Dataset Information

Relationship between inflammatory and coagulation biomarkers and cardiac autonomic function in HIV-infected individuals.

ABSTRACT: To examine the relationship between inflammatory and coagulation biomarkers and cardiac autonomic function (CAF) as measured by heart rate variability in persons with HIV.This analysis included 4073 HIV-infected persons from the Strategies for Management of Antiretroviral Therapy study. We examined the association between IL-6, high-sensitivity C-reactive protein (hsCRP) and D-dimer with heart rate variability measures (SDNN and rMSSD), both cross-sectionally and longitudinally.Cross-sectional analysis revealed significant inverse associations between IL-6, hsCRP and d-dimer with SDNN and rMSSD (p < 0.01 for all comparisons). However, longitudinal analysis failed to show a significant association between baseline IL-6, hsCRP and d-dimer with change in CAF over time.Cross-sectionally, higher levels of inflammatory and coagulation biomarkers were associated with lower levels of CAF in the Strategies for Management of Antiretroviral Therapy trial. Although deterioration in CAF was observed during followup, baseline levels of inflammatory and coagulation markers were not predictive of the decline in CAF over time.

SUBMITTER: Young LC

PROVIDER: S-EPMC4278423 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Relationship between inflammatory and coagulation biomarkers and cardiac autonomic function in HIV-infected individuals.

Young Lari C LC Roediger Mollie P MP Grandits Greg G Baker Jason J Somboonwit Charurut C Williams Ian I Lundgren Jens D JD Neaton James D JD Soliman Elsayed Z EZ

Biomarkers in medicine 20140101 9

<h4>Aim</h4>To examine the relationship between inflammatory and coagulation biomarkers and cardiac autonomic function (CAF) as measured by heart rate variability in persons with HIV.<h4>Materials & methods</h4>This analysis included 4073 HIV-infected persons from the Strategies for Management of Antiretroviral Therapy study. We examined the association between IL-6, high-sensitivity C-reactive protein (hsCRP) and D-dimer with heart rate variability measures (SDNN and rMSSD), both cross-sectiona ...[more]

PMID: 25402578

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Project description:ObjectivesThis study sought to determine whether biomarkers ST2, growth differentiation factor (GDF)-15, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity troponin I are elevated in patients infected with human immunodeficiency virus (HIV) and are associated with cardiovascular dysfunction and all-cause mortality.BackgroundHIV-infected patients have high rates of cardiovascular disease. Markers of myocardial stress may identify at-risk patients and provide additional prognostic information.MethodsBiomarkers and echocardiograms were assessed in 332 HIV-infected patients and 50 age- and sex-matched control subjects. Left ventricular systolic dysfunction was defined as ejection fraction <50%, diastolic dysfunction (DD) as stage 1 or higher, and pulmonary hypertension as pulmonary artery systolic pressure ≥35 mm Hg. Mortality data were obtained from the National Death Index.ResultsPatients with HIV had a median age of 49 years, and 80% were male. Compared with control subjects, HIV-infected patients had higher adjusted percent estimates of all biomarkers except ST2 and interleukin-6. Among HIV-infected patients, 45% had DD; only ST2 was associated with DD (relative risk [RR]: 1.36; p = 0.047). Left ventricular systolic dysfunction was rare in this cohort (5%). Pulmonary hypertension was present in 27% of HIV-infected patients and was associated with GDF-15 (RR: 1.18; p = 0.04), NT-proBNP (RR: 1.18; p = 0.007), and cystatin C (RR: 1.54; p = 0.03). Thirty-eight deaths occurred among HIV-infected patients over a median of 6.1 years. In adjusted analysis, all-cause mortality was independently predicted by ST2 (hazard ratio [HR]: 2.04; p = 0.010), GDF-15 (HR: 1.42; p = 0.0054), high-sensitivity C-reactive protein (HR: 1.25; p = 0.023), and D-dimer (HR: 1.49; p = 0.029). Relationships were unchanged when analyses were restricted to virally suppressed HIV-infected patients receiving antiretroviral therapy.ConclusionsAmong HIV-infected patients, ST2 and GDF-15 were associated with both cardiovascular dysfunction and all-cause mortality, and these variables may be useful at identifying those at risk for developing cardiovascular events and death.

Project description:ObjectiveInflammation may contribute to brain white matter health in people living with HIV who report cognitive symptoms despite adherence to combination antiretroviral therapy and viral suppression. We explored relationships between diffusion tensor imaging (DTI) metrics of white matter, plasma biomarkers of immune activation, and cognitive function in the HIV-infected population.DesignRetrospective study of older adults living with HIV who are combination antiretroviral therapy adherent, virally suppressed, and self-report cognitive symptoms.MethodsMRI, blood draws, and standardized neuropsychological test scores were collected from HIV-infected individuals. DTI metrics (fractional anisotropy, mean diffusivity, radial diffusivity, axial diffusivity) and plasma biomarkers (soluble CD163, soluble CD14, neopterin, IFN γ-induced protein 10, monocyte chemoattractant protein 1) were quantified. Statistical analysis explored associations between biomarker levels or neuropsychological test scores and DTI metrics using region of interest analyses and a voxelwise approach.ResultsA total of 43 participants with median (interquartile range) age of 64 (62-66 years), CD4 cell count of 600 (400-760 cell/μl) who were all virally suppressed (<100 copies/ml) were selected. Higher levels of monocyte chemoattractant protein 1 associated with lower fractional anisotropy and higher mean diffusivity (P < 0.05) across white matter tracts including corpus callosum, corona radiata, and superior longitudinal fasciculus. Higher neopterin associated with higher mean diffusivity in the genu of corpus callosum, and higher soluble CD14 associated with lower fractional anisotropy in the bilateral superior corona radiata (P < 0.05). Worse global performance and speed domain scores associated with higher mean diffusivity and lower fractional anisotropy, and worse executive domain scores associated with lower fractional anisotropy (P < 0.05).ConclusionElevated inflammatory plasma biomarkers link to white matter abnormalities among virally suppressed individuals. DTI abnormalities associate to cognitive performance. We conclude that inflammatory processes impact clinically relevant brain health indices despite viral suppression.

