Coronary Plaques, and Heart Rhythm Changes in People with HIV
disease is a growing concern as people with
HIV live longer, but the complex relationship between HIV infection itself,
immune activation triggered by the virus, and antiretroviral
drugs used to treat it remains poorly understood.
studies presented at the 48th International Conference
on Antimicrobial Agents and Chemotherapy (ICAAC 2008) in late October shed
further light on factors associated with cardiovascular risk in HIV positive patients.
artery disease is increasingly recognized as a potential complication of long-term
antiretroviral therapy (ART).
The disease is characterized by atherosclerosis, or build-up of plaques and loss
of blood vessel elasticity.
Hadigan and colleagues from the National Institutes of Health performed computed
tomography (CT) coronary angiography to measure non-calcified plaque volume and
coronary calcium scores in HIV positive and HIV negative individuals.
background, the researchers noted that while several studies have investigated
surrogate markers for coronary artery disease, such as carotid artery wall (intima-media)
thickness and endothelial function, little data are available on the extent of
coronary artery plaques in HIV-infected patients.
present study included 22 HIV positive adults (20 men, 2 women) and 22 HIV negative
sex-matched control subjects. The HIV positive patients had been diagnosed with
HIV for a mean of 14 years and had been on ART for a mean of 8 years. Overall,
they had well-controlled HIV disease, with 77% currently on ART (about one-quarter
including a protease inhibitor), 70% with an undetectable viral load, and a mean
CD4 count of about 560 cells/mm3.
were required to have at least 1 cardiovascular risk factor (e.g., smoking, hypertension,
dyslipidemia, diabetes, first degree relative with early coronary artery disease).
Framingham cardiovascular risk scores were calculated, revealing that 45% of HIV
positive patients and control subjects had a > 10% risk.
Atherosclerosis was present in 86% of
the HIV patients (7 with moderate and 1 with severe artery narrowing).
There was no significant difference between
HIV positive and HIV negative participants in terms of:
Plaque volume (87 vs 57 mm3; P > 0.1);
Coronary calcium score (107 vs 146; P
Calcium score percentile (44 vs 40; P
Average Framingham risk score (12.8 vs
10.3; P = 0.20).
Among all participants combined, plaque
volume was significantly correlated with coronary calcium scores (P = 0.01) and
calcium percentile (p < 0.0001), as well as age (P = 0.04).
However, no correlation was noted between
Framingham risk scores and coronary calcium scores or plaque volume among HIV
positive or HIV negative participants.
Among the HIV positive patients, there
was a strong positive correlation between plaque volume and duration of ART (P
= 0.04), but not duration of protease inhibitor use specifically.
Plaque volume was not correlated with
duration of HIV infection or viral load.
There was a slight correlation between
higher CD4 count and lower plaque volume, but this did not reach statistical significance
(P = 0.06).
extent of coronary artery plaque appears similar between HIV positive adults and
controls with similar degrees of underlying coronary artery disease risk,"
the investigators concluded. "Among HIV positive patients, however, duration
of antiretroviral therapy was more closely associated with plaque volume than
traditional markers of coronary artery disease risk such as Framingham risk score.
CCMD, and NHLBI, National Institutes of Health, Bethesda, MD.
another study, E.L. Falcone and colleagues from Tufts Medical Center looked at
the association between serum micronutrient levels and surrogate markers of atherosclerosis
in 298 HIV positive adult participants in the Nutrition for Healthy Living cohort.
measured serum selenium, zinc, vitamin A, and vitamin E levels, as well as carotid
artery intima-media thickness (cIMT), and coronary artery calcium. They also assessed
cardiovascular risk factors, HIV viral load, CD4 cell count, HAART use, cIMT,
and coronary artery calcium for each micronutrient tertile (third of the study
population). Age, race, smoking history, systolic blood pressure, and blood glucose
levels did not differ significantly between the tertiles.
CD4 counts increased and HIV viral loads
decreased significantly with higher zinc levels.
Participants with higher vitamin E levels
were more likely to have detectable coronary artery calcium (50% vs 44% vs 67%;
P = 0.004).
Those with higher vitamin E also were
more likely to have increased common cIMT > 0.8 mm (5% vs 4% vs 17%; P = 0.002).
In a multivariate analysis, increasing
serum vitamin E level was significantly associated with higher common and internal
cIMT (P 0.031 and 0.035).
study shows that elevated serum vitamin E levels are associated with abnormal
early and late surrogate markers of atherosclerosis, and may increase the risk
of cardiovascular complications in HIV-infected adults," the researchers
concluded. "Studies are needed to determine if HIV-infected adults should
be cautioned about the risks of excess vitamin E intake."
Medical Center, Boston, MA.
A. Mangli and colleagues, also from Tufts, looked at QT interval as a potential
marker of premature atherosclerosis in HIV positive patients.
Normal heart rhythm
interval refers to the distance between the "Q" and "T" segments
of an electrocardiogram (EKG) wave (see illustration). Heart rate-corrected QT
(QTc) interval has been associated with carotid and coronary disease and mortality
in the general population, the investigators noted as background. Further, EKG
changes have been demonstrated in HIV positive patients, and certain antiretroviral
medications have been linked to prolonged QTc interval.
researchers measured carotid intima media thickness and coronary artery calcium
scores in 333 Nutrition for Healthy Living participants. QT interval was measured
on resting EKGs and corrected for heart rate using standard equations. Baseline
characteristics were assessed for each QTc tertile.
6% of study participants had a prolonged
Cardiovascular risk profiles and HIV-specific
factors were similar across QTc tertiles, except that those in the upper tertile
were more likely to be older, female, of higher body mass index, and to have the
Common cIMT was significantly correlated
with QTc (R = 0.1661; P = 0.003), but internal cIMT was not.
Patients in the higher QTc tertiles more
frequently had elevated coronary artery calcium scores (43% vs 29%; P = 0.035).
In a multivariate regression adjusted
for sex, age, and race, the association of QTc tertiles and common cIMT remained
significant (0.59 vs 0.60 vs 0.64; P = 0.038).
on these findings, the researchers concluded, "Long QTc is associated with
carotid and coronary atherosclerosis in HIV-infected patients and may be useful
as a marker of subclinical cardiovascular disease in this population. EKG recordings
in all HIV infected patients should be given consideration on a routine basis."
Medical Center, Boston, MA; Tufts Univ. School of Medicine, Boston, MA.
Hadigan, l Healey, N Muldoon, and others. Coronary Plaque Volume by CT Angiography
Correlates with Duration of Antiretroviral Therapy. 48th International Conference
on Antimicrobial Agents and Chemotherapy (ICAAC 2008). Washington, DC. October
25-28, 2008. Abstract H-2311.
L Falcone, A Mangili, and CA Wanke. Serum Micronutrient Levels and Markers of
Subclinical Atherosclerosis in HIV-Infected Adults. 48th International Conference
on Antimicrobial Agents and Chemotherapy (ICAAC 2008). Washington, DC. October
25-28, 2008. Abstract H-2309.
Mangili, JV Bonnaig, J Gerrior, and others. QT Interval as a Marker of Premature
Atherosclerosis in HIV Infected Patients. 48th International Conference on Antimicrobial
Agents and Chemotherapy (ICAAC 2008). Washington, DC. October 25-28, 2008. Abstract