Sudden cardiac death and HIV

Studies have found that HIV-positive people are at heightened risk for cardiovascular disease—heart attack, stroke and other complications. The reasons for this heightened risk are not clear, but here are some possibilities:

• HIV infection causes the release of chemical signals that trigger inflammation and ultimately weaken blood vessels and may accelerate cardiovascular disease (CVD).
• Surveys have found that there are high rates of tobacco smoking among some HIV-positive people.
• Problems associated with sudden cardiac death (SCD) may be relatively common among HIV-positive people, including pulmonary hypertension, an enlarged heart and abnormal electrical activity in the heart.

The risk for many CVD-related issues appears or grows worse as people age. So, as HIV-positive people live longer because of the effects of potent combination therapy for HIV (commonly called ART or HAART) heart problems may become more of a concern.

Researchers at San Francisco General Hospital reviewed the medical records of nearly 3,000 patients with HIV, searching for cases of SCD. Among 230 deaths that occurred between the years 2000 and 2009, 13% of deaths were caused by SCD. People who died from SCD, compared to other causes, were more likely to have a history of heart problems.

Study details

The research team reviewed medical records of 2,860 HIV-positive patients from San Francisco General Hospital. All were adults and were enrolled in the study between April 2000 and August 2009.

Researchers reviewed medical records and death certificates. Deaths that occurred “in a hospice or due to overdose, violence, suicide, a cancer or opportunistic infections were excluded” from analysis for SCD, according to the researchers. After these exclusions, there were 230 deaths to analyse.

The average profile of participants was as follows:

• 87% men, 13% women
• age – 39 years
• CD4+ count – 353 cells
• viral load – 13,000 copies/ml
• 21% of participants had undetectable viral load in their blood

On average, they were monitored by the hospital for four years.

Results

Out of a total of 230 deaths, 35 were heart related, of which 30 were caused by SCD.

Other causes of death among patients who died during the study were as follows:

• AIDS-related infections and cancers – 57%
• other natural causes of death (lumped into this category were deaths due to non-AIDS cancers, liver disease and blood poisoning from bacterial infections) – 11%
• overdoses, suicides, unknown causes – 19%
• sudden cardiac death – 13%

Focus on SCD

During the course of the study, the proportion of deaths due to SCD did not increase. However, by 2003 researchers noticed that SCD “was often the leading cause of non-AIDS natural deaths.”

The researchers found that “more than half of [participants] had histories of tobacco, alcohol or drug use.” All of these could have contributed to poor overall health.

At their last clinic visit before dying, 33% of participants who subsequently died from SCD reported the following symptoms:

• chest pain
• palpitations
• fainting
• shortness of breath

Overall, 83% of participants who subsequently died from SCD were prescribed cardiac medicines. Many also underwent cardiac ultrasound scans, which revealed further heart problems. Cardiograms also showed disturbances in heart rhythms in 60% of participants and uncovered evidence of prior heart attacks in four people.

Comparing deaths

Researchers compared the medical profiles of participants who had SCD with those who died of AIDS-related complications.

People with SCD tended to have higher CD4+ counts (321 cells vs. 87 cells) and lower viral loads (6,000 copies/ml vs. 63,000 copies/ml) compared to those who died from AIDS-related causes.

The researchers found that factors such as ethnicity and gender were not significantly different between people who had SCD and those who died from other causes. People who had SCD were slightly older (49 years) compared to other people who died (45 years).

Importantly, people who died from SCD were significantly more likely to have the following issues:

• previous heart attack
• swollen heart muscles
• weak hearts
• abnormal heart rhythms
• higher-than-normal blood pressure
• abnormal levels of cholesterol in the blood

Factors such as the following affected a similar proportion of patients in each group:

• type 2 diabetes
• chronic kidney disease
• chronic lung disease

The rate of death due to SCD was nearly five-fold greater than expected in a group of HIV-negative people of similar age and ethnicity.

Why these findings?

What are the reasons for this relatively larger rate of SCD in HIV-positive people? Researchers are not certain but they note that among HIV-negative people SCD is associated with heart disease. In the present study, many people who were found to have had SCD had cardiovascular disease risk factors associated with SCD.

More than half of people with SCD had modest CD4+ cell counts (312 cells) and suppressed viral loads. The research team suggests that even “patients on effective ART remain at risk [for SCD].”

The present study was retrospective in nature and designed to assess and document causes of death. The study was not designed to find out why SCD occurred.

Research teams in North America and Western Europe who have also investigated causes of death need to confirm that SCD is elevated among their HIV-positive patients. If this is the case, research into inflammation as a possible underlying cause of SCD may be a useful approach. The potential impact of specific anti-HIV medicines on SCD risk would require a different study.

What to do?

The study authors note that because many participants who developed SCD commonly had cardiac symptoms they encourage health care providers to consider “aggressive primary prevention of cardiovascular disease…in HIV-infected patients, especially those with traditional CVD risk factors.”

They also note that implantable cardioverter defibrillators (ICDs) have saved the lives of some HIV-positive people at high risk for SCD. Studies of these devices used in HIV-positive people need to be conducted.

REFERENCE:

Tseng ZH, Secemsky EA, Dowdy D, et al. Sudden cardiac death in patients with HIV infection. Journal of the American College of Cardiology. 2012; 59(21):1891-6.