Results from two studies indicate that elevated nonfasting triglyceride levels are associated with cardiovascular events such as a heart attack, with one study finding that triglyceride levels measured after fasting does not show this association, according to studies in the July 18 issue of JAMA1.
Triglyceride levels are usually measured in the fasting state, which could exclude certain types of lipoprotein particles (“remnant” lipoproteins), a possible risk factor for atherosclerosis, according to background information in the article. However, except for the first hours in the early morning, most individuals are in the nonfasting state most of the time. “Atherosclerosis may be a postprandial [occurring after a meal] phenomenon in which remnant lipoproteins play a dominant role. If this is true, increased levels of nonfasting triglycerides, reflecting increased levels of remnant lipoproteins, may predict risk of myocardial infarction (MI; heart attack), ischemic heart disease (IHD), and death,” the authors write.
Børge G. Nordestgaard, M.D., D.M.Sc., of Herlev University Hospital, Herlev, Denmark, and colleagues tested the hypothesis that very high levels of nonfasting triglycerides are associated with an increased risk of heart attack, IHD, and death in the general population. The study included 7,587 women and 6,394 men from the general population of Copenhagen, age 20 to 93 years, who were followed up from baseline (1976-1978) until 2004 (average follow-up 26 years).
The researchers found that with increasing levels of nonfasting triglycerides, levels of remnant lipoprotein cholesterol increased. During the follow-up, 1,793 participants experienced a heart attack, 3,479 developed IHD, and 7,818 died. In men and women, the cumulative incidence of heart attack, IHD, and death increased with increasing levels of nonfasting triglyceride levels.
Among women, the adjusted risk for heart attack increased for each higher category of triglyceride levels (from 1-mmol/L to greater than 5-mmol/L), with the increase in risk (adjusted for other factors) ranging from 1.7 times to 5.4 times, compared to those with triglyceride levels of less than 1-mmol/L. For men, the increased adjusted risk for heart attack for each higher category of triglyceride levels ranged from 1.4 to 2.4. Risk of IHD and death also generally increased with higher triglyceride levels.
“We found that nonfasting triglyceride levels independently predict MI, IHD, and death, particularly in women. These findings may reflect the effects of remnant lipoproteins and therefore may be of considerable interest when designing future trials of agents aimed at reducing triglyceride levels or attenuating atherogenic metabolic abnormalities. If our findings are confirmed, clinical care might be simplified by using nonfasting lipid profiles for atherosclerosis risk prediction,” the researchers conclude.
In a related study of over 25,000 initially healthy women, higher triglyceride levels measured after not fasting is associated with an increased risk for cardiovascular events, but his association was not found for triglyceride levels measured after fasting, according to a study in the same issue of the journal2.
Sandeep Bansal, M.D., of Brigham and Women’s Hospital and the Harvard School of Public Health, Boston, and colleagues conducted a study to determine the association of triglyceride levels (fasting vs. nonfasting) and risk of future cardiovascular events. The study included 26,509 initially healthy U.S. women (20,118 fasting and 6,391 nonfasting) participating in the Women’s Health Study, enrolled between November 1992 and July 1995. Triglyceride levels were measured in blood samples obtained at time of enrollment.
During a median (midpoint) follow-up of 11.4 years, 1,001 participants experienced a new cardiovascular event (including 276 nonfatal heart attacks, 265 ischemic strokes, 628 coronary revascularizations, and 163 cardiovascular deaths).
“In this large-scale, prospective cohort of initially healthy U.S. women, we observed that higher nonfasting triglyceride levels were strongly associated with an increased risk of future cardiovascular events, independent of baseline cardiac risk factors, levels of other lipids, and markers of insulin resistance. In contrast, fasting triglyceride levels showed little independent association with cardiovascular events. Associations were particularly strong among individuals who had their blood drawn 2 to 4 hours after a meal, and this relationship weakened as more time elapsed postprandially,” the authors write.
“Our observations may have implications for the design and conduct of clinical trials evaluating triglyceride-lowering medications. To date, almost all clinical trials of pharmaceutical agents targeting triglyceride levels have relied on fasting levels as inclusion criteria. However, if levels measured in the fasting state are not the best marker for the atherogenicity associated with hypertriglyceridemia, then it is possible that these trials will have targeted the wrong patient populations. By contrast, previous studies have demonstrated the benefits of several classes of drugs on postprandial elevations in triglyceride levels. Thus, based on the data presented here, future end point reduction trials of triglyceride-lowering agents might consider participant inclusion on the basis of nonfasting rather than fasting triglyceride levels.”
In an accompanying editorial in the same edition of the journal3, Patrick E. McBride, M.D., M.P.H., of the University of Wisconsin School of Medicine and Public Health, Madison, comments on the two studies regarding triglyceride levels and risk of cardiovascular events.
“In the end, is it the triglyceride levels or the associated changes in metabolism that explains the high risk associated with postprandial triglyceride levels? This question is important scientifically, but in clinical practice the argument may be as academic as the debate about which came first, the chicken or the egg. For clinicians, it is important to recognize that when triglyceride levels are between 150 and 1000 mg/dL, the risk for atherosclerosis-related events is significantly increased. 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.”
1. JAMA. 2007; 298(3):299-308.
2. JAMA. 2007; 298(3):309-316.
3. JAMA. 2007; 298(3):336-338.