Associations Between Macrophage Colony‐Stimulating Factor and Monocyte Chemotactic Protein 1 in Plasma and First‐Time Coronary Events: A Nested Case–Control Study
Open accessAbstract
Background: Myeloid cells play a central role in atherosclerosis. We investigated the associations between the plasma levels of growth factors and chemokines that regulate myeloid cell homeostasis and function and the risk of first‐time acute coronary events in middle‐aged persons. Methods and Results: We measured baseline plasma levels of macrophage colony‐stimulating factor; monocyte chemotactic protein 1; C‐C motif chemokine ligands 3, 4, and 20; C‐X‐C motif chemokine ligands 1, 6, and 16; and C‐X3‐C motif chemokine ligand 1 in 292 participants who had a coronary event during follow‐up and 366 controls matched for age, sex, and time of inclusion who remained event free. Study participants were recruited from the Malmö Diet and Cancer Study population cohort and had no previous history of coronary artery disease. We found a strong independent negative association between macrophage colony‐stimulating factor and incident coronary events in a forward stepwise Cox proportional hazards model including all biomarkers alongside the classic Framingham risk factors (age, sex, smoking, total cholesterol, high‐density lipoprotein cholesterol, systolic blood pressure), diabetes mellitus, and medication. Conversely, monocyte chemotactic protein 1 had the strongest independent positive association with the outcome. The addition of macrophage colony‐stimulating factor and monocyte chemotactic protein 1 significantly improved the predictive ability of a model including traditional risk factors alone (C statistic 0.81 [95% CI 0.78–0.84] versus 0.67 [95% CI 0.63–0.71]; net reclassification index 0.52 [0.42–0.62]; P <0.001). The combined model led to a 54% net downclassification of participants who did not have a coronary event during follow‐up and was particularly effective in the intermediate‐risk group. Conclusions: High levels of macrophage colony‐stimulating factor and low levels of monocyte chemotactic protein 1 in plasma characterize middle‐aged persons at low risk to develop clinically manifested coronary artery disease.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Modified lipids activate intimal inflammatory cells to secrete pro-inflammatory chemokines and cytokines, promoting further recruitment of myeloid inflammatory cells, particularly inflammatory monocytes, in mice and humans.
“The modified lipids then activate the inflammatory cells present in the intima, which respond by secreting pro-inflammatory chemokines and cytokines that in turn activate circulating leukocytes and the local endothelial cells, thereby promoting further recruitment of inflammatory cells of myeloid origin, particularly a specific subset of circulating monocytes with inflammatory potential, as shown”
From Inflammation and its resolution in atherosclerosis: mediators and therapeutic opportunities (2019) · cites this paper as [20]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
DeLong, E. R., DeLong, D. M., & Clarke-Pearson, D. L. (1988) · Biometrics · doi:10.2307/2531595 · Cited by 22,649 · see citing works
Macrophages in atherosclerosis: a dynamic balance
Moore, K. J., Sheedy, F. J., & Fisher, E. A. (2013) · Nature reviews. Immunology · doi:10.1038/nri3520 · Cited by 2,559 · see citing works
Extensions of net reclassification improvement calculations to measure usefulness of new biomarkers
Pencina, M. J., D’Agostino, R. B., & Steyerberg, E. W. (2010) · Statistics in Medicine · doi:10.1002/sim.4085 · Cited by 2,478 · see citing works
