The characteristics of the 2,789 study participants are shown in ; two-thirds were from the WIHS, the median age was 44.3 years (range 20.2-83.0), and 48% were African-American. More than one-half of the participants were overweight or obese (body mass index (BMI) > 25), 21% had low-density lipoprotein-cholesterol (LDL-c) greater than 3.38 mmol/L (130 mg/dl), 30% had high-density lipoprotein-cholesterol (HDL-c) lower than 1.04 mmol/L (40 mg/dl), and 11% had systolic blood pressure (SBP) above 140 mmHg. Diabetes mellitus (DM) was documented in 16% of participants, but only 5% of those who were fasting at the time of the study visit had a fasting glucose level > 6.94 mmol/L (125 mg/dl). Approximately two-thirds (69%) of participants were infected with HIV, among whom 13% had a CD4+ cell count less than 200 (cells/ml) and 70% were taking HAART at the time of the ultrasound examination.
Cohort characteristics at the time of the carotid ultrasound evaluation and univariate comparisons of each characteristic with carotid distensibility.
In addition to the gender difference between the MACS and WIHS cohorts, the distributions of all other characteristics included in differed significantly between the cohorts except diabetes, fasting glucose, and the duration of HAART exposure among those who were taking HAART at the time of the examination. Compared to HIV-uninfected participants, those infected with HIV were significantly less likely to have education beyond high school, more likely to have a history of injection drug use (IDU), more likely to have a family history of MI, and had significantly lower BMI, LDL-c, and SBP levels (data not shown).
Overall, the median carotid distensibility was 16.8 × 10-6N-1m2, and the relationship between distensibility and age was similar in the two cohorts (). In univariate analyses, distensibility was significantly associated with age, race/ethnicity, history of injection drug use, family history of MI, and all the clinical characteristics included in . Distensibility was also significantly lower among persons infected with HIV and among current HAART users who had initiated HAART more than 5 years earlier.
Figure 1 Natural log transformed carotid arterial distensibility by age, stratified by cohort (blue: Women’s Interagency HIV Study (WIHS), black: Multicenter AIDS Cohort Study (MACS)). The vertical dashed line corresponds to age 40 which was an eligibility (more ...)
HIV infection remained significantly associated with lower distensibility (PD -4.3, 95% CI -7.4 to -1.1) in the multiple regression analysis (). The effect of HIV was greater in the MACS (PD -5.5) than in the WIHS (PD -1.9), but the difference between the cohorts was not statistically significant (p-value for interaction 0.24). Other characteristics that were independently associated with lower distensibility in this model were older age, African-American and Hispanic race/ethnicity, higher BMI, higher LDL-c, lower HDL-c, and higher SBP. We then added covariates for the use of blood pressure medications and cholesterol lowering medications to the regression models, but these cofactors were not independently associated with distensibility (data not shown) and their inclusion did not alter any inferences drawn from the results in .
Carotid arterial distensibility by human immunodeficiency virus (HIV), adjusted for demographic, behavioral, and clinical cofactors.
To examine the association between HIV-related immunosuppression and distensibility, we stratified the HIV infected subgroup by CD4+ cell count. HIV-infected participants with fewer than 200 CD4+ cells had significantly less distensible carotid arteries (PD -10.5, 95% CI -14.5 to -6.2) (, model 1) compared to those who were not infected with HIV, and the association between advanced HIV-related immunosuppression and distensibility did not differ significantly between MACS (PD -6.9) and WIHS (PD -9.2) (p-value for interaction 0.46) or between African-Americans (PD -9.9) and non-African-Americans (PD -9.5) (p-value for interaction 0.42).
Carotid arterial distensibility by CD4+ cell count and highly active antiretroviral therapy (HAART) use.
Among the 1931 HIV-infected participants, distensibility was significantly lower among those taking HAART in the MACS (PD -4.2, 95% CI -7.0 to -1.4), but not in the WIHS or in the overall model (, model 2). Among the 1317 HAART users, distensibility was also significantly lower in MACS participants who had been taking HAART for more than 5 years (PD -4.6, 95% CI -8.5 to -0.6), but duration of HAART use was not significantly associated with distensibility in the WIHS or overall models (, model 3). Finally, distensibility was similar among participants taking PI-based and non-PI-based HAART regimens (, model 4).