Abstract
BackgroundIn 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.MethodsProspective, 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.ResultsMyocardial 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).ConclusionMen 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 RegistrationNIH Clinical Trials NCT00656851
Highlights
In the general population, peripheral metabolic complications (MC) increase the risk for left ventricular dysfunction
We found that men with metabolic complications that include peripheral insulin resistance, with or without well-controlled Human immunodeficiency virus infection (HIV) infection, have altered myocardial glucose utilization per unit insulin and left ventricular relaxation and that these alterations appear to be interrelated
Total fat content measured by dual-energy X-ray absorptiometer (DXA) was greater in the groups with MC compared to the groups without MC, and total fat content in HIV-/MC+ was greater than all other groups (Table 1)
Summary
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. Individuals infected with the human immunodeficiency virus (HIV) are at a greater risk for cardiovascular disease [1], myocardial infarction [2], and left ventricular dysfunction [3,4,5] than the general population. The combination of impaired myocardial fatty acid metabolism (or decreased cardiac efficiency) and reduced myocardial glucose utilization, especially in the presence of metabolic inflexibility [32,33], may result in an impaired ability to generate ATP for contraction [34]. Impaired myocardial glucose utilization may limit the heart’s tolerance to ischemia, impair cardiac energetics and function [39,40] and predict worse outcomes following myocardial infarction [41]
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