24 July 2012 

Cardiovascular disease and EAT in HIV-positive people

The heart is a large muscle that helps move blood around the body. Despite its vital pumping action, the heart is not entirely muscle—about 20% of this organ consists of a fatty layer called EAT (epicardial adipose tissue). This layer serves as a source of energy for the heart, as it is rich in saturated fat. Many fatty tissues can release hormones, called adipokines, that affect the health of arteries and other parts of the cardiovascular system, and researchers think that EAT can produce such hormones.

Affecting heart health

In studies of HIV-negative people who have coronary artery disease, researchers have found evidence of inflammation within EAT. Moreover, in such people, EAT contained cells of the immune system such as macrophages and T-cells. EAT in obese people produced chemical signals that incited inflammation in other cells.

Researchers are not certain precisely how EAT plays a role in heart disease but they suspect that excess EAT could affect the functioning of heart muscles and increase inflammation within the heart’s blood vessels.

EAT and other parts of the body

Researchers have made the following discoveries about EAT:

  • The volume of EAT is linked to the fat that is deposited deep in the belly (visceral fat) and often is wrapped around vital organs there.
  • Excess EAT has been associated with abnormal levels of blood sugar and a reduced sensitivity to insulin—both precursors of diabetes—and thickening of the arteries.
  • Disturbances to the electrical activity of the heart have also been associated with having excess EAT.

Given the interest in EAT and cardiovascular disease in HIV-negative people, researchers have turned to studying EAT in HIV-positive people. Using repeated high-resolution CT scans of the chest, a research team in Modena, Italy, has measured changes in EAT over a period of 18 months in more than 200 HIV-positive volunteers who were taking potent combination anti-HIV therapy (commonly called ART or HAART). During their study, the researchers also measured the degree of calcium that was deposited in arteries. This calcium, which comes from the dead cells and cellular debris that accumulate along blood vessels because of inflammation, forms sticky deposits called plaque.

The Italian researchers found that, overall, men tended to have greater increases in EAT than women. Increased volume of EAT was linked to increased deposits of calcium in the arteries. Researchers think that part of the reason for the excess EAT and calcium deposits in some participants may be due to abnormal stimulation of the immune system by chronic HIV infection.

Study details

Researchers recruited 240 participants between January 2005 and June 2011. All were adults and had been taking potent anti-HIV therapy for the previous 18 months. None had experienced a heart attack, stroke or peripheral vascular disease or had undergone cardiovascular surgery.

Upon entering the study, participants’ average profile was as follows:

  • 68% men, 32% women
  • age – 47 years
  • CD4+ cell count – 500 cells
  • viral load – less than 40 copies/ml
  • 50% did not engage in physical exercise
  • 40% had higher-than-normal blood pressure
  • BMI (body mass index) – a relative assessment of fatness was within a range considered healthy

Two CT scans were done an average of 18 months apart. These provided information about EAT and calcium deposits in the arteries.


Men generally had significantly larger amounts of EAT (88 mm3) than women (61 mm3). Also, increases in the volume of EAT were linked to being male.

During the study, the proportion of participants whose volume of EAT increased was 64%. EAT volume was stable or decreased among the remaining participants.

Increased deposits of calcium in the coronary arteries occurred among 10% of participants, most of whom were men. Participants who had increased coronary artery calcium deposits were more likely to have an increase in the volume of their EAT during the study.

The immune system and cardiovascular disease

Infections by viruses and other germs cause the immune system to become activated and release chemical signals that incite inflammation. This is a normal response and usually helps to alert cells and tissues of the immune system to an infection. It also helps alter metabolism and affects the behaviour of many organ-systems in a way that is helpful to fight infections. However, after the infection has been brought under control, the immune system is generally able to return to its normal state as levels of activation and inflammation fall. Because the immune system (and its cells) is distributed throughout the body, an activated immune system affects the functioning of many other organ-systems, including the heart and blood vessels.

HIV infection causes the immune system to become activated. This activation is somewhat decreased when HIV-positive people take ART, but because ART does not cure HIV, the immune system continues to be activated. Thus, studies have found that HIV-positive people are at increased risk for cardiovascular disease. It is not yet known precisely how HIV increases the risk for cardiovascular disease, but many teams are investigating possible reasons for this elevated risk.

In reviewing their medical records and extracting and analysing data, the Italian researchers found an association between the increase in CD4+ cells detected after participants began to take ART and an increase in the volume of EAT. This does not mean that CD4+ cells caused the growth of EAT. Rather, the researchers suspect that some of the CD4+ cells were activated and that these activated cells caused inflammation within the EAT. Unfortunately, the research team did not conduct the detailed immunological sub-studies needed to assess CD4+ cells to find out if they were activated.

The findings from Italy are another piece of the puzzle in the growing connection between HIV and cardiovascular disease. Moreover, they underscore the importance of investigating calcium deposits in the arteries and changes in the volume of EAT.

Studies in HIV-negative and obese people have found that significant changes to the diet can reduce EAT. Studies in HIV-positive people are needed to find out if decreasing the volume of EAT can be done with diet and exercise and other attempts to reduce inflammation in the short term. Long-term monitoring is needed to assess if such interventions result in improved health among HIV-positive people.


CATIE’s fact sheet on HIV and cardiovascular disease

                                                                                                                        —Sean R. Hosein


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