New study to assess the risk of heart disease in diabetics

In a new international partnership, Dr. Randy Nelson, a researcher at Arizona State University's Biodesign Institute, and Dr. Tai E-Shyong , associate professor at Singapore's National University Hospital, National University Health System (NUHS), have teamed up to assess the risk of heart disease in diabetics with greater accuracy.

The new study, funded by Singapore's National Medical Research Council, will focus on patients in Singapore with and without diabetes, a known risk factor of cardiovascular disease. The research team will examine blood samples from individuals, providing an early glimpse into the key role of a cholesterol component, the so-called 'good cholesterol,' known as high-density lipoprotein, or HDL. The team's goal is to identify more accurate HDL biomarkers-tell-tale protein signatures-that have the potential to be earlier and more accurate predictors of cardiovascular disease risk.

The stakes could hardly be higher. Heart disease has reliably ranked as the number one killer of both men and women, with more than 7 million deaths per year worldwide. This year, heart disease will cost the U.S. health care industry a staggering 475.3 billion dollars, according to the American Heart Association and the National Heart, Lung, and Blood Institute (NHLBI).

Nelson points to the ability of the Singapore investigators to collect a large number of patient samples as a key component of success. This is possible because of the research infrastructure that has been put in place for population-based research during the past several years through the government and health care providers. "The ability to collect data within specific populations and subpopulations is highly attractive for researchers," said Nelson.

Along with this rich patient population, the team will rely on Nelson's sophisticated suite of technology, called mass spectrometric immunoassays, that can detect cholesterol profile differences between individuals with atomic level precision. "With Dr. Nelson's technology, we now have the ability to tease out lipoprotein profiles at a level of detail that was not possible before," said Tai, who is also an associate professor with the department of medicine, Yong Loo Lin School of Medicine, National University of Singapore.

The proper balance of two main forms of cholesterol is essential for maintaining a healthy heart-HDL, the "good cholesterol," and it's counterpart, low density lipoprotein, or LDL. High levels of the "bad cholesterol" (LDL) in the blood can lead to the buildup of harmful plaques in blood vessels. High LDL levels have long been a telltale sign of increased risk for angina, heart attack, heart disease, stroke, and other related, life-threatening complications.

While high levels of "bad cholesterol" (LDL) in the blood signal an increased risk to health, the opposite is true of HDL-too little is hazardous to cardiovascular fitness, permitting cholesterol to accumulate in blood vessels, forming deposits which can impede blood flow, even in patients with normal LDL levels. Specifically, an HDL blood level of less than 40 mg/dL in men or 50 mg/dL in women, provides insufficient protection from plaque formation.

But as it turns out, the HDL picture is not so simple. To begin with, some patients with even high levels of HDL show no improvement in their protection from cardiovascular disease. Equally perplexing at first was the discovery of a particular mutation of HDL known as ApoA-1 Milano. Individuals bearing this mutation had low levels of good cholesterol, yet their HDL proved highly effective in preventing atherosclerosis.

According to Nelson, such apparent contradictions to the accepted role of HDL cholesterol are due to a range of protein subclasses that exist within the makeup of HDL "What starts out as just HDL," said Nelson, "turns into several different proteins, each of which, in turn, can exist in a of number different molecular forms."

Tai notes that the outcome of their project could have a significant impact on cardiovascular medicine. "In the prevention of heart disease today, precise risk assessment is critical to the decision making process," said Tai. The higher the risk an individual faces, the more aggressive treatment is. What we look at currently is the average risk for the group. With the kind of data that will be generated from this study, we may be able to divide patients into smaller and smaller groups with more precise risk estimates. This will lead to much more individualized treatment."

The Biodesign-NUHS collaboration is a first step along the path to a better understanding of HDL's role in human health, promoting earlier diagnoses and more effective treatments. "There's 100 years of biology leading up to what we are starting to see," Nelson notes. "We have a better set of eyes now."