Triglycerides
linked to heart attack risk
Higher
triglyceride levels were independently associated with a higher risk of
myocardial infarction, or heart attack, in the large D:A:D study, according to
a report at the 17th Conference on Retroviruses and Opportunistic
Infections (CROI) last week in San Francisco.The researchers suggested,
however, that triglyceride levels have limited prognostic value after taking
cholesterol levels into account, and therapies to reduce triglycerides are
unlikely to address the underlying problem.
Several studies have found
that people with HIV have an elevated risk of cardiovascular disease and
related outcomes such as heart attacks, but the underlying physiological
processes, risk factors and optimal management are not fully understood D:A:D
(Data Collection on Adverse events of Anti-HIV Drugs) – which currently
includes more than 33,000 participants in Europe, Australia, and the US – was
one of the first large observational studies to show a higher rate of heart
attacks in HIV-positive people, as well as an association with protease
inhibitor use.Some antiretroviral drugs, especially protease
inhibitors, can cause abnormal levels of blood lipids including total
cholesterol, LDL (bad) cholesterol, HDL (good) cholesterol and triglycerides.
But elevated triglycerides can also be due to obesity, insulin resistance,
fatty liver disease and other causes.In the analysis presented at CROI, D:A:D
investigators sought to determine the relationship between triglyceride levels
and heart attack risk after taking into account total cholesterol and HDL
levels. Elevated total cholesterol and LDL levels are linked to increased
cardiovascular risk, while elevated HDL is protective.
The researchers collected
information about triglyceride levels and the incidence of myocardial
infarction (heart attack) amongst 30,703 cohort members who had at least one
triglyceride measurement available (the average number of measurements was
ten).About three-quarters of the D:A:D participants were men, half were white,
and the median age was 39 years. With regard to HIV status, most had taken
antiretroviral therapy, one-third had suppressed viral load and the median CD4
cell count was just over 400 cells/mm3. More than one-third were
current smokers and about 20% were ex-smokers, but other traditional
cardiovascular risk factors were uncommon, including obesity (4%), diabetes
(3%) and previous cardiovascular disease (2%).Triglyceride levels were
stratified into six groups ranging from below 0.90 to above 3.45 mmol/l.
Statistical analyses were undertaken to determine if there was an independent
association between triglyceride levels and heart attacks.These analyses took
into account traditional cardiovascular risk factors such as age, sex, body
mass index, diabetes, smoking, family history and use of lipid-lowering drugs,
as well as HIV-related factors such as viral load and CD4 count. In a separate
model, the investigators also adjusted for total cholesterol and HDL levels.
Regardless
of whether they were measured while fasting or after eating, triglyceride
levels were higher on average in men, older people and obese individuals.
Levels were also higher in people with better controlled HIV disease, including
current use of antiretroviral therapy, viral load below 500 copies/ml and CD4
count above 600 cells/mm3.
A total of 580 heart
attacks were reported during 178,835 person-years of follow-up. The incidence
of myocardial infarction increased as triglyceride levels rose. For people with
the lowest triglyceride levels below 0.90 mmol/l, the incidence of heart
attacks was 0.11 per 100 person-years. Incidence increased steadily as
triglycerides rose, reaching 0.69 per 100 person-years for patients with levels
above 3.45 mmol/l.An initial statistical analysis showed that each doubling of
triglyceride levels increased the relative risk of a heart attack by 67% (RR
1.67). After adjusting for other known cardiovascular risk factors and HIV-related
factors, however, the relative risk was reduced to 32% (RR 1.32).But elevated
total cholesterol and LDL levels were also associated with increased heart
attack risk, as were low HDL levels. When these other blood lipid levels were
accounted for, the relative risk of heart attacks associated with elevated
triglycerides fell further, to 11% (RR 1.11), but was still statistically
significant.The D:A:D investigators concluded that, "Higher triglyceride
levels were independently associated with an increased risk of myocardial
infarction in HIV-positive persons."
However, they added that
the 11% residual effect of triglyceride levels after adjusting for non-lipid
and lipid risk factors was very small compared with the original unadjusted
effect of 67%, and cautioned that using medications such as fibrates to lower
triglycerides is unlikely to have a major impact on the risk of myocardial
infarction.As for study limitations, the researchers noted that even adjusting
for use of antiretroviral therapy, they could not compare drug-related
triglyceride increases versus those due to other causes. Moreover, they could
not establish a causal link between triglyceride levels and myocardial
infarction given the observational nature of the study.
Prof.
John Kurakar
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