Subclinical Carotid Atherosclerosis in HIV-Infected Patients

Abstract

Background and Purpose-Whether or not combination antiretroviral therapy (CART) alone directly contributes to accelerating atherosclerosis in HIV-infected patients has not been studied in depth. This study aimed to ascertain the relationship between this therapy and subclinical carotid atherosclerosis according to cardiovascular risk. Methods-Sixty-eight HIV-infected patients with Յ1 cardiovascular risk factors and 64 with Ն2 risk factors completed the study protocol consisting of clinical, laboratory, and vascular evaluation by carotid high-resolution B-mode ultrasonography. Univariate and multivariate logistic regression analyses were performed with the presence of subclinical carotid atherosclerosis, defined by carotid intima-media thickness Ͼ0.8 mm or the presence of plaque being the dependent variable. Results-Among the 132 enrolled patients, 93 (70.5%) were on CART and 39 (29.5%) had never been on antiretroviral therapy. In accordance with cardiovascular risk stratification, subclinical carotid atherosclerosis was found in 26.6% (17 of 64 patients) of the very low-risk group (10-year coronary risk Ͻ5%), 35.3% (12 of 34 patients) of the low-risk group (10-year coronary risk between 5% and 9%) and 76.5% (26 of 34 patients) of the moderate/high-risk group (10-year coronary risk Ն10%). Thus, 55 (41.7%) of the 132 HIV-infected patients had subclinical carotid atherosclerosis, and independent variables associated with carotid atherosclerosis (odds ratio; 95% CI) were: CART exposure (10.5; 2.8 to 39) and 10-year coronary risk Ն10% (4.2; 1.5 to 12). In very low coronary risk patients (Ͻ5%), age (per 10-year increment: 4.01; 1.12 to 14.38), systolic blood pressure (per unit mm Hg 1.07; 1.01 to 1.14), and CART exposure (8.65; 1.54 to 48.54) were independently associated with subclinical carotid atherosclerosis. Conclusions-CART should be considered a strong, independent predictor for the development of subclinical atherosclerosis in HIV-infected patients, regardless of known major cardiovascular risk factors and atherogenic metabolic abnormalities induced by this therapy. (Stroke. 2006;37:812-817.)

High Prevalence of Carotid Plaque Identified Using Standard Carotid Ultrasound Techniques in HIV-Positive Patients with Low to Moderate Vascular Risk

“…Although protease inhibitor exposure was not significantly associated with abnormal carotid ultrasound in our analysis, we found that longer duration of antiretroviral therapy was associated with an abnormal result. This finding was also found in an observational study by Jericho [25]. One possible explanation for why we were unable to detect a significant association with protease inhibitors exposure could be related to the short follow-up time in our study.…”

“…Our results are consistent with the literature and they support the notion that certain traditional risk factors for HIV disease progression are important contributors to atherosclerotic disease in the HIV population. Previous observational studies that investigated the relationship between traditional risk factors and carotid ultrasound surrogate markers in HIV patients have found similar results [23][24][25][26]. However, our analysis failed to demonstrate a significant association between carotid ultrasound abnormality and other traditional risk factors such as dyslipidemia, diabetes mellitus, hypertension and smoking.…”

Cardiovascular complications in the acquired immunodeficiency syndrome

“…Similar results were also reported by Hsue et al 92 and by Currier et al 93 in case-control studies suggesting that traditional risk factors may contribute to atherosclerosis in HIV-infected patients independently of PI exposure. Alonso-Villaverde et al reported that HIV-infected patients with subclinical atherosclerosis have higher circulating levels of monocyte chemoattractant protein-1 (MCP-1), especially of the allele MCP-1-2518G, compared to patients without atherosclerotic lesions, independently of HAART regimen 94 .Different results were reported by Maggi et al who observed a higher than expected prevalence of premature carotid lesions in PI-treated patients compared to PI-naive patients 95 .Similar results have been reported in a study by Jerico et al in 68 HIV-infected patients 96 . These authors conclude, stating that HAART should be considered a strong, independent predictor for the development of subclinical atherosclerosis in HIV-infected patients, regardless of known major cardiovascular risk factors and atherogenic metabolic abnormalities induced by this therapy 96 .…”

Increasing incidence of ischemic stroke in patients with HIV infection

“…Similarly, longer exposure to HIV, even at low viral load levels, may allow for the direct effects of the virus to increase stroke risk. Second, combination antiretroviral therapy directly causes immune activation and metabolic and endothelial dysfunction that can accelerate atherosclerosis [9][10][11] and lead to symptomatic ischemic vascular events. 12,13 Third, hepatotoxicity is a known complication of combination antiretroviral drug treatment, 14 and in our multivariable analyses among factors independently linked to coexistent HIV infection with stroke hospitalization, mild liver disease had by far the strongest association.…”