Tuesday, February 12, 2008
Researchers say treating both is like arresting the "Bonnie and Clyde" of heart disease
In order to reduce the risk of heart attack and other acute heart problems, it may be best to lower elevated triglyceride, a blood fat, together with LDL cholesterol, the so-called "bad" cholesterol, rather than lowering LDL alone. That is the conclusion of a study published February 12, 2008, in the online version of the Journal of the American College of Cardiology. The print version of the journal will be out February 19.
The study, led by Michael Miller, M.D., director of preventive cardiology at the University of Maryland Medical Center and associate professor of medicine and epidemiology at the University of Maryland School of Medicine, analyzed data from a study of heart patients, first reported in 2004. "The trouble with triglyceride is the company it keeps," says Dr. Miller. "LDL and triglyceride work together to make a bad situation worse."
The original study, known as Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22, did not evaluate the impact of reducing both LDL and triglyceride. Its focus was solely on the reduction of LDL. The study looked at more than 4,000 patients hospitalized for a heart attack or other acute coronary events who were then treated randomly with one of two statin medications. Cholesterol and other blood fat levels were measured after 30 days on the treatment and patients were followed for two years.
Statins are a group of drugs known to reduce LDL, a substance which can build up in vessels to form plaque and impede blood flow. Triglycerides give muscles energy; they can be stored as fat.
The 2004 study showed for the first time that intensive LDL-lowering therapy that reduced levels to below 70 milligrams per deciliter (mg/dL) translated into reduced heart attacks and death due to cardiovascular disease compared to the standard of care at the time. National treatment guidelines were changed after the study results came out, with the optional recommendation to lower LDL cholesterol below 70 mg/dL as the primary goal after a heart attack.
Dr. Miller says that while LDL forms plaque, elevated triglycerides do not. But working together, they form a destructive partnership, similar to that of a well-known early-20th century criminal duo. "Think of LDL as the bad guy. LDL is like Clyde, triglyceride is like Bonnie. LDL and triglyceride are the Bonnie and Clyde of heart disease," says Dr. Miller.
"If you just looked at Clyde, you would say, 'No surprise that he’s a problem, that he’s mischievous, that he’s going to be devastating.' Unlike Clyde, Bonnie is crafty and as slick as the blood fats. When she teams up with Clyde, the duo becomes more dangerous than either one acting alone," says Dr. Miller. Clyde Barrow and Bonnie Parker, notorious suspects in a murderous crime spree in the 1930s, were shot to death in a police ambush in 1934."
Dr. Miller says enzymes break down triglyceride-rich particles into what are known as "remnants." A person with high levels of triglyceride "is likely to have more remnants, which are just as bad as LDL cholesterol. Both LDL and the remnants raise the risk for heart disease," says Dr. Miller.
Christopher P. Cannon, M.D., of Brigham and Women’s Hospital in Boston, a co-investigator on the current study, says, "Triglycerides are 'the other bad cholesterol,' and lowering them appears to lead to further benefit beyond lower LDL." Dr. Cannon led the original 2004 study.
In the new analysis, the group with the highest risk of cardiac events such as heart attack had a combination of high LDL and high triglyceride. "If you have a high level of both LDL and triglycerides, your risk is two-to-five times greater compared to having either one," says Dr. Miller. The only exception is in people who have a genetic abnormality that causes extremely high LDL levels, as high as 300, 400 or 500 mg/dL.
A reduced risk for heart disease was found in people whose LDL was lowered to less than 70 mg/dL and whose triglyceride was lowered to less than 150 mg/dL. For each 10 mg/dL drop in triglyceride levels during treatment, there was a 2.3 percent lower risk of a new cardiac problem, after adjusting for LDL levels.
The study’s bottom line, says Dr. Miller, is that "reducing elevated LDL is necessary but not sufficient alone to reduce the risk of a cardiac event. The combination of a low LDL and low triglyceride may be a better strategy in heart attack survivors." Diet, exercise and fish oil can reduce triglyceride, as can some medications.