Nonfasting Triglyceride Levels Linked to Increased Cardiovascular Risk

HERLEV, Denmark, July 17 -- Elevated nonfasting triglycerides are associated with increased risk of fatal and nonfatal cardiac events, according to results of two large, long-term, prospective cohort studies.
In both studies, published in the July 18 issue of the Journal of the American Medical Association, the risk appeared to be greatest for women.
The first study, conducted by Borge G. Nordestgaard, M.D., D.M.Sc., of Herlev University Hospital, and colleagues, found that women who had nonfasting triglycerides of 442.5 mg/dL or more were 16.8 times more likely to have a myocardial infarction (multifactorially adjusted HR 5.4) than women who had nonfasting triglycerides of less than 88.5 mg/dL (P<0.001 for trend).
Among men, adjusted hazard ratio for MI was 4.6 (multifactorially adjusted HR 2.4) for those who had nonfasting triglycerides of 442.5 mg/dL or more compared with men whose nonfasting triglycerides were less than 88.5 mg/dL (P<0.001 for trend).
Likewise, for both men and women, the risks for ischemic heart disease and death increased in tandem as nonfasting triglycerides increased, but again the risks were greatest for women -- an age-adjusted HR of 5.9 (multifactorially adjusted HR 2.6) for ischemic heart disease and an HR of 4.3 (multifactorially adjusted HR 3.3) for death versus 2.9 (1.5) and 2.0 (1.8) respectively for men (P<0.001 for trend).
In the second study, Paul M. Ridker, M.D., M.P.H., of Brigham and Women's Hospital in Boston, and colleagues, reported that after adjusting for total cholesterol, HDL cholesterol, and insulin resistance, nonfasting triglyceride levels were a strong predictor of cardiovascular events in 6,391 women enrolled in the Women's Health Initiative (P=0.006 for trend).
In addition to confirming nonfasting serum triglyceride level as an independent predictor of events, a secondary analysis of the WHI data found that triglyceride levels measured two to four hours after a meal were the strongest predictors of events (95% CI for highest versus lowest tertile of triglycerides 4.48, 1.98-10.15 (P<0.001 for trend).
The Danish researchers followed 7,587 women and 6,394 men, ages 20 to 93, who lived in the Copenhagen area from 1976 to 1978. The participants were followed for a mean of 26 years.
The participants were categorized by baseline nonfasting triglyceride levels, 88.5-176.1 mg/dL, 177.0-264.6 mg/dL, 265.5-353.0 mg/dL, 354.0-441.6 mg/dL, and 442.5 mg/dL or more.
Among the findings:
For each respective category increase above 88.5 mg/dL, the age-adjusted HR for MI among women were 2.2, 4.4, 3.9, 5.1 and 16.8 and for men they were 1.6, 2.3, 3.6, 3.3, and 4.6 (P<0.001 for trend for both).
For ischemic heart disease the category specific age-adjusted HRs for women were 1.7, 2.8, 3.0, 2.1, and 5.9 and for men the corresponding age-adjusted HRs were 1.3, 1.7, 2.1, 2.0, and 2.9 (P<0.001 for trend for both).
Mortality age-adjusted HRs for women were 1.3, 1.7, 2.2, 2.2, and 4.3 and for men they were 1.3, 1.4, 1.7, 1.8, and 2.0 (P<0.001 for trend for both).
Dr. Ridker and colleagues assessed triglycerides from blood samples taken from November 1992 through July 1995 from the 26,509 women enrolled in the WHI. Of those, 20,118 samples were fasting triglycerides and 6,391 were nonfasting. During a median follow-up of more than 11 years, there were 1,001 incident cardiac events.
Among the findings:
After adjusting for age, blood pressure, smoking, and use of hormone therapy both fasting and nonfasting triglycerides were predictive of cardiovascular events.
When the samples were adjusted for total cholesterol, HDL, and measures of insulin resistance, fasting triglycerides levels were no longer predictive (P=0.90 for trend).
It's difficult to determine whether it's the high triglyceride levels or the risk factors associated with high triglycerides that are responsible for the increased events observed in both studies, wrote Patrick E. McBride, M.D., M.P.H., of the University of Wisconsin, in an accompanying editorial.
Elevated triglyceride levels have a substantial effect on lipoprotein metabolism, which explains much of the controversy about the role of serum triglycerides as a risk factor for CHD, he added.
One reason to focus on nonfasting triglyceride levels in the pathogenesis of cardiovascular disease, the authors of both studies noted, is because postprandial triglyceride-rich remnant lipoproteins can penetrate the endothelial cell layer and reside in the subendothelial space, where they can contribute to the formation of foam cells, a hallmark of early atherosclerosis.
For clinicians, Dr. McBride said, the significance of the studies is clear, risk for atherosclerosis-related events was significantly increased when triglyceride levels are between 150 mg/dL and 1000 mg/dL.
"Therefore, it is important to aggressively and comprehensively treat patients with dyslipidemias that include high levels of triglycerides, low levels of HDL-C, and the presence of small LDL-C particles, using both lifestyle change and medications if necessary," Dr. McBride concluded.
Dr. Nordestgaard noted that the Danish finding was limited by its sample, which included only white participants. Moreover "the relatively small sample sizes and wide confidence intervals in groups with the highest triglycerides are of concern," they wrote.
Dr. Ridker acknowledged that the WHI study also had design limitations including the fact that participants were not randomly assigned to fasting versus nonfasting triglyceride testing.
Additionally, the findings about timing of postprandial phlebotomy was not straightforward because the last meal prior to blood draw was not given in a standardized manner.
The Danish study was funded by the Danish Heart Foundation, the Danish Medical Research Council, the Research Fund at Rigshospitalet, Copenhagen University Hospital, and European Union, Sixth Framework Priority. Dr. Nordestgaard reported that he was a consultant for Merck, Pfizer, B.G. Medicine, and AstraZeneca.
The study by Ridker et al was funded by the Donald W. Reynolds Foundation, the Leducq Foundation, the National Heart, Lung, and Blood Institute, Abbott Laboratories and the National Cancer Institute. Dr. Ridker reported research support from the American Heart Association, the Doris Duke Charitable Foundation, the Leducq Foundation, the National Cancer Institute, the National Heart, Lung, and Blood Institute, the Donald W. Reynolds Foundation, the James and Polly Annenberg La Vea Charitable Trusts, Abbott, AstraZeneca, Bayer, Bristol-Myers-Squibb, Dade-Behring, Isis Pharmaceutical, Novartis, Pharmacia, Roche, Sonofi-Aventis, and he is listed as a coninventor on patents held by Brigham and Women's Hospital.
Dr. McBride received honoraria from Bristol-Myers Squibb, Kos, Liposcience, Merck, Pfizer, Reliant, and Schering Plough and previously served as a consultant for Merck.Primary source: Journal of the American Medical AssociationSource reference: Nordestgaard B et al "Nonfasting Triglycerides and Risk of Myocardial Infarction, Ischemic Heart Disease, and Death in Men and Women" JAMA. 2007; 298:299-308. Additional source: Journal of the American Medical AssociationSource reference: Bansal S et al "Fasting Compared With Nonfasting Triglycerides and Risk of Cardiovascular Events in Women" JAMA. 207; 298:309-316. Additional source: Journal of the American Medical AssociationSource reference: McBride PE "Triglycerides and Risk for Coronary Heart Disease" JAMA. 2007; 298:336-338.