Context

Abnormalities in the osteoprotegerin (OPG)/receptor activator of nuclear factor-κB ligand (RANKL) axis have been observed in HIV-infected persons and have been implicated in cardiovascular disease (CVD) pathogenesis in the general population.

Objective

To determine associations of serum OPG and RANKL concentrations with HIV infection and subclinical atherosclerosis.

Design

Cross-sectional study nested within the Multicenter AIDS Cohort Study.

Setting

Four US academic medical centers.

Participants

There were 578 HIV-infected and 344 HIV-uninfected men.

Main outcome measures

Coronary artery calcium (CAC) was measured by noncontrast cardiac computed tomography, and coronary stenosis and plaque characteristics (composition, presence, and extent) were measured by coronary computed tomography angiography. All statistical models were adjusted for traditional CVD risk factors.

Results

OPG concentrations were higher, and RANKL concentrations were lower among HIV-infected men compared with HIV-uninfected men (P < 0.0001 each). Among HIV-infected men, higher OPG concentrations were associated with the presence of CAC, mixed plaque, and coronary stenosis >50%, but not with plaque extent. In contrast, among HIV-uninfected men, higher OPG concentrations were associated with the extent of both CAC and calcified plaque, but not with their presence. RANKL concentrations were not associated with plaque presence or the extent among HIV-infected men, but among HIV-uninfected men, lower RANKL concentrations were associated with greater extent of CAC and total plaque.

Conclusions

OPG and RANKL are dysregulated in HIV-infected men, and their relationship to the presence and extent of subclinical atherosclerosis varies by HIV status. The role of these biomarkers in CVD pathogenesis and risk prediction may be different in HIV-infected men.

Objective

To examine whether altered levels of adipokines, adipose-derived peptides associated with myocardial infarction in the general population, may contribute to subclinical coronary atherosclerosis in HIV-infected persons.

Design

Nested cohort study.

Methods

We studied HIV-infected (HIV+) and HIV-uninfected (HIV-) men in the Multicenter AIDS Cohort Study with noncontrast computed tomography (CT) to measure coronary artery calcium and regional adiposity; 75% additionally underwent coronary CT angiography to measure plaque composition and stenosis. Adiponectin and leptin levels were assessed. Multiple regression models were used to assess associations between adipokine levels and HIV disease parameters, regional adiposity, and plaque adjusted for age, race, HIV serostatus, and cardiovascular disease (CVD) risk factors.

Results

Significant findings were limited to adiponectin. HIV-positive men (n=493) had lower adiponectin levels than HIV-negative men (n=250) after adjusting for CVD risk factors (P<0.0001), which became nonsignificant after adjustment for abdominal visceral and thigh subcutaneous adipose tissue. Among HIV-positive men, lower adiponectin levels were associated with higher CD4 T-cell counts (P=0.004), longer duration of antiretroviral therapy (P=0.006), and undetectable HIV RNA levels (P=0.04) after adjusting for age, race, and CVD risk factors; only CD4 cell count remained significant after further adjustment for adipose tissue. In both groups, lower adiponectin levels were associated with increased odds of coronary stenosis more than 50% (P<0.007). Lower adiponectin levels were associated with increased extent of plaque in HIV-positive and of mixed plaque in HIV-negative men.

Conclusion

Adiponectin levels were lower in HIV-infected men and related to the severity of subclinical atherosclerosis, independent of traditional CVD risk factors.