GlycA, a Pro-Inflammatory Glycoprotein Biomarker, and Incident Cardiovascular Disease: Relationship with C-Reactive Protein and Renal Function

Abstract

ObjectiveGlycA is a novel nuclear magnetic resonance spectroscopy-measured biomarker of systemic inflammation. We determined whether GlycA is associated with incident cardiovascular disease (CVD) in men and women, examined whether this association with CVD is modified by renal function, and compared this association with high sensitivity C-reactive protein (hsCRP).Research design and methodsA prospective cohort study was performed among 4,759 subjects (PREVEND study) without a history of CVD and cancer. Incident CVD was defined as the combined endpoint of cardiovascular morbidity and mortality. Cox regression analyses were used to examine associations of baseline GlycA and hsCRP with CVD.Results298 first CVD events occurred during a median follow-up of 8.5 years. After adjustment for clinical and lipid measures the hazard ratio (HR) for CVD risk in the highest GlycA quartile was 1.58 (95% CI, 1.05–2.37, P for trend = 0.004). This association was similar after further adjustment for renal function (estimated glomerular filtration rate and urinary albumin excretion). After additional adjustment for hsCRP, GlycA was still associated with incident CVD (HR: 1.16 per SD change (95% CI, 1.01–1.33), P = 0.04). Similar results were obtained for hsCRP (HR per SD change after adjustment for GlycA: 1.17 (95% CI 1.17 (95% CI, 1.01–3.60), P = 0.04). CVD risk was highest in subjects with simultaneously higher GlycA and hsCRP (fully adjusted HR: 1.79 (95% CI, 1.31–2.46), P<0.001).ConclusionGlycA is associated with CVD risk in men and women, independent of renal function. The association of GlycA with incident CVD is as strong as that of hsCRP.

Comparison of the Predictive Value of GlycA and Other Biomarkers of Inflammation for Total Death, Incident Cardiovascular Events, Noncardiovascular and Noncancer Inflammatory-Related Events, and Total Cancer Events

“…Consistent with our findings, Gruppen et al (14 ) found in their prospective cohort study, PREVEND, of 4759 subjects free of overt CVD but including a large subgroup who had albuminuria, that GlycA was associated with CVD events independently of renal function. The association of GlycA with incident CVD was as strong as that of hsCRP.…”

“…GlycA is a composite biomarker that senses the integrated concentrations and glycosylation states of several of the most abundant acute-phase proteins in serum. The limited available information about GlycA finds that it is associated with incident CVD and risk for type 2 diabetes mellitus in initially healthy women (12)(13)(14).…”

Inflammatory glycoproteins in cardiometabolic disorders, autoimmune diseases and cancer

“…GlycA, the NMR signal derived from multiple inflammatory glycoproteins, was demonstrated to predict future CVD and T2DM (Table 2) [71][72][73]. GlycA was shown to be related to the leptin/adiponectin ratio, suggesting that adipose tissue-associated low-grade inflammation could be involved in the regulation of inflammatory glycoproteins [49].…”

“…In the Women's Health Study (WHS), GlycA was associated with CVD events, independent of traditional risk factors [71]. In the Prevention of Renal and Vascular End-stage Disease (PREVEND) study, GlycA was associated with incident CVD, defined as the combined end-point of CV morbidity and mortality, independent of clinical and lipid measures as well as renal function [72]. Baseline concentrations of GlycA in the Justification for the Use of Statins in Prevention: an Interventional Trial Evaluating Rosuvastatin (JUPITER) trial were significantly associated with incident CVD events, even when adjusting for established risk factors and a family history of premature coronary heart disease [73].…”

GlycA, a novel proinflammatory glycoprotein biomarker, and high-sensitivity C-reactive protein are inversely associated with sodium intake after controlling for adiposity: the Prevention of Renal and Vascular End-Stage Disease study

“…GlycA is regarded as a marker of low-grade systemic inflammation (16)(17)(18). Evidence has been accumulating that GlycA may predict CVD as well as incident type 2 diabetes mellitus (T2DM) (17,(19)(20)(21).…”