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Genes Tie Blood Fat to Heart Disease
Date:5/6/2010

Mutation can increase risk by up to 40 percent, researchers say

THURSDAY, May 6 (HealthDay News) -- Scientists have long debated the role triglyceride levels might play in heart disease, and finally they have genetic evidence linking high concentrations of the blood fat to an increased risk of heart trouble.

Until now, cholesterol levels were the key targets of heart disease prevention efforts, but experts say a new report in the May 8 issue of The Lancet may revise that thinking.

Triglycerides, a major source of human energy, are produced by the liver or derived from foods. "Despite several decades of research, it has remained uncertain whether raised levels of triglyceride can cause heart disease," said lead researcher Nadeem Sarwar, a lecturer in cardiovascular epidemiology at the University of Cambridge in England.

"We found that people with a genetically programmed tendency for higher triglyceride levels also had a greater risk of heart disease," Sarwar said. "This suggests that triglyceride pathways may be involved in the development of heart disease."

To explore a genetic link between triglycerides and heart disease, Sarwar's team collected data on 302,430 people who participated in 101 studies. "We employed novel genetic approaches -- so-called 'Mendelian randomization analysis,'" he said.

Specifically, the researchers looked at mutations in the apolipoprotein A5 gene, a known determinant of triglyceride concentrations. They found that for every copy of the variant, there was a 16 percent increase in triglyceride concentrations, so two copies increased triglyceride levels 32 percent.

People with two such variants had a 40 percent increased risk of developing heart disease, the researchers calculated.

Although these genetic findings indicate a causative role for triglyceride pathways in the development of heart disease, they do not replace the need for large randomized clinical trials of medications that lower blood triglyceride levels, Sarwar said.

Such trials should help establish whether reducing triglyceride concentration can reduce the risk of heart disease, he said. "There are several medications currently available or under development that can influence blood triglyceride levels," he noted.

Drug maker Novartis, the British Heart Foundation and the UK Medical Research Council funded the study.

Dr. Gregg C. Fonarow, a professor of cardiovascular medicine and director of the Ahmanson-UCLA Cardiomyopathy Center at the University of California, Los Angeles, also said more research is needed.

"Elevated LDL cholesterol has been definitively established as a major modifiable cardiovascular risk factor," he said. "There is also strong evidence that low levels of HDL identify individuals at increased risk for cardiovascular events. However, the independent role that elevated triglyceride levels play in cardiovascular risk has been more difficult to establish and controversial," he said.

This study suggests a modest independent association between triglycerides and coronary heart disease, Fonarow said.

"Despite these findings it still remains to be demonstrated whether lowering triglyceride levels in patients with -- or at risk for -- cardiovascular disease will in and of itself reduce the risk of cardiovascular events and if so by how much," he said.

Another expert, Dr. Byron Lee, an assistant professor of cardiology at the University of California, San Francisco, suggested the study could alter the guidelines for heart prevention. "Traditionally, clinicians have focused only on getting our patients' LDL down and our HDL up because we thought that these were the major players in heart disease," he said.

"However, this study indicates that we need to now worry about high triglyceride levels as well," he added.

More information

For more information on heart disease, visit the American Heart Association.



SOURCES: Nadeem Sarwar, Ph.D., lecturer in cardiovascular epidemiology, University of Cambridge, England; Gregg C. Fonarow, M.D., professor, medicine, and director, Ahmanson-UCLA Cardiomyopathy Center, University of California, Los Angeles; Byron Lee, M.D., assistant professor, cardiology, University of California, San Francisco; May 8, 2010, The Lancet


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