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May 27, 2010
 |  BC Innovations  |  Targets & Mechanisms

The case against triglycerides

Although the harmful effectsof certain lipids such as low-density lipoprotein cholesterol on the cardiovascular system are well established, the role of triglycerides in heart disease has been suspected but less clear. Now, a large-scale epidemiological study provides evidence that increased triglycerides are indeed associated with a greater risk of coronary artery disease.1The question now is whether the converse is true: Can lowering triglycerides protect against CAD?

Triglycerides are lipids consisting of several fatty acids linked to a glycerol molecule. They are the primary source of lipid-derived energy in the body and are transported through the blood in cholesterol-rich lipoprotein particles. In CAD, these particles accumulate as atherosclerotic plaques within the walls of the coronary artery, leading to myocardial infarction (MI).

The physical association between triglycerides and cholesterol has confounded previous efforts to distinguish whether high levels of triglycerides are themselves harmful. For example, CAD patients with high triglycerides also typically have high low-density lipoprotein (LDL) cholesterol.

"There has been uncertainty for 50 years as to whether elevated triglycerides can cause heart disease," said Nadeem Sarwar, university lecturer in cardiovascular epidemiology at the University of Cambridge and corresponding author of the study, which was published in The Lancet.

"Because triglyceride levels are correlated with other lipid levels," testing the effect of triglycerides alone on CAD risk has been difficult, noted Sarwar. Getting an answer from an interventional trial of compounds that lower triglycerides is "impossible," he added, because medications that affect triglycerides also affect other lipids, such as LDL and high-density lipoprotein (HDL) cholesterol.

Thus, Sarwar's group decided to study the natural variation in triglyceride levels using a combination of genetic and epidemiological methods. "We found that people who carried a genetic variant that elevated triglycerides had higher risk of coronary heart disease," he said.

Tri and tri again

To unravel the effect of triglycerides on CAD, Sarwar's team turned to a relatively common genetic variant in...

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