Circulating Adhesion Molecules VCAM-1, ICAM-1, and E-selectin in Carotid Atherosclerosis and Incident Coronary Heart Disease Cases

Hwang, Shih Jen; Ballantyne, Christie M.; Sharrett, A. Richey; Smith, Louis C.; Davis, C. E.; Gotto, Antonio M.; Boerwinkle, Eric

doi:10.1161/01.cir.96.12.4219

Cited by 1,255 publications

(965 citation statements)

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“…We now extend these findings to a wider age range, and show that soluble CD14 predicts incident HF and all‐cause and CVD mortality. sICAM1 is a cell adhesion molecule that previously has been associated with CVD, including myocardial infarction, in case‐control studies 33, 34. We now show that sICAM1 predicts not only ASCVD, but also all‐cause mortality and CVD mortality.…”

Section: Discussionsupporting

confidence: 54%

Protein Biomarkers of Cardiovascular Disease and Mortality in the Community

Lyass

Courchesne

et al. 2018

JAHA

202

218

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BackgroundThe discovery of novel and highly predictive biomarkers of cardiovascular disease (CVD) has the potential to improve risk‐stratification methods and may be informative regarding biological pathways contributing to disease.Methods and ResultsWe used a discovery proteomic platform that targeted high‐value proteins for CVD to ascertain 85 circulating protein biomarkers in 3523 Framingham Heart Study participants (mean age, 62 years; 53% women). Using multivariable‐adjusted Cox models to account for clinical variables, we found 8 biomarkers associated with incident atherosclerotic CVD, 18 with incident heart failure, 38 with all‐cause mortality, and 35 with CVD death (false discovery rate, q<0.05 for all; P‐value ranges, 9.8×10−34 to 3.6×10−2). Notably, a number of regulators of metabolic and adipocyte homeostasis were associated with cardiovascular events, including insulin‐like growth factor 1 (IGF1), insulin‐like growth factor binding protein 1 (IGFBP1), insulin‐like growth factor binding protein 2 (IGFBP2), leptin, and adipsin. In a multimarker approach that accounted for clinical factors, growth differentiation factor 15 (GDF15) was associated with all outcomes. In addition, N‐terminal pro‐b‐type natriuretic peptide, C‐reactive protein, and leptin were associated with incident heart failure, and C‐type lectin domain family 3 member B (CLEC3B; tetranectin), N‐terminal pro‐b‐type natriuretic peptide, arabinogalactan protein 1 (AGP1), soluble receptor for advanced glycation end products (sRAGE), peripheral myelin protein 2 (PMP2), uncarboxylated matrix Gla protein (UCMGP), kallikrein B1 (KLKB1), IGFBP2, IGF1, leptin receptor, and cystatin‐C were associated with all‐cause mortality in a multimarker model.ConclusionsWe identified numerous protein biomarkers that predicted cardiovascular outcomes and all‐cause mortality, including biomarkers representing regulators of metabolic homeostasis and inflammatory pathways. Further studies are needed to validate our findings and define clinical utility, with the ultimate goal of improving strategies for CVD prevention.

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Section: Discussionsupporting

confidence: 54%

Protein Biomarkers of Cardiovascular Disease and Mortality in the Community

Lyass

Courchesne

et al. 2018

JAHA

202

218

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“…The Atherosclerosis Risk in Communities (ARIC) investigators found elevated sICAM-1, but not sVCAM-1, in patients with carotid intima-media thickness 41.0 mm, as compared to controls with intima-media thickness o0.68 mm. 19 In another large cohort study, neither soluble cell adhesion molecule was linearly associated with intima-media thickness. 27 This was, however, increased in patients who had sICAM-1 levels in the highest tertile.…”

Section: Soluble Icam-1 and Vcam-1 As Markers Of Atherosclerosismentioning

confidence: 97%

“…Several large studies that have demonstrated an association between sICAM-1 and incident vascular disease have failed to show a similar relation for sVCAM-1. 19,20,22,25 Similarly, levels do not appear to be elevated in patients with stable coronary heart disease. 17 Perhaps the most persuasive evidence of an association between soluble cell adhesion molecules and atherosclerosis comes from studies that have correlated levels with measures of atheroma in vivo.…”

