Cited by 1,229Atherosclerosis and Cardiovascular DiseasesLipoproteins and Cardiovascular HealthAcute Myocardial Infarction Research

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Plasma concentration of soluble intercellular adhesion molecule 1 and risks of future myocardial infarction in apparently healthy men

Ridker, Paul M, Hennekens, Charles H, Roitman-Johnson, Beatrice, Stampfer, Meir J, Allen, Jean·1998·The Lancet

DOI 10.1016/s0140-6736(97)09032-6

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Abstract

Background The intercellular adhesion molecule ICAM-1 mediates adhesion and transmigration of leucocytes to the vascular endothelial wall, a step proposed to be critical in the initiation and progression of atherosclerosis. Whether concentrations of soluble ICAM-1 (sICAM-1) are raised in apparently healthy individuals who later suffer acute myocardial infarction is unknown.Methods We obtained baseline plasma samples from a prospective cohort of 14,916 healthy men enrolled in the Physicians' Health Study. With a nested case-control design, we measured sICAM-1 concentrations for 474 participants who developed a first myocardial infarction, and 474 controls (participants who remained healthy throughout the 9-year follow-up). Cases were matched to controls according to age and smoking status at the time of myocardial infarction.Findings We found a significant association between increasing concentration of sICAM-1 and risk of future myocardial infarction (p = 0.003), especially among participants with baseline sICAM-1 concentrations in the highest quartile (> 260 ng/mL; relative risk 1.6 [95% Cl 1.1-2.4], p = 0.02). This association was present overall as well as among non-smokers, and persisted after control for lipid and non-lipid risk factors. In multivariate analyses, the risk of future myocardial infarction was 80% higher for participants with baseline sICAM-1 concentrations in the highest quartile (relative risk 1.8 [1.1-2.8], p = 0.02). Similar risk estimates were seen among non-smokers. We found slight but significant correlations between sICAM-1 and fibrinogen, high-density-lipoprotein cholesterol, homocysteine, triglycerides, tissue-type plasminogen-activator antigen, and C-relative protein, but adjustment for these altered the risk little. The risk of myocardial infarction associated with raised concentrations of sICAM-1 seemed to increase with length of follow-up.Interpretation Our data support the hypothesis that cellular mediators of inflammation have a role in atherogenesis and provide a clinical basis to consider antiadhesion therapies as a novel means of cardiovascular disease prevention.

