Atherosclerosis in Patients Infected With HIV Is Influenced by a Mutant Monocyte Chemoattractant Protein-1 Allele

Abstract

Background— Patients infected with HIV present with premature atherosclerosis, and the 2 diseases share common pathogenic pathways. We investigated mutations in the monocyte chemoattractant protein-1 (MCP-1) and CCR-2 genes, which are known to control aspects of these pathways, to ascertain whether they are involved in atherogenesis in these patients. Methods and Results— We performed carotid and femoral artery ultrasonography to detect subclinical atherosclerosis in patients infected with HIV (n=183). MCP-1–2518G and CCR-2 64I polymorphisms were determined in the HIV group and in a population-based control group (n=348). We also determined MCP-1 circulating levels in the HIV group. The presence of MCP-1–2518G in the group of patients with subclinical atherosclerosis was significantly higher than in patients without atherosclerotic lesions (47.5% versus 18.2%, respectively; P <0.001). Furthermore, the patients with atherosclerotic lesions had higher MCP-1 plasma concentrations than did patients without lesions (74.15 [4.03] versus 57.81 [3.67] pg/mL, respectively; P =0.03). When adjusted for known cardiovascular risk factors, the MCP-1–2518G allele was associated with subclinical atherosclerosis (OR 5.72, 95% CI 1.74 to 18.80, P =0.004). Compared with measurements conducted ≈2.5 years earlier in a subset of 40 patients, intima-media thickness (IMT) in the carotid artery progressed at a mean rate of 0.06 mm/y more rapidly in patients bearing the MCP-1-mutated allele ( P =0.08). Conclusions— HIV-infected patients with the MCP-1–2518G allele have a 5-fold increased risk for atherosclerosis, as assessed by ultrasonography.

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

“…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.…”

Polymorphisms in CCL2&CCL5 chemokines/chemokine receptors genes and their association with diseases

“…There is evidence implicating the MCP-1-2518*G allele as a critical factor in the pathogenesis of various diseases accompanying HIV infection. Thus, the study by Alonso-Alonso-Villaverde et al showed that HIV-infected patients with the MCP-1-2518*G allele have a 5-fold increased risk for atherosclerosis 144 . Furthermore, GG homozygotes had 4.7-fold higher likelihood of developing HIV-associated dementia 27 .…”

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 .…”