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(Circulation. 2004;110:2204-2209.)
© 2004 American Heart Association, Inc.

Vascular Medicine

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

Carlos Alonso-Villaverde, MD; Blai Coll, MD; Sandra Parra, MD; Manuel Montero, MD; Nahum Calvo, MD; Mònica Tous, PhD; Jorge Joven, MD; Lluis Masana, MD

From the Servei de Medicina Interna (C.A.-V., S.P., L.M.), Institut de Recerca en Ciències de la Salut (B.C.), Servei de Radiologia (M.M., N.C.), and Centre de Recerca Biomèdica (M.T., J.J.) of the Hospital Universitari de Sant Joan, Reus, Spain.

Reprint requests to Carlos Alonso-Villaverde, MD, PhD, Servei de Medicina Interna, Hospital Universitari de Sant Joan, 43201 Reus, Spain. E-mail cavillaverde{at}grupsagessa.com

Received November 6, 2003; de novo received March 4, 2004; revision received May 13, 2004; accepted May 25, 2004.

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.

Key Words: atherosclerosis • HIV • inflammation • genotype • prevention

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