Baltimore, MD - In post-ACS patients, low on-treatment triglyceride levels are associated with a lower risk of recurrent CHD events, independent of LDL- and non-HDL-cholesterol levels, an analysis of the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 (PROVE-IT TIMI-22) trial has shown [1]. The finding, say investigators, lends support to the idea that in the post-ACS setting, achieving low triglyceride levels, in addition to low LDL-cholesterol levels, should also be a consideration.

"Triglycerides have been put on the back burner a little, and that's in part due to the fact that for such a long time clinicians haven't really known what to do with them," said lead investigator Dr Michael Miller (University of Maryland Medical School, Baltimore, MD). "What this study shows is that triglycerides are important at every level of LDL cholesterol and that in post-ACS patients, low triglycerides are associated with reduced risk of events and add to the LDL story."

The results of the study are published in the February 12, 2008 issue of the Journal of the American College of Cardiology.

Speaking with heartwire, Miller noted that so little attention is paid to triglycerides that the National Cholesterol Education Program (NCEP) does not even have a target goal for patients, although <150 mg/mL, the level used in the classification of the metabolic syndrome, is often applied. Many clinicians believe that triglycerides are an "important part of the puzzle," said Miller, but their role in preventing future events, especially in ACS patients, has been deemphasized.

Previous analyses have shown that triglycerides predict future coronary events, but the association weakens after adjustment for other risk factors, including glucose and HDL cholesterol. Still, patients with mixed hyperlipidemia, a combination of high triglycerides and high LDL-cholesterol levels, tend to be at greater risk for coronary disease than those with isolated elevated LDL cholesterol or triglycerides alone, and with this in mind, Miller and the PROVE-IT investigators wanted to determine the role triglycerides might have in predicting events in this ACS population.

PROVE-IT, a study previously reported by heartwire, was one of the first "lower-is-better" studies testing the hypothesis that a lower absolute LDL-cholesterol level in patients with ACS is associated with a reduced risk of events, while also evaluating the efficacy and safety of aggressive LDL-cholesterol lowering. In the original study, atorvastatin 80 mg reduced the primary end point, a composite of death and major cardiovascular events, more than pravastatin 40 mg. In this new analysis, Miller and colleagues assessed the relationship between on-treatment levels of triglycerides and LDL cholesterol on the composite of death, MI, and recurrent ACS.

In an adjusted analysis, on-treatment triglyceride levels <150 mg/dL were associated with a 20% reduced risk of CHD compared with patients with triglyceride levels >150 mg/dL. For every 10-mg/dL decrease in on-treatment triglyceride levels, the incidence of death, MI, and recurrent ACS decreased approximately 1.5%, even after adjustment for LDL, non-HDL, and other covariates.

In addition, examining the treatment effect of triglyceride levels <150 mg/dL when LDL-cholesterol levels were reduced to <70 mg/dL, investigators observed a 28% reduction in the risk of CHD compared with patients with elevated LDL cholesterol (>70 mg/mL) and triglycerides (>150 mg/dL). Overall, the reduction in events was greatest among those who achieved the dual target of low LDL and low triglyceride levels.

"We should not be thinking only about reducing LDL-cholesterol levels in our post-ACS patients but rather reducing LDL and triglycerides, as this appears to be better in terms of reducing future events," said Miller.

Miller explained that triglycerides, in themselves, are not atherogenic because they are broken down into free fatty acids and stored or used as a source of energy in the body. They are not, he noted, taken up into plaque. However, triglycerides are hydrolyzed by lipases from triglyceride-rich lipoproteins, such as chylomicrons or VLDL cholesterol, into cholesterol-rich remnant particles. It is these cholesterol-rich remnant particles that are atherogenic, said Miller, "perhaps just as atherogenic as LDL cholesterol." In this way, triglycerides can serve as a marker for these atherogenic particles.

"It stands to reason that if you have high LDL levels and high triglyceride levels, you're going to be at higher risk," said Miller. With diet and exercise, triglycerides are easier to reduce than LDL cholesterol, said Miller, and with attention to diet and an exercise program, triglyceride levels can be reduced anywhere between 20% and 40%.