Mar 052013
AHA Learn and Live

People with HIV have about twice the risk of myocardial infarction as those not infected with the virus, as well as increased risks for end-stage renal disease (ESRD) and some cancers, researchers found.

But for the most part, there’s little evidence to suggest those events come at a younger age in HIV-positive people.

The findings come from two related studies among U.S. veterans, one presented here at the Conference on Retroviruses and Opportunistic Infections (CROI) and the other appearing online in JAMA Internal Medicine.

In the journal, researchers led by Matthew Freiberg, MD of the University of Pittsburgh School of Medicine in Pittsburgh reported on data from more than 82,000 veterans used to estimate the rate of MI among both HIV-positive and HIV-negative participants.

An overlapping group of researchers led by Keri Althoff, PhD, of Johns Hopkins University studied members of the same group – the Veterans Aging Cohort Study Virtual Cohort – and reported on evidence for and against premature aging in relation to heart attack, ESRD, HIV-associated cancers, and other cancers.

Because of the success of antiretroviral therapy, Freiberg and colleagues noted, people with HIV are living longer and may be at risk for diseases of aging, including heart disease. But determining how HIV affects the risk for MI has been difficult. Several studies have reported an association, but they have had serious limitations, they added.

To overcome some of those problems, they looked at 82,429 vets, of whom 27,350 were HIV-positive, with a median follow-up of 5.9 years. The main outcome measure was acute MI.

Overall, the two groups were demographically similar, and Freiberg and colleagues adjusted for HIV status, age, sex, race/ethnicity, hypertension, diabetes, dyslipidemia, smoking, hepatitis C infection, body mass index, renal disease, anemia, substance use, CD4 cell count, HIV RNA, antiretroviral therapy, and incidence of heart attack.

They found that there were 871 acute MIs over the period from April 1, 2003 to Dec. 31, 2009, of which 41.7% occurred in the HIV-positive group.

Across three decades of age, the average rate of MI per 1,000 person-years “was consistently and significantly higher for HIV-positive compared with uninfected veterans,” Freiberg’s group reported. The rates per 1,000 person-years were:

  • among those ages 40 to 49: 2.0 for the HIV-positive group versus 1.5 for the HIV-negative group
  • 50 to 59: 3.9 versus 2.2
  • 60 to 69: 5.0 versus 3.3


All the differences were significant at P<0.05.

In a multivariate analysis, adjusting for Framingham risk factors, comorbidities, and substance use, HIV-positive veterans had a hazard ratio of 1.48 for heart attack compared with uninfected vets, the researchers reported.

They cautioned that because the study sample was overwhelmingly male, the result might not apply to women. They also noted that, among other limitations, the study was observational so there might be unmeasured factors that help account for the findings.

Nonetheless, the study was able to overcome many of the limitations of earlier research and “demonstrate a clear and consistent excess risk of MI,” commented Patrick Mallon, MBBcH, PhD, of Mater Misericordiae University Hospital in Dublin, Ireland.

What remains uncertain is where the excess risk comes from, he wrote in a commentary in the journal, and is a question that will require further research. More research is also needed into the risk in women with HIV and into ways to reduce the risk of MI in HIV-positive people, he added.

Althoff and colleagues posed a different question: Does HIV mean premature aging in terms of earlier onset of aging-related diseases?

To find out they looked at incidence rates of MI, ESRD, and cancer among the vets, as well as the average age at which events occurred.

The study population was slightly larger than in the Freiberg analysis, including 31,454 HIV-positive people, matched by age, race, and clinical site with 68,558 HIV-negative controls. The study covered a shorter period from October 2003 to September 2008.

They found that for MI, there were 286 events in the HIV-negative group and 231 in the HIV-positive group (HR 1.81, 95% CI 1.4 to 2.2). But there was no significant difference in the average age of heart attack at 55.3 in both groups.

For ESRD, there were 502 events in the HIV-negative group and 346 in the HIV-positive group (HR 1.43, 95% CI 1.22 to 1.66). The average age of onset was 58.5 in the HIV-negative group and 55.3 in the HIV-positive group, but the difference was not significant after adjustment.

For HIV-associated cancers, there were 565 events in the HIV-negative group and 579 in the HIV-positive group (HR 1.84, 95% CI 1.62 to 2.09). In this case there was a significant in the average age of diagnosis: Those with HIV received their cancer diagnosis on average 7 months earlier.

For non-HIV cancers, there were 1,254 events in the HIV-negative group and 509 in the HIV-positive group (HR 0.95, 95% CI 0.85 to 1.06). Once again, there was a small but significant difference in the average age at diagnosis as those with HIV were diagnosed 5 months earlier.

As with the other study, Althoff and colleagues cautioned that the participants were mostly male, so that the results might not apply to women.

The JAMA Internal Medicine study had support from the National Heart, Lung, and Blood Institute and the National Institute on Alcohol Abuse and Alcoholism. Freiberg did not report any conflicts of interests.

The commentary had support from the Science Foundation Ireland and the Irish Health Research Board. Mallon reported financial links with Abbott, Merck Sharp and Dohme, Pfizer, Gilead, GlaxoSmithKline, Roche, Janssen-Cilag, ViiV Healthcare, and Boehringer-Ingelheim.

The study presented at CROI had support from the National Institute of Allergy and Infectious Diseases. Althoff did not report any conflicts of interest.

From the American Heart Association:


Primary source: JAMA Internal Medicine
Source reference:
Freiberg MS, et al “HIV infection and the risk of acute myocardial infarction” JAMA Intern Med 2013; DOI: 10.1001/jamainternmed.2013.3728.

Additional source: JAMA Internal Medicine
Source reference:
Mallon PWG “Getting to the heart of HIV and myocardial infarction” JAMA Intern Med 2013; DOI: 10.1001/jamainternmed.2013.264.

Additional source: Conference on Retroviruses and Opportunistic Infections
Source reference:
Althoff K, et al “HIV+ adults are at greater risk for myocardial infarction, non-AIDS cancer, and end-stage renal disease, but events occur at similar ages compared to HIV- Adults” CROI 2013; Abstract 59.



Michael Smith

HIV Linked to Higher Risk of Heart Attack