Hashimoto, D., Chow, A., Noizat, C., Teo, P., Beasley, M. B., Leboeuf, M., Becker, C. D., See, P., Price, J., Lucas, D., et al. (2013) · Immunity · doi:10.1016/j.immuni.2013.04.004 · Cited by 2,311 · see citing works
Assarsson, E., Lundberg, M., Holmquist, G., Björkesten, J., Bucht Thorsen, S., Ekman, D., Eriksson, A., Rennel Dickens, E., Ohlsson, S., Edfeldt, G., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0095192 · Cited by 1,874 · see citing works
Serbina, N. V., & Pamer, E. G. (2006) · Nature Immunology · doi:10.1038/ni1309 · Cited by 1,658 · see citing works
Colony-stimulating factors in inflammation and autoimmunity
Hamilton, J. A. (2008) · Nature reviews. Immunology · doi:10.1038/nri2356 · Cited by 1,305 · see citing works
Local proliferation dominates lesional macrophage accumulation in atherosclerosis
Robbins, C. S., Hilgendorf, I., Weber, G. F., Theurl, I., Iwamoto, Y., Figueiredo, J.-L., Gorbatov, R., Sukhova, G. K., Gerhardt, L. M. S., Smyth, D., et al. (2013) · Nature Medicine · doi:10.1038/nm.3258 · Cited by 1,041 · see citing works
Smith, J. D., Trogan, E., Ginsberg, M., Grigaux, C., Tian, J., & Miyata, M. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.18.8264 · Cited by 721 · see citing works
Berglund, G., Elmståhl, S., Janzon, L., & LARSSON, S. A. (1993) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.1993.tb00647.x · Cited by 640 · see citing works
Fleetwood, A. J., Lawrence, T., Hamilton, J. A., & Cook, A. D. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.8.5245 · Cited by 607 · see citing works
Zernecke, A., Shagdarsuren, E., & Weber, C. (2008) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.107.161174 · Cited by 376 · see citing works
Colony stimulating factors and myeloid cell biology in health and disease
Hamilton, J. A., & Achuthan, A. (2013) · Trends in Immunology · doi:10.1016/j.it.2012.08.006 · Cited by 285 · see citing works
Deo, R., Khera, A., McGuire, D. K., Murphy, S. A., Neto, J. D. P. M., Morrow, D. A., & de Lemos, J. A. (2004) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2004.07.047 · Cited by 270 · see citing works
Elevated CD14 <sup>++</sup> CD16 <sup>−</sup> Monocytes Predict Cardiovascular Events
Berg, K. E., Ljungcrantz, I., Andersson, L., Bryngelsson, C., Hedblad, B., Fredrikson, G. N., Nilsson, J., & Björkbacka, H. (2012) · Circulation: Cardiovascular Genetics · doi:10.1161/circgenetics.111.960385 · Cited by 257 · see citing works
Self-citationMcDermott, D. H., Yang, Q., Kathiresan, S., Cupples, L. A., Massaro, J. M., Keaney, J. F., Larson, M. G., Vasan, R. S., Hirschhorn, J. N., O’Donnell, C. J., et al. (2005) · Circulation · doi:10.1161/circulationaha.105.543579 · Cited by 230 · see citing works
Gautier, E. L., Jakubzick, C., & Randolph, G. J. (2009) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.108.180505 · Cited by 216 · see citing works
Neutrophils in Atherosclerosis
Döring, Y., Drechsler, M. D., Soehnlein, O., & Weber, C. (2014) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.114.303564 · Cited by 208 · see citing works
Incidence of stroke is related to carotid IMT even in the absence of plaque
Rosvall, M., Janzon, L., Berglund, G., Engström, G., & Hedblad, B. (2004) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2004.10.015 · Cited by 208 · see citing works
Zernecke, A., & Weber, C. (2014) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.113.301655 · Cited by 193 · see citing works
Coordinate regulation of tissue macrophage and dendritic cell population dynamics by CSF-1
