Glycosylation Signatures of Inflammation Identify Cardiovascular Risk

Lawler, Patrick R.; Mora, Samia

doi:10.1161/circresaha.116.310005

Cited by 17 publications

(19 citation statements)

References 15 publications

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Section: Discussionmentioning

confidence: 99%

“…GlycA is derived from glycosylation of five major acute phase inflammatory proteins and may be a more stable marker of systemic inflammation than some of the other traditional markers. (10, 26) Targeting inflammation has become increasing recognized as an important CVD prevention strategy. (5–7) Findings from the recent Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS) further highlight that reductions in CVD, independent of lipids, can be made by targeting systemic inflammation.…”

Section: Discussionmentioning

confidence: 99%

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Associations of ideal cardiovascular health with GlycA, a novel inflammatory marker: The Multi‐Ethnic Study of Atherosclerosis

Benson

Tibuakuu

Zhao

et al. 2018

Clinical Cardiology

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Background: Unhealthy lifestyles and inflammation contribute to cardiovascular disease (CVD). GlycA is a novel biomarker of systemic inflammation representing posttranslational glycosylation of acute phase reactants and associated with increased clinical CVD risk. Hypothesis: We hypothesized that ideal cardiovascular health (CVH), as assessed by (higher) Life’s Simple Seven (LS7) scores, would be associated with lower GlycA levels among individuals free of CVD in a multi-ethnic community-based population. Methods: This was a cross-sectional study of 6,479 MESA participants [53% women; mean age 62±10 years] with GlycA levels measured at baseline by NMR spectroscopy. The LS7 metrics (smoking, physical activity, diet, body mass index, blood pressure, cholesterol, and glucose) were each scored as ideal (2), moderate (1), or poor (0). Total scores were summed and categorized as optimal (12–14), average (8–11) and inadequate (0–7). Linear regression assessed percent difference in GlycA by LS7 scores, after adjusting for age, sex, ethnicity, education, income, family history of CVD and other inflammatory biomarkers. Results: GlycA levels were 403.4±63.1, 374.4±59.2 and 350.3±56.2 micromoles per liter (μmol/L) for inadequate, average, and optimal CVH, respectively (p-trend<0.001). After multivariable adjustment, GlycA remained independently and inversely associated with CVH categories, with a lower mean GlycA level of 5 μmol/L (95% CI 4.5–5.8) for each 1unit increment in LS7 score. Conclusions: Among this group of ethnically-diverse individuals without CVD, suboptimal CVH is associated with higher GlycA levels, independent of traditional inflammatory biomarkers. Strategies aimed at improving CVH might reduce GlycA, which could be a marker of reduced risk of future CVD events.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Associations of ideal cardiovascular health with GlycA, a novel inflammatory marker: The Multi‐Ethnic Study of Atherosclerosis

Benson

Tibuakuu

Zhao

et al. 2018

Clinical Cardiology

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“…Studies in a multi-ethnic cohort revealed a positive association between glycosylated acute phase protein (GlycA: a novel biomarker of systemic inflammation) and suboptimal cardiovascular health (169). Study results indicated that GlycA, derived from glycosylation of major acute inflammatory proteins and a stable biomarker of systemic inflammation compared to other markers (167,170) could be deployed for biomonitoring populations that have different lifestyles (dietary preferences, smoking etc.) or experience chemical exposures (occupational workers).…”

Section: Proteomicsmentioning

confidence: 99%

“…Studies conducted with heart muscle cells have revealed key pathway-associated proteins that could serve as markers of non-chemical exposures. The protein kinase C (PKC) is one of the key molecules involved in cell signaling through endothelial nitric oxide synthase (NOS) and Akt signaling that has been suggested as a marker ( 167 ). Similarly, proteins involved in mitochondrial signaling in the myocardium of different cardiac phenotypes are reflected in stress response and energy metabolism in mitochondria.…”

Section: Developments In the Fieldmentioning

confidence: 99%

Use of an Exposome Approach to Understand the Effects of Exposures From the Natural, Built, and Social Environments on Cardio-Vascular Disease Onset, Progression, and Outcomes

