Use of Coronary CT Angiography to Detect Early Noncalcified Plaque in Asymptomatic HIV-Positive Patients
Two oral presentations reported on the incidence of coronary artery calcification in HIV patients.
Wendy Post and colleagues from the Multicenter AIDS Cohort Study (MACS) investigated the association of age with subclinical coronary atherosclerosis (Noncalcified Coronary artery Plaque (NCP) in a cross sectional observational study in 873 MSM (n=571 HIV positive and 302 HIV negative) enrolled in four U.S. urban cohorts.1
NCP is an early stage of atherosclerosis but is more serious than established calcified plaque as it may be more prone to thrombus formation and plaque rupture. Gradual expansion of sub-clinical plaque are less associated with myocardial infarctions (MI) and sudden coronary deaths (SCD) than cute plaque rupture accounts for 75% of MI and 50% of SCD.
All men received non-contrast cardiac computed tomography (CT) scans with 660 eligible patients also receiving coronary CT angiography to detect NCP and mixed plaque, and stenosis. Plaques were graded and scored by degree of stenosis, size and composition. Participants were aged 40 to 70 years, without prior cardiac or coronary surgery and weighed less than 300 pounds (a limitation for CT scans). HIV-positive patients were mostly (88.6%) on ART, 80% of whom had undetectable viral load, were younger (by about 30 months), with a lower BMI (26.1 vs 27.4). They were more likely to be current smokers (32% vs 21%), and have dyslipidaemia (lower LDL and HDL and higher trigylcerides).
Coronary plaque of any type was present in 77% of HIV-positive vs 62% of -negative men. This difference in this rate was significant after adjusting for CVD risk factors (OR 1.80; p=0.009). There was a similar association with NCP (p=0.002), and a trend for mixed plaque (p=0.053), but no association for either calcified plaque or stenosis >50%.
In both groups, any plaque was associated with older age [OR (95%CI) per year: 1.13 (1.09-1.17) vs 1.06 (1.03-1.09), respectively; both p<0.0001] but with NCP this was only significantly associated with age in HIV-positive group (p=0.002). By contrast, associations between age and the presence of any type of plaque did not defer by HIV status.
These analysis however adjusted for age and race but not CVD risk factors. There was no association between the presence of plaque or NCP with traditional HIV risk factors including nadir CD4 count, viral load, a history of AIDS and duration of HAART exposure. Nadir CD4, detectable viral load, duration of ART were independently associated with stenosis >50%.
Although the degree of coronary calcium burden in the general population is predictive of CVD events, these people tend to also have high rates of non-calcified plaque. However, in the Q&A session, it was pointed out that while the prevalence of coronary calcium was higher in HIV-positive patients, both groups in this study had similar rates of coronary calcium burden.
A second study, presented by Steven Grinspoon from Massachusetts General Hospital also used CTA to investigate morphologic features of coronary plaques in 102 HIV-positive to 41 HIV-negative controls, prospectively enrolled and matched for traditional CVD risk factors (but all asymptomatic for CVD disease), looking at the relationship with markers of immune dysregulation.2
Similar to the previous study, this group have also reported higher rates of subclinical plaque, mostly non-calcified, in HIV-positive compared to HIV-negative patients and that additionally this is associated with higher levels of circulating sCD163 (a marker of activated macrophages).
The study analysed more than 2500 coronary segments with previous identified plaque (out of a maximum 18 per patient). Duration of HIV infection was 13 years (+/- 6.5) and 95% were on antiretroviral therapy (80% undetectable), with a mean duration of 7 years (3-11) on ART.
The prevalence of high-risk attenuated or positively remodeled plaque was significantly higher for in the HIV-positive group (7.9% vs zero for the highest risk three feature analysis, p=0.02), with HIV patients having higher numbers of plaques (0-4 plaques, p=0.01), with a significant association with HIV status in the adjusted analysis (p=0.02).
Several inflammatory and immune markers were higher in the HIV-positive group including IL-6 (p=0.01), LPS (p=0.0004) and sCD163 (p=0.0007) but not d-dimer (p=0.93), CRP (p=0.49) or MCP-1 (p=0.13), with a trend for sCD14 (p=0.08) but in the multivariate model, only sCD163 retained a strong association with risk of vulnerable plaque (p=0.009).
In the question session, the non-prediction of age and smoking was explained by these traditional factors having a close association with calcified but not non-calcified plaque and that these are relatively young patients (mean age 44) who have had little time to build up coronary calcium.
This group also studied a small group of elite controllers, compared to HIV-positive suppressed patients and HIV-negative controls, but reported few differences, perhaps to low numbers under-powering comparisons.3
It is also notable that a late breaker poster from the same group reported similarly higher plaque (34.7 vs 12.0%, p = 0.04) and correlation to increased sCD163 (p=0.006) in 60 HIV-positive women (median age 47, HIV duration 15 years, 84% undetectable), compared to 30 HIV-negative controls.4
These studies were important for their focus on patients with sub-clinical atherosclerosis. The highlight specific potential risks for HIV-positive patients related to immune activation that are additional to traditional risks seen in general population studies and which occur even with suppressed viral load.
Coranry calcium burden, which may be the most predictive for future events was not different by HIV status in the MACS cohort.
While coronary artery calcification score is important in the general population non-calcified plaques have been found to be important as well.
Non-calcified plaques appear to be more vulnerable for getting dislodged from the arterial wall and get thrombus in the distal places. These finding may have implications for the risk of myocardial infarctions and optimal timing for CVD screening for aging in HIV-positive patients.
Unless stated otherwise, all references are to the Programme and Abstracts of the 20th Conference on Retroviruses and Opportunistic Infections, 3-6 March 2013, Altanta, GA.
- Post W et al. Age and noncalcified coronary plaque in the Multicenter AIDS Cohort Study. 20th CROI, 3-6 March 2013, Atlanta. Oral abstract 62. Fourth webcast.
- M Zanni et al. Increased coronary atherosclerotic plaque vulnerability features on computed tomography angiography among HIV+ subjects vs matched HIV- controls. 20th CROI, 3-6 March 2013, Atlanta. Oral abstract 63. Fifth webcast.
- Post W et al. Elite controllers and coronary plaque in the Multicenter AIDS Cohort Study. 20th CROI, 3-6 March 2013, Atlanta. Poster abstract 758.
- Fitch K et al. Non-calcified coronary plaque and macrophage activation markers are increased in HIV+ women. 20th CROI, 3-6 March 2013, Atlanta. Late breaker poster abstract 185LB.
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Satyajit Das is with University Hospital Coventry.