Effects of human immunodeficiency virus and metabolic complications on myocardial nutrient metabolism, blood flow, and oxygen consumption: a cross-sectional analysis

W Todd Cade, Dominic N Reeds, E Turner Overton, Pilar Herrero, Alan D Waggoner, Victor G Davila-Roman, Sherry Lassa-Claxton, Robert J Gropler, Pablo F Soto, Melissa J Krauss, Kevin E Yarasheski, Linda R Peterson, W Todd Cade, Dominic N Reeds, E Turner Overton, Pilar Herrero, Alan D Waggoner, Victor G Davila-Roman, Sherry Lassa-Claxton, Robert J Gropler, Pablo F Soto, Melissa J Krauss, Kevin E Yarasheski, Linda R Peterson

Abstract

Background: In the general population, peripheral metabolic complications (MC) increase the risk for left ventricular dysfunction. Human immunodeficiency virus infection (HIV) and combination anti-retroviral therapy (cART) are associated with MC, left ventricular dysfunction, and a higher incidence of cardiovascular events than the general population. We examined whether myocardial nutrient metabolism and left ventricular dysfunction are related to one another and worse in HIV infected men treated with cART vs. HIV-negative men with or without MC.

Methods: Prospective, cross-sectional study of myocardial glucose and fatty acid metabolism and left ventricular function in HIV+ and HIV-negative men with and without MC. Myocardial glucose utilization (GLUT), and fatty acid oxidation and utilization rates were quantified using 11C-glucose and 11C-palmitate and myocardial positron emission tomography (PET) imaging in four groups of men: 23 HIV+ men with MC+ (HIV+/MC+, 42 ± 6 yrs), 15 HIV+ men without MC (HIV+/MC-, 41 ± 6 yrs), 9 HIV-negative men with MC (HIV-/MC+, 33 ± 5 yrs), and 22 HIV-negative men without MC (HIV-/MC-, 25 ± 6 yrs). Left ventricular function parameters were quantified using echocardiography.

Results: Myocardial glucose utilization was similar among groups, however when normalized to fasting plasma insulin concentration (GLUT/INS) was lower (p < 0.01) in men with metabolic complications (HIV+: 9.2 ± 6.2 vs. HIV-: 10.4 ± 8.1 nmol/g/min/μU/mL) than men without metabolic complications (HIV+: 45.0 ± 33.3 vs. HIV-: 60.3 ± 53.0 nmol/g/min/μU/mL). Lower GLUT/INS was associated with lower myocardial relaxation velocity during early diastole (r = 0.39, p < 0.001).

Conclusion: Men with metabolic complications, irrespective of HIV infection, had lower basal myocardial glucose utilization rates per unit insulin that were related to left ventricular diastolic impairments, indicating that well-controlled HIV infection is not an independent risk factor for blunted myocardial glucose utilization per unit of insulin.

Trial registration: NIH Clinical Trials NCT00656851.

Figures

Figure 1
Figure 1
(A) Myocardial glucose extraction fraction (%), and (B) Myocardial glucose utilization normalized to plasma insulin concentration (nmol/g/min/μU/mL) in HIV+ and HIV-negative men with and without metabolic complications (MC).
Figure 2
Figure 2
Lower myocardial glucose utilization per unit plasma insulin (i.e. lower insulin sensitivity) predicted worse left ventricular diastolic function among all men. MC = metabolic complications.
Figure 3
Figure 3
Myocardial glucose utilization plotted against fasting plasma insulin concentration. HIV-/MC- β = 7.36, HIV-/MC+ β = - 1.87, HIV+/MC- β = 0.37, HIV+/MC+ β = - 2.61.

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