Using data collected in a well-known, long-term heart study here, Spokane researchers have discovered what they believe is a link between elevated levels of phosphorus in the bloodstream and a deadly form of heart disease.

The researchers also found that reduced kidney function in a patient can predict development of that type of heart disease, which is marked by coronary-artery calcification and is difficult to treat, says Dr. Katherine Tuttle. Tuttle, the medical and scientific director at Providence Medical Research Center here, conducted the research along with Ph. D. biostatistician Robert Short, who works both at Providence and as assistant director of the Washington Institute for Mental Illness: Research and Training at Washington State University here.

Their findings could lead to a treatment for people with reduced kidney function to treat coronary-artery calcification, Tuttle says. Elevated levels of phosphorus in the bloodstream, which enter the body mostly from the food we eat and are absorbed through the small intestine, are associated with reduced kidney function, as normally functioning kidneys remove excess phosphorus.

"We were able to use statistical modeling to look at what happened to levels of kidney function and blood phosphorus over time and ask, did they predict who would develop coronary-artery calcification and who would not, and it did," she says.

The data for the study were drawn from the Spokane Heart Study, which was launched by Washington State University here in 1994 and has tracked the health of 883 participants over 15 years.

Coronary-artery calcification is an early sign of what's called atherosclerosis, or hardening of the arteries, which leads to heart attacks. Atherosclerosis involving coronary-artery calcification is especially dangerous because it doesn't respond well to conventional treatments for heart disease that focus on reducing cholesterol levels, Tuttle says.

She says that armed with the correlation between increased levels of phosphorus and coronary-artery calcification, a useful treatment for that condition could be determined soon in the form of a common drug, niacin, that's been on the market for many years.

Tuttle says being able to analyze long-term data makes the results very valuable.

"This is novel and original work. This was a very, very big deal on a national level and among our professional societies," Tuttle says.

The results of the recent research have been recognized as significant by the American Society of Nephrology, and are published in its current Clinical Journal of the American Society of Nephrology.

In the Spokane Heart Study, participants came into the laboratory every two years, filled in questionnaires on their health and emotional state, and had blood work, urine testing, and coronary calcium scanning done.

Tuttle and Short discovered the correlation between phosphorus and coronary-artery calcification in patients who were healthy when they entered the heart study and hadn't been diagnosed with diabetes or early-stage kidney disease, even after adjusting for other factors and examining the data in different ways.

"There are different ways to do statistical models. We did multiple different types of statistical models, and each one came to the same conclusion," Tuttle says.

She says it's what happens next that could make a difference for patients.

"We're glad we made the observation, but what matters on the other side is we might have learned something that will help people," Tuttle says.

Tuttle has applied for a National Institutes of Health grant to conduct a pilot study using niacin to reduce phosphorus in the body to see if it has a positive effect on coronary-artery calcification.

In the proposed study, about 80 patients at each of two test sites—Providence Sacred Heart Research Center here and Brown University Medical School, in Providence, R.I.—would receive one of two types of niacin or be in a control group that would receive a placebo. One formulation of the drug reduces the amount of phosphorus in the body and the amount of lipids, which can be a factor in coronary-artery disease. The other formulation of niacin that would be tested only reduces the amount of phosphorus.

The pilot study would last only 12 weeks, just long enough to see if it would change the blood chemistry in the way that the researchers predict, then they would seek to conduct a larger study.

"It doesn't take long to change blood chemistry. We want to generate data quickly, so we could move forward to a larger study if it's warranted," Tuttle says.

Tuttle says it will be early spring before Providence finds out if it will receive the grant.

The current and planned research is important in its own right, Tuttle says, but it's also a step toward reinvigorating the Spokane Heart Study. That study had fallen by the wayside for a couple of years after being plagued by funding issues that resulted in an internal review at WSU, she says. Now, WSU is injecting pilot money to keep the heart study going until additional grants kick in to help cover it, Tuttle says.

A group of researchers and doctors here, including Tuttle, Short, Pullman-based WSU psychiatrist Bruce Wright, Spokane cardiologists Pierre Leimgruber and Brian Fus, and Dennis Dyck, WSU's vice chancellor for research, are determined to reinvigorate the heart study, Tuttle says.

"I got involved because I thought it was a community resource, and (it's exciting) to see how quickly it could actually move to the clinical domain where we could possibly treat people," Tuttle says.

The significance of the Spokane Heart Study is that conclusions can be drawn by documenting the changes in people's health over time, she says.

"If you follow people who enter a study as healthy individuals and follow them over time, you get a photo album over time, rather than a snapshot," she says. The study originally was envisioned as a several-decade study, but the group now would like to increase its span, like a similar study that began in 1948 in Framingham, Mass., which now is studying subsequent generations of the participants' adult children and grandchildren.

"We'd like to carry it on indefinitely," Tuttle says. "We view it as our community's version of the Framingham Heart Study."