Tagliani, E., Shi, C., Nancy, P., Tay, C.-S., Pamer, E. G., & Erlebacher, A. (2011) · The Journal of Experimental Medicine · doi:10.1084/jem.20110866 · Cited by 181 · see citing works
Homeostasis in the mononuclear phagocyte system
Jenkins, S. J., & Hume, D. A. (2014) · Trends in Immunology · doi:10.1016/j.it.2014.06.006 · Cited by 178 · see citing works
Hashimoto, D., Chow, A. T., Greter, M., Saenger, Y. M., Kwan, W.-H., Leboeuf, M., Ginhoux, F., Ochando, J., Kunisaki, Y., van Rooijen, N., et al. (2011) · The Journal of Experimental Medicine · doi:10.1084/jem.20101709 · Cited by 172 · see citing works
Gijsbers, K., Gouwy, M., Struyf, S., Wuyts, A., Proost, P., Opdenakker, G., PENNINCKX, F. M., Ectors, N., Geboes, K. J., & Damme, J. V. (2004) · Experimental Cell Research · doi:10.1016/j.yexcr.2004.09.027 · Cited by 158 · see citing works
Hoogeveen, R. C., Morrison, A. C., Boerwinkle, E., MILES, J., Rhodes, C. E., SHARRETT, A., & Ballantyne, C. M. (2005) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2005.03.007 · Cited by 147 · see citing works
Jones, C. V., & Ricardo, S. D. (2013) · Organogenesis · doi:10.4161/org.25676 · Cited by 147 · see citing works
de Villiers, W. J. S., Fraser, I. P., Hughes, D. A., Doyle, A., & Gordon, S. (1994) · The Journal of Experimental Medicine · doi:10.1084/jem.180.2.705 · Cited by 128 · see citing works
Swierczak, A., Cook, A. D., Lenzo, J. C., Restall, C. M., Doherty, J. P., Anderson, R. L., & Hamilton, J. A. (2014) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-13-0190 · Cited by 127 · see citing works
Chemokines and Incident Coronary Heart Disease
Herder, C., Baumert, J. J., Thorand, B., Martin, S., Löwel, H., Kolb, H., & Köenig, W. (2006) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000235691.84430.86 · Cited by 125 · see citing works
Cotoi, O. S., Dunér, P., Ko, N., Hedblad, B., Nilsson, J. Å., Björkbacka, H., & Șchiopu, A. (2013) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.113.302432 · Cited by 111 · see citing works
Self-citationUnique Proteomic Signatures Distinguish Macrophages and Dendritic Cells
Becker, L., Liu, N.-C., Averill, M. M., Yuan, W., Pamir, N., Peng, Y., Irwin, A. D., Fu, X., Bornfeldt, K., & Heinecke, J. W. (2012) · PLoS ONE · doi:10.1371/journal.pone.0033297 · Cited by 102 · see citing works
Murayama, T., Yokode, M., Kataoka, H., Imabayashi, T., Yoshida, H., Sano, H., Nishikawa, S., Nishikawa, S., & Kita, T. (1999) · Circulation · doi:10.1161/01.cir.99.13.1740 · Cited by 95 · see citing works
Discovery of New Risk Markers for Ischemic Stroke Using a Novel Targeted Proteomics Chip
Lind, L., Siegbahn, A., Lindahl, B., Stenemo, M., Sundström, J., & Ärnlöv, J. (2015) · Stroke · doi:10.1161/strokeaha.115.010829 · Cited by 84 · see citing works
Monocyte chemoattractant protein-1 and atherosclerosis: Is there room for an additional biomarker?
Coll, B., Alonso‐Villaverde, C., & Joven, J. (2007) · Clinica Chimica Acta · doi:10.1016/j.cca.2007.04.019 · Cited by 80 · see citing works
Yano, T., Miura, T., Whittaker, P., et al. (2006) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2005.09.037 · Cited by 74 · see citing works
Inoue, I., Inaba, T., Motoyoshi, K., Harada, K., Shimano, H., Kawamura, M., Gotoda, T., Oka, T., Shiomi, M., Watanabe, Y., et al. (1992) · Atherosclerosis · doi:10.1016/0021-9150(92)90261-e · Cited by 65 · see citing works
Shaposhnik, Z., Wang, X., & Lusis, A. J. (2010) · Journal of Lipid Research · doi:10.1194/jlr.m005215 · Cited by 64 · see citing works
Saitoh, T., Kishida, H., Tsukada, Y. T., Fukuma, Y., Sano, J., Yasutake, M., Fukuma, N., Kusama, Y., & Hayakawa, H. (2000) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(99)00583-5 · Cited by 64 · see citing works
