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Triglycerides Predict Heart Risk When Glucose Tolerance Is Normal

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Provocative Findings, If Real

This study addresses a very complicated and confusing question. There are as may answers to the question of the relationship between triglycerides and cardiovascular risk as there are studies looking at it.

In a previous study, an unadjusted analysis found that triglyceride levels in the fasting state were highly predictive of cardiovascular events, but that relationship was completely lost after adjustment for multiple variables, in particular other lipids. This led us to believe that triglycerides may be a marker of cardiovascular risk but that they are not causally related, and when other risk factors are included, they do not contribute to risk.

However, in the Women’s Health Study and another study, non-fasting triglycerides did predict cardiovascular risk after adjustment for multiple variables.

The current study certainly confirmed that fasting triglycerides did not predict cardiovascular risk in the whole cohort, and it also found that postprandial triglycerides did not predict risk after adjusting for other risk factors.

However, they found that both the fasting and postprandial triglyceride levels predicted cardiovascular outcomes in those who had normal glucose tolerance, but not in those with impaired glucose tolerance or diabetes mellitus. This is something that has not been reported before.

There are some limitations and weaknesses in this study. The relatively small sample size for what is essentially an epidemiologic study and the relatively short follow-up – and, as a consequence, the small number of cardiovascular events – really does limit the conclusions. It doesn’t invalidate them, but it does mean that we cannot just assume that this is a proven case.

Also, the combined endpoint was rather soft. The hospitalization endpoint allows for a subjective element. Furthermore, there is no indication of the mechanism responsible for the findings.

Despite those limitations, this is a very, very interesting finding, if real. This was the first study designed to assess whether glucose metabolism status impacts the ability of triglyceride levels to predict cardiovascular risk. From this small study and with its limitations, the answer is, "Yes." I do not understand why there was no prediction in those with glucose intolerance or diabetes.

I think the results are provocative and, if real, have important clinical implications in terms of identifying those who need to treat triglyceride levels as distinct from other variables. I do believe this study requires confirmation.

Dr. Philip Barter of the Heart Research Institute, Sydney, Australia, has been a consultant, advisor, or lecturer for AstraZeneca, CSL, Merck, Novartis, Pfizer, Roche, and Sanofi Aventis. He made these comments during the meeting as the official discussant of the paper.


 

FROM THE ANNUAL CONGRESS OF THE EUROPEAN SOCIETY OF CARDIOLOGY

PARIS – Postprandial triglyceride levels helped assess cardiovascular risk in patients with normal glucose tolerance but provided no extra prognostic information in those with impaired glucose tolerance or diabetes in a prospective study of 514 consecutive patients with stable coronary artery disease.

In the Homburg Cream and Sugar Study participants who were undergoing coronary angiography ate a standardized dinner at 6 p.m., fasted overnight, and at 8 a.m. drank 250 ml of cream containing 75 g of fat. Three hours later those who were not receiving treatment for diabetes also drank 250 ml of water containing 75 g of glucose.

Investigators then measured fasting and postprandial triglyceride concentrations, followed by insulin concentrations and glucose tolerance. Follow-up 12 and 18 months later identified cardiovascular events.

Diabetes was present in 46% of patients, and only 25% had completely normal glucose tolerance. Patient characteristics were typical of those with coronary artery disease, Dr. Ulrich Laufs and his associates reported at the annual congress of the European Society of Cardiology.

For the cohort as a whole, postprandial triglyceride levels did not correlate with the primary outcome, a composite of cardiovascular deaths or hospitalizations for cardiovascular events. A weak correlation between fasting triglycerides and the primary outcome became non-significant in multivariate analysis.

Fasting triglyceride levels, and to an even greater extent postprandial triglyceride levels, were independent markers for the primary cardiovascular outcomes, said Dr. Laufs of Saarland University Hospital, Homburg, Germany. In patients with diabetes and impaired fasting glucose, however, absolute fasting and postprandial triglyceride levels were high but did not independently predict risk of cardiovascular death or hospitalization.

The highest tertile of triglyceride concentrations – levels above 150 mg/dL – in patients with normal glucose tolerance predicted a tripling in risk for the cardiovascular endpoints, compared with the middle and lowest tertiles. The highest tertile of postprandial triglyceride levels predicted a four-fold increased risk in patients with normal glucose tolerance. The study controlled for the effects of other risk factors, including other lipids, age, and sex.

These findings were "a little bit surprising," he said.

The study was designed to help address ongoing debate about whether triglyceride levels add to other measures of cardiovascular risk. "There is evidence from primary prevention studies and from mechanistic basic science studies that maybe the triglyceride-rich lipoproteins that are increased after a meal may be especially atherogenic," Dr. Laufs said.

Photo credit: Sherry Boschert/Elsevier Global Medical News

Dr. Ulrich Laufs presents his findings at the annual congress of the European Society of Cardiology.

Triglycerides are regulated not only by the time and type of meal but other factors as well. Importantly, glucose metabolism influences triglyceride kinetics, the study showed. Compared to patients with diabetes, those without diabetes had lower concentrations of fasting and absolute triglycerides and increased postprandial triglycerides. The relative increase, however, was similar between these two groups, he said.

"For the majority of patients, the primary consequence of this analysis is that we have to look very carefully at glucose metabolism," he said. "We may have to focus more on patients with normal glucose tolerance. If those patients have high fasting triglycerides, they have increased risk. It may be interesting in the future to look at whether these patients may benefit from intervention."

The study was limited by looking at only the first 5 hours after a meal, statin therapy in 95% of patients, the absence of genetic testing, and a predominantly Caucasian cohort, he said.

Dr. Laufs has been a speaker for nearly all pharmaceutical companies dealing with lipids.

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