Plasma S100A8/A9 Correlates With Blood Neutrophil Counts, Traditional Risk Factors, and Cardiovascular Disease in Middle-Aged Healthy Individuals

Cotoi, Ovidiu Simion; Dunér, Pontus; Ko, Nayoung; Hedblad, Bo; Nilsson, Jan; Björkbacka, Harry; Schiopu, Alexandru

doi:10.1161/atvbaha.113.302432

Cited by 85 publications

(81 citation statements)

References 40 publications

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“…S100A8/A9 (MRP8/14) is a heterodimeric protein complex synthesized by activated neutrophils and abundant in various inflammatory diseases, including psoriasis where levels are upregulated in lesional skin 50 . Of note, while S100A8/A9 plays an important role in increasing circulating neutrophils, and may thereby contribute to cardiovascular disease pathogenesis 51,52 , it is not a neutrophil-specific marker. In our study, we demonstrated that S100A8/A9 was associated with PASI score.…”

Section: Discussionmentioning

confidence: 98%

Severity of Psoriasis Associates With Aortic Vascular Inflammation Detected by FDG PET/CT and Neutrophil Activation in a Prospective Observational Study

Naik

Natarajan

Stansky

et al. 2015

ATVB

162

153

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Objective To understand whether directly-measured psoriasis severity is associated with vascular inflammation assessed by 18F-fluorodeoxyglucose positron emission tomography computed tomography (FDG PET/CT). Approach In depth cardiovascular and metabolic phenotyping was performed in adult psoriasis patients (n=60) and controls (n=20). Psoriasis severity was measured using psoriasis area severity index (PASI). Vascular inflammation was measured using average aortic target-to-background ratio using FDG PET/CT. Results Both the psoriasis patients (28 men, 32 women, mean age 47 years) and controls (13 men, 7 women, mean age 41 years) were young with low cardiovascular risk. PASI scores (Median 5.4; IQR 2.8-8.3) were consistent with mild to moderate skin disease severity. Increasing PASI score was associated with an increase in aortic TBR (β=0.41, p=0.001), an association that changed little after adjustment for age, sex and Framingham risk score. We observed evidence of increased neutrophil frequency (mean psoriasis: 3.7±1.2; vs 2.9±1.2; p=0.02) and activation by lower neutrophil surface CD16 and CD62L in blood. Serum levels of S100A8/A9 (745.1±53.3 vs 195.4±157.8 ng/mL; p<0.01) and neutrophil elastase-1 (43.0±2.4 vs 30.8±6.7 ng/mL; p<0.001) were elevated in psoriasis. Finally, S100A8/A9 protein related to both psoriasis skin disease severity (β=0.53; p=0.02) and vascular inflammation (β=0.48; p=0.02). Conclusions Psoriasis severity is associated with vascular inflammation beyond cardiovascular risk factors. Psoriasis increased neutrophil activation and neutrophil markers, and S100A8/A9 related to both skin disease severity and vascular inflammation.

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Section: Discussionmentioning

confidence: 98%

Severity of Psoriasis Associates With Aortic Vascular Inflammation Detected by FDG PET/CT and Neutrophil Activation in a Prospective Observational Study

Naik

Natarajan

Stansky

et al. 2015

ATVB

162

153

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“…S100A8/A9 was also shown to correlate with carotid intima-media thickness (IMT) in a small subgroup of diabetic patients without CAD [84] and in middle-aged individuals with no previous history of CVD [26]. Circulating neutrophil numbers presented similar associations with carotid IMT, independently of traditional CV risk factors [26].…”

Section: S100a8/a9 and Atherosclerosismentioning

confidence: 99%

S100A8 and S100A9: DAMPs at the Crossroads between Innate Immunity, Traditional Risk Factors, and Cardiovascular Disease

