protein, estimated glomerular filtration rate, serum albumin level and total/HDL cholesterol ratio, but were inversely related to BMI, systolic blood pressure, and hemoglobin level (P