Pre-ART Levels of Inflammation and Coagulation Markers Are Strong Predictors of Death in a South African Cohort with Advanced HIV Disease

BACKGROUND: Levels of high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and D-dimer predict mortality in HIV patients on antiretroviral therapy (ART) with relatively preserved CD4+ T cell counts. We hypothesized that elevated pre-ART levels of these markers among patients with advanced HIV would be associated with an increased risk of death following the initiation of ART. METHODS: Pre-ART plasma from patients with advanced HIV in South Africa was used to measure hsCRP, IL-6 and D-dimer. Using a nested case-control study design, the biomarkers were measured for 187 deaths and two controls matched on age, sex, clinical site, follow-up time and CD4+ cell counts. Odds ratios were estimated using conditional logistic regression. In addition, for a random sample of 100 patients, biomarkers were measured at baseline and 6 months following randomization to determine whether ART altered their levels. RESULTS: Median baseline biomarkers levels for cases and controls, respectively, were 11.25 vs. 3.6 mg/L for hsCRP, 1.41 vs. 0.98 mg/L for D-dimer, and 9.02 vs. 4.20 pg/mL for IL-6 (all p<0.0001). Adjusted odds ratios for the highest versus lowest quartile of baseline biomarker levels were 3.5 (95% CI: 1.9-6.7) for hsCRP, 2.6 (95%CI 1.4-4.9) for D-dimer, and 3.8 (95% CI: 1.8-7.8) for IL-6. These associations were stronger for deaths that occurred more proximal to the biomarker measurements. Levels of D-dimer and IL-6, but not hsCRP, were significantly lower at month 6 after commencing ART compared to baseline (p<0.0001). CONCLUSIONS: Among patients with advanced HIV disease, elevated pre-ART levels of hsCRP, IL-6 and D-dimer are strongly associated with early mortality after commencing ART. Elevated levels of inflammatory and coagulation biomarkers may identify patients who may benefit from aggressive clinical monitoring after commencing ART. Further investigation of strategies to reduce biomarkers of inflammation and coagulation in patients with advanced HIV disease is warranted. TRIAL REGISTRATION: Parent study: ClinicalTrials.gov NCT00342355

Cardiovascular symptoms and signs in evaluating cardiac murmurs in children

Background: The aim of the present study was to determine the usefulness of cardiovascular symptoms and signs in the recognition of significant congenital heart lesions that required surgical or catheter interventions in different pediatric age groups. Methods: A retrospective chart review was carried out of 110 patients with significant heart anomalies that required surgical or catheter interventions (group I) and 113 children, presenting with cardiac murmurs, with congenital heart conditions not requiring any interventions. (group II) Results: Clinical symptoms or signs were significantly more common in group I than in group II subjects (85% vs 32%, P < 0.0001). The odds of having significant lesions requiring interventions in the presence of either cardiovascular symptoms or signs were 37.5 (95% confidence interval [CI]: 6.5-218.1) for neonates, 14.5 (95%CI: 4.7-51.7) for infants, and 8.0 (95%CI: 3.3-19.2) for children and adolescents. In neonates, the negative predictive values of the absence of symptoms or signs in isolation were relatively low at 64% and 65%, respectively. In children beyond infancy, the positive predictive values of the presence of symptoms or signs in isolation were also low at 62% and 68%, respectively. Conclusions: Clinical assessment of cardiovascular symptoms and signs remains useful in the evaluation of the significance of pathological cardiac murmurs in children in the present era of technology. Nonetheless, the predictive values vary with different pediatric age groups. © 2008 Japan Pediatric Society.link_to_subscribed_fulltex