Lorraine L. Janeczko

March 13, 2013

ATLANTA, Georgia — HIV-positive adults are 50% more likely to have a heart attack than people without human immunodeficiency virus, according to a new study of United States veterans.

The results, published online March 4 in JAMA Internal Medicine, coincided with the Conference on Retroviruses and Opportunistic Infections (CROI), where they were first presented.

Dr. Matthew Freiberg

"We were able to show that comparing people who have sustained low viral loads to uninfected people, there was still an increased risk up to 39%," lead investigator Matthew Freiberg, MD, from the University of Pittsburgh in Pennsylvania, told Medscape Medical News. "That's important because if you're taking your meds, you still have risk."

The researchers analyzed data from 84,459 participants from the Veterans Aging Cohort Study over a median follow-up period of 5.9 years.

"We used a control group that was as similar to HIV-infected people as possible to minimize the risk of confounding so we saw that our results were due to HIV and not something else, such as smoking," Dr. Freiberg said.

His team found that 41.7% of the 871 myocardial infarctions occurred in the HIV-positive group.

Over three decades of age, the researchers found that the mean MI rate was "consistently and significantly higher" among HIV-positive veterans compared with those who were uninfected (P < .05 for all).

Table. Number of Acute Myocardial Infarctions per 1000 Person-Years

Age, years HIV-Positive Veterans HIV-Negative Veterans
40 to 49 2.0 1.5
50 to 59 3.9 2.2
60 to 69 5.0 3.3


After the investigators adjusted for Framingham risk factors, comorbidities, and substance use, they found an increased risk for incident myocardial infarction in the HIV-positive veterans (hazard ratio 1.48; 95% confidence interval 1.27-1.72).

Dr. Steven Grinspoon

Asked by Medscape Medical News to comment on the findings, Steven Grinspoon, MD, from Massachusetts General Hospital in Boston, said, "This is a very important study with robust results that advances the field."

He pointed out that this study is among the largest to date and demonstrates the effect across multiple ages adjusting for differences in cardiovascular (CV) risk factors.

This is a very important study with robust results that advances the field.

"This extends the findings from prior studies in a larger cohort, which, because of its size, was better able to control for various risk factors," Dr. Grinspoon said. "We've seen from other studies that there is an increase in acute myocardial infarction rate, but this study reinforces and extends prior data and is very important."

Dr. Jason Baker

Jason Baker, MD, from the University of Minnesota in Minneapolis, added in a telephone interview that the findings — combined with a growing body of evidence that ongoing inflammation among antiretroviral-treated HIV patients is contributing to greater subclinical and clinical CV disease — suggest that additional prevention strategies are needed.

"Currently, there are no HIV-specific cardiovascular prevention strategies. Guideline committees may need to consider whether more aggressive treatment goals are needed for traditional risk factors such as cholesterol and blood pressure, among HIV positive patients, as is the case with diabetes," said Dr. Baker, who was not involved in the study. "In the meantime, these findings reinforce the need for HIV providers to emphasize risk-factor modification strategies, such as smoking cessation, that are known to be effective."

Unanswered Questions

Dr. Priscilla Hsue

"The precise mechanism of how HIV infection increases CV risk and acute MI is unknown so the best biomarkers to identify cardiovascular disease in HIV-infected individuals and the best therapies to lower HIV-associated inflammation to reduce cardiovascular risk still needs to be determined," Priscilla Hsue, MD, told Medscape Medical News. Dr. Hsue, from the University of California in San Francisco, was not involved in the present analysis.

Dr. Grinspoon added, "The evidence is getting to be pretty convincing that there is an increased risk. But now the question is why the increased risk is there, what to do about it, and how to treat patients. How do we identify the patients with increased risk and target them for therapy to reduce that risk? These are the critical questions."

Dr. Baker noted, "Additional clinical trials are needed to determine if adjunct anti-inflammatory approaches, or more aggressive risk factor modification, can reduce CV risk among antiretroviral-treated patients."

Dr. Freiberg said, "We have tools to predict people at high risk, like the Framingham risk score, and that certainly can be applied to people with HIV. But it's not clear if it's the best tool. So I think you're going to be seeing a lot of research trying to see if there is a better way to predict risk."

"As for treatment, will we be doing more than just treating risk factors and giving people antiretrovirals in the future? Maybe. And from this meeting at CROI, a lot of people are focusing on inflammation. Will we have drugs that target inflammation to help these people? Maybe. We don't know yet, but a lot of groups are working on that. This is definitely a very interesting unanswered question," he said.

Dr. Freiberg pointed out that researchers trying to understand the mechanisms involved in increased heart attacks in people with HIV are examining a complicated picture. "When you're looking at the Mona Lisa, you look at the big picture, not just her nose," he said. "We need to explore the big research picture, not just one paper."

This study was funded by the National Institutes of Health. Dr. Freiberg, Dr. Grinspoon, Dr. Baker, and Dr. Hsue have reported no relevant financial relationships.

JAMA Intern Med. Published online March 4, 2013. Abstract