Circulating Soluble CD163, Associations With Cardiovascular Outcomes and Mortality, and Identification of Genetic Variants in Older Individuals: The Cardiovascular Health Study

Background Monocytes/macrophages participate in cardiovascular disease. CD163 (cluster of differentiation 163) is a monocyte/macrophage receptor, and the shed sCD163 (soluble CD163) reflects monocyte/macrophage activation. We examined the association of sCD163 with incident cardiovascular disease ev...

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Veröffentlicht in:Journal of the American Heart Association Jg. 11; H. 21; S. e024374
Hauptverfasser: Durda, Peter, Raffield, Laura M., Lange, Ethan M., Olson, Nels C., Jenny, Nancy Swords, Cushman, Mary, Deichgraeber, Pia, Grarup, Niels, Jonsson, Anna, Hansen, Torben, Mychaleckyj, Josyf C., Psaty, Bruce M., Reiner, Alex P., Tracy, Russell P., Lange, Leslie A.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: England John Wiley and Sons Inc 01.11.2022
Wiley
Schlagworte:
Aged
Antigens, CD - blood
Antigens, Differentiation, Myelomonocytic - genetics
Asialoglycoprotein Receptor
Biomarkers
cardiovascular diseases
Cardiovascular Diseases - diagnosis
Cardiovascular Diseases - epidemiology
Cardiovascular Diseases - genetics
CD163 Antigen
Female
Genome-Wide Association Study
Heart Failure
Humans
Longitudinal Studies
Male
monocytes
Original Research
risk factors
CD163 antigen
monocytes
risk factors
cardiovascular diseases
genome‐wide association study
humans
ISSN:2047-9980, 2047-9980
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Zusammenfassung:Background Monocytes/macrophages participate in cardiovascular disease. CD163 (cluster of differentiation 163) is a monocyte/macrophage receptor, and the shed sCD163 (soluble CD163) reflects monocyte/macrophage activation. We examined the association of sCD163 with incident cardiovascular disease events and performed a genome-wide association study to identify sCD163-associated variants. Methods and Results We measured plasma sCD163 in 5214 adults (aged ≥65 years, 58.7% women, 16.2% Black) of the CHS (Cardiovascular Health Study). We used Cox regression models (associations of sCD163 with incident events and mortality); median follow-up was 26 years. Genome-wide association study analyses were stratified on race. Adjusted for age, sex, and race and ethnicity, sCD163 levels were associated with all-cause mortality (hazard ratio [HR], 1.08 [95% CI, 1.04-1.12] per SD increase), cardiovascular disease mortality (HR, 1.15 [95% CI, 1.09-1.21]), incident coronary heart disease (HR, 1.10 [95% CI, 1.04-1.16]), and incident heart failure (HR, 1.18 [95% CI, 1.12-1.25]). When further adjusted (eg, cardiovascular disease risk factors), only incident coronary heart disease lost significance. In European American individuals, genome-wide association studies identified 38 variants on chromosome 2 near (top result rs62165726, =3.3×10 ),19 variants near chromosome 17 gene (rs55714927, =1.5×10 ), and 18 variants near chromosome 11 gene . These regions replicated in the European ancestry ADDITION-PRO cohort, a longitudinal cohort study nested in the Danish arm of the Anglo-Danish-Dutch study of Intensive Treatment Intensive Treatment In peOple with screeNdetcted Diabetes in Primary Care. In Black individuals, we identified 9 variants on chromosome 6 (rs3129781 =7.1×10 ) in the region, and 3 variants (rs115391969 =4.3×10 ) near the chromosome 16 gene Conclusions Monocyte function, as measured by sCD163, may be predictive of overall and cardiovascular-specific mortality and incident heart failure.
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R. P. Tracy and L. A. Lange contributed equally.
For Sources of Funding and Disclosures, see page 12.
ISSN:2047-9980
2047-9980
DOI:10.1161/JAHA.121.024374