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Atorvastatin improves metabolic control and endothelial function in Type 2 diabetic patients: A placebo-controlled study
Nora, E. D., Passaro, A., Zamboni, P., Calzoni, F., Fellin, R., & Solini, A. (2003) · Journal of Endocrinological Investigation · doi:10.1007/bf03345126 · Cited by 47
The effect of alcohol consumption on endothelial adhesion molecule expression
Sacanella, E., & Estruch, R. (2003) · Addiction Biology · doi:10.1080/13556210310001656376 · Cited by 47
“In fact, this latter application has already been used in large epidemiological studies with good correlations.(30,32,45) However, it would”
Method
Gene-Centric Meta-Analysis of Lipid Traits in African, East Asian and Hispanic Populations
Elbers, C. C., Guo, Y., Tragante, V., van Iperen, E. P. A., Lanktree, M. B., Castillo, B. A., Chen, F., Yanek, L. R., Wojczynski, M. K., Li, Y. R., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0050198 · Cited by 47
“sICAM1 has been associated with several common diseases such as diabetes, heart disease, stroke, and malaria [46,47].”
Background
Contribution of insulin resistance to vascular dysfunction
Anfossi, G., Russo, I., Doronzo, G., & Trovati, M. (2009) · Archives of Physiology and Biochemistry · doi:10.1080/13813450903136791 · Cited by 49
“, 1998), as well as an increase of circulating levels of specific markers of endothelial activation, such as von Willebrand factor, thrombomodulin, E-selectin, P-selectin, soluble ICAM (sICAM) and soluble VCAM-1 (sVCAM) (Hwang et al., 1997; Cosentino & Luscher, 1998; Ridker et al., 1998; Malik et al., 2001).”
Background
THE CLINICAL EPIDEMIOLOGY OF CARDIOVASCULAR DISEASES IN CHRONIC KIDNEY DISEASE: Uremia‐Related Metabolic Cardiac Risk Factors in Chronic Kidney Disease
Madore, F. (2003) · Seminars in Dialysis · doi:10.1046/j.1525-139x.2003.16031.x · Cited by 47
Effect of smoking cessation on markers of inflammation and endothelial cell activation among individuals with high risk for cardiovascular disease
Halvorsen, B. L., Sagen, E. L., Ueland, T., Aukrust, P., & Tonstad, S. (2007) · Scandinavian Journal of Clinical and Laboratory Investigation · doi:10.1080/00365510701283878 · Cited by 46
“There is also accumulating evidence from prospective studies showing that circulating levels of sICAM-1 can predict CAD events in initially healthy people as well as in patients at high risk or with overt CAD [13].”
Background
Connecting the role of C-reactive protein and statins in cardiovascular disease
Ridker, P. M. (2003) · Clinical Cardiology · doi:10.1002/clc.4960261508 · Cited by 46
Medroxyprogesterone acetate versus norethisterone: effect on estradiol-induced changes of markers for endothelial function and atherosclerotic plaque characteristics in human female coronary endothelial cell cultures
Mueck, A. O., Seeger, H., & Wallwiener, D. R. (2002) · Menopause The Journal of The North American Menopause Society · doi:10.1097/00042192-200207000-00008 · Cited by 46
“showed that a soluble form of adhesion molecules can be measured in the serum.(21) Evidence is growing that they emerge from shedding of membrane-associated adhesion molecules and thus indirectly reflect the expression of adhesion molecules on endothelial cells.”
Background
Reduced Expression of Endothelial Cell Markers after Long-term Transdermal Hormone Replacement Therapy in Women with Coronary Artery Disease
Arnesen, H., Hofstad, A.-E., Os, I., & Seljeflot, I. (2000) · Thrombosis and Haemostasis · doi:10.1055/s-0037-1613947 · Cited by 46
“In addition, an association between plasma levels of soluble ICAMs and risk for future myocardial infarction in healthy men, was recently reported (18).”
Background
Risk Factors Associated with Different Stages of Atherosclerosis in Colombian Patients with Rheumatoid Arthritis
Rojas‐Villarraga, A., Ortega‐Hernandez, O., Gómez, L. F., Pardo, A. L., López-Guzmán, S., Arango-Ferreira, C., Zapata, M. E. H., Betancur, J. F., Pineda-Tamayo, R. A., Díaz, F. J., et al. (2008) · Seminars in Arthritis and Rheumatism · doi:10.1016/j.semarthrit.2008.01.019 · Cited by 45
s-ICAM-1 and s-VCAM-1 in healthy men are strongly associated with traits of the metabolic syndrome, becoming evident in the postprandial response to a lipid-rich meal
Rubin, D., Claas, S., Pfeuffer, M., Nothnagel, M., Fölsch, U. R., & Schrezenmeir, J. (2008) · Lipids in Health and Disease · doi:10.1186/1476-511x-7-32 · Cited by 45
“In contrast, Ridker et al. [ 9 ] found a slight but significant correlation between sICAM-1 and fasting triglycerides in patients with risk for future myocardial infarction.”
ABO blood group associations with markers of endothelial dysfunction in the Multi-Ethnic Study of Atherosclerosis
Larson, N. B., Bell, E. J., Decker, P. A., Pike, M., Wassel, C. L., Tsai, M. Y., Pankow, J. S., Tang, W., Hanson, N. Q., Alexander, K., et al. (2016) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2016.05.049 · Cited by 45
