Assessment of arterial elasticity among HIV-positive participants with high CD4 cell counts: a substudy of the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial

Abstract

Objectives: Both HIV infection and antiretroviral therapy (ART) may increase cardiovascular disease (CVD) risk. Assessments of vascular function and structure can be used to study the pathogenesis and progression of CVD, including the effects of ART and other interventions. The objective of this report is to understand methods to assess vascular (dys)function and report our experience in the Arterial Elasticity Substudy in the Strategic Timing of AntiRetroviral Treatment (START) trial.

Methods: We review literature and analyze baseline data from the Arterial Elasticity Substudy, which estimated vascular (dys)function through analysis of the diastolic blood pressure (BP) waveform. Linear regression was used to study cross-sectional associations between baseline clinical factors and small or large arterial elasticity.

Results: Arterial elasticity measurement was chosen for its improved measurement reproducibility over other methodologies and the potential of small arterial elasticity to predict clinical risk. Analysis of baseline data demonstrates that small artery elasticity is impaired (lower) with older age and differs by race and between geographical regions. No HIV-specific factors studied remained significantly associated with arterial elasticity in multivariate models.

Conclusions: Longitudinal analyses in this substudy will provide essential randomized data with which to study the effects of early ART initiation on the progression of vascular disease among a diverse global population. When combined with future biomarker analyses and clinical outcomes in START, these findings will expand our understanding of the pathogenesis of HIV-related CVD.

Trial registration: ClinicalTrials.gov NCT00867048 NCT01776151.

Keywords: HIV infection; arterial elasticity; cardiovascular disease; vascular dysfunction.

© 2015 British HIV Association.

Figures

Figure 1. Analysis of the Blood Pressure (BP) Waveform Assessed at the Radial Artery

An example of a radial artery blood pressure (BP) waveform is presented with systole and diastole designated, along with early (P1) and late (P2) systolic peak. Analysis of the systolic pulse waveform is used to generate the peripheral augmentation index (AIx), which is defined as P2/P1 ratio. During diastole, the initial maxima represents capacitance of the proximal aorta and major branches following cardiac ejection. Contour effects later in diastole results from a rebound wave, reflecting elasticity in the smaller arteries. The approach applied in START Arterial Elasticty Substudy to analyse the diastolic BP waveform employs a mathematical model, which treats the circulatory system as a modified Windkessel model (converts intermittent flow from heart to continuous steady flow). This mathematical model estimates the large arterial elasticity (previously named proximal artery or capacitance compliance) and small arterial elasticity (previously named distal artery or oscillatory compliance).

Figure 2. Waveform Contour and Vessel Function Is Altered with HIV Infection

Reprinted with permission (JAIDS 2009) (32). Representative radial artery blood pressure (BP) waveforms are shown for an HIV-negative control (A) and an untreated HIV-positive participant (B). Waveforms are plotted by BP along the y-axis over time along x-axis, systole and diastole are estimated, and resting BP along with estimates of large and small arterial elasticity (LAE and SAE) are reported. Differences in contour can be appreciated throughout the pulse waveform, including during the diastolic decay that is analysed to estimate LAE and SAE values.