Project description:BackgroundIn the Strategies for Management of Anti-Retroviral Therapy trial, all-cause mortality was higher for participants randomized to intermittent, CD4-guided antiretroviral treatment (ART) (drug conservation [DC]) than continuous ART (viral suppression [VS]).We hypothesized that increased HIV-RNA levels following ART interruption induced activation of tissue factor pathways, thrombosis, and fibrinolysis.Methods and findingsStored samples were used to measure six biomarkers: high sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), amyloid A, amyloid P, D-dimer, and prothrombin fragment 1+2. Two studies were conducted: (1) a nested case-control study for studying biomarker associations with mortality, and (2) a study to compare DC and VS participants for biomarker changes. For (1), markers were determined at study entry and before death (latest level) for 85 deaths and for two controls (n = 170) matched on country, age, sex, and date of randomization. Odds ratios (ORs) were estimated with logistic regression. For each biomarker, each of the three upper quartiles was compared to the lowest quartile. For (2), the biomarkers were assessed for 249 DC and 250 VS participants at study entry and 1 mo following randomization. Higher levels of hsCRP, IL-6, and D-dimer at study entry were significantly associated with an increased risk of all-cause mortality. Unadjusted ORs (highest versus lowest quartile) were 2.0 (95% confidence interval [CI], 1.0-4.1; p = 0.05), 8.3 (95% CI, 3.3-20.8; p < 0.0001), and 12.4 (95% CI, 4.2-37.0; p < 0.0001), respectively. Associations were significant after adjustment, when the DC and VS groups were analyzed separately, and when latest levels were assessed. IL-6 and D-dimer increased at 1 mo by 30% and 16% in the DC group and by 0% and 5% in the VS group (p < 0.0001 for treatment difference for both biomarkers); increases in the DC group were related to HIV-RNA levels at 1 mo (p < 0.0001). In an expanded case-control analysis (four controls per case), the OR (DC/VS) for mortality was reduced from 1.8 (95% CI, 1.1-3.1; p = 0.02) to 1.5 (95% CI, 0.8-2.8) and 1.4 (95% CI, 0.8-2.5) after adjustment for latest levels of IL-6 and D-dimer, respectively.ConclusionsIL-6 and D-dimer were strongly related to all-cause mortality. Interrupting ART may further increase the risk of death by raising IL-6 and D-dimer levels. Therapies that reduce the inflammatory response to HIV and decrease IL-6 and D-dimer levels may warrant investigation.

Project description:BackgroundIt is unclear how cardiac autonomic function, as indicated by heart rate (HR), heart rate variability (HRV), HR increase during exercise, and HR recovery after exercise, is related to blood pressure (BP). We aimed to examine the observational and genetic evidence for a potential causal effect of these HR(V) traits on BP.MethodsWe performed multivariable adjusted linear regression using Lifelines and UK Biobank cohorts to investigate the relationship between HR(V) traits and BP. Linkage disequilibrium score regression was conducted to examine genetic correlations. We used two-sample Mendelian randomization (2SMR) to examine potential causal relations between HR(V) traits and BP.ResultsObservational analyses showed negative associations of all HR(V) traits with BP, except for HR, which was positively associated. Genetic correlations were directionally consistent with the observational associations, but most significant genetic correlations between HR(V) traits and BP were limited to diastolic blood pressure (DBP). 2SMR analyses suggested a potentially causal relationship between HR(V) traits and DBP but not systolic blood pressure (SBP). No reverse effect of BP on HR(V) traits was found. One standard deviation (SD) unit increase in HR was associated with a 1.82 mmHg elevation of DBP. In contrast, one ln(ms) unit increase of the root mean square of the successive differences (RMSSD) and corrected RMSSD (RMSSDc), decreased DBP by 1.79 and 1.83 mmHg, respectively. For HR increase and HR recovery at 50 s, every additional SD increase was associated with a lower DBP by 2.05 and 1.47 mmHg, respectively. Results of secondary analyses with pulse pressure as outcome were inconsistent between observational and 2SMR analyses, as well as between HR(V) traits, and therefore inconclusive.ConclusionBoth observational and genetic evidence show strong associations between indices of cardiac autonomic function and DBP, suggesting that a larger relative contribution of the sympathetic versus the parasympathetic nervous system to cardiac function may cause elevated DBP.

Dataset Information

Relationship between inflammatory and coagulation biomarkers and cardiac autonomic function in HIV-infected individuals.

Publications

Relationship between inflammatory and coagulation biomarkers and cardiac autonomic function in HIV-infected individuals.

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