Serum Tryptophan-Derived Quinolinate and Indole-3-Acetate Are Associated With Carotid Intima-Media Thickness and its Evolution in HIV-Infected Treated Adults.

BACKGROUND: HIV-infected individuals undergoing effective antiretroviral therapy (ART) present an increased risk of atherosclerotic cardiovascular disease. We identified serum metabolites associated with carotid intima-media thickness (c-IMT) and its evolution. METHODS: One hundred forty-three hydrophilic serum metabolites were measured by ultraperformance liquid chromatography coupled with high-resolution mass spectrometry in 49 HIV+ ART+, 48 HIV+ ART-naïve and 50 HIV-negative, age-matched, never-smoking male triads. Metabolites differentially altered between groups ("features") were defined as having a Benjamini-Hochberg-adjusted P value <.05 from a t test and >0.25 log2 absolute mean fold change in metabolite levels. c-IMT was measured across 12 sites at inclusion in all individuals and at the carotid artery (cca) after a median of 5.1 years in 32 HIV+ ART+ individuals. The difference in c-IMT (cross-sectional analysis) and slope of cca-IMT regression/progression per year (longitudinal analysis) for each log10 (area) increase in metabolite level were estimated with linear regression. RESULTS: Compared with HIV-, metabolite features of HIV+ ART+ were increased N6,N6,N6-trimethyl-L-lysine and decreased ferulate and 5-hydroxy-L-tryptophan, whereas features of HIV+ ART-naïve were increased malate, kynurenine, 2-oxoglutarate, and indole-3-acetate and decreased succinate and 5-hydroxy-L-tryptophan. In HIV+ ART+ individuals, quinolinate and/or indole-3-acetate were positively associated with c-IMT (P < .03), cca-IMT (P < .03), and cca-IMT progression (P < .008). These associations were not observed in HIV+ ART-naïve or HIV-negative individuals. In HIV+ ART+ individuals, the metabolites xanthosine and uridine, from nucleotide metabolism, and g-butyrobetaine, from lysine/dietary choline degradation, were also positively or negatively associated with c-IMT and/or cca-IMT (all P < .01), but not its evolution. CONCLUSIONS: In these highly selected HIV-positive ART-controlled males, 2 novel metabolites derived from tryptophan catabolism, indole-3-acetate and quinolinate, were associated with c-IMT and its progression.

Aortic stiffness aging is influenced by past profound immunodeficiency in HIV-infected individuals: results from the EVAS-HIV (EValuation of Aortic Stiffness in HIV-infected individuals).

OBJECTIVE: We compared aortic stiffness between HIV-infected and HIV-uninfected individuals and examined the determinants of vascular aging during HIV infection. METHODS: Aortic stiffness using carotid-femoral pulse wave velocity (cf-PWV) was evaluated cross-sectionally between HIV-infected individuals and uninfected controls frequency-matched for age and sex, and longitudinally in a subgroup of HIV-infected individuals. Determinants of elevated cf-PWV levels were assessed using logistic regression. Changes in cf-PWV levels during follow-up (mixed-effect linear regression) and risk factors for achieving cf-PWV below (Group 1) or above the median (Group 2) at last follow-up visit were evaluated only in HIV-infected individuals. RESULTS: A total of 133 HIV-infected and 135 HIV-uninfected individuals (mean age: 47.7 ±â€Š8.9 years, 91% men) were enrolled. Median cf-PWV at baseline was similar between HIV-infected individuals and controls [7.5 m/s (interquartile range = 6.7-8.4) vs. 7.5 m/s (interquartile range = 6.6-8.4), respectively; P = 0.64]. In multivariable analysis, only mean arterial pressure showed significant association with elevated cf-PWV in the overall population (P = 0.036). In HIV-infected individuals, elevated cf-PWV was associated with current smoking (P = 0.042), and nadir CD4 T-cell count less than 200 cells/µl (P = 0.048). Ninety-one HIV-infected individuals were followed for a mean 7.6 ±â€Š2.0 years. cf-PWV progression was associated with age (P = 0.018), mean arterial pressure (P = 0.020), and nadir CD4 T-cell count (P = 0.005). Patients from Group 2 had higher baseline waist circumference, pulse pressure, and nadir CD4 T-cell count less than 200 cells/µl. CONCLUSION: We observed no difference in aortic stiffness between HIV-infected and controls. Moreover, aortic stiffness aging was independently associated with past severe immunodeficiency, along with other traditional risk factors. Our results call for early antiretroviral initiation.