Schiopu

Cotoi

2013

Mediators of Inflammation

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204

156

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Amplification of innate immune responses by endogenous danger-associated molecular patterns (DAMPs) promotes inflammation. The involvement of S100A8 and S100A9, DAMPs belonging to the S100 calgranulin family, in the pathogenesis of cardiovascular disease is attracting an increasing amount of interest. S100A8 and S100A9 (also termed MRP8 and MRP14) preferentially form the S100A8/A9 heterodimer (MRP8/14 or calprotectin) and are constitutively expressed in myeloid cells. The levels of circulating S100A8/A9 in humans strongly correlate to blood neutrophil counts and are increased by traditional cardiovascular risk factors such as smoking, obesity, hyperglycemia, and dyslipidemia. S100A8/A9 is an endogenous ligand of toll-like receptor 4 (TLR4) and of the receptor for advanced glycation end products (RAGE) and has been shown to promote atherogenesis in mice. In humans, S100A8/A9 correlates with the extent of coronary and carotid atherosclerosis and with a vulnerable plaque phenotype. S100A8/A9 is locally released following myocardial infarction and amplifies the inflammatory responses associated with myocardial ischemia/reperfusion injury. Elevated plasma levels of S100A8/A9 are associated with increased risk of future coronary events in healthy individuals and in myocardial infarction survivors. Thus, S100A8/A9 might represent a useful biomarker and therapeutic target in cardiovascular disease. Importantly, S100A8/A9 blockers have been developed and are approved for clinical testing.

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“…An increased total WBC count is related to a higher risk of coronary artery disease (CAD) (hazard ratio: 1.04; 95% CI: 1.02–1.07; p=0.001) (2). Neutrophils have also been demonstrated to play a critical role in the progression of atherogenesis (3). However, low lymphocyte count can also predict the risk of reduced hemodynamics and aerobic capacity (4).…”

Section: Introductionmentioning

confidence: 99%

A combination of the neutrophil-to-lymphocyte ratio and the GRACE risk score better predicts PCI outcomes in Chinese Han patients with acute coronary syndrome

Zhou¹,

Wan²,

Fan³

et al. 2015

Anatol J Cardiol

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Objective:The aims of this study are to evaluate the relationship between the Global Registry of Acute Coronary Events (GRACE) risk score and neutrophil to lymphocyte ratio (NLR) and to determine whether a combination of these factors improves the predictive value for long-term cardiovascular events in Chinese Han patients with acute coronary syndrome (ACS).Methods:In this prospective, observational, and single-center study, NLRs (neutrophil count/lymphocyte count) were calculated from the complete blood count of 1050 patients with ACS, whereas GRACE risk scores were calculated from patients’ clinical parameters obtained on arrival at our hospital. Cox proportional hazards models were used to determine independent factors associated with cardiovascular events.Results:NLR was positively correlated with the GRACE risk score (r=0.66, p<0.001), and both the GRACE risk score (HR: 1.01; 95% CI: 1.01–1.02; p<0.001) and NLR (HR: 1.09; 95% CI: 1.06–1.14; p<0.001) independently predicted cardiovascular events. The area under the receiver operating characteristic (ROC) curve was 0.69 (95% CI: 0.64–0.72; p<0.001) when the GRACE score was calculated alone; however, it significantly increased (p<0.001) to 0.77 (95% CI: 0.74–0.80; p<0.001) when the GRACE score was combined with NLR.Conclusion:This study shows for the first time that NLR is positively associated with the GRACE risk score and demonstrates that a combination of these two factors may improve the predictive value for cardiovascular events in Chinese Han patients with ACS.

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Plasma S100A8/A9 Correlates With Blood Neutrophil Counts, Traditional Risk Factors, and Cardiovascular Disease in Middle-Aged Healthy Individuals

Cited by 85 publications

References 40 publications

Severity of Psoriasis Associates With Aortic Vascular Inflammation Detected by FDG PET/CT and Neutrophil Activation in a Prospective Observational Study

Severity of Psoriasis Associates With Aortic Vascular Inflammation Detected by FDG PET/CT and Neutrophil Activation in a Prospective Observational Study

S100A8 and S100A9: DAMPs at the Crossroads between Innate Immunity, Traditional Risk Factors, and Cardiovascular Disease

A combination of the neutrophil-to-lymphocyte ratio and the GRACE risk score better predicts PCI outcomes in Chinese Han patients with acute coronary syndrome

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