@article {880, title = {Soluble intracellular adhesion molecule-1 is associated with cardiovascular disease risk and mortality in older adults.}, journal = {J Thromb Haemost}, volume = {4}, year = {2006}, month = {2006 Jan}, pages = {107-13}, abstract = {

BACKGROUND: Intracellular adhesion molecule-1 (ICAM-1) regulates leukocyte-endothelial attachment, a process crucial to atherosclerosis. Circulating soluble ICAM-1 (sICAM-1) may serve as a marker of cardiovascular disease (CVD) progression.

OBJECTIVES: We examined the association of sICAM-1 with measures of subclinical CVD and risk of incident CVD events and death in older men and women (age > or = 65 years) from the Cardiovascular Health Study.

METHODS: Selected participants were free of clinical CVD at baseline. Non-exclusive incident case groups were angina (n = 534), myocardial infarction (n = 304), stroke (n = 327), and death (n = 842; CVD death = 310). A total 643 subjects were free of events during follow-up.

RESULTS: sICAM-1 was positively associated with C-reactive protein, interleukin-6 and fibrinogen and measures of subclinical CVD in these older men and women. In Cox regression models adjusted for age, gender, and race, increasing levels of sICAM-1 were associated with increased risk of all cause mortality in men and women. Hazard ratios (95\% confidence intervals) for a one standard deviation increase in sICAM-1 (89.7 ng mL(-1)) were 1.3 (1.1-1.4) in men and 1.2 (1.1-1.3) in women. sICAM-1 was associated with increased risk of CVD death in women (1.2; 1.0-1.5), but not men (1.1; 0.9-1.3). There were no associations of sICAM-1 with non-fatal CVD events.

CONCLUSIONS: While sICAM-1 was associated with death in older men and women, there was a more marked association between sICAM-1 and CVD death in women.

}, keywords = {Aged, Aged, 80 and over, Angina Pectoris, Biomarkers, Cardiovascular Diseases, Female, Humans, Incidence, Intercellular Adhesion Molecule-1, Male, Mortality, Myocardial Infarction, Regression Analysis, Risk Factors, Sex Factors, Solubility, Stroke}, issn = {1538-7933}, doi = {10.1111/j.1538-7836.2005.01678.x}, author = {Jenny, N S and Arnold, A M and Kuller, L H and Sharrett, A R and Fried, L P and Psaty, B M and Tracy, R P} } @article {1127, title = {Inflammatory biomarkers and decline in kidney function in the elderly: the Cardiovascular Health Study.}, journal = {Nephrol Dial Transplant}, volume = {25}, year = {2010}, month = {2010 Jan}, pages = {119-24}, abstract = {

BACKGROUND: Cross-sectional studies have demonstrated a consistent and linear association between circulating inflammatory markers and kidney function. The objective of this study was to determine whether elevated markers of inflammation are independently associated with longitudinal kidney function decline.

METHODS: This study included 4128 subjects from the Cardiovascular Health Study. Cystatin C was measured at baseline, 3 years later and 7 years later; eligible subjects had at least two measures. Cystatin C-based estimated glomerular filtration rate (eGFR(cysC)) was estimated, and rapid kidney function decline was defined as an annual loss of eGFR(cysC) >3 mL/min/1.73 m(2). Predictors included ten inflammatory and procoagulant biomarkers: C-reactive protein, interleukin-6, intercellular adhesion molecule-1, white blood cell count, fibrinogen, factor VII, factor VIII, D-dimer, plasmin-antiplasmin complex and serum albumin.

RESULTS: During the study, 1059 subjects (26\%) had a rapid decline in kidney function. In contrast to the other nine inflammatory or procoagulant biomarkers, serum albumin had a consistent and inverse association with rapid kidney function decline [final adjusted logistic regression model: 1.14-fold increased odds (95\% CI 1.06-1.23) of rapid decline per standard deviation lower albumin]. The lowest quartile of albumin had an odds ratio of 1.55 (95\% CI 1.23-1.96) for rapid decline compared with the highest quartile. These associations persisted after adjusting the albumin models for CRP, IL-6 and fibrinogen.

