Dataset Information

GlycA, a novel pro-inflammatory glycoprotein biomarker is associated with mortality: results from the PREVEND study and meta-analysis.

ABSTRACT:

Background

Chronic diseases are associated with an inflammatory response. We determined the association of two inflammatory markers, GlycA and high-sensitivity C-reactive protein (hsCRP), with overall and cause-specific mortality in a cohort of men and women.

Methods

Cox regression analyses were used to examine associations of GlycA and hsCRP with all-cause, cancer and cardiovascular mortality in 5526 subjects (PREVEND cohort; average follow-up 12.6 years).

Results

GlycA was associated with all-cause mortality (n = 838), independent of clinical risk factors and hsCRP (hazard ratio 1.43 [95% confidence interval (CI): 1.09-1.87] for top versus bottom quartiles). For hsCRP, the association with all-cause mortality was nonsignificant after adjustment for GlycA. GlycA and hsCRP were associated with cancer mortality in men (n = 248), but not in women (n = 132). Neither GlycA nor hsCRP was independently associated with cardiovascular mortality (n = 201). In a meta-analysis of seven population-based studies, including 8153 deaths, the pooled multivariable-adjusted relative risk of GlycA for all-cause mortality was 1.74 (95% CI: 1.40-2.17) for top versus bottom quartiles. The association of GlycA with all-cause mortality was somewhat stronger than that of hsCRP. GlycA and hsCRP were not independently associated with cardiovascular mortality. The associations of GlycA and hsCRP with cancer mortality were present in men, but not in women.

Conclusions

GlycA is significantly associated with all-cause mortality. GlycA and hsCRP were each not independently associated with cardiovascular mortality. The association of GlycA and hsCRP with cancer mortality appears to be driven by men.

SUBMITTER: Gruppen EG

PROVIDER: S-EPMC6851697 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Publications

GlycA, a novel pro-inflammatory glycoprotein biomarker is associated with mortality: results from the PREVEND study and meta-analysis.

Gruppen E G EG Kunutsor S K SK Kieneker L M LM van der Vegt B B Connelly M A MA de Bock G H GH Gansevoort R T RT Bakker S J L SJL Dullaart R P F RPF

Journal of internal medicine 20190724 5

<h4>Background</h4>Chronic diseases are associated with an inflammatory response. We determined the association of two inflammatory markers, GlycA and high-sensitivity C-reactive protein (hsCRP), with overall and cause-specific mortality in a cohort of men and women.<h4>Methods</h4>Cox regression analyses were used to examine associations of GlycA and hsCRP with all-cause, cancer and cardiovascular mortality in 5526 subjects (PREVEND cohort; average follow-up 12.6 years).<h4>Results</h4>GlycA wa ...[more]

PMID: 31260573

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Project description:Background Low-grade inflammation in the young may contribute to the early development of cardiovascular disease. We assessed whether circulating levels of glycoprotein acetyls (GlycA) were better able to predict the development of adverse cardiovascular disease risk profiles compared with the more commonly used biomarker high-sensitivity CRP (C-reactive protein). Methods and Results A total of 3306 adolescents and young adults from the Avon Longitudinal Study of Parents and Children (mean age, 15.4±0.3; n=1750) and Cardiovascular Risk in Young Finns Study (mean age, 32.1±5.0; n=1556) were included. Baseline associations between inflammatory biomarkers, body composition, cardiovascular risk factors, and subclinical measures of vascular dysfunction were assessed cross-sectionally in both cohorts. Prospective risk of developing hypertension and metabolic syndrome during 9-to-10-year follow-up were also assessed as surrogate markers for future cardiovascular risk. GlycA showed greater within-subject correlation over 9-to-10-year follow-up in both cohorts compared with CRP, particularly in the younger adolescent group (r=0.36 versus 0.07). In multivariable analyses, GlycA was found to associate with multiple lifestyle-related cardiovascular disease risk factors, cardiometabolic risk factor burden, and vascular dysfunction (eg, mean difference in flow-mediated dilation=-1.2 [-1.8, -0.7]% per z-score increase). In contrast, CRP levels appeared predominantly driven by body mass index and showed little relationship to any measured cardiovascular risk factors or phenotypes. In both cohorts, only GlycA predicted future risk of both hypertension (risk ratio [RR], ≈1.1 per z-score increase for both cohorts) and metabolic syndrome (RR, ≈1.2-1.3 per z-score increase for both cohorts) in 9-to-10-year follow-up. Conclusions Low-grade inflammation captured by the novel biomarker GlycA is associated with adverse cardiovascular risk profiles from as early as adolescence and predicts future risk of hypertension and metabolic syndrome in up to 10-year follow-up. GlycA is a stable inflammatory biomarker which may capture distinct sources of inflammation in the young and may provide a more sensitive measure than CRP for detecting early cardiovascular risk.

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:Placental P-glycoprotein (P-gp) acts to protect the developing fetus from exogenous compounds. This protection declines with advancing gestation leaving the fetus and fetal brain vulnerable to these compounds and potential teratogens in maternal circulation. This vulnerability may be more pronounced in pregnancies complicated by infection, which is common during pregnancy. Pro-inflammatory cytokines (released during infection) have been shown to be potent inhibitors of P-gp, but nothing is known regarding their effects at the developing blood-brain barrier (BBB). We hypothesized that P-gp function and expression in endothelial cells of the developing BBB will be inhibited by pro-inflammatory cytokines. We have derived brain endothelial cell (BEC) cultures from various stages of development of the guinea pig: gestational day (GD) 50, 65 (term ~68 days) and postnatal day (PND) 14. Once these cultures reached confluence, BECs were treated with various doses (10(0)-10(4 )pg/mL) of pro-inflammatory cytokines: interleukin-1? (IL-1?), interleukin-6 (IL-6) or tumor necrosis factor- ? (TNF-?). P-gp function or abcb1 mRNA (encodes P-gp) expression was assessed following treatment. Incubation of GD50 BECs with IL-1?, IL-6 or TNF-? resulted in no change in P-gp function. GD65 BECs displayed a dose-dependent decrease in function with all cytokines tested; maximal effects at 42%, 65% and 34% with IL-1?, IL-6 and TNF-? treatment, respectively (P<0.01). Inhibition of P-gp function by IL-1?, IL-6 and TNF-? was even greater in PND14 BECs; maximal effects at 36% (P<0.01), 84% (P<0.05) and 55% (P<0.01), respectively. Cytokine-induced reductions in P-gp function were associated with decreased abcb1 mRNA expression. These data suggest that BBB P-gp function is increasingly responsive to the inhibitory effects of pro-inflammatory cytokines, with increasing developmental age. Thus, women who experience infection and take prescription medication during pregnancy may expose the developing fetal brain to greater amounts of exogenous compounds - many of which are considered potentially teratogenic.

Dataset Information

GlycA, a novel pro-inflammatory glycoprotein biomarker is associated with mortality: results from the PREVEND study and meta-analysis.

Background

Methods

Results

Conclusions

Publications

GlycA, a novel pro-inflammatory glycoprotein biomarker is associated with mortality: results from the PREVEND study and meta-analysis.

Similar Datasets

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