Juárez

Hood

Song

et al. 2020

Front. Public Health

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Obesity, diabetes, and hypertension have increased by epidemic proportions in recent years among African Americans in comparison to Whites resulting in significant adverse cardiovascular disease (CVD) disparities. Today, African Americans are 30% more likely to die of heart disease than Whites and twice as likely to have a stroke. The causes of these disparities are not yet well-understood. Improved methods for identifying underlying risk factors is a critical first step toward reducing Black:White CVD disparities. This article will focus on environmental exposures in the external environment and how they can lead to changes at the cellular, molecular, and organ level to increase the personal risk for CVD and lead to population level CVD racial disparities. The external environment is defined in three broad domains: natural (air, water, land), built (places you live, work, and play) and social (social, demographic, economic, and political). We will describe how environmental exposures in the natural, built, and social environments "get under the skin" to affect gene expression though epigenetic, pan-omics, and related mechanisms that lead to increased risk for adverse CVD health outcomes and population level disparities. We also will examine the important role of metabolomics, proteomics, transcriptomics, genomics, and epigenomics in understanding how exposures in the natural, built, and social environments lead to CVD disparities with implications for clinical, public health, and policy interventions. In this review, we apply an exposome approach to Black:White CVD racial disparities. The exposome is a measure of all the exposures of an individual across the life course and the relationship of those exposures to health effects. The exposome represents the totality of exogenous (external) and endogenous (internal) exposures from conception onwards, simultaneously distinguishing, characterizing, and quantifying etiologic, mediating, moderating, and co-occurring risk and protective factors and their relationship to disease. Specifically, it assesses the biological mechanisms and underlying pathways through which chemical and non-chemical environmental Juarez et al. The Exposome and Cardiovascular Disease exposures are associated with CVD onset, progression and outcomes. The exposome is a promising approach for understanding the complex relationships among environment, behavior, biology, genetics, and disease phenotypes that underlie population level, Black: White CVD disparities.

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“…[37] While we recognize that these biomarkers reflect different domains in the inflammatory cascade, GlycA integrates multiple inflammatory pathways and thus may better capture the degree of systemic inflammation. [38] Kelesidis et al found that GlycA was the only biomarker of inflammation among hsCRP, IL-6, and D-dimer that decreased in all groups after treatment with atazanavir-, raltegravir-, darunavir-based initial ART. [37] Collectively, these findings support the notion that In conclusion, GlycA levels, integrating multiple inflammatory pathways, are higher among HIV-infected men than HIV-uninfected men and correlate well with other inflammatory and monocyte activation biomarker levels as well as with multiple measures of CT subclinical coronary atherosclerosis.…”

Section: Discussionmentioning

confidence: 98%

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

Tibuakuu

Fashanu²,

Zhao

et al. 2019

Aids

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CVD ancillary study, was involved in the CT data collection, and provided critical revisions to the paper. Dr. Budoff interpreted the cardiac CT scans for the study (CT Core Lab) and provided critical revisions to the paper. Dr. Otvos provided the GlycA measurements and provided critical revisions to the paper. Drs. Zhao, Brown, Guallar, Palella, Martinson, Akinkuolie, Haberlen, and Mora provided critical revisions to the paper. Dr. Michos, Fashanu, and Tibuakuu take full responsibility for its content. All authors reviewed the final draft and approve of its submission. The manuscript was also approved by the MACS Executive Committee. Disclosures: Dr. Brown has served as a consultant to Gilead Sciences, Merck, BMS, EMD-Serono, and Theratechnologies. Dr. Budoff has received research funds from GE Healthcare. Dr. Otvos is employed by LabCorp (formally LipoScence). Dr. Mora has received research grant support from Atherotech Diagnostics, and has received consulting fees from Quest Diagnostics for work outside the current study. Dr. Mora has a patent application on the use of GlycA for predicting risk of colorectal cancer. No other authors report any conflicts.

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Glycosylation Signatures of Inflammation Identify Cardiovascular Risk

Cited by 17 publications

References 15 publications

Associations of ideal cardiovascular health with GlycA, a novel inflammatory marker: The Multi‐Ethnic Study of Atherosclerosis

Associations of ideal cardiovascular health with GlycA, a novel inflammatory marker: The Multi‐Ethnic Study of Atherosclerosis

Use of an Exposome Approach to Understand the Effects of Exposures From the Natural, Built, and Social Environments on Cardio-Vascular Disease Onset, Progression, and Outcomes

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

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