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GlycA, a novel inflammatory marker, is associated with subclinical coronary disease.

ABSTRACT: OBJECTIVE:GlycA, a novel NMR biomarker of inflammation, has been associated with incident cardiovascular disease (CVD) in the general population, but its association with CVD among HIV-infected individuals is unknown. We examined the associations between GlycA and subclinical coronary plaque among HIV-infected and HIV-uninfected men participating in Multicenter AIDS Cohort Study (MACS). DESIGN:Cross-sectional analysis of 935 men with plasma measurement of GlycA and noncontrast cardiac computed tomography (CT) and/or coronary CT angiography. METHODS:We used multivariable Poisson and linear regression to assess associations of GlycA with prevalent coronary atherosclerosis and plaque extent, respectively. RESULTS:Mean?±?SD age was 54?±?7 years; 31% were black; 63% HIV-infected. GlycA levels were higher in HIV-infected compared with HIV-uninfected men (397?±?68 vs. 380?±?60??mol/l, P?=?0.0001) and higher for men with detectable viral load vs. undetectable (413?±?79 vs. 393?±?65??mol/l, P?=?0.004). After adjusting for HIV serostatus, demographic and CVD risk factors, every 1SD increment in GlycA level was associated with a higher prevalence of coronary artery calcium (CAC >0) [prevalence ratio 1.09 (95% CI 1.03-1.15)] and coronary stenosis at least 50% [1.20 (1.02-1.41)]. These associations were not significantly altered after adjusting for traditional inflammatory biomarkers or differ by HIV serostatus. Among men with plaque, GlycA was positively associated with the extent of CAC and total plaque. CONCLUSION:HIV infection was associated with higher GlycA levels. In both HIV-infected and HIV-uninfected individuals, GlycA was significantly associated with several measures of subclinical coronary atherosclerosis, independent of other CVD risk factors and inflammatory biomarkers. These findings suggest the potential role of GlycA in CVD risk stratification among HIV patients.

SUBMITTER: Tibuakuu M

PROVIDER: S-EPMC6559349 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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GlycA, a novel inflammatory marker, is associated with subclinical coronary disease.

Tibuakuu Martin M Fashanu Oluwaseun E OE Zhao Di D Otvos James D JD Brown Todd T TT Haberlen Sabina A SA Guallar Eliseo E Budoff Matthew J MJ Palella Frank J FJ Martinson Jeremy J JJ Akinkuolie Akintunde O AO Mora Samia S Post Wendy S WS Michos Erin D ED

AIDS (London, England) 20190301 3

<h4>Objective</h4>GlycA, a novel NMR biomarker of inflammation, has been associated with incident cardiovascular disease (CVD) in the general population, but its association with CVD among HIV-infected individuals is unknown. We examined the associations between GlycA and subclinical coronary plaque among HIV-infected and HIV-uninfected men participating in Multicenter AIDS Cohort Study (MACS).<h4>Design</h4>Cross-sectional analysis of 935 men with plasma measurement of GlycA and noncontrast car ...[more]

PMID: 30475263

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Project description:RATIONALE:GlycA, an emerging inflammatory biomarker, predicted cardiovascular events in population-based studies. Psoriasis, an inflammatory disease associated with increased cardiovascular risk, provides a model to study inflammatory biomarkers in cardiovascular disease (CVD). Whether GlycA associates with psoriasis and how it predicts subclinical CVD beyond high-sensitivity C-reactive protein in psoriasis is unknown. OBJECTIVE:To investigate the relationships between GlycA and psoriasis and between GlycA and subclinical CVD. METHODS AND RESULTS:Patients with psoriasis and controls (n=412) participated in a 2-stage study. We measured GlycA by nuclear magnetic resonance spectroscopy. National Institutes of Health (NIH) participants underwent 18-F Fluorodeoxyglucose Positron Emission Tomography Computed Tomography (18-FDG PET/CT) scans to assess vascular inflammation (VI) and coronary computed tomographic angiography to quantify coronary artery disease burden. Psoriasis cohorts were young (mean age=47.9), with low cardiovascular risk and moderate skin disease. high-sensitivity C-reactive protein and GlycA were increased in psoriasis compared with controls (GlycA: [PENN: 408.8±75.4 versus 289.4±60.2, P<0.0001; NIH: 415.8±63.2 versus 346.2±46, P<0.0001]) and demonstrated a dose-response with psoriasis severity. In stage 2, VI (?=0.36, P<0.001) and coronary artery disease (?=0.29, P=0.004) associated with GlycA beyond CV risk factors in psoriasis. In receiver operating characteristic analysis, GlycA added value in predicting VI (P=0.01) and coronary artery disease (P<0.01). Finally, initiating anti-tumor necrosis factor therapy (n=16) reduced psoriasis severity (P<0.001), GlycA (463.7±92.5 versus 370.1±78.5, P<0.001) and VI (1.93±0.36 versus 1.76±0.19, P<0.001), whereas GlycA remained associated with VI (?=0.56, P<0.001) post treatment. CONCLUSIONS:GlycA associated with psoriasis severity and subclinical CVD beyond traditional CV risk and high-sensitivity C-reactive protein. Moreover, psoriasis treatment reduced GlycA and VI. These findings support the potential use of GlycA in subclinical CVD risk assessment in psoriasis and potentially other inflammatory diseases.

