The debate over the role of uric acid in heart disease has been going on for more than 50 years, starting with a paper published in 1951 which found higher serum uric acid concentrations in patients with coronary heart disease (CHD) compared with controls. Since then, measurement of serum uric acid has been suggested as a predictor of CHD. But many of the studies on serum uric acid are epidemiologic studies and have come to different conclusions about how useful measurement of uric acid is.
This study, along with a systematic review which combines their findings with those of 15 previously published prospective studies of serum uric acid - 9,458 cases of CHD and 155,084 controls in all - answers the question of the role of uric acid in prediction of CHD. Using all studies, they show that there is a very small role for uric acid in the prediction of disease but in the eight studies where all possible confounders had been removed this predictive role was lost.
What this paper does not do is directly address the question of whether or not serum uric acid is involved in causing CHD although it does suggest that serum uric acid levels are unlikely to be a major determinant of CHD. So although improving diet, losing weight, and controlling blood pressure may all contribute to reducing both one's risk of CHD and one's serum levels of uric acid, uric acid levels do not help to usefully predict the risk of CHD.
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The body normally takes minerals like calcium and phosphorous circulating in the bloodstream and deposits them in the bones during bone reconstruction. With those processes shut down, scientists theorized, the bloodstream levels of minerals increase, raising pressure to deposit them elsewhere.
Hruska and his colleagues first showed that injection of BMP-7, previously shown to stop the bone disorder, also stopped vascular calcification. In another group of experimental mice, injections of a substance that binds to compounds with phosphorous but has no effect on the skeleton also stopped vascular calcification, proving that phosphorous was the key link.
"Serum phosphorous is a direct stimulus to the smooth muscle cells that line blood vessels, causing them to take on characteristics very similar to osteoblasts, the cells that form bone," Hruska explains.
The changed smooth muscle cells can deposit minerals outside their membranes, dramatically decreasing the flexibility of blood vessels and increasing the work the heart has to do to create a pulse.
"Vascular stiffness happens to patients with end-stage kidney failure when they go on dialysis, and it leads to many dangerous cardiovascular complications," Hruska says. "This study shows us that by treating the skeleton or otherwise decreasing phosphorous levels, we have the potential to produce a decrease in vascular calcification and marked improvements in cardiovascular outcome."
To follow up, Hruska plans a more direct study of the effects of BMP-7 on vascular calcification and further investigation of the skeleton-kidney links that lead to bone weakening in patients with kidney damage.
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