CONCLUSIONS: In contrast to nine other inflammatory and procoagulant markers, only lower baseline levels of serum albumin were consistently associated with a rapid decline in kidney function, as measured by cystatin C-based eGFR.

}, keywords = {Aged, Biomarkers, C-Reactive Protein, Cohort Studies, Cystatin C, Female, Glomerular Filtration Rate, Humans, Inflammation, Intercellular Adhesion Molecule-1, Interleukin-6, Kidney, Logistic Models, Longitudinal Studies, Male, Prospective Studies, Serum Albumin}, issn = {1460-2385}, doi = {10.1093/ndt/gfp429}, author = {Keller, Christopher and Katz, Ronit and Sarnak, Mark J and Fried, Linda F and Kestenbaum, Bryan and Cushman, Mary and Shlipak, Michael G} } @article {1169, title = {Large-scale genomic studies reveal central role of ABO in sP-selectin and sICAM-1 levels.}, journal = {Hum Mol Genet}, volume = {19}, year = {2010}, month = {2010 May 01}, pages = {1863-72}, abstract = {

P-selectin and intercellular adhesion molecule-1 (ICAM-1) participate in inflammatory processes by promoting adhesion of leukocytes to vascular wall endothelium. Their soluble levels have been associated with adverse cardiovascular events. To identify loci affecting soluble levels of P-selectin (sP-selectin) and ICAM-1 (sICAM-1), we performed a genome-wide association study in a sample of 4115 (sP-selectin) and 9813 (sICAM-1) individuals of European ancestry as a part of The Cohorts for Heart and Aging Research in Genome Epidemiology consortium. The most significant SNP association for sP-selectin was within the SELP gene (rs6136, P = 4.05 x 10(-61)) and for sICAM-1 levels within the ICAM-1 gene (rs3093030, P = 3.53 x 10(-23)). Both sP-selectin and sICAM-1 were associated with ABO gene variants (rs579459, P = 1.86 x 10(-41) and rs649129, P = 1.22 x 10(-15), respectively) and in both cases the observed associations could be accounted for by the A1 allele of the ABO blood group. The absence of an association between ABO blood group and platelet-bound P-selectin levels in an independent subsample (N = 1088) from the ARIC study, suggests that the ABO blood group may influence cleavage of the P-selectin protein from the cell surface or clearance from the circulation, rather than its production and cellular presentation. These results provide new insights into adhesion molecule biology.

}, keywords = {ABO Blood-Group System, Blood Platelets, Enzyme-Linked Immunosorbent Assay, European Continental Ancestry Group, Fluorescence, Genome-Wide Association Study, Humans, Intercellular Adhesion Molecule-1, P-Selectin}, issn = {1460-2083}, doi = {10.1093/hmg/ddq061}, author = {Barbalic, Maja and Dupuis, Jos{\'e}e and Dehghan, Abbas and Bis, Joshua C and Hoogeveen, Ron C and Schnabel, Renate B and Nambi, Vijay and Bretler, Monique and Smith, Nicholas L and Peters, Annette and Lu, Chen and Tracy, Russell P and Aleksic, Nena and Heeriga, Jan and Keaney, John F and Rice, Kenneth and Lip, Gregory Y H and Vasan, Ramachandran S and Glazer, Nicole L and Larson, Martin G and Uitterlinden, Andr{\'e} G and Yamamoto, Jennifer and Durda, Peter and Haritunians, Talin and Psaty, Bruce M and Boerwinkle, Eric and Hofman, Albert and Koenig, Wolfgang and Jenny, Nancy S and Witteman, Jacqueline C and Ballantyne, Christie and Benjamin, Emelia J} } @article {1287, title = {Genome-wide association analysis of soluble ICAM-1 concentration reveals novel associations at the NFKBIK, PNPLA3, RELA, and SH2B3 loci.}, journal = {PLoS Genet}, volume = {7}, year = {2011}, month = {2011 Apr}, pages = {e1001374}, abstract = {

