Triglyceride levels and cardiovascular events

Jul 18, 2007
High Nonfasting Triglyceride Levels Associated With
Increased Risk for Cardiovascular Events

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
journal, 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.”

References:
1. JAMA. 2007; 298(3):299-308.
2. JAMA. 2007; 298(3):309-316.
3. JAMA. 2007; 298(3):336-338.