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.
Further information
You can view abstract 127 on the official conference website.
You can also view a webcast and slides of this session on the official conference website.
Worm S et al. Triglycerides and the risk of myocardial infarction in the D:A:D study. Seventeenth Conference on Retroviruses and Opportunistic Infections, San Francisco, abstract 127, 2010.