Mean Coronary Cross-Sectional Area as a Measure of Arterial Remodeling Using Noncontrast CT Imaging in Persons With HIV

Abstract

Background Persons with HIV have a higher prevalence of coronary artery disease compared with their HIV-negative counterparts. Earlier identification of subclinical atherosclerosis may provide a greater opportunity for cardiovascular disease risk reduction. We investigated coronary cross-sectional area (CorCSA) by noncontrasted computed tomography imaging as a noninvasive measure of arterial remodeling among virally suppressed persons with HIV. Methods and Results We assessed 105 persons with HIV with a spectrum of cardiometabolic health. All participants underwent computed tomography imaging to assess the mean corCSA of the proximal left anterior descending artery and 28 participants underwent additional coronary computed tomography angiography. Partial Spearman rank correlations adjusted for cardiovascular disease risk factors were used to assess relationships of corCSA with anthropometric measurements, HIV-related factors, and plasma cytokines. Mean corCSA measured by noncontrast computed tomography and coronary computed tomography angiography were strongly correlated (ρ=0.91, P<0.0001). Higher mean corCSA was present in those with coronary artery calcium (P=0.005) and it correlated with participants' atherosclerotic cardiovascular disease risk score (ρ=0.35, P=0.01). After adjusting for established cardiovascular disease risk factors, we observed an inverse relationship between corCSA and CD4+ T-cell count (ρ=-0.2, P=0.047). Removal of age from the model strengthened the relationships between corCSA and antiretroviral therapy duration (from ρ=0.19, P=0.08 to ρ=0.3, P=0.01). CorCSA was also inversely correlated with plasma IL-10 (ρ=-0.25, P=0.03) but had no relationship with IL-6 (ρ=0.11, P=0.4) or IL-1β (ρ=0.08, P=0.5). Conclusions Positive coronary arterial remodeling, an imaging marker of subclinical atherosclerosis, is associated with a lower CD4 T-cell count, lower circulating IL-10, and possibly a longer antiretroviral therapy duration in persons with HIV. Registration Clinicaltrials.gov; Unique identifier: NCT04451980.

Keywords: cardiovascular diseases; coronary arterial calcium; coronary artery disease; cross‐sectional area; glycated hemoglobin A; interleukin‐10; interleukin‐6.

Figures

Figure 1. Mean corCSA is higher with coronary calcium and correlated with ASCVD risk.

Representative computed tomography image (CT) demonstrating the technique for measuring coronary cross‐sectional area (corCSA) of the proximal left anterior descending coronary artery (LAD) using previously published methods. The proximal 1.0 cm of the LAD was identified, at 3 equidistant points as labeled a, b, and c. The corCSA includes the area of the wall of the vessel as well as the lumen. Mean corCSA is the average of all 3 areas (A). Notched box plots showing mean corCSA by diabetes status (B) and by quantifiable calcium on CT imaging (C). Box plots showing current atherosclerotic cardiovascular disease (ASCVD) risk score in persons with HIV (PWH) with and without coronary artery calcium (CAC) (D) and correlation between ASCVD risk score and corCSA (E). Correlation plot of corCSA measurements obtained by noncontrast CT and coronary computed tomography angiography imaging (n=28). Analyses were performed using Kruskal–Wallis test (B), Mann–Whitney U tests (C and D), and Spearman rank correlation (E and F).

Figure 2. Mean coronary cross‐sectional area (corCSA) correlation with cardiovascular disease risk factors.

Unadjusted Spearman rank correlation plots of mean corCSA and weight (A), height (B), body mass index (C), waist circumference (D), age (E), low‐density lipoprotein cholesterol (LDL) (F), high‐density lipoprotein cholesterol (HDL) (G), hemoglobin A1c (H), triglycerides (I), and creatinine (J). Statistical analyses were performed using Spearman rank correlation.

Figure 3. Mean coronary cross‐sectional area (corCSA) correlates with age and waist circumference in adjusted models.

Partial Spearman rank correlation analysis adjusted for hypertension (HTN), smoker status, sex, statin use, and coronary artery calcium (CAC) prevalence in all persons with HIV (PWH) (n=105) (A), PWH without diabetes (n=38) (B), and PWH who were prediabetic/diabetic (n=68) (C). HDL indicates high‐density lipoprotein cholesterol; HsCRP, high‐sensitivity C‐reactive protein; and LDL, low‐density lipoprotein cholesterol.

Figure 4. Mean coronary cross‐sectional area (corCSA) positively correlates with duration of antiretroviral therapy (ART), cell‐associated HIV RNA/DNA, and negatively with CD4 T cell count.

Unadjusted correlation plots of mean corCSA and duration of ART in all persons with HIV (PWH) by diabetes status (A) and sex (B). Similar correlation plot of mean corCSA and HIV age (a calculation of the duration of ART divided by age at study enrollment) stratified by metabolic status (C) and sex (D). Mean corCSA was also measured against CD4 T‐cell count at the start of therapy (E), CD4 at study enrollment (F), cell‐associated HIV RNA (G), and cell‐associated HIV DNA (H). Spearman rank test was used for statistical analysis. Note that the correlations are rank‐based whereas the slopes are based on the original data, and therefore, they may not always be in the same direction (eg, Spearman's correlation=−0.016 for those who were nondiabetic in (F), but slightly positive slope with Pearson's correlation=0.17, P=0.33).

Figure 5. Mean coronary cross‐sectional area (corCSA) is correlated with antiretroviral therapy (ART) duration and the current CD4 T‐cell count.

Partial Spearman correlation analysis adjusted for cardiovascular disease risk factors (A), and with age removed from the model (B). CAC indicates coronary artery calcium; CVD, cardiovascular disease; HbA1c, hemoglobin A1c; HTN, hypertension; and PWH, persons with HIV.

Figure 6. Mean coronary cross‐sectional area (corCSA) correlation with HIV risk factors differs by diabetes among all PWH.

Partial Spearman correlation analysis adjusted for HbA1c, sex, and waist circumference in PWH without diabetes with (A) and without age (B). A similar analysis in PWH with prediabetes and diabetes adjusted for HbA1c, waist circumference, HTN, sex, and CAC prevalence with (C) and without age (D). ART indicates antiretroviral therapy; CAC, coronary artery calcium; HbA1c, hemoglobin A1c; HTN, hypertension; and PWH, persons with HIV.

Figure 7. Mean coronary cross‐sectional area (corCSA) is negatively associated with plasma IL‐10.

Box plots showing plasma cytokines from nondiabetic, prediabetic combined with diabetic PWH (A). Forest plot showing the adjusted (age, sex, HbA1c, HTN, waist circumference, smoker status, statin use, and the presence of CAC) correlation between corCSA and cytokines in all PWH (B), PWH without diabetes adjusted for age, HbA1c, sex, and waist circumference (C), and PWH who were prediabetic/diabetic adjusted for age, HbA1c, sex, waist circumference, and the presence of CAC (D). Mann–Whitney test and partial Spearman rank test were used for statistical analysis. CAC indicates coronary artery calcium; HbA1c, hemoglobin A1c; HTN, hypertension; and PWH, persons with HIV.