Modest triglyceride elevations linked to coronary artery disease risk

Even modest increases in blood levels of triglycerides, as well as a type of high cholesterol known as type III hyperlipidemia, are strongly associated with coronary artery disease in people with a family history of the disease, according to a new study in the April 5, 2005, issue of the Journal of the American College of Cardiology.

“We found that risk from high triglycerides depends on the kind of particle that is elevated. Remnants are very high risk particles and type III confers an eight- to 10-fold increase in risk. We also found that both high plasma triglycerides, even without type III hyperlipidemia, and low HDL appeared to be independently related to higher coronary artery disease risk without evidence for interaction,” said Paul N. Hopkins, M.D., M.S.P.H., at the University of Utah School of Medicine in Salt Lake City.

Remnants are lipoprotein particles that have had most of their triglycerides removed. The liver normally removes these remnant particles from the blood. In people with type III hyperlipidemia, these remnants build up to abnormal levels.

In this case-control study, the researchers analyzed blood samples from 653 individuals who had suffered a heart attack or undergone angioplasty or bypass surgery. Each of these patients also had a close family member with coronary artery disease. The blood test results were compared with those from 1,029 control subjects who were enrolled in two community health studies.

The odds ratio for coronary artery disease with elevated plasma triglycerides rose progressively to 11.4 in those with triglycerides 500 to 799 milligrams per deciliter (95% confidence interval 3.4 to 38.0, p < 0.0001) compared with those whose triglycerides were below 100 mg/dl, even after correction for HDL cholesterol, other elements of the metabolic syndrome, and other coronary artery disease risk factors. The risk of coronary artery disease associated with type III hyperlipidemia (found in 3.4% of cases) was also markedly increased independent of other risk factors (odds ratios of 5 to 10 depending on the model, all with p < 0.002).

“Total plasma triglyceride levels reflect a complex mixture of particles that have varying proclivity for promoting coronary artery disease. Knowing what particles are present will give the practitioner a better idea of risk,” Dr. Hopkins said.

“We are not aware of any other study that has looked at true, measured very low density lipoprotein cholesterol (VLDL-C) and LDL cholesterol in a substantial number of cases and controls. This study is unique in coming up with a population-based measure of the coronary artery disease risk associated with type III hyperlipidemia. It is also one of the largest studies to examine risk associated with more common forms of elevated triglycerides and low HDL cholesterol,” he added.

Dr. Hopkins said the results should prompt clinicians to pay more attention to type III hyperlipidemia and treat it aggressively, even when standard cholesterol measurements are not elevated.

“The prevalence of this condition in the general population is only around 0.5 percent, but it accounts for 3 or 4 percent of early heart attacks. The treatment is somewhat different from other forms of hyperlipidemia. Very early heart attacks can be seen in patients with more severe type III hyperlipidemia,” he said.

Dr. Hopkins noted that a case-control study like this one cannot determine absolute risk associated with the various lipid levels nor can it demonstrate whether the elevated triglycerides or type III hyperlipidemia preceded the coronary artery disease. However, the authors pointed out data from prospective studies that indicate little long-term change in untreated lipid levels after the diagnoses of coronary artery disease. Dr. Hopkins said that since most of the participants in this study were recruited in the mid-1990s, most were not receiving the type of aggressive lipid-lowering therapy that is more common today.

Frank Sacks, M.D., at the Harvard School of Public Health in Boston, Mass, who was not connected with this study, said it helps the field move beyond merely lowering LDL cholesterol to address other factors that affect heart disease risk.

“Although many studies show that the blood level of triglycerides is related to cardiovascular disease, this study provides a very close analysis of the ‘dose’ response between triglycerides and heart disease, confirming the importance of plasma triglycerides as an independent risk factor for cardiovascular disease. Triglycerides can be lowered by weight loss, a lower carbohydrate diet, and exercise. These results should be a spur to lifestyle changes, but also to the use of available drug therapy to reduce triglyceride levels, and to the development by the pharmaceutical industry of newer approaches,” Dr. Sacks said.

The American College of Cardiology, a 31,000-member nonprofit professional medical society and teaching institution, is dedicated to fostering optimal cardiovascular care and disease prevention through professional education, promotion of research, leadership in the development of standards and guidelines, and the formulation of health care policy.