Section: Soluble Icam-1 and Vcam-1 As Markers Of Atherosclerosismentioning

confidence: 97%

“…17 Likewise, several large epidemiological studies have demonstrated that apparently healthy subjects with elevated levels of sICAM-1 are at increased risk of developing overt coronary heart disease, peripheral vascular disease, carotid atherosclerosis and stroke. [18][19][20][21][22][23] Although VCAM-1 appears to play an important role in atherogenesis, 24 the data relating sVCAM-1 levels to atherosclerosis are less consistent than those for sICAM-1. Several large studies that have demonstrated an association between sICAM-1 and incident vascular disease have failed to show a similar relation for sVCAM-1.…”

Section: Soluble Icam-1 and Vcam-1 As Markers Of Atherosclerosismentioning

confidence: 99%

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Soluble integrin adhesion receptors and atherosclerosis: much heat and a little light?

Hillis

2003

J Hum Hypertens

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“…Similarly, other circulating proteins including VCAM1 138 , ICAM1 139 and P-selectin 140 have been measured in the plasma of patients and have been shown to be associated with the level of atherosclerosis. But again, in common with high-sensitivity CRP, what these 'downstream' measures represent in uncertain.…”

Section: Molecular Techniques-mentioning

confidence: 99%

Erratum: Inflammatory processes in cardiovascular disease: a route to targeted therapies

Ruparelia¹,

Chai²,

Fisher³

et al. 2017

Nat Rev Cardiol

189

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Inflammatory processes are firmly established as central to the development and complications of cardiovascular diseases. Elevated levels of inflammatory markers have been shown to be predictive of future cardiovascular events. The specific targeting of these processes in experimental models has been shown to attenuate myocardial and arterial injury, reduce disease progression, and promote healing. However, the translation of these observations and the demonstration of clear efficacy in clinical practice have been disappointing. A major limitation might be that tools currently used to measure 'inflammation' are insufficiently precise and do not provide information about disease site, activity, or discriminate between functionally important activation pathways. The challenge, therefore, is to make measures of inflammation that are more meaningful, and which can guide specific targeted therapies. In this Review, we consider the roles of inflammatory processes in the related pathologies of atherosclerosis and acute myocardial infarction (AMI), by providing an evaluation of the known and emerging inflammatory pathways. We highlight contemporary techniques to characterize and quantify inflammation, and consider how they might be used to guide specific treatments. Finally, we discuss emerging opportunities in the field, including current limitations and challenges that are the focus of ongoing study.Inflammation and its failure to resolve are firmly established as central to the development and complications of several cardiovascular diseases [1][2][3] . Elevated levels of markers of inflammation, such as C-reactive protein (CRP) and serum amyloid A (SAA), have been shown to be predictive of future cardiovascular events across a range of clinical settings [4][5][6] . The role of the innate immune system in the pathogenesis of cardiovascular diseases has been an area of particular focus, with the appreciation that targeting innate immune function Correspondence to R.P.C.: robin.choudhury@cardiov.ox.ac.uk. Author contributionsAll the authors researched data for the article, discussed its contents, and wrote, reviewed, and edited the manuscript before submission. Competing interests statementThe authors declare no competing interests. HHS Public AccessAuthor manuscript Nat Rev Cardiol. Author manuscript; available in PMC 2017 September 01. Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript in experimental models can variously attenuate disease progression and injury, and promote healing [7][8][9][10] .Processes of inflammation contribute to a broad range of cardiovascular diseases; however, in this Review, we consider the roles of inflammatory processes in the related pathologies of atherosclerosis and acute myocardial infarction (AMI), by providing an evaluation of known and emerging inflammatory pathways that are thought to be central to their pathogenesis, and the consequences of their activation. We highlight contemporary techniques to characterize and quantify inflammation, and consider h...

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Circulating Adhesion Molecules VCAM-1, ICAM-1, and E-selectin in Carotid Atherosclerosis and Incident Coronary Heart Disease Cases

Abstract: These data indicate that plasma levels of ICAM-1 and E-selectin may serve as molecular markers for atherosclerosis and the development of CHD.

Cited by 1,255 publications

References 49 publications

Protein Biomarkers of Cardiovascular Disease and Mortality in the Community

Protein Biomarkers of Cardiovascular Disease and Mortality in the Community

Soluble integrin adhesion receptors and atherosclerosis: much heat and a little light?

Erratum: Inflammatory processes in cardiovascular disease: a route to targeted therapies

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