September/October 2016 

U.S. researchers explore the impact of depression on heart attack risk

In Canada and other high-income countries, the widespread use of potent combination anti-HIV therapy (ART) has greatly decreased the risk of AIDS-related infections. As a result, ART users are living longer but are developing more health issues that are not related to AIDS. In the past 15 years researchers have found that these other health issues—such as cardiovascular disease, including heart attack and stroke—appear to be more common in HIV-positive people.

Part of the reason for the rise in heart attacks may be related to several factors, such as elevated rates of smoking, abnormal levels of cholesterol in the blood and elevated blood pressure. However, researchers suspect that there are other factors that can influence cardiovascular disease risk.

In a study with HIV-negative people who took part in a randomized clinical trial, researchers conducted long-term monitoring of a portion of participants and found that those who had depression and who were treated for it before cardiovascular disease occurred were significantly able to reduce their future risk of a heart attack.

Spurred by this finding (and results from other studies) researchers in the U.S. conducted a study to explore the impact that depression had on heart attack risk among HIV-positive people. Over the course of 11 years they found that adults with major depression (sometimes simply called depression) had a 30% elevated risk for developing a heart attack. This study was observational in nature and cannot prove that major depression caused a heart attack. However, its results are highly suggestive and add to the growing body of evidence that major depression plays a role in heart attack risk in HIV-positive people.

Study details

Researchers reviewed health-related data collected from 26,144 HIV-positive veterans in the U.S. Participants entered the study in 1998 and were monitored until the end of 2009.

Key average features of participants when they entered the study were as follows:

  • age – 48 years
  • 19% had major depression
  • 9% had persistent low-grade depression


After an average of six years of monitoring, 490 new heart attacks occurred. This is equivalent to saying that about 2% of study participants developed a heart attack.

Researchers found that participants with major depression had a 30% increased risk for developing a heart attack compared to participants without depression—a statistically significant difference.

The researchers arrived at this figure even after taking into account traditional cardiovascular disease risk factors (such as smoking) and HIV-specific factors.

The risk of a heart attack conferred by major depression fell to 25% (still statistically significant) when researchers took into account the following factors:

  • co-infection with hepatitis C virus
  • the presence of kidney disease
  • alcohol and/or cocaine abuse or dependence

Mild but persistent depression was not associated with an increased risk for cardiovascular disease.

Potential explanations

Researchers are not certain precisely how major depression likely increases the risk for a heart attack in some people, but there may be several potential explanations as follows:

  • Depression may increase inflammation in the body. As inflammation is already higher than normal among HIV-positive people, additional inflammation may hasten the development and onset of a heart attack
  • Depressed people may engage in unhealthy behaviours, such as smoking, not exercising, not taking ART every day as directed. Any or all of these together could increase the risk of a heart attack. ART reduces (but does not eliminate) HIV-related inflammation, and a randomized study of treatment interruption found that such interruptions increase inflammation and the risk of a heart attack or stroke.

The use of the anti-HIV drug efavirenz (Sustiva and in Atripla) has been linked to an increased risk of depression and, in very rare cases, suicide.  However, in this study, there was no clear connection between the use of efavirenz and depression.  In part this likely occurred because doctors seemed to avoid prescribing efavirenz to people who became depressed.

Note that the present study is observational in design. Such studies are good at finding associations but cannot prove, for instance, that major depression caused heart attacks. However, because this study monitored a relatively large number of participants over a long period, its findings are highly suggestive.

For the future

The present study, like nearly all studies of HIV-positive veterans, was made up overwhelmingly of men. Studies are needed among HIV-positive women to assess the impact of major depression on their health, particularly for heart attack risk. Researchers also need to understand how major depression could eventually be linked to a heart attack in some people. As well, researchers should prospectively study the impact of interventions, such as counselling and the use of antidepressants, on the future risk of heart attack in HIV-positive people who have major depression.


HIV and cardiovascular disease – CATIE fact sheet

—Sean R. Hosein


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