S100A12 as a Marker to Predict Cardiovascular Events in Patients With Chronic Coronary Artery Disease

Saito, Toshinobu; Hojo, Yukihiro; Ogoyama, Yukako; Hirose, Masahiro; Ikemoto, Tomokazu; Katsuki, Takaaki; Shimada, Kazuyuki; Kario, Kazuomi

doi:10.1253/circj.cj-12-0093

Cited by 33 publications

(24 citation statements)

References 28 publications

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“…17 In addition, a recent study in Japanese CHD individuals observed a significant association between EN-RAGE and future major adverse cardiac events. 18 To our knowledge, we are the first to investigate the association between EN-RAGE and CHD in a prospective population-based cohort study with long-term follow-up.…”

Section: Discussionmentioning

confidence: 99%

En-Rage

Ligthart

Sedaghat

Ikram

et al. 2014

ATVB

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Objective-Inflammation plays a key role in atherosclerosis. We hypothesized that novel inflammatory markers may predict the risk of coronary heart disease (CHD). Approach and Results-We investigated the association of 16 inflammatory biomarkers with the risk of CHD in a random subset of 839 CHD-free individuals in a prospective population-based cohort study. A Bonferroni corrected P value of 3.1×10 −3 was used as a threshold of statistical significance. The mean age at baseline was 72.8 years. During a median follow-up of 10.6 years, 99 cases of incident CHD were observed. Among all inflammatory biomarkers, neutrophilderived human s100a12 (extracellular newly identified receptor for advanced glycation end-products binding protein [EN-RAGE]) showed the strongest association with the risk of CHD (P value 2.0×10 −3 ). After multivariable adjustment for established cardiovascular risk factors, each standard deviation increase in the natural log-transformed EN-RAGE was associated with 30% higher risk of incident CHD (hazard ratio, 1.30; 95% confidence interval, 1.06-1.59). Further adjustment for previously studied inflammatory markers did not attenuate the association. Excluding individuals with prevalent type 2 diabetes mellitus, impaired kidney function, or individuals using antihypertensive medication did not change the effect estimates. Cause-specific hazard ratios suggested a stronger association between EN-RAGE and CHD mortality compared with stable CHD. Additional adjustment for previously studied inflammatory markers yielded slightly increased effect estimates (Table 2; Table IV in the online-only Data Supplement). Cumulative incidence curves for the tertiles of EN-RAGE adjusted for competing risks are depicted in Figure 2. The 10-year probability of first incident event of CHD was 0.05 (95% CI, 0.03-0.08) for the first tertile, 0.11 (95% CI, 0.07-0.14) for the second tertile, and 0.14 (95% CI, 0.10-0.18) for the third tertile. Conclusions-Our results highlight EN-RAGE as an inflammatoryAfter excluding participants with chronic kidney disease at baseline, the association between EN-RAGE and incident CHD attenuated slightly (1.28; 95% CI, 1.03-1.59; Table 3). Excluding participants with type 2 diabetes mellitus, the effect estimates of the association between EN-RAGE and CHD did not change: hazard ratio 1.29 (95% CI, 1.04-1.60) in the fully adjusted model. Finally, after excluding participants taking antihypertensive medication, the hazard ratio did not change (HR, 1.40; 95% CI, 1.05-1.87). ). DiscussionIn this prospective, population-based cohort study, we found that higher EN-RAGE levels were associated with an increased risk of CHD beyond conventional risk factors. Further adjustments for inflammatory markers, as well as excluding diseased individuals, did not change the results. These findings suggest proinflammatory EN-RAGE as a new inflammatory risk marker for CHD that represents a distinct inflammatory pathway compared with other inflammatory markers.Previous studies have observed increased levels of E...

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Section: Discussionmentioning

confidence: 99%

En-Rage

Ligthart

Sedaghat

Ikram

et al. 2014

ATVB

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“…Increased plasma levels of S100A8 and S100A9 can serve as marks for human cardiovascular disease, and their deletion protects aganist atherosclerosis to some degree [ 45 ]. As Another another number in S100 family, S100A12 is reported to function as a prediction marker for cardiovascular events in chronic coronary artery diseaseCAD [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

Weighted gene co-expression network analysis identifies specific modules and hub genes related to coronary artery disease

Liu

Jing

2016

BMC Cardiovasc Disord

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BackgroundThe analysis of the potential molecule targets of coronary artery disease (CAD) is critical for understanding the molecular mechanisms of disease. However, studies of global microarray gene co-expression analysis of CAD still remain limited.MethodsMicroarray data of CAD (GSE23561) were downloaded from Gene Expression Omnibus, including peripheral blood samples from CAD patients (n = 6) and controls (n = 9). Limma package in R was used to identify the differentially expressed genes (DEGs) between CAD and control samples. Using weighted gene co-expression network analysis (WGCNA) package in R, WGCNA was performed to identify significant modules in the network. Then, functional and pathway enrichment analyses were conducted for genes in the most significant module using DAVID software. Moreover, hub genes in the module were analyzed by isubpathwayminer package in R and GenCLiP 2.0 tool to identify the significant sub-pathways.ResultsTotal 3711 DEGs and 21 modules for them were identified in CAD samples. The most significant module was associated with the pathways of hypertrophic cardiomyopathy and membrane related functions. In addition, the top 30 hub genes with high connectivity in the module were selected, and two genes (G6PD and S100A7) were taken as key molecules via sub-pathway screening and data mining.ConclusionsA module associated with hypertrophic cardiomyopathy pathway was detected in CAD samples. G6PD and S100A7 were the potential targets in CAD. Our finding might provide novel insight into the underlying molecular mechanism of CAD.

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“…More recently, a pilot study supported these results and confirmed that S100A12 reflects the inflammatory response activity in patients with T2DM-related CAD. 22 However, the correlation between serum S100A12 levels and CAI scores was weak, and its clinical significance is yet to be further investigated.…”

Section: Discussionmentioning

confidence: 99%