The Overlooked Triglycerides

Summarized by Robert W. Griffith, MD
August 28, 2007

Summary

Raised nonfasting triglyceride levels are better predictors of subsequent heart attack, coronary heart disease, and death than fasting triglyceride levels, especially in women.

Introduction

People concerned with maintaining good health know they should take care of their total cholesterol, their low-density lipoprotein cholesterol (LDL-C), and their high-density lipoprotein cholesterol (HDL-C). They usually consider managing them in that order. When they've got their LDL-C (the 'bad' cholesterol) and their HDL-C (the 'good') under control, they may even consider looking at their triglyceride level. However, as a raised triglyceride is one of the factors for the metabolic syndrome, it should probably receive earlier attention.

Until now, the association between triglyceride level and cardiovascular events has been considered to be due to the interactive effect between triglycerides and other lipoproteins, such as HDL-C, the level of which is usually inversely related to triglyceride levels, i.e. when the HDL-C is high the triglyceride is low, and vice versa. The role of raised triglycerides has become clearer, thanks to two large, long-term studies reported in the Journal of the American Medical Association. In particular, the part played by postprandial lipid levels comes into prominence. Indeed, some researchers are describing atherosclerosis¹ as a postprandial phenomenon.

The Copenhagen City Heart Study

This was a study of over 7500 women and 6400 men living in Copenhagen, Denmark, aged between 20 and 80, who were enrolled in 1976-1978. The investigators aimed to determine whether non-fasting triglyceride levels could predict the risk of heart attack (myocardial infarction, or MI), ischemic heart disease (IHD)², and death.

Full lipid levels were obtained at baseline and at three 10-year intervals thereafter. The follow-up period averaged 26 years. Diagnoses of MI, IHD, and death were obtained from hospital records and national registries. (IHD was diagnosed on the basis of a previous MI or characteristic symptoms of stable or unstable angina pectoris.) For the purpose of analyses, the subjects were classified in to six categories, based on their non-fasting triglyceride levels: below 88.5 mg/dL, 88.5 - 178 mg/dL, 177 - 265 mg/dL, 266 - 353 mg/dL, 354 - 442 mg/dL, and above 442 mg/dL.

In a smaller separate study, triglyceride levels were found to be increased in those who had eaten their last meal in the previous 7 hours; the 'peak' interval was 4 hours. And in a fat tolerance test a similar but greater increase was seen, peaking again at 4 hours.

In men and women, the frequency of MI, IHD, and death increased with increasing levels of non-fasting triglyceride levels. In women, those with triglyceride levels above 442 mg/dL had much higher frequencies than the other groups and those seen in men. In men, risks were greater in those under 55 at entry, and in light vs. heavy alcohol drinkers.

In their discussion, the investigators maintain that it is not the triglycerides per se that cause atherosclerosis, but rather the cholesterol content of remnant lipoproteins, in particular small, dense LDLs. Fasting samples for triglycerides don't contain remnant lipoproteins.

The Women's Health Study

This study followed 26,500 initially healthy women for an average of 11 years. Triglyceride levels measured at baseline were sampled in the fasting state in 20,100 women and in a non-fasting state in 6400 women. This allowed comparison of the effects of fasting versus nonfasting triglycerides on risk for cardiovascular events to be determined.

The events recorded were nonfatal MI, nonfatal stroke, coronary revascularization procedures, and death due to cardiovascular causes. The participants were classified into groups - one set of 3 for fasting, one set of 3 for nonfasting - based on their triglyceride levels. The fasting-sample groups were: below 91 mg/dL, 91-147 mg/dL, and 148 mg/dL or above. The nonfasting groups were: below 105 mg/dL, 105-170 mg/dL, and 171 mg/dL or above.

Among all participants, the women with higher triglyceride levels were significantly more likely to have other cardiac risk factors and markers for the metabolic syndrome: high blood pressure, smoking, diabetes, postmenopausal, hormone usage, BMI, and C-reactive protein (CRP). Alcohol and exercise were inversely associated with triglyceride levels - i.e. more alcohol and more exercise were linked with lower triglyceride levels.

After adjusting for other cardiovascular risk factors, both fasting and nonfasting triglyceride levels predicted cardiovascular events. However, when measured in the nonfasting state (especially 2 to 4 hours after a meal), triglyceride levels were strongly associated with future risk. Fasting levels showed little independent association with cardiovascular events.

Conclusions

These studies, taken together, suggest that women have a greater risk associated with raised triglyceride levels, but the risk of raised postprandial triglyceride levels increases the cardiovascular risk for both sexes. Does this mean all future lipid level sampling should be done 2-4 hours after a meal, instead of fasting, as is usually requested? Probably yes. Indeed, other experts have suggested that postprandial triglyceride determination may be more reliable than LDL-C calculated using fasting blood sampling. Perhaps one needs to consider a "fat tolerance test" in analogy to the glucose tolerance test. An alternative would be to use "non-HDL-C" levels, which are simply total cholesterol minus HDL-C; they are accurate and reliable in a nonfasting situation. Non-HDL-C levels are more predictive of coronary heart disease risk than LDL-C when triglycerides are elevated, but they are a sum of all atherogenic lipoproteins.³

It's important to treat people when their triglycerides are between 150and 1000 mg/dL, as the risk for cardiac events is significantly raised. This may mean giving a statin pus niacin (nicotinic acid or vitamin B3), or a statin plus gemfibrazol (Lopid^®). It's not enough to look at the cholesterols and if they seem OK, to forget the rest.

Sources

• Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women. BG. Nordestgaard , M. Benn, P. Schnohr, A. Tybjaerg-Hansen, JAMA, 2007, pp. 299--308



• Fasting compared with nonfasting triglycerides and risk of cardiovascular events in women. S. Bansal , JE. Buring, N. Rifai,  et al. , JAMA, 2007, pp. 309--316

Footnotes
1. Atherosclerosis is a condition in which fatty material collects along the walls of arteries, called 'atheroma'; it thickens, hardens, and may eventually block the arteries. The atheroma plaque deposits make the artery less flexible; they can also break apart, causing pieces to move through the artery, causing a stroke or heart attack, depending on where they end up blocking the artery.
2. Ischemic heart disease - meaning disease that limits adequate oxygen reaching the heart muscle - is also known as coronary heart disease.
3. McBride PE. Triglycerides and risk for coronary heart disease. Editorial. JAMA 2007;298:336-338.

Related Links
American Heart Association: Triglycerides
Ask the Dietician: Triglycerides
Mayo Clinic: Triglycerides - Why Do They Matter?

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