Association of residual plasma viremia and intima-media thickness in antiretroviral-treated patients with controlled human immunodeficiency virus infection.

BACKGROUND: While residual plasma viremia is commonly observed in HIV-infected patients undergoing antiretroviral treatment (ART), little is known about its subclinical consequences. METHODS: This cross-sectional study included 47 male, never-smoking, non-diabetic patients with ≥4 years of ART and controlled HIV-replication (HIV-viral load, VL <20 copies/mL for ≥1 year). Residual HIV-VL was measured using an ultrasensitive assay (quantification limit: 1 copy/ml). Patients were categorized as having detectable (D; 1-20 copies/mL, n = 14) or undetectable (UD; <1 copies/mL, n = 33) HIV-VL. Linear regression was used to model the difference in total carotid intima-media thickness [c-IMT, measures averaged across common carotid artery (cca), bifurcation, and internal carotid artery] and cca-IMT alone across detection groups. Multivariable models were constructed for each endpoint in a forward-stepwise approach. RESULTS: No significant differences were observed between viremia groups with respect to median ART-duration (9.6 years, IQR = 6.8-10.9), nadir CD4+T-cell (208/mm3, IQR = 143-378), and CD4+T-cell count (555/mm3, IQR = 458-707). Median adjusted inflammatory markers tended to be higher in patients with D- than UD-viremia, with differences in IL-10 being significant (p = 0.03). After adjustment on age, systolic blood pressure, and insulin resistance, mean cca-IMT was significantly lower in patients with undetectable (0.668 mm±0.010) versus detectable viremia (0.727 mm±0.015, p = 0.002). Cca-IMT was also independently associated with age and insulin resistance. Mean adjusted total c-IMT was no different between viremia groups (p = 0.2), however there was large variability in bifurcation c-IMT measurements. CONCLUSIONS: Higher cca-IMT was observed in patients with detectable, compared to undetectable, HIV-VL in never-smoking ART-controlled patients, suggesting that residual HIV viremia may be linked to atherosclerosis.

Infection duration and inflammatory imbalance are associated with atherosclerotic risk in HIV-infected never-smokers independent of antiretroviral therapy.

OBJECTIVES: To determine whether the reported increased atherosclerotic risk among HIV-infected individuals is related to antiretroviral therapy (ART) or HIV infection, whether this risk persists in never-smokers, and whether inflammatory profiles are associated with higher risk. DESIGN: Matched cross-sectional study. METHODS: A total of 100 HIV-infected patients (50 ART-treated >4 years, 50 ART-naive but HIV-infected >2 years) and 50 HIV-negative controls were recruited in age-matched never-smoking male triads (mean age 40.2 years). Carotid intima-media maximal thickness (c-IMT) was measured across 12 sites. Pro-inflammatory [highly sensitive C-reactive protein (hs-CRP), resistin, interleukin-6, interleukin-18, insulin, serum amyloid A, D-dimer) and anti-inflammatory (total and high molecular weight adiponectin, interleukin-27, interleukin-10) markers were dichotomized into high/low scores (based on median values). c-IMT was compared across HIV/treatment groups or inflammatory profiles using linear regression models adjusted for age, diabetes, hypertension, and, for HIV-infected patients, nadir CD4 cell counts. RESULTS: Although adjusted c-IMT initially tended to be thicker in ART-exposed patients (P=0.2), in post-hoc analyses stratifying by median HIV duration we observed significantly higher adjusted c-IMT in patients with longer (>7.9 years: 0.760±0.008 mm) versus shorter prevalent duration of known HIV infection (<7.9 years: 0.731±0.008 mm, P=0.02), which remained significant after additionally adjusting for ART (P=0.04). Individuals with low anti-inflammatory profile (median score) had thicker c-IMT (0.754±0.006mm versus 0.722±0.006 mm, P<0.001), with anti-inflammatory markers declining as prevalent duration of HIV infection increased (P for linear trend <0.001). CONCLUSION: Known HIV duration is related to thicker c-IMT, irrespective of ART, in these carefully selected age-matched never-smoking HIV-treated and ART-naive male individuals. Higher levels of anti-inflammatory markers appeared protective for atherosclerosis.

