HIV-infected patients receiving antiretroviral therapy have an increased risk for cardiovascular disease. Several studies presented at the 12th CROI meeting attempted to assess cardiovascular disease risk in treated patients as compared to untreated HIV-infected patients and the general population.

C-Reactive Protein Levels in Patients with HIV: A Marker of Cardiovascular Risk or Chronic Infection?
P Hsue, J Lo, A Franklin, N Younes, et al.

This study is highly relevant to clinical practice. I as well as colleagues recently adopted the use of high-sensitivity C-reactive protein (CRP) as a predictor of stroke and myocardial infarction. I have been concerned that CRP levels may be elevated as a result of HIV infection itself, and the magnitude of increase may reflect a lack of viral control, thereby masking its ability as a marker of atherosclerosis. The results of this study indicate that I may have guessed correctly.

In this study, HIV-infected patients had higher CRP levels than HIV-uninfected, age-matched patients. Infected patients were also more likely to have CRP values above 10 mg/L (CRP levels >3.0 mg/L indicate high cardiovascular risk). These patients also had higher levels of carotid intimal thickness (a strong predictor of cardiovascular risk), but these levels did not correlate with CRP levels. Thus, CRP levels were not helpful in determining and monitoring the risk of cardiovascular disease.

Metabolic Syndrome and Markers of Early Atherosclerosis in a Cohort of HIV-infected Subjects
from Nutrition for Healthy Living
A Mangili, D Jacobson, J Gerrior, et al.

This study measured common internal carotid artery intramedial thickness and coronary calcium scores in HIV-infected patients with the metabolic syndrome. The investigators concluded these patients had greater carotid thickness and higher calcium scores

The subclinical atherosclerosis reflected by these measurements coupled with the presence of the metabolic syndrome helps identify those patients at greater cardiovascular risk and who should be treated aggressively.

Rapid Progression of Carotid Lesions in HAART-treated HIV-1 Patients
P Maggi, F Perilli, A Lillo, et al.

In this study, HIV-infected patients with premature (for their age) carotid lesions were followed over 24 months to assess cardiovascular disease progression. Of 102 patients, 51 were on protease inhibitor (PI)–based HAART and 51 were on nonnucleoside reverse transcriptase inhibitor–based treatment. Doppler studies were done at 12 and 24 months. Both groups had a high rate of plaque worsening with a faster progression in the PI group.

These results suggest the avoidance of PI-based regimens in patients with cardiac risk factors and underscore the need for close monitoring of these patients.

Lack of Evidence of Abnormal Myocardial Perfusion in HAART-treated, HIV-infected Mexican Patients
A Catzin-Kuhlmann, A Orea, L Castillo, et al.

This study tested the hypothesis that HIV-infected patients were more likely to have an abnormal myocardial perfusion compared with uninfected, age- and gender-matched individuals. Radionuclide imaging was done for 105 HIV-infected patients selected randomly from those attending an HIV clinic in Mexico City and for a community sample of 105 HIV-negative patients.

The patients were also assessed for dietary habits, blood pressure, body composition, plasma lipid profile, serum glucose, and homocysteine, At the initiation of antiretroviral treatment, the mean time from HIV diagnosis was 55 months. In the HIV-positive group, 91% had received combination therapy with 72% having received a protease inhibitor (PI). In the HIV group, 33% were current smokers.  The results showed that abnormal myocardial perfusion scans were found in 5% of the HIV-infected patients and 7.6% of the uninfected subjects. The severity of the abnormalities was similar in both groups.

The interesting findings in this trial are limited by the subjects being on HAART for only relatively short periods of time. Patients were on nucleoside reverse transcriptase inhibitors (NRTIs) for an average of 41 months, PIs for 7 months, and nonnucleoside reverse transcriptase inhibitors NNRTIs for 19 months. Patients had known HIV infection for an average 55 months. Ninety-one percent received combination antiretroviral therapy, 72% received a PI-containing regimen and 70% a NNRTI regimen.

One possible factor affecting the outcome of this study is that some cardiovascular risk factors (e.g., dyslipidemia, elevated  homocysteine and glucose levels) were not identified. I would like to see this study continued to learn if the HIV-infected group eventually developed heart disease and the extent of any disease compared to the group without HIV infection.

The Effect of HAART Initiation on Blood Pressure
E Seaberg, S Riddler , J Margolick , et al
The Association between Increasing Blood Pressure and Use of NNRTI and Lopinavir/Ritonavir
H Crane, S Van Rompaey, M Kitahata

The HAART/blood pressure study showed that initiating HAART results increased systolic and diastolic blood pressure, particularly among men with more advanced HIV disease before they started HAART. Among all men, each year of HAART resulted in a 6-mmHg increase in systolic blood pressure while the diastolic blood pressure remained constant. Therefore, the positive correlation between HAART exposure and higher systolic blood pressure suggests that these men may have an increased risk of clinical events related to hypertension.

In the second blood pressure study, the results showed an annual increase of 0.6 mmHg in systolic blood pressure in men with advanced HIV disease after they initiated antiretroviral treatment. This increase portends an increased risk of clinical events in HIV-infected patients receiving antiretroviral therapy. Additionally, the systolic increases occurred more so in patients on nonnucleoside reverse transcriptase inhibitor (NNRTI)–based regimens and on lopinavir/ritonavir versus those receiving single protease inhibitor (PI) regimens.

Perhaps boosted PIs and NNRTIs with their tendency to increase lipids should be avoided in patients with known cardiovascular risk.

My only concern about these two blood pressure studies is that the issue of heightened risk of heart disease may be confounded by the development of lipoatrophy and increase in abdominal girth. I also have noticed that there is an increase in systolic hypertension with patients as their HIV disease progresses. Is the increase in blood pressure in treated HIV patients a direct consequence of their treatment per se or simply an after effect of developing lipodystrophy and abdominal girth? This could explain why patients with HIV disease are quicker to develop hypertension.