Okazaki, T., Ebihara, S., Asada, M., et al. (2007) · American Journal Of Pathology · doi:10.2353/ajpath.2007.061191 · Cited by 60 · see citing works
Role of colony-stimulating factors in atherosclerosis
Di Gregoli, K., & Johnson, J. L. (2012) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e328357ca6e · Cited by 55 · see citing works
Huang, Y., & Pepe, M. S. (2009) · Biometrics · doi:10.1111/j.1541-0420.2009.01201.x · Cited by 45 · see citing works
Ikonomidis, I., Lekakis, J. P., Revela, I., et al. (2005) · European Heart Journal · doi:10.1093/eurheartj/ehi192 · Cited by 45 · see citing works
Rallidis, L. S., Zolindaki, M., Manioudaki, H. S., PAPASTERIADIS, E. G., Laoutaris, N. P., & Velissaridou, A. H. (2002) · Clinical Cardiology · doi:10.1002/clc.4960251106 · Cited by 36 · see citing works
Randolph, G. J. (2011) · Science · doi:10.1126/science.1208480 · Cited by 26 · see citing works
Rallidis, L. S., Zolindaki, M. G., Pentzeridis, P. C., et al. (2003) · Heart · doi:10.1136/heart.90.1.25 · Cited by 25 · see citing works
Overexpression of CXCL16 promotes a vulnerable plaque phenotype in Apolipoprotein E–Knockout Mice
Yi, G., Zeng, Q., Mao, X., et al. (2010) · Cytokine · doi:10.1016/j.cyto.2010.11.016 · Cited by 23 · see citing works
Sakurai, T., Yamada, M., Simamura, S., et al. (1996) · Cellular Immunology · doi:10.1006/cimm.1996.0177 · Cited by 13 · see citing works
Macrophage Inflammatory Protein-1β: A Novel Prognostic Biomarker in Atherosclerosis?
Vistnes, M. (2012) · Cardiology · doi:10.1159/000336484 · Cited by 9 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Inflammation and its resolution in atherosclerosis: mediators and therapeutic opportunities
Bäck, M., Yurdagul, A., Tabas, I., Öörni, K., & Kovanen, P. T. (2019) · Nature Reviews Cardiology · doi:10.1038/s41569-019-0169-2 · Cited by 1,341 · see citing works
Associations of Adiposity, Circulating Protein Biomarkers, and Risk of Major Vascular Diseases
Pang, Y., Kartsonaki, C., Lv, J., Fairhurst-Hunter, Z., Millwood, I. Y., Yu, C., Guo, Y., Chen, Y., Bian, Z., Yang, L., et al. (2021) · JAMA Cardiology · doi:10.1001/jamacardio.2020.6041 · Cited by 75 · see citing works
- Authors
- Schiopu, A., Bengtsson, E., Gonçalves, I., Nilsson, J., Fredrikson, G. N., & Björkbacka, H.
- Affiliations
- Department of Clinical Sciences Malmö, Lund University, Sweden
- Lund University (SE)
- Venue
- Journal of the American Heart Association
- Published
- 2016-09
- Volume
- 5
- Issue
- 9
- ISSN
- 2047-9980 (ISSN-L)
- PMC
- PMC5079003
- OpenAlex
- W2519028360
- Cited by
- 25
- References
- 48
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 4 · 2020: 4 · 2019: 5 · 2018: 3 · 2017: 2
- FWCI
- 2.02
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc
- Locations
- Journal of the American Heart Association (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Lund University Publications (Lund University) (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- macrophage colony-stimulating factor, MCP-1, chemokines, myeloid cells, atherosclerosis, acute coronary events, coronary artery disease risk, plasma biomarkers, risk prediction, middle-aged adults, Framingham risk factors
- MeSH terms
- Chemokine CXCL16, Aged, Female, Humans, Male, Middle Aged, Myocardial Infarction, Sweden, Cohort Studies, Proportional Hazards Models, Case-Control Studies, Macrophage Colony-Stimulating Factor, Myocardial Ischemia, Chemokine CCL2, Chemokine CXCL1, Chemokine CCL3, Chemokine CCL4, Chemokine CCL20, Chemokine CXCL6, Chemokine CX3CL1
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
