Introduction:
Cardiovascular disease is a major contributor to morbidity and mortality among women living with HIV (WLWH). We previously found HIV infection to be associated with carotid artery plaque, a marker of subclinical atherosclerosis. Plaque morphology and composition may predict plaque rupture and cardiovascular disease events. We characterized the association of HIV-related factors with carotid plaque echomorphology in the WIHS.
Methods:
Using B-mode ultrasound, we characterized plaque (focal intima-media thickness >1.5 mm) at 6 locations in the right carotid artery in 1,722 participants (1,230 HIV+, 492 HIV-) of the WIHS, a cohort study of women with or at risk for HIV at 6 US sites. Plaque echomorphologic features included relative echogenicity (>50% of plaque is echolucent vs >50% of plaque is echogenic) and surface morphology (smooth vs irregular, i.e., height variations along contour of plaque). We used multinomial logistic regression to assess the odds of each feature vs no plaque comparing HIV+ and HIV- women, adjusting for demographic (e.g., age, race/ethnicity, socioeconomic status), behavioral (e.g., drug/alcohol use, smoking, HCV infection, smoking), cardiometabolic (e.g., systolic blood pressure, BMI, lipids, diabetes) and HIV-related risk factors (e.g., antiretroviral therapy use, current CD4+ T-cell count, AIDS). We further stratified WLWH by CD4+ count (<200, 200-499, 500+ cells/uL) and HIV-1 RNA suppression.
Results:
Among 1,722 women (median age 40, IQR 33-46, 59% black, 29% Hispanic, 71% HIV+), 160 (9%) had at least one carotid plaque (128 HIV+, 32 HIV-). In unadjusted analyses, WLWH had more echolucent plaque (5.3% vs 2.6%, p=0.02) and plaques with smooth surface (2.7% vs 0.6%, p=0.005) than HIV-negative women. After covariate adjustment, HIV serostatus remained significantly associated with smooth plaque (odds ratio [OR] 3.45, 95% CI 1.12-10.62) but not with echolucent plaque (OR 1.60, 95% CI 0.84-3.05). Stratified by HIV viremia, WLWH with unsuppressed HIV viremia had significantly more smooth plaque (OR 3.34, 95% CI 1.26-8.87) than HIV- women, whereas suppressed WLWH did not (OR 1.79, 95% CI 0.55-5.83). In a dose-response manner, lower CD4+ count among WLWH was associated with smooth plaque (e.g., OR for <200 cells/uL compared with HIV-negative women 7.43, 95% CI 1.46-37.87), and this association was of greater magnitude than that with irregular plaque (OR 2.46, 95% CI 1.14-5.32). Low CD4+ count was also associated with both echolucent (OR 3.36 for <200 cells/uL vs HIV-negative, 95% CI 1.29-8.77) and echogenic plaque (OR 2.65, 95% CI 1.18-5.96).
Conclusions:
Unsuppressed viremia and low CD4+ count, which are markers of suboptimal HIV care, were associated with certain echomorphologic features of carotid plaque. Further work should assess whether these features differentially lead to cardiovascular morbidity and mortality in WLWH.
Monocyte activation and cardiovascular disease in HIV infection