Project description:BackgroundSubjects with Type 1 diabetes mellitus (T1DM) have an increased incidence of heart failure (HF). Several pathophysiological mechanisms have been involved in its development. The aim of this study was to analyze the potential contribution of the advanced lipoprotein profile and plasma glycosylation (GlycA) to the presence of subclinical myocardial dysfunction in subjects with T1DM.MethodsWe included subjects from a Danish cohort of T1DM subjects (Thousand & 1 study) with either diastolic and/or systolic subclinical myocardial dysfunction, and a control group without myocardial dysfunction, matched by age, sex and HbA1c. All underwent a transthoracic echocardiogram and an advanced lipoprotein profile obtained by using the NMR-based Liposcale® test. GlycA NMR signal was also analyzed. Systolic dysfunction was defined as left ventricular ejection fraction ≤ 45% and diastolic dysfunction was considered as E/e'≥12 or E/e' 8-12 + volume of the left atrium > 34 ml/m2. To identify a metabolic profile associated with the presence of subclinical myocardial dysfunction, a multivariate supervised model of classification based on least squares regression (PLS-DA regression) was performed.ResultsOne-hundred forty-six subjects had diastolic dysfunction and 18 systolic dysfunction. Compared to the control group, patients with myocardial dysfunction had longer duration of diabetes (p = 0.005), and higher BMI (p = 0.013), serum NTproBNP concentration (p = 0.001), systolic blood pressure (p < 0.001), albuminuria (p < 0.001), and incidence of advanced retinopathy (p < 0.001). The supervised classification model identified a specific pattern associated with myocardial dysfunction, with a capacity to discriminate patients with myocardial dysfunction from controls. PLS-DA showed that triglyceride-rich lipoproteins (TGRLs), such as VLDL (total VLDL particles, large VLDL subclass and VLDL-TG content) and IDL (IDL cholesterol content), as well as the plasma concentration of GlycA, were associated with the presence of subclinical myocardial dysfunction.ConclusionProatherogenic TGRLs and the proinflammatory biomarker Glyc A are strongly associated to myocardial dysfunction in T1DM. These findings suggest a pivotal role of TGRLs and systemic inflammation in the development of subclinical myocardial dysfunction in T1DM.

Project description:BackgroundInflammatory markers are elevated in patients with dementia. Evidence for an association between inflammation and cognitive function in dementia-free individuals is sparse, inconsistent, and predominantly restricted to the elderly. Assessment of inflammatory markers in young adults as predictors of cognitive function in midlife, well before the onset of overt dementia, is lacking. Furthermore, rarely has the relation with longitudinal change in inflammatory markers been examined.ObjectiveTo examine the association of the inflammatory markers C-reactive protein (CRP), fibrinogen, white blood cell count (WBC) and GlycA, a novel NMR-determined biomarker of systemic inflammation, measured in young adulthood and of GlycA change over 13 years follow-up with cognitive function in midlife.Methods507 participants of the Jerusalem Lipid Research Clinic (LRC) study were assessed at 3 time points over 18-22 years. First, the inflammatory variables GlycA, CRP, fibrinogen, and WBC were measured in blood samples drawn at ages 28-32. Then, in blood samples drawn a mean 13 years later (range, 12-16 years) at ages 41-46, GlycA was again measured (in 484 individuals). Subsequently at ages 48-52, on average 7 years later, global cognitive function and its five specific component domains were assessed with a NeuroTrax computerized test battery. Multiple regression and multivariable logistic models were applied.ResultsInverse unadjusted associations were shown for baseline levels and longitudinal change in inflammatory markers and measures of cognition. Multiple regression models were adjusted for age at cognitive assessment, sex, socio-demographic characteristics, baseline measures of leisure-time vigorous activity, smoking status and body mass index (BMI) at ages 28-32, change in smoking status and BMI between ages 28-32 and 41-46, and depression assessed at the time of cognitive testing. The highest quintile of GlycA change, but not the baseline inflammation measures, was inversely related to global cognition (standardized ? = -.109, p = .011) as well as to the information processing speed and memory domains (standardized ? = -.124, p = .008 and-.117, p = .014, respectively). The multivariable-adjusted odds ratio for low ranked global cognitive function (lowest fifth) comparing the extreme quintiles of GlycA change was 4.8 (95%CI, 1.7-13.5, p = .003; p for trend = .031).ConclusionsIn this longitudinal study of a novel systemic inflammatory marker in a population-based cohort of young adults, GlycA increase over 13 years, but not baseline measures of inflammation, was associated with poorer cognitive function in midlife.

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GlycA, a novel inflammatory marker, is associated with subclinical coronary disease.

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GlycA, a novel inflammatory marker, is associated with subclinical coronary disease.

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