Decrease in left atrium volume after successful balloon mitral valvuloplasty: an echocardiographic and hemodynamic study.

BACKGROUND: Left atrium (LA) remodeling has a crucial adverse impact on outcome and prognosis in mitral stenosis. Few studies have reported the effect of balloon mitral valvuloplasty (BMV) on LA volume. The aim of this study was to assess the evolution of LA volume immediately and 1 month after successful BMV in patients in sinus rhythm. METHODS: Thirty-three consecutive patients (70% women; age 31 ± 8 years; range 19-45) with moderate to severe mitral stenosis (mitral valve area ≤1.5 cm(2) ) who underwent successful BMV were included prospectively. Using two-dimensional echocardiography, and according to the prolate ellipse method, LA volume and LA volume indexed to body surface area were determined before BMV, and 24 hours and 1 month after BMV. Tricuspid and pulmonary regurgitation jets were recorded systematically using continuous-wave Doppler. Pulmonary artery-right ventricular (PA-RV) gradients, reflecting pulmonary pressures, and pulmonary vascular resistance were measured. RESULTS: Mitral valve area increased from 0.88 ± 0.16 to 1.55 ± 0.26 cm(2) (P < 0.0001). Mean mitral valve gradient (MVG) decreased from 16 ± 6 to 6 ± 2 mmHg (P < 0.0001) immediately after BMV. Indexed LA volume fell from 56 ± 14 to 48 ± 12 mL/m(2) (P = 0.0002) immediately after BMV and to 45 ± 13 mL/m(2) at 1 month (P < 0.0001). Only patients with a median LA volume ≥55 mL/m(2) before BMV had a significant reduction in LA volume (P = 0.0001). Decrease in LA volume was correlated with decreases in PA-RV peak diastolic gradient (r = 0.45, P = 0.008) and MVG (r = 0.35, P = 0.04). CONCLUSION: In patients with mitral stenosis in sinus rhythm, successful BMV results in an immediate decrease in LA volume. This reduction, maximal immediately after BMV, correlates with decreases in MVG and PA-RV peak diastolic gradient, and is significant only when LA volume before BMV is severely enlarged.

Is the aortic root dilated in obstructive sleep apnoea syndrome?

BACKGROUND: Obstructive sleep apnoea syndrome (OSAS) is associated with an increased risk of arterial hypertension (AH), coronary artery disease, atrial arrhythmias, heart failure, stroke and death. Whether OSAS influences aortic root size has not been fully investigated. The aim of our study was to investigate aortic root diameter and aortic stiffness in OSAS. METHODS: Using transthoracic Doppler echocardiography, we evaluated 76 patients with OSAS (mean age 52.7 +/- 9.5 years, 70 men [92%]) with no overt cardiovascular disease. The following parameters were measured offline: aortic diameter at Valsalva sinuses, aortic regurgitation (AR) grade, left ventricular (LV) mass, LV ejection fraction (LVEF, Simpson rule), systolic pulmonary artery pressure (sPAP). Aortic stiffness (carotid-femoral pulse wave velocity, PWV) was measured non-invasively using SphygmoCor technology. RESULTS: Mean duration of OSAS was four years and 84% of patients were being treated with continuous positive airway pressure. AH was documented in 39 (51%) patients. The mean aortic root diameter was 35.3 +/- 3.8 mm (26.9-44.6 mm) and the prevalence of aortic root dilatation was 3.9% (3 of 76 patients). On univariate analysis, age and sex were significant predictors of aortic root dilatation whereas arterial hypertension was not. CONCLUSIONS: The prevalence of aortic root enlargement was not increased in OSAS. Only age and sex and not arterial hypertension, were associated with aortic dilatation.