“Soluble forms of CAMs Eselectin (sE-Selectin), P-selectin (sP-selectin), and ICAM-1 (sICAM1) are biomarkers of inflammation, and increased circulation with one or more of these markers has been associated with coronary artery disease [12], myocardial infarction [13] and atherosclerosis [14e16].”
Background
Elevated soluble ICAM‐1 levels induce immune deficiency and increase adiposity in mice
Wang, H., Babic, A. M., Mitchell, H. A., Liu, K., & Wagner, D. D. (2005) · The FASEB Journal · doi:10.1096/fj.04-3094fje · Cited by 45
“In inflammation, sICAM-1 levels reflect endothelial cell activation, and indeed there is increasing evidence that patients with high levels of sICAM-1 are at risk for cardiovascular disease (12, 13).”
Background
Effects of enalapril and losartan on circulating adhesion molecules and monocyte chemotactic protein-1
Jilma, B., Li‐Saw‐Hee, F. L., Wagner, O. F., Beevers, D. G., & Lip, G. Y. H. (2002) · Clinical Science · doi:10.1042/cs1030131 · Cited by 45
Cellular adhesion molecules and peripheral arterial disease
Brevetti, G., Schiano, V., & Massimo Chiariello, A. (2006) · Vascular Medicine · doi:10.1191/1358863x06vm645ra · Cited by 44
HIV , highly active antiretroviral therapy and the heart: a cellular to epidemiological review
Lambert, C., Sandesara, P. B., Hirsh, B. J., Shaw, L. J., Lewis, W., Quyyumi, A. A., Schinazi, R., Post, W. S., & Sperling, L. S. (2015) · HIV Medicine · doi:10.1111/hiv.12346 · Cited by 44
“…are underway as to whether contributors [soluble intercellular adhesion molecules (sICAMs), tissue plasminogen activator molecules (t-PAs) and plasminogen activator inhibitor (PAI-1)] to this “dysfunction cascade” could be used as biomarkers to more reliably predict risk [61,62,109–113].”
Association of sICAM-1 and MCP-1 with coronary artery calcification in families enriched for coronary heart disease or hypertension: the NHLBI Family Heart Study
Tang, W., Pankow, J. S., Carr, J. J., Tracy, R. P., Bielinski, S. J., North, K. E., Hopkins, P. N., Kraja, A. T., & Arnett, D. K. (2007) · BMC Cardiovascular Disorders · doi:10.1186/1471-2261-7-30 · Cited by 44
“Prospective epidemiological studies have found increased risk of incident or recurrent coronary heart disease (CHD) associated with higher baseline levels of sICAM-1 and MCP-1 [15-18], but it is unclear whether sICAM-1 and MCP-1 reflect the burden of subclinical coronary atherosclerosis.”
The potential anti-inflammatory benefits of improving physical fitness in hypertension
Edwards, K. M., Ziegler, M. G., & Mills, P. J. (2007) · Journal of Hypertension · doi:10.1097/hjh.0b013e328165ca67 · Cited by 43
Effect of nicotine replacement and quitting smoking on circulating adhesion molecule profiles (sICAM‐1, sCD44v5, sCD44v6)
Palmer, R. M. J., Stapleton, J., Sutherland, G., Coward, P. Y., Wilson, R. F., & Scott, D. A. (2002) · European Journal of Clinical Investigation · doi:10.1046/j.1365-2362.2002.01067.x · Cited by 44
Additive effect of interleukin-6 and C-reactive protein (CRP) single nucleotide polymorphism on serum CRP concentration and other cardiovascular risk factors
Paik, J. K., Kim, O. Y., Koh, S. J., Jang, Y., Chae, J. S., Kim, J. Y., Kim, H. J., Hyun, Y. J., Cho, J. R., & Lee, J. H. (2006) · Clinica Chimica Acta · doi:10.1016/j.cca.2006.11.011 · Cited by 44
Effects of Nebivolol on Endothelial Gene Expression during Oxidative Stress in Human Umbilical Vein Endothelial Cells
Garbin, U., Pasini, A. F., Stranieri, C., Manfro, S., Mozzini, C., Boccioletti, V., Pasini, A., Cominacini, M., Evangelista, S., & Cominacini, L. (2008) · Mediators of Inflammation · doi:10.1155/2008/367590 · Cited by 44
“Several studies have reported increased plasma levels of E-selectin and ICAM-1 in patients with hypertension, diabetes, and hypercholesterolemia [25– 28]; moreover in patients at cardiovascular risk, plasma concentration of ICAM-1 can predict adverse outcome [27, 28].”
Background
Physical performance is associated with markers of vascular inflammation in patients with coronary heart disease
Schumacher, A., Peersen, K., Sommervoll, L., Seljeflot, I., Arnesen, H., & Otterstad, J. E. (2006) · European Journal of Cardiovascular Prevention & Rehabilitation · doi:10.1097/01.hjr.0000188244.54287.96 · Cited by 44
Soluble Receptors for Advanced Glycation End Products (sRAGE) as a Predictor of Restenosis Following Percutaneous Coronary Intervention
McNair, E. D., Wells, C. R., Qureshi, A. M., Basran, R., Pearce, C., Orvold, J., Devilliers, J., & Prasad, K. (2010) · Clinical Cardiology · doi:10.1002/clc.20815 · Cited by 44
Diagnostic value of CRP and Lp(a) in coronary heart disease
Erbağcı, A. B., Tarakçıoğlu, M., Aksoy, M. F., Kocabaş, R., Nacak, M., Aynacıoğlu, A. Ş., & Sivrikoz, C. (2002) · Acta Cardiologica · doi:10.2143/ac.57.3.2005389 · Cited by 44
Combined hormone replacement therapy improves endothelial function in healthy postmenopausal women
Gužič‐Salobir, B., Keber, I., Seljeflot, I., Arnesen, H., & Dežman, L. V. (2001) · Journal of Internal Medicine · doi:10.1046/j.1365-2796.2001.00910.x · Cited by 44
Dramatic Decline in Circulating Intercellular Adhesion Molecule-1 Concentration on Quitting Tobacco Smoking
