(American Health Newswire) -- The presence of calcium in coronary arteries is a much better predictor of heart attack and stroke than C-reactive protein among people with normal levels of LDL cholesterol, according to this study.

Results of the study have important implications for deciding whether cholesterol-lowering statin medication should be prescribed for people who have heart disease risk factors but normal levels of LDL, the so-called "bad" cholesterol. An estimated 6 million American adults fall into that gray-zone category.

The goal of the new study, which followed 2,083 people for six years, was to further refine who was at higher risk and, therefore, might benefit from taking statin medications.

"This was a direct comparison to see which patients with a normal LDL level of less than 130 mg/dL would have the greater risk of having a heart attack or stroke-those with evidence of calcium in coronary arteries, as determined on a cardiac CT test, or those with high levels of C-reactive protein, which is measured in blood and is an indicator of inflammation somewhere in the body," Michael J. Blaha, M.D. M.P.H, a cardiology fellow at the Johns Hopkins University School of Medicine and the Johns Hopkins Heart and Vascular Institute, who is the lead author of the study, was quoted as saying.

Blaha and colleagues found that 95 percent of the heart attacks, strokes or heart-related deaths in the study population occurred in people with some measurable calcium in their heart arteries. Meanwhile, 13.4 percent of those with the highest levels of coronary calcium (with scores greater than 100 on a calcium scoring test) had a heart attack or stroke during the study, whereas only 2 percent of those with high C-reactive protein in their blood, but no calcium buildup, had a heart attack or stroke.

In their study, the researchers determined that high levels of C-reactive protein in the blood, a score at or above 2 milligrams per liter, offered little predictive value after accounting for such risk factors as age, gender, ethnicity, hypertension, obesity, diabetes, smoking and a family history of heart disease.  

"A calcium test directly looks for the disease we propose to treat with statins. Without measurable amounts of calcium, which indicates atherosclerosis, you are likely to be at very low risk in the short-term," explained Dr. Blaha.

"While not everyone needs a calcium scoring test," Dr. Blaha said, "we believe looking for calcification in coronary vessels in certain patients makes sense in order to predict who may benefit from statin therapy because the test gets right to the heart of the disease we want to treat."

SOURCE: The Lancet, published online August 23, 2011

(American Health Newswire) - Researchers have discovered a protein (Runx3) that is a potent suppressor of breast cancer growth.

"People suggested that Runx3 might be a tumor suppressor in breast cancer because they found that it is down-regulated in a lot of breast cancer cell lines and breast cancer tissues," University of Illinois medical biochemistry professor Lin-Feng Chen, who led the study, was quoted as saying.

In this study, Chen and his colleagues at Nagasaki University discovered that a significant proportion of mice lacking one of two Runx3 genes spontaneously developed mammary gland tumors at 14 or 15 months of life - an age corresponding to age 40 to 50 in humans.

"We found mammary tumors growing in about 20 percent of the female mice lacking a copy of the Runx3 gene," Chen said. None of the mice with two normal copies of the gene developed tumors.

The researchers also found that estrogen receptor alpha (ER-alpha), a well-known culprit in the development of many breast tumors, was up-regulated in the mouse tumors. ER-alpha is overexpressed in about 75 percent of human cases of breast cancer, and enhanced ER-alpha expression in normal breast tissue is associated with an increased risk of breast cancer, Chen said.

Circulating estrogen binds to ER-alpha and initiates a chain of events that alter gene expression in the targeted cell. This is a normal part of cellular signaling, but in ER-positive breast cancers, the overexpression of ER-alpha leads to enhanced tumor cell survival, growth and proliferation.  

The researchers found that when Runx3 was re-introduced into ER-alpha positive breast cancer cell lines, it suppressed the growth of the cancer cells and inhibited the potential of the cancer cells to form tumors in the mouse. Further experiments revealed that Runx3 actually targeted ER-alpha signaling by inducing the degradation of ER-alpha.

"By regulating the cellular levels of ER-alpha, Runx3 appears to control the cell's response to circulating estrogen, thus playing an important role in the onset of breast cancer," Chen said.

Chen sees three potential benefits that spring from this study. First, the researchers have discovered a mouse model of spontaneously occurring mammary tumors that corresponds to an age of increased risk of breast cancer in humans.

Second, Chen hopes to develop a simple test to measure Runx3 levels in mammary tissue.

"We know from other people's studies that Runx3 is inactivated in the early stages of breast cancer," he said. "So we might be able to use Runx3 as a biomarker of early stage breast cancer."

And third, since the Runx3 gene appears to be intact but inactivated in breast cancer, future studies will focus on reversing its inactivation, Chen said.

"If you can reactivate Runx3, then you can suppress tumor growth," he said.

SOURCE: Oncogene, published online June 27, 2011