Special Coverage of 43rd IDSA Meeting: Texas researchers find a new independent predictor of mortality among HIV patients
Special Coverage of 43rd IDSA Meeting
Texas researchers find a new independent predictor of mortality among HIV patients
Abnormal ECGs have diagnostic potential
As a growing number of HIV researchers enter their third decade of studying the epidemic, unusual and interesting findings, as a byproduct of early research, have cropped up, and some of these were presented at the recent annual meeting of the Infectious Diseases Society of America (IDSA) of, which was held in San Francisco, Oct. 6-9, 2005.
One discovery that may surprise many HIV clinicians is that an electrocardiogram could be used as an independent predictor of all-cause mortality among HIV patients.1
"The real promise of this research is that electrocardiograms are easy to perform, and they may provide prognostic information about how someone might do with their HIV disease," says Brian Agan, MD, an associate director of clinical interventions at the Tri-Service AIDS Clinical Consortium in Rockville, MD. Agan also is a clinical research physician in the department of infectious diseases at Wilford Hall USAF Medical Center in San Antonio, TX.
The study involved 223 HIV-positive individuals of which about 73% had normal electrocardiogram results in the early 1990s, Agan says. Another 15% had borderline results, and 12% had abnormal electrocardiograms, Agan says.
In the groups with normal and borderline findings, 36% had died since the initial electrocardiogram, while in the group with abnormal readings, 68% had died, Agan says.
"The other place to get information is in the median survival in each of those three groups, and this is where we did a statistical test," Agan says.
In the normal group, the median survival since having the electrocardiogram was 146 months, while the borderline group had a not-quite-significant, median survival of 114 months. The group with abnormal findings had a significant difference, with a median survival of 44 months, Agan says.
Wilford Hall was involved in HIV research since the beginning of the epidemic in the early 1980’s, Agan says.
"Wilford Hall helped to craft one of the earliest staging systems, which has great prognostic value," Agan notes. "So it’s an area of interest for us to look at prognostic factors."
Then 14 years ago, a study about cardiovascular disease in HIV was initiated at the medical center, Agan says.
"It was designed to be a longitudinal subset study of patients who volunteered to be studied for EKGs," Agan explains. "A baseline set of data were collected and analyzed."
Since then, many of the subjects have died, but enough remain alive that investigators thought it might be useful to look at the original data set and see what outcomes were associated with abnormalities on the electrocardiograms, Agan says.
"It came to us that as we look for noninvasive markers of HIV disease, that the EKG might provide some insight into HIV," Agan says. "With 12 to 15 years of follow-up, we identified that an abnormal EKG or a borderline EKG was associated with an increased mortality, based on the Kaplan-Meier survival analysis."
Since the electrocardiogram information was collected before the advent of highly active antiretroviral therapy (HAART), the findings have added power, says Kevin Steel, DO, a cardiology fellow at Wilford Hall USAF Medical Center.
"These patients weren’t influenced by HAART, which might affect the cardiovascular system," Steel explains. "We’re considering as potential future investigation to do EKGs with people on HAART, but I suspect the effect might not be as profound."
Since HIV patients on HAART are less likely to have active HIV disease, one of the possibilities for future research is a follow-up assessment on the same cohort of patients with another electrocardiogram, Agan says.
Researchers involved in the study have some interesting hypotheses about why abnormal electrocardiogram findings have this predictive feature, Agan and Steel say.
"We suspect an elevated ESR or sedimentation rate may be indirectly related to HIV disease activity in the body, and it also reflects in the electrocardiograms drawn at baseline," Steel says.
People with worse HIV disease have more inflammation, and that ultimately could be why they have a higher mortality rate, Agan says.
"There are other possibilities, as well, including the fact that the sedimentation rate can be associated with many different features, and we have not yet had time to analyze all of the different associated features," Agan says.
"For example, people could have more of some other type of infection that leads to more inflammation," Agan adds. "Based on preliminary analysis, we don’t see any evidence of that within our group, but it will need to be excluded."
In the cohort of patients there was no viral load data because these patients pre-dated the viral load assay, Agan says.
Also, the findings were noted to be irrespective of CD4 cell counts, but since investigators couldn’t account for viral load, that’s something else that needs to be considered as this research proceeds, Agan says.
One of the challenges investigators faced was capturing the cause of death for the subjects involved in the original research, Agan says.
"There’s been a developing infrastructure of capturing information," Agan says. "Of those patients with a known cause of death, the larger portion of that group died of an infection, not of a cardiovascular cause."
Only 3% in the study died of a cardiovascular cause, Agan says.
"That lends evidence and support to the idea that the electrocardiogram is not a marker for a cardiac cause of death, but is an indirect marker for HIV-related cause of death," Agan says.
These findings mean that clinicians could use an electrocardiogram as a simple tool to prognosticate the potential for disease in HIV patients they see for the first time, Steel says.
"There is a great promise here for being able to use a simple, inexpensive and non-invasive tool to help understand the potential outcomes for somebody with HIV infection," Agan says.
"The last thing I’d say is I think it’s very interesting that it may be giving us a window into understanding a little bit more about the pathogenesis of HIV disease," Agan says.
"We’re starting to understand more about cardiovascular complications," Agan adds. "But I think the linkage between inflammation and abnormal EKG and mortality brings the idea that this is one more area where the immune system may be playing a significant role in pathogenesis of HIV disease."
Reference:
- Steel K, et al. The Electrocardiogram predicts mortality in HIV positive individuals. Presented at the 43rd Annual Meeting of the Infectious Diseases Society of America, Oct. 6-9, 2005, in San Francisco, CA. Abstract: 805.
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