Scott, D. A., Stapleton, J., Wilson, R. F., Sutherland, G., Palmer, R. M. J., Coward, P. Y., & GUSTAVSSON, G. (2000) · Blood Cells Molecules and Diseases · doi:10.1006/bcmd.2000.0304 · Cited by 44
The mechanisms of thrombotic risk induced by hormone replacement therapy
Cano, A., & van Baal, W. M. (2001) · Maturitas · doi:10.1016/s0378-5122(01)00270-5 · Cited by 44
“[175] Ridker PM, Hennekens CH, Roitman-Johnson B,”
Background
Soluble intercellular adhesion molecule-1 is related to endothelial vasodilatory function in healthy individuals
Holmlund, A., Hulthe, J., Millgård, J., Sarabi, M., Kahan, T., & Lind, L. (2002) · Atherosclerosis · doi:10.1016/s0021-9150(02)00234-4 · Cited by 44
Is Type 2 Diabetes Mellitus a Vascular Condition?
Hu, F. B., & Stampfer, M. J. (2003) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000094360.38911.71 · Cited by 44
Circulating adhesion molecules in obstructive sleep apnea and cardiovascular disease
Pak, V. M., Grandner, M. A., & Pack, A. I. (2014) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2013.01.002 · Cited by 43
Role of environmental toxicants in the development of hypertensive and cardiovascular diseases
Habeeb, E. A., Aldosari, S. A., Saghir, S. A., Cheema, M., Momenah, T., Husain, K. M., Omidi, Y., Rizvi, S. A. A., Akram, M., & Ansari, R. A. (2022) · Toxicology Reports · doi:10.1016/j.toxrep.2022.03.019 · Cited by 50
“A positive association between long-term well-water As exposure and plasma levels of soluble ICAM-1 and soluble VCAM-1 (biomarkers to predict future CVD), biomarkers of endothelial dysfunction, and vascular inflammation is observed in an As-exposed population of Araihazar, Bangladesh [15,155,37].”
Background
Mechanisms of action for arsenic in cardiovascular toxicity and implications for risk assessment
Sidhu, M. S., Desai, K. P., Lynch, H. N., Rhomberg, L. R., Beck, B. D., & Venditti, F. J. (2015) · Toxicology · doi:10.1016/j.tox.2015.02.008 · Cited by 43
“…iAs-related skin lesions in Bangladesh, there was a positive association with plasma levels of soluble ICAM-I (sICAM-1) and soluble VCAM-1 (sVCAM-1) (Chen et al., 2007b), markers indicative of potential development of CVD (Blankenberg et al., 2001; Ridker et al., 1998, 2000; States et al., 2009).”
Background
Circulating adhesion molecules, matrix metalloproteinase-9, plasminogen activator inhibitor-1, and myeloperoxidase in coronary artery disease patients with stable and unstable angina
Tretjakovs, P., Jurka, A., Bormane, I., Miķelsone, I., Elksne, K., Krieviņa, G., Reihmane, D., Verbovenko, J., & Bahs, G. (2011) · Clinica Chimica Acta · doi:10.1016/j.cca.2011.10.009 · Cited by 43
Differential Associations Between Soluble Cellular Adhesion Molecules and Atherosclerosis in the Dallas Heart Study
Rohatgi, A. K., Owens, A. W., Khera, A., Ayers, C. R., Banks, K., Das, S. R., Berry, J. D., McGuire, D. K., & de Lemos, J. A. (2009) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.109.190553 · Cited by 43
Baseline ICAM-1 and VCAM-1 are Increased in Initially Healthy Middle-Aged Men who Develop Cardiovascular Disease during 6.6 Years of Follow-Up
Schmidt, C. B., Hulthe, J., & Fagerberg, B. (2008) · Angiology · doi:10.1177/0003319708316899 · Cited by 43
“In contrast to data on baseline levels of ICAM-1, no evidence of an association between baseline VCAM-1 levels and risk of future cardiovascular events has been shown.(7,8) Introduction”
Result
Multiple inflammatory markers in patients with significant coronary artery disease
Videm, V., Wiseth, R., Gunnes, S., MADSEN, H. O., & Garred, P. (2006) · International Journal of Cardiology · doi:10.1016/j.ijcard.2006.07.005 · Cited by 43
“Different markers of endothelial activation have been related to atherosclerosis and/or future risk of cardiovascular events [17–19].”
Background
Effects of Transdermal Estrogen Replacement Therapy on Cardiovascular Risk Factors
Menon, D. V., & Vongpatanasin, W. (2006) · Treatments in Endocrinology · doi:10.2165/00024677-200605010-00005 · Cited by 42
Pathologic markers of allograft arteriopathy: insight into the pathophysiology of cardiac allograft chronic rejection
Labarrere, C. A., Nelson, D. R., & Park, J.-W. (2001) · Current Opinion in Cardiology · doi:10.1097/00001573-200103000-00006 · Cited by 43
Mechanisms of Arsenic Exposure-Induced Hypertension and Atherosclerosis: an Updated Overview
Balarastaghi, S., Rezaee, R., Hayes, A. W., Yarmohammadi, F., & Karimi, G. (2022) · Biological Trace Element Research · doi:10.1007/s12011-022-03153-2 · Cited by 41
“plasma concentration of sICAM-1 and the risk of cardiovascular diseases [105], including myocardial infarction [106] and carotid artery atherosclerosis [107].”
Background
Increased prevalence of coronary artery disease risk markers in patients with chronic hepatitis C – a cross-sectional study
Roed, T., Kristoffersen, U. S., Knudsen, A. D., Wiinberg, N., Lebech, A., Almdal, T., Thomsen, R. W., Kjær, A., & Weis, N. M. (2014) · Vascular Health and Risk Management · doi:10.2147/vhrm.s53557 · Cited by 42