Soluble ICAM-1 (sICAM-1) is an endothelium-derived inflammatory marker that has been associated with diverse conditions such as myocardial infarction, diabetes, stroke, and malaria. Despite evidence for a heritable component to sICAM-1 levels, few genetic loci have been identified so far. To comprehensively address this issue, we performed a genome-wide association analysis of sICAM-1 concentration in 22,435 apparently healthy women from the Women{\textquoteright}s Genome Health Study. While our results confirm the previously reported associations at the ABO and ICAM1 loci, four novel associations were identified in the vicinity of NFKBIK (rs3136642, P = 5.4 {\texttimes} 10(-9)), PNPLA3 (rs738409, P  =  5.8 {\texttimes} 10(-9)), RELA (rs1049728, P =  2.7 {\texttimes} 10(-16)), and SH2B3 (rs3184504, P =  2.9 {\texttimes} 10(-17)). Two loci, NFKBIB and RELA, are involved in NFKB signaling pathway; PNPLA3 is known for its association with fatty liver disease; and SH3B2 has been associated with a multitude of traits and disease including myocardial infarction. These associations provide insights into the genetic regulation of sICAM-1 levels and implicate these loci in the regulation of endothelial function.

}, keywords = {ABO Blood-Group System, Cohort Studies, Female, Gene Frequency, Genetic Loci, Genome, Human, Genome-Wide Association Study, Genotype, Humans, I-kappa B Kinase, Intercellular Adhesion Molecule-1, Lipase, Membrane Proteins, Models, Genetic, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Proteins, Transcription Factor RelA}, issn = {1553-7404}, doi = {10.1371/journal.pgen.1001374}, author = {Par{\'e}, Guillaume and Ridker, Paul M and Rose, Lynda and Barbalic, Maja and Dupuis, Jos{\'e}e and Dehghan, Abbas and Bis, Joshua C and Benjamin, Emelia J and Shiffman, Dov and Parker, Alexander N and Chasman, Daniel I} } @article {6081, title = {Adhesion molecules, endothelin-1 and lung function in seven population-based cohorts.}, journal = {Biomarkers}, volume = {18}, year = {2013}, month = {2013 May}, pages = {196-203}, abstract = {

CONTEXT: Endothelial function is abnormal in chronic obstructive pulmonary disease (COPD); whether endothelial dysfunction causes COPD is unknown.

OBJECTIVE: Test associations of endothelial biomarkers with FEV1 using instrumental variables.

METHODS: Among 26 907 participants with spirometry, ICAM-1, P-selectin, E-selectin and endothelin-1 were measured in subsets.

RESULTS: ICAM-1 and P-selectin were inversely associated with FEV1 among European-Americans (-29 mL and -34 mL per standard deviation of log-transformed biomarker, p < 0.001), as was endothelin-1 among African-Americans (-22 mL, p = 0.008). Genetically-estimated ICAM-1 and P-selectin were not significantly associated with FEV1. The instrumental variable for endothelin-1 was non-informative.

CONCLUSION: Although ICAM-1, P-selectin and endothelin-1 were inversely associated with FEV1, associations for ICAM-1 and P-selectin do not appear causal.

}, keywords = {African Continental Ancestry Group, Biomarkers, Cohort Studies, E-Selectin, Endothelin-1, Endothelium, Vascular, European Continental Ancestry Group, Female, Gene Expression, Humans, Intercellular Adhesion Molecule-1, Lung, Male, Middle Aged, P-Selectin, Pulmonary Disease, Chronic Obstructive, Respiratory Function Tests, Spirometry}, issn = {1366-5804}, doi = {10.3109/1354750X.2012.762805}, author = {Oelsner, E C and Pottinger, T D and Burkart, K M and Allison, M and Buxbaum, S G and Hansel, N N and Kumar, R and Larkin, E K and Lange, L A and Loehr, L R and London, S J and O{\textquoteright}Connor, G T and Papanicolaou, G and Petrini, M F and Rabinowitz, D and Raghavan, S and Redline, S and Thyagarajan, B and Tracy, R P and Wilk, J B and White, W B and Rich, S S and Barr, R G} }