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.
Highlights
It is increasingly recognized that protein glycosylation, i.e. the enzymatic process whereby a glycan moiety is added to a protein, affects many physiological processes including the innate immune system, thereby modulating inflammatory responses [1,2,3]
After additional adjustment for high sensitivity C-reactive protein (hsCRP), GlycA was still associated with incident cardiovascular disease (CVD) (HR: 1.16 per SD change, P = 0.04)
CVD risk was highest in subjects with simultaneously higher GlycA and hsCRP (fully adjusted HR: 1.79, P
Summary
It is increasingly recognized that protein glycosylation, i.e. the enzymatic process whereby a glycan (polysaccharide) moiety is added to a protein, affects many physiological processes including the innate immune system, thereby modulating inflammatory responses [1,2,3]. Numerous studies have shown that higher circulating levels of acute phase proteins, in particular high sensitivity C-reactive protein (hsCRP), predict future development of cardiovascular disease (CVD) [4,5,7,8], the possibility that CRP may play a causal role in derangements of inflammatory processes involved in the pathogenesis of atherosclerosis has been questioned [9,10]. GlycA is a recently developed nuclear mass resonance (NMR) spectroscopy-derived biomarker of systemic inflammation [11,12]. This NMR signal arises from the N-acetyl methyl groups of the N-acetylglucosamine residues located on specific glycan branches of circulating plasma proteins, mainly α1-acid glycoprotein (oromucosoid), haptoglobin, α1-antitrypsin, α1-antichymotrypsin and transferrin. It has been established that GlycA is strongly correlated with hs-CRP, which supports the contention that GlycA is a marker of low-grade systemic inflammation [11,13]
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