Authors: Ridker, P. M., Hennekens, C. H., Roitman-Johnson, B., Stampfer, M. J., & Allen, J.
Affiliations: Brigham and Women's Hospital (US)
R&D Systems (United States) (US)
Corresponding author: Ridker, Paul M
ORCID: Ridker, Paul M
Hennekens, Charles H
Stampfer, Meir J
Venue: The Lancet
Publisher: Elsevier BV
Published: 1998-01
Volume: 351
Issue: 9096
Pages: 88-92
ISSN: 0099-5355 (ISSN-L)
0140-6736
DOI: 10.1016/s0140-6736(97)09032-6
OpenAlex: W2138809584
Cited by: 1,229
References: 35
Citations by year: 2026: 7 · 2025: 10 · 2024: 8 · 2023: 10 · 2022: 16 · 2021: 16 · 2020: 17 · 2019: 23 · 2018: 14 · 2017: 28 · 2016: 27 · 2015: 25 · 2014: 38 · 2013: 27 · 2012: 36
FWCI: 26.16
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: The Lancet (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Acute Myocardial Infarction Research
Keywords: soluble intercellular adhesion molecule-1, sICAM-1, myocardial infarction, atherosclerosis, inflammation, endothelial cell adhesion, anti-adhesion therapy, cardiovascular risk, fibrinogen, homocysteine, tissue plasminogen activator, C-reactive protein, healthy men, Physicians' Health Study
MeSH terms: Antioxidants, Arteriosclerosis, Aspirin, Double-Blind Method, Humans, Male, Middle Aged, Myocardial Infarction, Platelet Aggregation Inhibitors, Prospective Studies, Risk Factors, Multivariate Analysis, Case-Control Studies, Intercellular Adhesion Molecule-1, beta Carotene

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Plasma concentration of soluble intercellular adhesion molecule 1 and risks of future myocardial infarction in apparently healthy men

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